ColumtJia ® nibergitp ^^ ^^ intfjeCitpof^eto^orfe COLLEGE OF PHYSICIANS AND SURGEONS Reference Library Given by «-<^— VLji^r^ Ij^ Digitized by the Internet Archive in 2010 with funding from Columbia University Libraries http://www.archive.org/details/textbookofphysiOOhowe A TEXT-BOOK OF PHYSIOLOGY FOR MEDICAL STUDENTS AND PHYSICIANS BY WILLIAM K. HOWELL, Ph.D., M. D., Sc. D., LL.D. PROFESSOR OF PHYSIOLOGY IN THE JOHNS HOPKINS UNIVERSITY', BALTIMORE 3ftftb JEDition, a;borougbl^ TReviseD PHILADELPHIA AND LONDON W. B. SAUNDERS COMPANY Copyright, tgos, by W. B. Saunders and Company. Reprinted February, 1906, September, 1906, and January, 1907. Revised, reprinted, and recopyrighted August, 1907. Reprinted January, 1908, and October, 1908. Revised, reprinted, and recopyrighted August, 1909. Reprinted January, 1910, and July, 1910. Revised, reprinted, and recopyrighted August, 1911. Reprinted January, 1912, and October, 1912. Revised, reprinted, and recopyrighted September, 1913 Copyright, 1913, by W. B. Saunders Company Registered at Stationers' Hall, London, England PRINTED IN AMERICA PRESS OF W. B. BAUNDERd COMPANV PHILADELPHIA PREFACE TO THE FIFTH EDITION. In preparing this edition the author has attempted, as in former editions, to keep the book abreast of current investiga- tions in physiology. Since the pubhcation of the fourth edition important changes have occurred in physiological views, particu- larly in regard to the difficult subject of metabolism. The active work going on in physiology and physiological chemistry has added greatly to our knowledge of the details of intermediary metabolism in the body, and in some respects has brought into question what before were considered established theories or principles in regard to the processes of nutrition. The indication, for example, that the animal body, under certain conditions, may obtain some of its necessary nitrogen for the synthesis of protein from inorganic sources would have seemed almost impossible a few years ago. In the same line, the valuable work that is accumulating in relation to the specific functions of the different proteins in growth and in maintenance opens a field of investigation that bids fair to be of fundamental importance in dietetics. In an actively growing science changes of this character are, of course, occurring con- stantly. Arising usually among some limited group of workers, they soon, when significant, permeate the whole subject. A text- book must attempt the difficult and somewhat hazardous task of recognizing the point when such views have matured sufficiently 1 2 PREFACE. to render them important in the presentation of the science to beginning students. The author in making this revision has kept this necessity in mind, and hopes that the present edition has not overlooked any significant advance in the subject of physiology during the past two years. W. H, Howell. September, 1913. PREFACE. In the preparation of this book the author has endeavored to keep in mind two guiding principles: first, the importance of simphcity and lucidity in the presentation of facts and theories; and, second, the need of a judicious limitation of the material selected. In regard to the second point every specialist is aware of the bewildering number of researches that have been and are being published in physiology and the closely related sciences, and the difficulty of justly estimating the value of conflicting results. He who seeks for the truth in any matter under discussion is often- times forced to be satisfied with a suspension of judgment, and the writer who attempts to formulate our present knowledge upon almost any part of the subject is in many instances obliged to present the literature as it exists and let the reader make his own deductions. This latter method is doubtless the most satis- factory and the most suitable for large treatises prepared for the use of the specialist or advanced student, but for beginners it is absolutely necessary to follow a different plan. The amount of material and the discussion of details of controversies must be brought within reasonable limits. The author must assume the responsibility of sifting the evidence and emphasizing those con- clusions that seem to be most justified by experiment and obser- vation. As far as material is concerned, it is evident that the selection of what to give and what to omit is a matter of judg- ment and experience upon the part of the writer, but the present author is convinced that the necessary reduction in material should be made by a process of elimination rather than by con- densation. The latter method is suitable for the specialist with his background of knowledge and experience, but it is entirely unfitted for the elementary student. For the purposes of the latter brief, comprehensive statements are oftentimes misleading, or fail at least to make a clear impression. Those subjects that are presented to him must be given with a certain degree of full- ness if he is expected to obtain a serviceable conception of the facts, and it follows that a treatment of the wide subject of physi- ology is possible, when undertaken with this intention, only by t.he adoption of a system of selection and elimination. The fundamental facts of phvsiology, its principles and modes 3 4 PREFACE. of reasoning are not difficult to understand. The obstacle that is most frequently encountered by the student lies in the com- plexity of the subject, — the large number of more or less dis- connected facts and theories wliich must be considered in a dis- cussion of the structure, physics, and chemistry of such an intri- cate organism as the human bod3^ But once a selection has been made of those facts and principles which it is most desirable that the student should know, there is no intrinsic difficulty to prevent them from being stated so clearly that the}^ may be comprehended by an5'one who possesses an elementar}'- knowledge of anatomy, physics, and chemistry. It is doubtless the art of presentation that makes a text-book successful or unsuccessful. It must be admitted, however, that certain parts of physiology, at this par- ticular period in its development, offer peculiar difficulties to the writers of text-books. During recent years chemical work in the fields of digestion and nutrition has been very full, and as a result theories hitherto generally accepted have been subjected to crit- icism and alteration, particularly as the important advances in theoretical chemistry and physics have greatly modified the attitude and point of view of the investigators in physiology. Some former views have been unsettled and much information has been collected which at present it is difficult to formulate and apply to the explanation of the normal processes of the animal body. It would seem that in some of the fundamental problems of metabolism physiological investigation has pushed its experi- mental results to a point at which, for further progress, a deeper knowledge of the chemistry of the body is especially needed. Cer- tainly the amount of work of a chemical character that bears di- rectly or indirectly on the problems of physiology has shown a re- markable increase within the last decade. Amid the conflicting results of this literature it is difficult or impossible to follow always the true trend of development. The best that the text-book can hope to accomplish in such cases is to give as clear a picture as possible of the tendencies of the time. Some critics have contended that only those facts or conclu- sions about which there is no difference of opinion should be pre- sented to medical students. Those who are acquainted with the subject, however, understand that books written from this standpoint contain much that represents the uncertain compromises of past generations, and that the need of revision is felt as fre- quently f(jr such books as for those constructed on more liberal principles. There does not seem to be any sound reason why a text-book for medical students should aim to present only those conclusions that have crystallized out of the controversies of other times, and ignore entirely the live issues of the day which are PREFACE. O of SO much interest and importance not only to physiology, but to all branches of medicine. With this idea in mind the author has endeavored to make the student realize that physiology is a growing subject, continually widening its knowledge and read- justing its theories. It is important that the student should grasp this conception, because, in the first place, it is true; and, in the second place, it may save him later from disappointment and distrust in science if he recognizes that many of our conclu- sions are not the final truth, but provisional only, representing the best that can be done with the knowledge at our command. To emphasize this fact as well as to add somewhat to the interest of the reader short historical resumes have been introduced from time to time, although the question of space alone, not to men- tion other considerations, has prevented any extensive use of such material. It is a feature, however, that a teacher might develop with profit. Some knowledge of the gradual evolution of our present beliefs is useful in demonstrating the enduring value of experimental work as compared with mere theorizing, and also in engendering a certain appreciation and respect for knowledge that has been gained so slowly by the exertions of successive generations of able investigators. A word may be said regarding the references to literature inserted in the book. It is perfectly obvious that a complete or approximately complete bibliography is neither appropriate nor useful, however agreeable it may be to give every worker full recognition of the results of his labors. But for the sake of those who may for any reason wish to follow any particular subject more in detail some references have been given, and these have been selected usually with the idea of citing those works which themselves contain a more or less extensive discussion and litera- ture. Occasionally also references have been made to works of historical importance or to separate papers that contain the experi- mental evidence for some special view. TABLE OF CONTENTS. SECTION I. THE PHYSIOLOGY OF MUSCLE AND NERVE. PAGE Chapter I. — The Phenomenon of Contraction 17 The Histological Structure of the Muscle Fiber, 18. — Its Appearance by Polarized Light, 19. — The Extensibility and Elasticity of Muscular Tissue, 20. — The Inde- pendent Irritability of Muscle, 23. — Definition and Enumeration of Artificial Stim- uh, 24. — The Duration of the Simple Muscle Contraction, 25. — The Curve of a Simple Muscle Contraction, 26. — The Latent Period, 27. — The Phases of Short- ening and Relaxation, 27. — Isotonic and Isometric Contractions, 28. — Maximal and Submaximal Contractions, 28. — -Effect of Temperature upon the Simple Con- traction, 29. — Effect of Veratrin on the Simple Contraction, 31. — Contracture, 32. — Fatigue, the Treppe, and Effect of Rapidly Repeated Stimulation, 3-1. — The Wave of Contraction and Means of Measuring, 36. — Idiomuscular Contractions, 36. — The Energy Liberated during a Muscular Contraction, 36. — The Propor- tional Amount of this Energy Utilized in Work, 38. — The Curve of Work and the Absolute Power of a Muscle, 39. — -Definition of Tetanus or Compound Con- traction, 41. — The Summation of Contractions, 42. — Discontinuity of the Proc- esses of Contraction in Tetanus, 43. — The Muscle-tone, 43. — The Rate of Stimu- lation Necessary for Complete Tetanus, 44. — The Tetanic Nature of Voluntary Contractions, 45. — The Ergograph, 47. — Results of Ergographic Experiments, 49. — Sense of Fatigue, 50. — Muscle Tonus, 50. — Rigor Mortis and Rigor Ca- loris, 52. — The Occurrence and Structure of Plain Muscle Tissue, 55.; — Distinctive Properties of Plain Muscle, 55. — The General Properties of Cardiac Muscular Tissue, 57. — The Contractility of Cilia and Their General Properties, 57. Chapter II. — The Chemical Composition of Muscle and the Chem- ical Changes of Contraction and of Rigor Mortis 60 The Composition of Muscle Plasma, 60. — The Proteins of Muscle, 61. — The Carbohydrates of Muscle, 62. — Phosphocarnic Acid, 63. — Lactic Acid in Muscle, 63. — The Nitrogenous Extractives of Muscle, 64. — Pigments of Muscle, 64.— Enzymes of Muscle, 64. — Inorganic Constituents of Muscle, 65. — The Chem- ical Changes in Muscle during Contraction, 65. — The Chemical Changes during Rigor Mortis, 69. — The Relation of the Waste Products to Fatigue, the Chemical Theory of Fatigue, 69.— Theories of the Mechanism of the Contraction of Muscle, Chapter III. — The Phenomenon of Conduction. Properties of THE Nerve Fiber 74 General Statement Regarding Property of Conductivity, 74.— Structure of the Nerve Fiber, 74 —Function of the M^-elin Sheath, 7.5.— Chemistry of the /7a . ' ^^-^rJ^^ Nerve Trunk an Anatomical Unit Only, 78.— Definition -A, D °n AT Efferent Nerve Fibers, 78.— Classification of Nerve Fibers, 79. — Ihe Bell-Magendie Law of the Composition of the Anterior and the Posterior Roots of the Spinal Nerves, 80.— Cells of Origin of the Anterior and Posterior Root I'lbers, 82.— Origin of the Afferent and Efferent Fibers in the Cranial Nerves, »^.— Independent Irritability of Nerve Fibers, Artificial Nerve Stimuli, S3.— JJu Bois-Rejoiiond's Law of Stimulation bv the Galvanic Current, 85.— Electro- tonus, 8b — -Ffliiger's Law of Stimulation, 88.— The Opening and the Closing ietanus, sa.—Mode of Stimulating Nerves in Man, 89.— Motor Points of jNIuscles, 90.— Physical and Physiological Poles, 92. Chapter IV. — The Electrical Phenomena Shown by Nerve and Muscle 94 The Demarcation Current, 94. — Construction of the Galvanometer, 96. — Con- struction of the Caoillary Electrometer, 99. — Non-polarizable Electrodes, 99. — Action Current or Negative Variation, 101. — Monophasic and Diphasic Action Currents, 102. — The Rheoscopic Frog Preparation, 103. — Relation of Action Current to the Contraction Wave and Nerve Impulse, 104. — The Electrotonic Currents, 106.— The Core-model, 107. 8 TABLE OF CONTENTS. PAGE Chapter V. — The Nature of the Nerve Impulse and the Nutri- TiATE Relations of Nerve Fiber and Nerve Cell 109 Historical, 109. — Velocity of the Xerve Impulse, 110. — Relation of the Nen-e Impulse to the Wave of Xegatfvity, 112. — Direction of Conduction in the Nerve, 113. — Effect of \arious Influences on the Xerve Impulse, 11-1. — The Refractory Period. 110. — The Fatifiue of Xerve Fibers, 110. — The Metabolism of the Xerve Fiber During Functional Activity, IIS. — Theories of the Xerve Impulse, 119. — Qualitative Differences in Xerve Impulses, 121. — Doctrine of Specific Xerve Ener- gies, 121. — Xutritive Relations of Xerve Fibers and Xerve Cells, 122. — Nerve Degeneration and Regeneration, 124. — Degenerative Changes in the Central End of the Xeuron, 120. SECTION II. THE PHYSIOLOGY OF THE CENTRAL NERVOUS SYSTEM. Chapter VI. — Structure and General Properties of the Nerve Cell 128 The Xeuron Doctrine, 128. — The Varieties of Neurons, 130. — Internal Structure of the Xer\-e Cell, 133. — General Physiology of the Xerve Cell, 134. — Sum- mation of Stimuli in X'erv-e Cell, 137. — Respon.se of the X^erve Cell to Varying Rates of Stimulation, 137. — The Refractory Period of the Xerve Cell, 138. Chapter VII. — Reflex Actions 139 Definition and Historical, 139.— The Reflex Arc, 139.— The Reflex Frog, 141.— Spinal Reflex Movements, 141. — Theory of Co-ordinated Reflexes, 143. — Spinal Reflexes in Mammals, 144. — Dependence of Co-ordinated Reflexes upon the Excitation of the Sensory Endings, 144. — Reflex Time, 145. — Inhibition of Reflexes, 146. — Reflexes Through Peripheral Ganglia, Axon Reflexes, 149. — The Tonic Acti\dty of the Spinal Cord, 151. — Effects of the Removal of the Spinal Cord, 152. — Knee-jerk, 153. — Reinforcement of the Knee-jerk, 153. — Is the Knee- jerk a Reflex Act? 155. — Conditions Influencing the Extent of the Knee-jerk, 157. — The Knee-jerk and Spinal Reflexes as Diagnostic Signs, 158. — Other Spinal Reflexes, 158. Chapter VIII. — The Spinal Cord as a Path of Conduction 160 Arrangement and CIa.ssification of the Xerve Cells in the Cord, 160. — General Relations of the Gray and White Matter in the Cord, 102. — The Methods of Determining the Tracts of the Cord, 162. — CJeneral Classification of the Tracts of the Cord, 163. — The Xames and TiOcations of the Long Tracts, 165. — The Termination in the Cord of the Fibers of the Posterior Root, 166. — Ascend- ing or Afferent Paths in the Posterior Funiculi, 167. — Ascending or Afferent Paths in the Lateral Funiculi, 170. — The Spinal Paths for the Cutaneous Senses (Touch, Pain, Temperature), 172. — The Homolateral or Contralateral Con- duction of the Cutaneous Impulses, 174. — The Descending or Efferent Paths in the .\nterolateral Columns (Pyramidal System), 176. — Less Well-known Tracts in the Cord, 178. Chapter IX. — The General Physiology of the Cerebrum and Its Motor Functions 180 The HistoloKy of the Cortex, 181. — The Classification of the Systems of Fibers in the Cerebnim (Projection, Association, and Commissural), 182. — Physio- logical Deductions from the Histology of the Cortex, 1K4. — Extirpation of the Cerebnim, 187. — Localization of Functions in the Cerebrum, Historical, 189. — The Motor .Vroas of the Cortex, 192. — Differences in Piiralysis from Injury to the .Spinal Neuron anrl the Pyramidal Neuron, 194. — \'<)liuil;iry Motor Paths Other than the Pyramidal Tract, 195. — The Crossed Control of the Muscles and Bilateral Motor Representation in the Cortex, 195. — Are the Motor Areas Exclusively Motor? 196 Chapter X. — The Sense .\reas and the Association Areas in the Cortex 198 The Tirxly-senw Area, 199. — The Course of the Lemniscus, 201. — The Center for Vision, 203. — Histological Evidence of tlixyg(fn and CJlher Gases, 420. — The Iron in (he Hemoglobin, 421. — Crystals of Hemoglobin, 422. — Absorption .Spectra Ilciiioglobin and Oxyhemoglobin, 423. — Derivative Compounds of Hemoglobin, 427. -Origin and Fate of the Red Cor- puscli's, 429.— Variations in the Numbcir of lU-A Corpuscles, 431. — Physiology of the HlS. — With the Gases of the Blood, 589. — With Temperature of the Blood, 590. Chapter XXXII. — The ^'AsoMOTOR Nerves and Their Physiological Activity 592 Hiatorical, 592. — Methods Used to Determine Vasomotor Action, 593. — The Piethysmograph, 594.— General Distribution and Course of the A'asoconstrictor Nerve Fibers, .596. — Tonic Activity of the ^'asoconst^ictors, 599. — The Vaso- constrictor Center, 599. — Vasoconstrictor Reflexes, Pressor and Depressor Fibers, 601. — Depressor Nerve of the Heart, 004. — Vasoconstrictor Centers in the Spinal Cord, 005. — Rhythmical Activity of the \'a.soconstrictor Center, 605. — Course and Distribution of the Dilator Fibers, 606. — General Properties of Vasodilator Fibers, 607. — Vasodilator Center and Refle.xes, 608. — ^■a.sodila- tation Due to -\ntidromic Impulses, 609. — Regulation of the Blood-supply by Chemical and Mechanical Stimuli, 610. Chapter XXXIII. — The Vasomotor Supply of the Different Organs 612 Vasomotors of the Heart, 612. — Vasomotors of the Pulmonary Arteries, 613. — Circulation in the Brain and Its Regulation, 614. — Arterial Supply, 614. — Venous Supply, 617. — The Meningeal Spaces, 616. — Intracranial Pressure, 618. — Effect of Changes in .\rterial Pressure upon the Blood Flow through the Brain, 620. — The Regulation of the Brain Circulation, 621. — \'asomotor Nerves of the Head Region, 624. — Of the Trunk and the Limbs, 625. — Of the Abdominal Organs, 625.— Of the Genital Organs, 626.— Of the Skeletal Muscles, 626.— The N'aso- motor Nerves to the Veins, 627. — The Circulation of the Lymph, 628. SECTION VI. PHYSIOLOGY OF RESPIRATION. Chapter XXXIV. — Historical Statement. The Organs of Exter- nal Respiration and the Respiratory Movements 630 Historical, 630. — Anatomy of Organs of Respiration, 634. — Thorax as a Closed Cavity, 634.— Normal Position of the Thorax, 635. — Inspiration by Contraction of the Diaphragm, 636. — Inspiration by Elevation of the Ribs, 637. — -The Muscles of In.spiration, 0.38. — Muscles of Expiration, 638. — Quiet and Forced Respiratory Movements, Eupnea and Dyspnea, 639. — Costal and Abdominal Tn-jms of Res- piration, 640. — Accessory Respiratory Movements, 641. — Rcgistrulion of the Respiratory Movements, 641. — Volumes of Air Respired, \ilal Capacity, Tidal Air, Complemental .\ir, Supplemental Air, Residual Air, Minimal Air, 643. — Size of the Bronchial Tree, 645. — Artificial Respiration, 645. Chapter XXXV. — The Pressure Conditions in the Lungs and Thorax and Their Influence upon the Circulation 647 The Intrapulmonic Pressure and Its Variations, 047. — Intrathoracic Pressure, 648. — Vanations of, with Forced and I'nusual Respirations, 649. — Origin of the Negative Pressure in the Thorax, 650. — Pneumothorax, 651. — Aspiratory Action of the Thorax, 651. — Respiratory Waves of Blood-pressure, 652. Chaiter XXXVI. — The Chemical and Physical Changes in the Aih a.vd the Blood Caused by Respiration 0,55 The In.spired and I'^xpired Air, 655. — Physical Changes in the Expired Air, 650. — Injurious Action of lOxplred Air, 6.56. — Ventilation, 65H. — The (Jascs of the BlcK)d, (')')'.). — 'I'he Pressure of Ciitses, 662. — .'XbHorptioii of Gases in I,i<|uidH, 662. — The Tension of (Jasj.'S in .Solution, 664. — The Contlitioii of Nitrogen in the Blood, 666. — Condition of Oxvgen in the Blood, 666. — Conflition of Carbon Di- oxld in (lie Bloofl, 66H. — The I'hysiral Theory of Respiration, 669. — Cjaseous Exchanges in the LungH, 670. — Exchange of Gases in the Tissues, 672. — Secre- tory Activity of Lungs, 672. CiiAiTKR XXX VIL — Innehvatio.n of the Respiratory Movements. , 074 The I{/-Hpiratory Center, 674. — Spinal Respiratory O-nlers, 675. ^Automatic Activity of the Respiratory CenlaiidH won: displaced only temnorariiy by the movement and fell bjw;k into thciir normal position w(juld indicate that they may have a more W)lid structure. * Kuhne, "Archiv fur pathologische Anatomie," 26, 222, 1S0.*J. THE PHENOMENON OF CONTRACTION. 19 Disregarding the nuclei, the muscle plasma consists of two different structures: the fibrils, which are long and thread-like and run the length of the fiber, and the inter- vening sarcoplasm. The fibrils consist of alternating dim and light discs or segments, which, falling together in the different fibrils, give the cross-striation that is character- istic. In mammalian muscles the fibrils are grouped more or less distinctly into bundles or columns (sarcostyles), between which lies the scanty sarcoplasm. The relative amount of sarcoplasm to fibrillar substance varies greatly in the striped muscles of different animals, as is indicated in the accompanying illustrations. The evidence from compara- tive physiology indicates that the fibrils are the contractile element of the fiber, while the sarcoplasm, it may be assumed, pos- sesses a general nutritive function. Among mammals there are certain muscles in which the amount of sarcoplasm within each fiber is relatively large, and this sarcoplasm, having the granular structure common to undifferentiated protoplasm, interferes with the clearness of striation of the fibers. Fibers of this latter sort are usually of a deeper color than those in which the sarco- plasm is less abundant, and the two varie- ties have been designated as the red (more abundant sarcoplasm) and the pale fibers. Muscles containing chiefly the less clearly striated red fibers, for example, the dia- phragm and the heart, are characterized physiologically by a slower rate of contrac- tion and by a relatively small susceptibility to fatigue. The so-called red and pale fibers may occur in the same muscle. The sepa- rate fibrils, like the entire fiber, show two kinds of substance, the alternating dim and light bands, and these two materials are obviously different in physical structure as seen by ordinary light. When examined by polarized light, this difference becomes more evident, for the dim substance possesses the property of double refraction. When the muscle fiber is placed between crossed Nicol prisms the dim bands Fig. 3.— To show the appearance of the dim (anisotropic) and light (isotropic) bands at rest and in contraction, as seen by ordinary and by polar- ized light. The figure rep- resents a muscle fibril (beetle) in which the lower portion has been fixed in a condition of contraction. On the left the relations of the dim and light bands are shown as they appear in ordinary light, in the re- laxed (upper part), and the contracted (lower part) state. On the right the re- lations of the bands are shown as they appear when placed between crossed Nicol prisms. The white spaces represent the dim bands. 20 THE PHYSIOLOGY OF MUSCLE AND NERVE. appear bright, while the light hands remain dark, as is shown in Fig. 3. From this standpoint the material of the light bands in the normal fibrils is spoken of as isotropous, and that in the dim bands as anisotropous. The anisotropic material of the dim bands consists of doubly refracting positive uniaxial particles, and Engelmann has claimed that such particles may be discovered in all contractile tissues.* The inference made by him is that this anisotropic substance is the contractile material in the pro- toplasm, the machinery, so to speak, through which its shortening is accomplished. Engelmann supports this conclusion by the statement that during contraction the size of the dim bands in- creases at the expense of the material in the light bands. f This theory is indicated in the schema given in Fig. 3. The relative changes in appearance of the anisotropic and isotropic bands during the phase of contraction, which are shown in the figure, may be explained on the assumption that the anisotropic sub- stance absorbs or imbibes water from the isotropic layer. Engel- mann has used such an assumption as the basis for a theory of the shortening of the muscle (p. 72). Unfortunately, the histological changes indicated in Fig. 3 have not been wholly corroborated by later observers. Hiirthle + states that during contraction the anisotropic band may shrink to less than one-half its width, while the isotropic layer shows no change. He finds in this appearance a confirmation of the view that the anisotropic substance consti- tutes the active contractile material of the muscle, but there is no evidence, ho thinks, to support the assumption that the change in the anisotropic layer is due to imbibition of water from the isotropic layer or from any other source. The Extensibility and Elasticity of Muscular Tissue. — Muscular tissue, when acted upon by a weight, extends quit(^ readily, and when the weight is removed, it regains its original form l)y virtue of its elasticity. In our bodies the muscles stretched from bone to bone are, in fact, in a state of elastic tension. If a muscle is severed by an incision across its belly the ends retract. The extensibility and elasticity of the muscles add to the effective- ness of the muscular-skeletal machinery. A muscle that is in a state of elastic teasion contracts more promptly and more effec- tively for a given stimulus than one which is (>ntirely relax(!d. Moreover, in our joints tlu; arrangement of antagonists — flexors and extensors — is such that tiie contraction of one moves the bone against the pull of the (!xt(!nsil)le and (elastic antagonist. *Thi.s filaiin has been denied, see EIIIh, " Ameriean Journal of Physiology," :ii, :i7(), ]m:',. t lii'dennann, "Klcft,ro-j)hyHiology," vol. i, tranHlatcd by Welby, and Engebiiarin, "An'hiv fijr (Jic n'-saiiiiiitc IMiy.siolonic," IS, 1. X Iliirlhle, "Archiv I. d. ge.s. Phy.sioloKie," I'id, 1, 1009. THE PHENOMENON OF CONTRACTION. 21 It would seem that the movements of the skeleton must gain much in smoothness and delicacy by this arrangement. The physical advantages of the extensibility and elasticity of mus- cular tissue are evident not only in the contractions of our volun- tary muscles, but, as we shall see, in a striking way also in the circulation, in which the force of the heart beat is stored and economically distributed by the elastic tension of the distended arteries. The extensibility of muscular tissue has been studied in comparison with the extensibility of dead elastic bodies. With Fig. 4. — a, Curve of extension of a rubber band, to show the equal extensions for equal increments of weight. The band had an initial load of 17 gms., and this was increased by increments of 3 gms. in each of the nine extensions, the final load being 44 gms. The line joining the ends of the ordinates is a straight line, b, Curve of extension of a frog's muscle (gastrocnemius). The initial load and the increment of weight were the same as with the nibber. The curve shows a decreasing extension for equal increments. The line join- ing the ends of the ordinates is curved. regard to the latter it is known that the strain that the body undergoes is proportional, within the limits of elasticity, to the stress put upon it. If, for instance, weights are attached to a rubber band suspended at one end, the amount of extension of the band will be directly proportional to the weights used. If the extensions are measured the relationship may be represented as shown in Fig. 4, the equal increments in weight being indicated by laying off equal distances on the abscissa, and the resulting extensions by the height of the ordinates dropped from each point. If the ends of the ordinates are joined, the result is a straight line. When a similar experiment is made with a living muscle it is found that the extension is not proportional to the weight used. The amount of extension is greatest in the begin- ning and decreases proportionately with new increments of weight. If the results of such an experiment are plotted, as above, representing the equal increments of weight by equal distances along the abscissa and the resulting extensions by ordi- nates dropped from these points, then upon joining the ends of 22 THE PHYSIOLOGY OF MUSCLE AND NERVE. the ordinates we obtain a curve concave to the abscissa. At first the muscle shows a relatively large extension, but the effect becomes less and less with each new increment of weight, the curve at the end approaching slowly to a horizontal. If the weight is increased until it is sufficient to overcome the elasticity of the muscle the curve is altered — it becomes convex to the abscissa, or, in other words, the amount of extension increases with increasing increments of weight up to the point of rupture, as shown in the accompanying curve* (Fig. 5). Haycraftf calls attention to the fact that under normal conditions the physiological extension of the frog's muscles in the body is equal to that produced by a weight of 10 to 15 gms., and that when the excised muscle is extended by weights below this limit it follows the law of dead elastic bodies, giving equal extensions for equal incre- ments of weight. It is only after pass- ing this limit that the law stated above holds good. It should be added also that the amount of deformation ex- hibited by a muscle or other living tissue placed under a stress varies with the time that the stress is allowed to act. The muscle is composed of vis- cous material, and yields slowly to the force acting upon it. In experiments of this kind, therefore, the weights should be allowed to act for equal intervals of time. It has been shown that the extensibility of a muscle is greater in the contracted than in the resting state. The curve of extension described above for skeletal muscle holds also for so-called plain muscle. This latter tissue forms a portion of the walls of tiie various viscera, the stomach, bladder, uterus, blood-vessels, etc., and the facts shown by the above curve enter frequently into the explanation of the physical phenomena exhibited by the viscera. For instance, it follows from this curve that the force of the heart beat will cause less exj)ansion in an artery already distended l)y a high })](Kxl-])ressure than in one in which the blood-jiressure is lower. * See Marcy, " Du rnouvcment daiiH les fonctions do la vie," 180S, p. 284 t Haycraft, "Journal of Physiology," 31, 392, 1904. Fig. .'). — C'urvf given by Marey to show the effect upon the extension of muscle caused by increasing the load regularly to the point of rupture: From o to a the extension of the muscle decreases as the weight increases, giving a curve concave to the abscissa; at a the limit of elasticity is passed and the muscle lengthens by increasing extensions for equal increments; at X rupture (750 gms. for frog's gastrocnemius) . THE PHENOMENON OF CONTRACTION. 23 The Irritability and Contractility of Muscle. — Under normal conditions in the body a muscle is made to contract by a stimulus received from the central nervous system through its motor nerve. If the latter is severed the muscle is paralyzed. We owe to Haller, the great physiologist of the eighteenth century, the proof that a muscle thus isolated can still be made to contract by an artificial stimulus — e. g., an electrical shock — applied directly to it. This significant discovery removed from physiology the old and harmful idea of animal spirits, which were supposed to be generated in the central nervous system and to cause the swelling of a muscle during contraction by flowing to it along the connecting nerve. But to remove a muscle from the body and make it contract by an artificial stimulus does not prove that the muscle substance itself is capable of being acted upon by the stimulus, since in such an experiment the endings of the nerve in the muscle are still intact, and it may be that the stimulus acts only on them and thus affects the mus- cle indirectly. In a number of ways, however, physiologists have found that the muscle substance can be made to contract by a stimulus applied directly to it, and therefore exhibits what is known as independent irritabilitj". The term irritability, according to modern usage, means that a tissue can be made to exhibit its peculiar form of functional activity when stimulated, — e. g., a muscle cell will contract, a gland cell will secrete, etc., — and inde- pendent irritability in the case under consideration means simply that the muscle gives its reaction of contraction when artificial stimuli are applied directly to its substance. This conception of irritabiht}' was first introduced by Francis Ghsson (1597-1677), a celebrated English physician.* Subsequent writers frequently used the term as synonymous with contractility and as appHcable only to the muscle. But it is now used for all living tissues in the sense here indicated. A simple proof of the independent irritability of a striated muscle is obtained by cutting the motor nerve going to it and stimulating the muscle after several days. We know now that in the course of several days the severed nerve fibers degenerate completely down to their terminations in the muscle fibers, and the muscle, thus freed from its nerve fibers by the process of degeneration, can still be made to contract by an artificial stimulus. The classical proof of the independent irri- tabihty of muscle fibers was given by Claude Bernard, the great French physiologist of the nineteenth century. He made use of the so-called arrow poison of the South American Indians. This substance or mixture of substances is known generally under the name curare; it is prepared from the juices of several plants (strychnos) (Thorpe) . The poisonous part of the material is soluble * See Foster's "History of Physiology," p. 2S7. 24 THE PHYSIOLOGY OF MUSCLE AND NERVE. in water, and Bernard showed that when such an extract is injected into the blood or hvpoderniically it paralyzes the motor nerv^es at their peripheral end, so that direct stimulation of these nerves is ineffective. Direct stimulation of the muscle substance, on the contrary, causes a contraction.* We are justified, therefore, in saying that skeletal muscle possesses the properties of independ- ent contractility (Haller) and independent irritability (Ber- nard). By the former term we mean that the shortening of the muscle is due to active processes developed in its own tissue, by the latter we mean that the muscular tissue may be made to enter into contraction by artificial stimuli applied directly to its own substance. This latter property cannot be said to hold for all the tissues. Whether a nerve cell or a gland cell may be made to enter into its specific form of activity by the direct appli- cation of an artificial stimulus is still an undetermined question. Artificial Stimuli. — If we designate the stimulus that the muscle receives normally from its nerve as its normal stimulus, all other forms of energy which maj?^ be used to start its contraction may be grouped under the designation artificial stimuli. Experi- ments have shown that a contraction maj- be aroused by mechani- Fig. 6. — i lie induction ooil as used for physiolopifal purposes (du Bois-ReymonJ pattern): A, The primary coil; B, the secondary coil; !■", hindins posts to which are at- tached the wires from the battery, thev connect with the ends of coil A: P", binding posts connecting with ends of coil B, througn which the induction current is led off; 8, the slide. with scale, in which coil B is moved to alter its distance from A. cal Stimuli, — for instance, by a sharp blow applied to the muscle; by thermal stimuli, — that is, by a sudden change in temperature; by chemical stimuli, — for example, by the action of concentrated solu- tions of salts, and finally by electrical stimuli. In ])ractice, how- ever, only the last form of stimulus is found to be convenient. The mechanical and thermal stimuli cannot be well applied without at the same tim<' injuring the musch' substance, and the same is prob- al)ly true of chemical si imuH, wliicii ])ossess t he disadvantage, more- over, of not exciting simultaneously the dilfercnt fibers of which the mu.scle is composed. Electrical stimuli, on the contrary, are * "Lec;on8 sur les effetH des subHtances toxiques et mddicamenteuses," 1H.')7, pp. 23S el aerj. THE PHENOMENON OF CONTRACTION. 25 applied easily, are readily controlled as regards their intensity, and affect all the fibers simultaneously, thus giving a co-ordinated contraction of the entire bundle, as is the case with the normal stimulus. For electrical stimulation we may use the galvanic current taken directly from the battery, or the induced or so-called faradic current obtained from an induction coil. Under most conditions the latter is more convenient, since it gives brief shocks, the strength and number of which can be controlled readily. The form in which this instrument is used in experimental work in physiology we owe to du Bois-Reymond; hence it is frequently known as the du Bois-Reymond induction coil. Experimental physiology owes a great deal to this simple and serviceable in- Fig. 7. — Schema of induction apparatus. — {Lombard.) b represents the galvanic battery connected by wires to the primary coil, A. On the course of one of these wires is a key (K) to make and break the current. B shows the principle of the secondary coil, and the connection of its two ends with the nerve of a nerve-mvisele preparation. When the battery current is closed or made in A, a brief current of high intensity is induced in B. This is known as the making or closing shock. Wlien the battery current b broken in A, a second brief induction current is aroused in B. This is known as the breaking or opening shock. strument. A figure and brief description of the apparatus are appended (Figs. 6 and 7). Simple Contraction of Muscle. — Experiments may be made upon the muscles of various animals, but ordinarily in physiolog- ical laboratories one of the muscles (gastrocnemius) of the hind leg of the frog is employed. If such a muscle is isolated and connected with the terminals from an induction coil it may be stimulated by a single shock or by a series of rapidly repeated shocks. The contraction that results from a single stimulus is designated as a simple contraction. In the frog's muscle it is very brief, lasting for 0.1 second or less; but in this, as in other respects, cross-striated muscular tissue varies in different animals,* as is shown b}^ the accompanying table, which gives a general idea of the range of rapidity of contraction: * Cash, "Archiv f. Anat. u. Phj'siol.," 1880, suppl. volume, p. 147. 26 THE PHYSIOLOGY OF MUSCLE AND NERVE. DURATION OF A SIMPLE MUSCULAR CONTRACTION. Insect 0.003 sec. Rabbit (Marey) 0.070 " Frog 0.100 " Terrapin 1.000 " The series may be continued by the figures obtained from the plain muscle, thus: The involuntary muscle (mammal) 10.00 Foot mu.scle of slug* (Ariolimax) 20.00 The duration of the simple contraction varies considerably in the muscles of different parts of the same animal. Thus, according to Cash, the hyoglossal muscle in the frog requires 0.205 to 0.3 second, while the gastrocnemius takes 0.12 second; in the tortoise the pectoralis major requires 1.8 seconds, the omohyoid only 0.55 second; in the rabbit the soleus (a red muscle) requires 1 second, the gastrocnemius (a pale muscle) 0.25 second. On examining into these differences it may be shown that the variations bear a relation to the special functions of the muscles. Rapidity of contraction and maintenance of contraction are two properties which are capable of being altered by the processes of adaptation, either together or independently, to suit the needs of the organism. The distribution of the pale and red muscles in such an animal as the rabbit bears out this idea. It will be remembered also that these two varieties show a difference in histological structure (p. 19). The Curve of Contraction. — When a contracting muscle is attached to a lever this lever may be made to write upon a smoked surface and thus record the movement, more or less magnified according to the leverage chosen. If the recording surface is sta- tionary the record obtained is a straight line and indicates only the extent of the shortening. If, however, the recording surface is in movement during the contraction the record will be in the form of a curve, which, making u.se of the system of right-angled co-ordinates, will indicate not only the full extent of the shoi'tening, but also the amount of shortening or sub.sofjuent I'cluxation at any moment during the entire period. To oljtain such records from the rapidly contracting frog's muscle it is evident that the recording surface must move with considerable rapidity and with a uniform velocity. A curve of this kinrl is represented in Fig. 8. C represents the axis of abscissas and gives the factor of time. A vertical ordinate erected at any point on C gives the extent of shortening at that moment. Below the curve of the mus(;le is the record of the vibrations of a tuning fork giving 100 double vibrations per second; that is, the distance fi-om crest to crest represents an •Carlson, " Amc.r'ic.nn Journui of PhyHioiony,'' 10, 418, 1904. THE PHENOMENON OF CONTRACTION. 27 interval of ttt of a second. Three principal facts are brought out by an analysis of the curve: I. The latent period. By this is meant that the muscle does not begin to shorten until a certain time after the stimulus is applied. On the curve the stimulus Fig. S.^Curve of simple muscular contraction. enters the muscle at S, and the distance between this point and the beginning of the rise of the curve, interpreted in time, is the latent period. II. The phase of shortening, which has a definite course and at its end immediately passes into III., the phase of relaxation. The Latent Period. — In the contraction of the isolated frog's muscles as usually recorded the latent period amounts to 0.01 sec, but it is generally assumed that this period is exaggerated by the method of recording used, since the elasticii':}^ of the muscle itself prevents the immediate registration of the movement. By improve- ments in methods of technique the latent period for a fresh muscle may be reduced to as little as 0.005 or even 0.004 sec. Under the conditions in the body, however, the muscle contracts against a load, as when lifting a lever; hence, we may assume that normally there is a lost time of at least 0.01 sec. after the stimulus enters the muscle. In addition to the latent period due to the elasticity of the muscle it is certain that a brief amount of time actually elapses after the stimulus enters the muscle before the act of shortening begins ; some time is taken up in the chemical changes and the effect of these changes in putting the mechanism of con- traction into play (see below on the Theor}^ of Muscle Contractions). The latent period varies greatly in muscles of different kinds, and in the same muscle varies with its conditions as regards temperature, fatigue, load to be raised, etc. The Phases of Shortening and of Relaxation.^ — In the normal frog's muscle the phase of shortening for a simple contraction occu- pies about 0.04 second, while the relaxation may be a trifle longer, 0.05 sec. In muscles whose duration of contraction differs from that of the frog the time values for the shortening and the relaxation 28 THE PHYSIOLOGY OF MUSCLE AND NERVE. exhibit corresponding differences. As we have seen, the appearance of the muscle fiber when viewed by polarized light indicates that during the phase of shortening the most marked physical change occurs in the anisotropic band. Whatever may be the nature of this change, it is evidently a reversible one. After reaching its maximum it proceeds in the opposite direction, the particles return to their original position, and a relaxation occurs. Many conditions, some of which will be described below, alter the time necessary for these processes, that is, the duration of the simple contraction. It is noteworthy that it is the phase of relaxation which may be most easily prolonged or shortened by varying conditions. Isotonic and Isometric Contractions. — In the method of recording the shortening of the muscle that is described above the muscle is supposed to con- tract against a constant load which it can lift. Such a contraction is spoken of as an isotonic contraction. If the muscle is allowed to contract against a tension too great for it to overcome — a stiff spring, for instance — it is prac- tically prevented from shortening, and a contraction of this kind, in which the length of the muscle remains unchanged, is spoken of as an isometric contraction. A curve of such a contraction may be obtained by magnifying greatly, by means of levers, the slight change in the stiff spring against which the muscle is contracting. Such a curve gives a picture of the liberation of energy within the muscle during contraction. The usual oval form of dynamometer employed to record the grip of the flexors of the fingers gives an isometric record of the energy of contraction of these muscles. FiK. 9. — Effect, of varyinK the ntreiiKth of HtimuluH. The figure shown the effect upon the gaHtrocnemiuM mu.scle of a frog of Kradually incroa.siiiK the .'itirnuhi.M (hreakiiiK iiiduction KhofHc; until niaximurn contractioriH were oht-iined. The .stiniuh were (lieii dccreaHOfl in HtrcnKth arifl the contractionH fell off throuRh a HericH of Rradually decreaHiriK Kulmiaxirnal coiilract.ioriK. 'J'he KcricH u[) and clow the bane line are due to the elawtic extension of the muscle by the weight dur- irif.' relaxati'jn.) Effect of Strength of Stimulus upon the Simple Contraction. —The strength of electrical stimuli can be varied conveniently and THE PHENOMENON OF CONTRACTION. 29 with great accuracy. When the stimulus is of such a strength as to produce a just visible contraction it is spoken of as a minimal stimulus and the resulting contraction as a minimal contraction. Stimuli of less strength than the minimal are designated as sub- minimal. If one increases gradually the intensity of the electrical current used as a stimulus without altering its duration, beginning with a stimulus sufficient to cause a minimal contraction, the result- ing contractions increase proportionally up to a certain maximum beyond which further increase of stimulus, other conditions remain- ing the same, causes no greater extent of shortening. Contrac- tions between the minimal and the maximal are designated as submaximal.* (See Fig. 9.) Effect of Temperature upon the Simple Contraction. — Varia- tions in temperature affect both the extent and the duration of the contraction. The relationship is, however, not a simple one in the case of the frog's muscle upon which it has been studied most fre- quently. If we pay attention to the extent of the contraction alone it will be found that at a certain temperature, 0° C, or slightly below, niHill ! I Hill I Fig. 10. — Curve showing the effect of temperature. The temperatures at which the contractions were obtained are indicated on the figure. In this experiment a large resis- tance was introduced into the secondary circuit so that changes in the resistance of the muscle itself due to heating could not affect the strength of the stimulus. the muscle loses its irritability entirely. As its temperature is raised a given stimulus, chosen of such a strength as to be maximal for the muscle at room temperatures, causes greater and greater contractions up to a certain maximum, which is reached at about 5° to 9° C. As the temperature rises beyond this point the con- tractions decrease somewhat to a minimum that is reached at about 15° to 18° C. Beyond this the contractions again increase in * Fick, " Untersuchungen iiber elektrische Nervenreizung," Braun- schweig, 1864. 30 THE PHYSIOLOGY OF MUSCLE AND NERVE. extent to a second maximum at about 26° to 30° C, this maxi- mum being in some cases greater, and in others less than the first maximum. Beyond the second maximum the contractions again decrease rather rapidly as the temperature rises until at a certain temperature. 37° C, irritability is entirely lost (Fig. 10). If the tem- perature is raised somewhat beyond this latter point heat rigor makes its appearance, and the muscle may be considered as dead. The re- lationship between temperature and extent of contraction, therefore, may be expressed by a curve such as is represented in Fig. 11, in which there are two maxima and two points at which irritability is lost . The second maximum indicates a fact of general physiological in- terest, — namely, that in all of the tissues of the body there is a certain high temperature at which optimum activity is exhibited, and if the temperature is raised beyond this point functional activity becomes ViK. 11. — Curve to show the cffeot of a rioC fif tempMirature frfim 0° (". to .'f froK'.s muHclo. The relative dura- tions at the fiifferent temporaturcH are represented by the height of the cor- responding ordinateH. more and more depressed. The point of optiniuni effect is not iden- tical for the different tissues of the same animal, much less so for those of different animals, but the fact may be emphasized that in no case do protoplasmic tissues withstand a very high temperature. THE PHENOMENON OF CONTRACTION. 31 Functional activity is lost usually at 45° C. or below. The duration of the contraction shows usually in frogs' muscles a simple relation- ship to the changes of temperature. At low temperatures, 4 or 5° C, the contractions are enormously prolonged, particularly in the phase of relaxation ; but as the temperature is raised the duration of the contractions diminishes, at first rapidly, then more slowly, to a certain point — about 18° to 20° C, beyond which it remains more or less constant in spite of the changes in extent of shortening. The relationship between duration of contraction and temperature may therefore be expressed by such a curve as is shown in Fig. 12, in which the heights of the ordinates represent the relative durations of the contractions. Muscles from different frogs show considerable minor variations in their reactions to changes in temperature, and we may suppose that these variations depend upon differences in nutritive condition. In this, as in many other respects, the reac- tions obtained from so-called winter frogs after they have prepared for hibernation are more regular and typical than those obtained in the spring or summer. Effect of Veratrin. — The alkaloid veratrin exhibits a peculiar and interesting effect upon the contraction of muscle. A muscle taken from a veratrinized animal and stimulated in the usual way by a single stimulus gives a contraction such as is exhibited in the accompanying curve (Fig. 13). Two peculiarities are shown by the curve: (1) The phase of shortening is not altered, but the phase of relaxation is greatly prolonged. (2) The curve shows two summits, — that is, after the first shortening there is a brief relaxation followed by a second, slower contraction. The cause of this second shortening is not known. Biedemann has sug- gested that it is due to the presence in the muscle of the two kinds of fibers — red and pale — which were spoken of on p. 26, and that Fig. 13. — Curve showing the effect of veratrin. the veratrin dissociates their action, but this explanation, ac- cording to Carvallo and Weiss,* is disproved by the fact that muscles composed entirely of white or red fibers show a similar result from the action of veratrin. It would seem more probable, * "Journal de la physiol. et de la path, generale," 1899. 32 THE PHYSIOLOGY OF MUSCLE AND NERVE. therefore, that two tUfferent contraction processes are initiated by the stimuhis. one much more rapid than the other. Many other facts in physiology speak for this general view that a muscle may, according to conditions, give either a quick contraction (twitch) or a more slowly developing contraction, with, a prolonged phase of relaxation (tone contraction). This latter feature constitutes the characteristic peculiarity of the curve of a veratrin contraction. A somewhat similar effect is produced by the action of glycerin, nicotine, etc. We have in such substances reagents that affect one phase of the contraction process without materially influenc- ing the other. As regards the veratrin effect, it becomes less and less marked if the muscle is made to give repeated contractions, but reappears after a suitable period of rest. The peculiar action of the veratrin is, therefore, antagonized seemingly by the chemical products formed during contraction. Contracture. — The prolonged relaxation that is so character- istic of the veratrinized muscles may be observed in frog's muscle under other circmnstances, and is described usually as a con- dition of contracture. By contracture we mean a state of main- tained contraction or, looking at it from the other point of view, a state of retarded relaxation. This condition is often exhibited in a most interesting way when a muscle is repeatedly stimulated. In some cases it develops at the beginning of a series of contractions, as is represented in Fig. 14, which pictures the phenome- non as it was first described.* In other cases it ai)pears later on in the curve, preceding or following the development of the state of fatiguo. Whenever it occurs th(! effect is to hold the nuiscle in a state of maintained contraction or tone, on which is su{)cr|)osed the scries of (luick contractions and relaxations due to the separate stimuli. When the condition develops early in the func- tional activity of the muscle (Fig. 14) further activity usually causes it to dis- appear, and the condition of the mus(!le as a mechanism for pr<)mi)t short(>ning and relaxation is improved. We have in this fac^t apparently an indication of one way in which the "warming up" exercise before athlet ic contests may be of value;. When the contraction app(>ars late in th(t series of ("ont ract ions it is usually permanent, that is to say, it wears off only as the muscle relaxes slowly from fatigue. Toward the end of such a .series the nmsclc is oft(>n practically in a state of continuous contraction, a condition whicli would nullify its ordinary use in lo(H)motion. It seems ])ossil)lc that certain (Con- ditions of tonic Hpa.sm or cramps which occur during life may involve this process, for exarni>le, the teni[)orary crain)) that sometimes attacks a playcT m athletic gam(!s, or the (!urious spasmodic; (condition known as int(;rmitt(;nt- claudication, in which the muscKcs on ex(;rci.s(! are thrown into a state of tonic contraction. From the i)hysiologi{;al standpoint the phenomenon of contracture when (;omf)are(l with thai of the simple contracrtioti in(li(!ates the po.ssibiiily that two difTerenl c()tit ract ion pro(;esses may take |>la(;e in nuiscle, one involving the state of lone and, therefore, the length and h;irdne.SH of the niu.scl(!, the oth(!r controlling the movements proper. This sugg(!sti()n has been made by a number of authorsf on various grounds. It has b(;en sug- * Tiogel, "Pfluger's Archiv fiir die gesammte Physiologic," etc., 13, 71, 1876. tSoe especially Uexkull, "Zentralblatt f. Physiologic," 1908, 22, 33; also Guenther, "American Journal of Physiology," HK)r), 14, 73. THE PHENOMENON OF CONTRACTION. 33 gested by some that there are two different contractile substances in muscle, one giving the usual quick contraction, known as a "twitch," the other the slower contraction, which exhibits itself as tone or contracture.* It would be equally as permissible to suppose that there are two kinds of chemical processes which may occur in muscle, one which occurs with explosive suddenness and causes the "twitch," and one which takes place slowly and causes the main- * loteyko, "Travaux du laboratoire de Physiologic," Institut Solvav, 1902, 5, 229. 3 34 THE PHYSIOLOGY OF MUSCLE AND NERVE. tained contraction shown in contracture. This latter point of view is sup- ported by the work of Hill, referred to below, which shows that during: con- tracture there is a constant production of heat — that is to say, the condition is one really of maintainetl or continuous contraction, and not simply a case of a retardation of the physical processes of relaxation. BM ■ M|M m ^^^KMi^KWi ^^i^^^^^^^^^^i 'M iH^^I i Fig. 15. — Effect of repeated stimulation; complete curve, showing late contracture. The muscle was stimulated by induction shocks at the rate of 50 per minute. The separate contractions are so close together that they can not be distinguished. Fig. 10. — Inflect of repeated stimulation, curve .showing no coiitractureor very little. The muscle was stimulated by induction shocks at the rate of r>l) iier minute. A very Blight contracture is shown in the beginning, but subsequently tlic contractions show only a dimini.shed extent, the rate of relaxation remaining apparently unchanged. The Effect of Rapidly Repeated Contractions. — When a muscle is stimiilat(!d n'jx'utcdly hy stimuli of c(|iial strciiigth that fall into the muscle at equal intervals the contractions show certain features that, in a general way, are constant, although the precise degree in which they are exhibited varies curiously in different animals. Such curves arc exhibited in Figs. 14, 15, and 16, and the features worthy of note may be specified l)riefly as follows: THE PHENOMENON OF CONTRACTION. 35 1. The Introductory Contractions. — The first three or four con- tractions decrease sHghtly in extent, showing that the muscle at first loses a little in irritability on account of previous contractions. This phenomenon is frequently absent. 2. The Staircase or " Treppe." — After the first slight fall in height has passed off the contractions increase in extent with great regularity and often for a surprisingly large number of contractions. This gradual increase in extent of shortening, with a constant stimulus, was first noticed by Bowditch upon the heart muscle, and was by him named the phenomenon of "treppe," the German word for staircase. It indicates that the effect of activity is in the beginning beneficial to the muscle in that its irritability steadily increases, and the fact that the same result has been ob- tained from heart muscle, plain muscle, and nerve fibers indicates that it may be a general physiological law that functional activity leads at first to a heightened irritability. According to Lee,* the " treppe " in muscle is due to an initial increase of irritability set up by the chemical products formed during contraction. 3. Contracture. — This phenomenon of maintained contraction has been described above. In frogs' muscles stimulated repeat- edly it makes its appearance, as a rule, sooner or later in the series of contractions; but there is a curious amount of variation in the muscles of different individuals in this respect. 4. Fatigue. — After the period of the " treppe " has passed, the contractions diminish steadily in height, until at last the muscle fails entirely to respond to the stimulus. This progressive loss of irritability in the muscle caused by repeated activity is designated as fatigue. It will be considered more in detail under the head of Compound Muscular Contractions and in Chapter II. The curve obtained in an experiment of this kind illustrates in a striking way one of the general characteristics of living matter, namely, that every effective stimulus applied to it leaves a record, so to speak. The muscle in this case is in a changed condition after each stimulus, as is indicated by the difference in its re- sponse to the succeeding stimulus. While it cannot be said that a similar effect has been shown in all tissues, still the evidence in general points that way, and some of the complicated phenomena exhibited by living matter, such as memory, habits, immunity, etc., are referable in the long run to this underlying peculiarity. Lee has discovered the interesting fact that while in frog's muscle, as a rule, fatigue is accompanied by a prolongation of the curve, especially of the phase of relaxation, this does not hold for mammalian muscle. In the latter mviscle the successive contractions become smaller as fatigue sets in, but their diiration is not increased. * See "American Journal of Physiology," 1907, 18, 267. 36 THE PHYSIOLOGY OF MUSCLE AND NERVE. The Contraction Wave. — Under ordinary conditions the fibers of a muscle when stimulated contract simultaneously or nearly so, and the whole extent of the muscle is practically in the same phase of contraction at a given instant. It is comparatively easy to show, however, that the process of contraction spreads over the fibers, from the point stimulated, in the form of a wave which moves with a definite velocity. In a long muscle with parallel bundles of fibers one may prove, by proper recording apparatus, that if the muscle is stimulated at one end a point near this end enters into contraction before a point farther off. Knowing the difference in time between the appearance of the contraction at the two points and the distance apart of the latter, we have the data for determin- ing the velocity of its propagation. In frog's muscles this velocity is found to be equal to 3 or 4 meters per second, while in human muscle, at the body temperature, it is estimated at 10 to 13 meters per second. Kno\ving the time it takes this wave to pass a given point (d) and its velocity (v), its entire length is given by the formula I = vd. In the frog's muscle, therefore, with a velocity of 3000 mm. per second, and a duration of, say, 0.1 second, the product (3000X0.1 =300 mms.) gives the length of the wave or the length of muscle which is in some phase of contraction at any given instant. Under normal conditions the muscle fibers are stimulated through their motor plates, which are situated toward the middle of the fiber, or perhaps one muscle fiber may have two or more motor plates, giving two or more points of stimula- tion. It follows, therefore, from this anatomical arrangement and the great velocity of the wave that all parts of the fibers are in contraction at the same instant and, indeed, in nearly the same phase of contraction. Under abnormal conditions nmscles may exhibit fibrillar contractions; that is, separate fibers or bundles of fibers contract and relax at different times, giving a flickering, trembling movement to the nuiscle. Idiomuscular Contractions. — In a fatigued or moribund muscle mechan- ical stimulation may gi\e a localized contraction which does not spread or spreads very slowly, sliowin^ that the ahiionnal changes in the muscle prevent trie excitation from travciliiif!; at its normal velocity. A localized contraction of this kind was dcjsignatcd hy Sehiff as an idiomuscular contraction. It may be produced in tiie nnisele of a nouronuiscular appai'atus as a whole, ^^'edenski has called attention to the fact that in the neuromus- cular apparatus the motor end-plate is a sensitive link in the chain, and that, when the nerve is stimulated strongly wdth artificial stimuli at least, this structure falls into a condition in which it fails to conduct the nerve impulse to the muscle. It may be, therefore, that in sustained voluntary contractions the end-plate or the specialized receptive substance in which the nerve fibers terminate fails first, and is directly responsible for the failure of the apparatus to ])erform furth(>r work.* That the fatigue in ordinary vol- untary contractions affects the muscles before the motor nerve centers is indicated by the experiments of Storey, f Making use of a weight ergograi)h and experimenting upon the abductor indices, he found that after fatiguing this muscle to voluntary contractions with a certain weight, rcniioval of the weight enabled the individual to make contractions as high and as rai)id as before the fatigue. On the other hand, if, after removing the weight, the muscle was stimulated electrically, the contractions were lower and slower than before the fatigue. So far as our knowledge goes, therefore, fatigue as it appears in sustained voluntary {;onti-ac.tions is due probably i)rimarily to a less of irritability in the muscle and in t he recieptive apparatus bet.wecn nerve and muscle. The motor n(;rve fibers do not fat igu(>, and as regards t,he motor nerve centers, it is not possible as yet to say what may be their relative sus- ceptibility to fatigue. A significant fact, re])orted by Pip(>r, is that th(^ motor nerve cent'TS when fatigued discharge their impulses at a rate; of jx'rhaps one- half the normal. Sense of Fatigue. — It should be noted in passing that in con- tinued vohintary c(;ntractions wc are conscious of a sense of fatigue,, which eventually loads us, if possible, to discontinue our efforts. This sensation must arise from a stimulation of scnsoiy nerve fibers within the muscle or its tendons, and it may be regartled as an important regulation whereby we are prevented from pushing our musculur exertions to the point of "straining." Muscle Tonus. — In addition to the conditions of contraction and of relaxation the living nniscle (sxhibits the ))hen()men()n of "tone." By muscle ioiw. we mean a state of continuous shortening or contraction which under normal conditions is slight in extent and vari(!S from time to time. This condition is dependent upon ♦ I' or further evidence, sec Burridgc, ".Journal of I'iiysiology," 1911, 41, 285. t Story, "AmfTJcan Journal of Physiology," 100.''>, S, 855. THE PHENOMENON OF CONTRACTION. 51 the connection of the muscle with the nerve centers, and we may assume that under normal circumstances the motor centers are continually discharging subminimal nerve impulses into the muscles which cause chemical changes similar in kind to those set up by an ordinary voluntary effort, but differing apparently in the fact that they are slow and continuous, instead of a series of rapidly repeated processes, the result being that the muscles enter into a state of contraction which, while slight in extent, is more or less continuous. According to this view, the whole neuromuscular apparatus is in a condition of tonic activity, and this state may be referred in the long run to the continual inflow of sensory impulses into the central nervous system. That is, the tonus of the skeletal muscles is not only dependent on the nerve centers (neurogenic), but is in reality an example of reflex stimulation of these centers. The tone of any particular muscle or group of muscles may be destroyed, therefore, by cutting its motor nerve, or less completely by severing the sensory paths from the same region. If, for in- stance, one severs in a dog the posterior roots of the spinal nerves innervating the leg, there will be a distinct loss of muscular tone, although the motor nerves remain intact. The underlying cause of tone is poorly understood. It may be, as implied above, simply a condition of subdued tetanus due to a constantly acting series of sub-minimal stimuli, or it may be an order of contraction quite different from the usual visible movements; that is to say, the shortening in the case of tonus may be due to a substance or mech- anism in the muscle-fibers different from that which subserves the ordinary quick movements which we designate as contractions. However this may be, the fact of muscle tone is important in a number of ways. It is of value, without doubt, for the normal nutrition of the muscle, and, as is explained in the chapter on Animal Heat, it plays a very important part in controlling the production of heat in the body. The extent of muscle tone varies with many conditions, the most important of which, perhaps, are external temperature and mental activity. With regard to the first, it is known that, as the external temperature falls and the skin becomes chilled, the sensor}" stimulation thus produced acts upon the nerve centers and leads to an increased discharge along the motor paths to the muscle. The tone of the muscles increases and may pass into the visible movements of shivering. By this means the production of heat within the body is increased automatically. Similarly, an increase in mental activity, so-called mental concentration, whether of an emotional or an intellectual kind, leads, by its effect on the spinal motor centers, to a state of greater muscle tonus, the increased muscular tension being, indeed, visible to our eyes. 52 THE PHYSIOLOGY OF MUSCLE AND NERVE. The Condition of Rigor. — When the muscle substance dies it becomes rigid, or goes into a condition of rigor: it passes from a viscous to a solid state. The rigor that appears in the muscles after somatic death is designated usually as rigor mortis, and its oc- currence explains the death stiffening in the cadaver. It is charac- terized by several features: the muscles become rigid, they shorten, they develop an acid reaction, and they lose their irritability to stimuli. Whether all of these features are necessary parts of the condition of rigor mortis it is difficult to say; the matter will be discussed brief!}' lielow. Some of the facts which have been ob- served regarding rigor mortis are as follows: After the death of an individual the muscles enter into rigor mortis at different times. Usually there is a certain sequence, the order given being the jaws neck, trunk, upper limbs, lower limbs, the rigor taking, therefore, a descending course. The actual time of the apj^earance of the rigidity varies greatly, however; it mav come on within a few minutes or a number of hours may elapse before it can be detected, the chief de- termining factor in this respect being the condition of the muscle itself. Death after great muscvdar exertion, as in the case of hunted animals or soldiers killed in battle, is usually followed quickly by muscle rigor; indeed, in extreme cases it may develop almost imme- diately. Death after wasting diseases is also followed by an early FiK. '2T>. — Curve of normul riKor inortiH, Ka.strocneiiiiuM muscle of frofi;. The curve wa« obtained upon a kymoKrui>l)ion making one revolution in eiRlit dayw. The marks on the line lielow tlic curve indicate interval of wix hours. It will be seen that the shortening required eiKhteen hours, the relaxation about seventy-two hours. rigor, which in this case is of a more f('(!})le character and shorter duration. 'J'lu; development of rigor is very much hastened by many drugs that bring alxnit the raj)id death of the muscle substance, such as veratrin, hydrocyanic acid, caffein, and chloroform. A frog's mus- cle exposed to chloroform vai)or goes into rigor at once iuid shortens to a remarkaljle exlcnl. Jiigor is said also to occur inon; rai)idly in a muscle still connected wilh Uk; central nervous system than THE PHENOMENON OF CONTRACTION. 53 in one whose motor nerve has been severed. After a certain interval, which also varies greatly, — from one to six days in human beings, — the rigidity passes off, the muscles again become soft and flexible; this phenomenon is known as the release from rigor. In the cold-blooded animals the development of rigor is very much slower than in warm-blooded animals. Upon an isolated frog's muscle the most striking fact regarding rigor mortis is the shortening that the muscle undergoes. This shortening or contraction comes on slowly, as is shown in the accompanying figure, but in extent it exceeds the simple contraction obtainable from the living muscle by means of a maximal stimulus. This part of the phenomenon is, however, much less marked apparently in mammalian muscle. The usual explanation that is given of rigor is that it is due to a coagulation of the fluid substance, the muscle plasma, of which the fibers are constituted. During life the proteins exist in a liquid or viscous condition; after death they coagulate into a solid form. This view is referred to again in the chapter dealing with the chemistry of muscle and nerve; it has received much support from the investigations of Kiihne,* who proved that the muscle plasma is really coagulable. After first freezing and mmcing the muscles he succeeded in squeezing out the plasma from the living fibers and showed that it subsequently clotted. While the coagulation theory of rigor explains the greater rigidity of the muscle, it does not furnish in itself a satisfactory explanation of the shortening, and the fact, as stated above, that the rigidity may occur without the shortening indicates that this latter process may possibty be due to changes that precede the appearance of rigidity. In addition to the rigor mortis that occurs after death at ordinary temperatures, a condition of rigor may be induced rapidly by raising the temperature of the muscle to a certain point. Rigor induced in this way is designated as heat rigor or rigor caloris. Much uncertainty has prevailed as to whether heat rigor is different essentially from death rigor. According to some phj^siologists, the processes may be regarded as the same, the heat rigor being simply a death rigor that is rapidly develojoed by the high temperature, this latter condition accelerating the chemical changes leading to rigor, as is the case, for instance, in the action of cliloroform. This view is supported by a study of the chemical changes that take place under the two conditions, as will be described later, and by the fact that some of the conditions that influence one phenomenon have a parallel effect upon the other. For instance, death rigor is accel- erated by previous use of the muscle, and the same is true for heat rigor. While a resting frog's muscle begins to go into heat rigor, * Kiihne, "Ai-cliiv f. Physiolosie," 1859, p. 788. 54 THE PHYSIOLOGY OF MUSCLE AND NERVE. as judged b}^ the shortening, at 37° to 40° C; a muscle that has been greatly fatigued shows the same phenomenon at 25° to 27° C* According to other observers, heat rigor is due to an ordinarj^ heat coagulation of the proteins present in the muscle fiber, and it has been claimed that a separate contraction may be obtained on heating for each of the proteins said to exist in the muscle fiber.t More recent observations^ seem to show that when a frog's muscle is gradually heated, only two really distinct contractions are obtained, one at 39° C. (38° to 40°) or slightly lower, and one at 50° C. (49° to 51°). Mammalian muscle gives also two contractions when heated, one at 47° C. (46° to 50°) and one at 62° C. (61° to 64°). In each of these cases the second contraction is due to the action of heat on the connective-tissue elements of the muscle. The first contraction is, therefore, the one that is characteristic of the muscular substance proper and the one that marks the occurrence of heat rigor. At the tempertures stated, 39° C. for frog's muscle and 47° C. for mammalian muscle, the viscous material within the sarco- lemma coagulates. It does not follow necessarily that this coagula- tion is the direct cause of the shortening. Meigs § states that plain muscle heated to 50° C. lengthens instead of shortening, although at that temperature much of its contained protein is coagulated. In striated muscle, on the other hand, coagulation may be produced by alcohol without any noticeable shortening. It may be, therefore, that coagulation and shortening are separate results following upon the chemical changes preceding the death of the muscle substance. The coagulation produced in heat rigor is apparently more complete and resistant than that of death rigor, for ordinary d(!ath rigor passes off after a certain interval, even if putnsfactive processes are excluded; the rigor from heat or from chloroform, on the contrary, shows no release. With r(>gard to the specific cause of the coagulation of death rigor nothing final can be said. The interesting researches of Fletcher and Hopkins || indicate; that during the survival period between the loss of the normal cinnilation and the ai)pearan(;(; of rigor chemical changes are going on in the living substance which result in the formation and accumulation of lactic acid. When the process of production of the lactic acid ceases, the muscle has lost its irritability, and then soon enters into the state of rigor. If diiiiiig this survival * Latirn«!r, "Arn(Tif;;in Joiimji,! of I'hysioloK.y/' 2, 29, 1S99. t Jinxlio and Itichunlsoii, " I'tiilosopliifal Trans., Roy. So(!.," London, 1809, 191, p. 127; .-dso InaK.aki, " ZcilsoJirin f. liiol.," 19()(;, 48, 313. t Vrooman, " liio-chcrriical .Jouni.al," 1907, 2, 'MV.i. ^ Moi^H, "Anicrican .Journal of JMiy.siolofry," 24, 1 and 178, 1909. |i Flctchor and ilopkins, ".Journal of I'Jiysiolof^y," 1907, 35, 247. THE PHENOMENON OF CONTRACTION. 55 period the muscle is kept well supplied with oxygen, no lactic acid accumulates in the muscle, and when the muscle finally loses its irritability, no rigor occurs. These facts would seem to implicate the lactic acid in some way in the process of clotting and of rigor. Rigor of muscles may be caused by other specific conditions which kill the muscle and bring on coagulation of the muscle-substance; by the action of distilled water, for example, the so-called water rigor, or by the action of an excess of calcium salts, calcium rigor. PLAIN OR SMOOTH MUSCULAR TISSUE. Occurrence and Innervation. — Plain or long striated muscular tissue occurs in the walls of all the so-called hollow viscera of the body, such as the arteries and veins, the alimentary canal, the genital and urinary organs, the bronchi, etc., and in other special localities, such as the intrinsic muscles of the eyeball, the muscles attached to the hair follicles, etc. In structure it differs funda- inentally from cross-striated muscle, in that it occurs in the form of relatively minute cells, each with a single nucleus, which are united to form, in most cases, muscular membranes constituting a part of the walls of the hollow viscera. Each muscle-cell is spindle shaped, contains a single elongated nucleus, and the cyto- plasm is traversed by fine fibrils (myofibrillse) which are said to continue from one cell to another. As in the case of the striated muscle, these fibrils are supposed to constitute the contractile element. The muscle-cells, in most cases at least, are supplied with nerve fibers which originate directly from the so-called sympathetic nerve-cells, and only indirectly, therefore, from the central nervous system. Speaking generally, the contractions of this tissue are removed from the direct control of the will, being regulated by reflex and usually unconscious stimulations from the central nervous system. All the important movements of the internal organs, or, as they are sometimes called, the organs of vegetative life, are effected through the activity of this contractile tissue. From this stand- point their function may be regarded as more important than that of the mass of the voluntary musculature, since so far as the mere maintenance of the life of the organism is concerned, the proper action and co-ordination of the movements of the visceral organs is at all times essential. Distinctive Properties. — ^The phenomena of contraction shown by plain muscles are, in general, closely similar to those already studied for striated muscle, the one great difference being the much greater sluggishness of the changes. Plain muscles differ 56 THE PHYSIOLOGY OF MUSCLE AND NERVE. among themselves, of course, as do the striated muscles, but, speak- ing generally, the simple contractions of plain muscle have a very long latent period that may be a hundred or five hundred times as long as that of cross-striated muscle, and the phases of shortening and of relaxation are also similarly prolonged; so that the whole movement of contraction is relatively slow and gentle (see Fig. 26). Plain muscle responds to artificial stimuli, but the electrical current is ob\dously a less adequate — that is, a less normal — stimulus for this tissue than for the striped muscle. The amount of current necessary to make it contract is far greater. The amount of con- traction varies with the strength of stimulus, — that is, the tissue gives submaximal and maximal contractions. Two successive stimuli properly spaced will cause a larger or summated contraction, and a series of stimuli will give a fused or tetanic contraction. The rate of stimulation necessar}^ to produce tetanus is, of course, much slower than for cross-striped muscle. The stomach muscle of the frog, for instance, requires only one stimulus at each five sec- onds to cause tetanus.* A distinguishing and important charac- teristic of the plain muscle is its power to remain in tone, — that FiK. 26. — Curve of simple contraction of plain muscle. The middle line is the time record, markinK intervals of a second. The lowermost line indicates at the break the rno- ment of stimulation (short-lasting, tetanizinn current). It will be seen that the latent ijeriod between beginning of stimulation and beginning of contraction is e(|ual to about three i»ecoIld^. is, to remain for long periods in a condition of greater or less con- traction. Doubtless this tonic contraction under normal relations is usually dci)endf'iit ujjon .stimulation received through the ner- vous system (neurogenic tonus), but the inusclo, when completely isolated from the central nervous system, whether in or out of the bofly, continues to exhibit the phenomenon of tone to a *Hchu\i'A, "Zur PhysioloKif <\cr liinKsgfsslrciftcn (Klatton) Muskeln," "Archiv f. PliyHirtiofjic," su[)[)l. volume, ]. 244; Ilulliburton, ".lourruil of PhysioloKy," «, i'-i'-i, IHHH; Stewart, and Soilinan, ihid., 24, 427, IXOO. m THE CHEMISTRY OF MUSCLE. 61 terminology employed has not been uniform, and the facts so far as they are known to us seem to be obviously incomplete. Ac- cording to von Fiirth, two proteins may be obtained from mam- malian muscle by extracting it with dilute saline solutions, — namely, myosin and myogen, the latter existing to three or four times the amount of the former. Myosin belongs to the globulin group of proteins (see appendix) ; it is coagulated by heat at 44° to 50° C, it is precipitated by dialysis or by weak acids, it is easily precipi- tated from its solutions by adding an excess of neutral salts, such as sodium chlorid, magnesium or ammonium sulphate. With the last salt it is completely precipitated when the salt is added to one-half saturation or less. Its most interesting property, how- ever, is that on standing at ordinary temperatures it passes over into an insoluble modification which separates out as a sort of clot. Following the terminology used for the blood, this insoluble modification is called myosin fibrin. Myogen, the other protein, seems to fall into the group of albumins rather than globulins. It is not precipitated by dialysis and requires more than half saturation with ammonium sulphate for its complete precipitation. It is coagulated by heat at a temperature of 55° to 65° C. Solutions of myogen on standing also undergo a species of clotting, the in- soluble protein that is formed in this case being called myogen fibrin. It appears, however, that in changing to myogen fibrin the myogen passes through an intermediate stage, designated as soluble myogen fibrin, in which its temperature of heat coagulation is as low as 30° to 40° C, — the lowest temperature recorded for any protein. As was stated in the paragraph on muscle rigor, it is known that frog's muscle goes into heat rigor at about 37° to 40° C, and in accordance with this fact it is stated that a protein, soluble my- ogen fibrin, which is not present in mammalian muscle, occurs normally in the muscle of the frog and also of the fishes. On the basis of these facts the rigiditj^ of death rigor is explained by as- suming that both of these proteins exist in the Hving muscle, and that after death they undergo a partial or complete coagulation according to the following schema: Myosin. Myogen. Y Y Myosin fibrin. Soluble myogen fibrin. I Myogen fibrin. It may be doubted whether these proteins exist as such in the living muscle. Extracts must of necessity be made after the muscle plasma is dead and probably coagulated. Myogen is said not to occur in the muscles of the invertebrates. It should 62 THE PHYSIOLOGY OF MUSCLE AND NERVE. be added that after the most complete extraction with saline solutions the muscle fiber still retains much protein material, and its structural appearance, so far as cross-striation is con- cerned, remains unaltered. The portion of protein material thus left in the muscle fiber as a sort of skeleton framework is designated as the muscle stroma; it is not soluble in solu- tions of neutral salts, but dissolves readily in solutions of dilute alkalies. In striped muscle this so-called stroma forms about 9 per cent, of the weight of the muscle; while in the heart muscle it makes about 56 per cent., and in the smooth muscle, 72 per cent. It is at present uncertain whether the. myosin and m3'ogen represent the protein constituents of the contractile ele- ments of the muscle fibers or of the undifferentiated portion, the sarcoplasm. The proteins of plain muscle tissue and of cardiac muscle have not received so much attention as those of voluntary muscle. It is stated, however, that the proteins exti acted from these tissues by salt solutions are coagulable on standing, as in the case of the extracts of voluntar}^ muscle. In plain muscle two proteins, in addition to some nucleopiotein, are described,' one belonging to the albumin and one to the globulin class, but the identity or relationship of these proteins to those above de- scribed has not been established. In heart muscle, myosin and myogen occur in practically the same propoi-tions as in voluntaiy muscle, but the amount of stroma left undissolved after treatment with saline solutions is, as stated alcove, much greater than in skeletal muscle.* The Carbohydrates of Muscle. — Muscle contains a certain amount of sugar (dextrose or dextrose and isomaltose), and also un power of converting the sugar brought to it by the blood into glycogen. It is a synthetic reaction in which the simple molecule of the monosaccharide (dextrose) is converted by dehydration and condensation to the larger molecule of the i)olysaccharide (glycogen). It is repre- sented in j)rinciple by the reaction n(CoH,A)-M(IL()) == (C„H,.,().,)n. The glycogen thus formed is stored in the muscle and forms a constant con.stituent (jf well-nourished mus(!le in the resting *Vinf('nl and LcwIh, "Joiirruil of PliywioloK.v," 20, 445, 1001; also "Zcit- Hrhrifl f. phyHioioji;. ('hemic," 'M, 417, iOOl-'i; Stcvv;irt :uu\ Solltnan, loc. cil.; von Furth, "(Icnenil Review. Hundbucli dcr IJiocliciriic," vol, 2, ])Mrt 2, p. 244. THE CHEMISTRY OF MUSCLE. 63 condition, the amount varying between 0.5 and 0.9 per cent, of the weight of the muscle. The glycogen thus stored in the muscle is consumed by the tissue during its activity, and it is assumed that before it is thus consumed it is converted back into sugar by the action of an amylolytic enzyme contained in the muscle. The glycogen, therefore, itself represents a local deposit of carbohydrate nutritive material. The sugar and the glycogen must be con- sidered as one from the standpoint of the nutrition of the muscle. During muscular activity the store of glycogen is used up, and if the activity is sufficiently prolonged it may be made to disap- pear entirely. Among the many uncertain and contradictory statements regarding the chemical changes in active muscle, this fact stands out in pleasant contrast as one that is satisfactorily demonstrated. Phosphocamic Acid (Nucleon). — A peculiar substance containing phos- phorus was discovered by Siegfried in the muscle extracts.* This substance seems to resemble the proteins, but has a complex and peculiar structure, as is shown by its split products when hydrolyzed by boiling with baryta water. Under these conditions there are formed carbon dioxid, phosphoric acid, a carbohydrate body, succinic and lactic acids, and a crystallizable nitrogen- ous acid body which is designated as carnic acid (CioHuNsOj). Lactic Acid (C-jHi-Og). — Lactic acid is found in varying amounts in the extracts of muscle. The acid that is obtained is the so-called ethidene lactic acid or a-hydroxypropionic acid (CH jCHOHCOOH ) , and differs from the lactic acid found in sour milk in that it ro- tates the plane of polarized light to the right. The lactic acid in sour milk is produced by bacterial fermentation, and is inactive to polarized light, because it exists in racemic form ; that is, it con- sists of equal amounts of the right-handed form which turns the plane of polarization to the right and of the left-handed form which turns it to the left. In the muscle the right-handed form is found mainly or only, and this form, therefore, is frequently designated as sarcolactic (or paralactic) acid. Recent work indicates that in the perfectly resting muscle lactic acid is present only in traces. The amount is greatly increased during contraction or in the processes leading to rigor. This substance would seem, therefore, to represent an intermediary product in the metabolism of contraction and in the metabolism of dying. The Nitrogenous Extractives (Nitrogenous Wastes). — Muscle extracts contain numerous crystallizable nitrogenous substances which are regarded as the end-products of the disassimilation or catabolism of the living protein material of the muscle. The number of these substances that have been found in traces or * Siegfried, " Zeitschrift f. physiol. Cliemie," 21, 360, 1896 ; also 2S, 524, 1899. 64 THE PHYSIOLOGY OF MUSCLE AND NERVE. weighable quantities is rather large. They have aroused great interest because their structure throws some light on the nature of protein catabolisni. The one that occurs in largest amount is creatin, C^HoNjO,, or methyl-guanidin-acetic acid, NHCNHj- NCH3CH.,C00H. Creatin may be present in amounts equal to 0.3 per cent, of the weight of the muscle. It has been supposed to be given off to the blood and eventually excreted in the urine as creatinin (C4H7N3O), which is formed from creatin by the loss of a molecule of water (see p. 835). Another nitrogenous body A\ith basic properties which occurs in amounts about equal to the creatin is carnosin, C9H,4N.j03.* It is ])robably a derivative of histidin, since on hydrolysis it yields histidin and alanin (Gule- \\dtsch). Nothing is known of its physiological significance. In addition there is a group of Ijodies supposed to represent the end-products of the breaking up of the nucleins of the muscle, all of which belong to the so-called purin bases. These are: Uric acid (aH.N.O,), xanthin (C,H,N,0.,), hypoxanthin (C,H4N,,0), guanin (C.H.NsO), adenin (C.H.N,,), and carnin (CvHsKtO^). They mil be referred to more fully in the section on Nutrition. Several other nitrogenous extractives have been isolated and named, but there is perhaps some doubt as to their chemical indi- viduality. These nitrogenous products are found in the various meat extracts and meat juices used in dietetics. While they possess no direct nutritive value, it seems probable (see chapter on CJastric Digestion) that they may l)e very effective indirectly by stinmlating the secretion of the gastric glands. Pigments. — The red color of many muscles is believed to be due to the presence of a special pigment which resembles in its structure and its properties the hemoglobin of the red blood corpuscles, and perhaps is identical with it. This ]:)igment is known as myohematin or myochrome. It belongs presumably to the group of so-called respiratory pigments, which have the property of holding oxygen in loose combination, and by virtue of this property it takes part in the absorption of oxygen by the muscular tissue. Enzymes. — A number of unorganized ferments or enzymes have been described by one observer or another. In this tissue as in others the processes of nutrition seem to be connected with the development of special enzymes. A i)roteolytic enzyme capable of digesting proteins has been described by Brucke and others; an amylolytic enzyme capable of converting the glycogen to sugar l;y Nasse; a glycolytic enzyme capable of destroying the sugars by Brunton, Cohrdieim, and others; a lipase capable of si)litting th(! fats Ijy Kastle and Lo(!venhart; and, finally a coagulating * von I'urtli iiiid Sclivvarz, "I'ioclicmisclic Zcilscliiiri ," 1911, ;{(), 4Vi. THE CHEMISTRY OF MUSCLE. 65 enzyme responsible for the coagulation of the muscle plasma after death by Halliburton. The Inorganic Constituents. — Muscle tissue contains a number of salts, chiefly in the form of the chlorids, sulphates, and phos- phates of sodium, potassium, calcium, magnesium, and iron. As in other tissues, the potassium salts predominate in the tissue itself. In frog's muscle the entire ash constitutes about 0.88 per cent, of the dry material of the muscle, and of this ash the potassium and the phosphoric acid together make up more than 80 per cent. (Urano). These inorganic constituents are most important to the normal activity of the muscle, and, indeed, in two ways: first, in that they maintain a normal osmotic pressure within the substance of the fibers and thus control the exchange of water with the surrounding lymph and blood; second, in that they are necessary to the normal structure and irritability of the living muscular tissue. Serious variations in the relative amounts of these salts cause marked changes in the properties of the tissues, as is explained in the section on Nutrition, in which the general nutritive importance of the salts is discussed, and also in the section dealing with the cause of the rhythmical activity of the heart. Chemical Changes in the Muscle during Contraction and Rigor. — Perhaps the most significant change in the muscle during contraction is the production of carbon dioxid. After increased muscular activity it may be shown that an animal gives off a larger amount of carbon dioxid in its expired air. In such cases the carbon dioxid produced in the muscles is given off to the blood, carried to the lungs, and then exhaled in the expired air. Pettenkofer and Voit, for instance, found that during a day in which much muscular work was done a man expired nearly twice as much CO2 as during a resting day. The same fact can be shown directly upon an isolated muscle of a frog made to con- tract by electrical stimulation. The carbon dioxid in this case diffuses out of the muscle in part to the surrounding air, and in part remains in solution, or in chemical combination as car- bonates, in the liquids of the tissue. It has been shown by Hermann* and others that a muscle that has been tetanized gives off more carbon dioxide than a resting muscle when their contained gases are extracted by a gas pump. This COo arises from the oxidation of the carbon of some of the constituents of the muscle, and its existence is an indication that in their final stages the changes in the muscle are equivalent in those of ordinary combus- tion at high temperatures, the burning of wood or fats, for * Hermann, " Untersuchungen iiber den Stoffwechsel der Muskeln, etc.," Berlin, 1867. 66 THE PHYSIOLOGY OF MUSCLE AND NERVE. instance. Moreover, the formation of the CO, in the muscle is accompanied by the production of heat, as in combustion; and for the same amount of CO, produced in the two cases the same amount of heat is liberated. Fletcher* has discovered the significant fact that the increased elimination of CO, following upon contraction is clearly shown only when the muscle is well supplied with oxygen. In the absence of oxygen contraction may cause no increase in the CO, given off. This fact seems to be in accord with prevalent ideas regarding the nature of the muscular metabolism, according to which the chemical processes take place in two stages. In the first the complex energy- yielding material, sugar, for example, undergoes a splitting process which results in the formation of intermediary products, such as lactic acid. In the second stage these intermediary products are oxidized, provided, as Fletcher points out, there is an adequate supply of oxygen. Under normal conditions a sufficient amount of oxygen is furnished by the circulating blood, but under pathological conditions and in the excised muscle the supply may not be adequate, and as a result the intermediary products are not oxidized completely. Under such conditions less heat is produced in the muscle, and the intermediary products accumulate in the tissue unless carried off as such in the blood. The fact that a muscle will continue to contract on stimulation even when in an atmosphere free from oxygen was formerly interpreted to mean that some oxygen had been stored previously by the muscle antl tiiat con- tractions were possible only as long as this supply hekl out. But since it has been found that the contractions under these circumstances are not accom- panied by an output of carbon di-oxid, tliis supposition has been rendered doubtful. It has been suggested, on the contrary, tliat tiie energy for the contractions in these cases may be obtained from other than oxidative changes, for example, from the small amount of heat-energy liberated in the splitting of sugar into lactic acid. Disappearance of the Gh/cogen. — An equally positive chemical change in the muscle during contraction is the disappearance of its contained glycogen. Satisfactory proof has been furnished that the amount of glycogen in a muscle disappears more or less in propor- tion to the extent and duration of the contractions, and that after prolonged muscular activity, especially in the starving animal, the supply may be exhausted entirely. In what way the glycogen is consumed is not completely known; the matter is discussed in the next paragraph and in the section on Nutrition. It is the general belief in j)liysi()U)gy to-day that under normal conditions the glycogen of the muscle, after being cijanged to sugar, furnishes * Fletcher, "Journal of Physiology," 1902, 28, 474. THE CHEMISTRY OF MUSCLE. 67 the material from which the energy necessary for contraction is obtained. The Forviation of Lactic Acid. — The lactic acid that is present in the muscle is believed to be increased in quantity by muscular activity. Attention was first called to this point by du Bois- Reymond, who showed that the reaction of the tetanized muscle is distinctly acid, while that of the resting muscle is neutral or slightly alkaline. This fact can be demonstrated by the use of litmus paper, but perhaps more strikingly by the use of acid fuchsin.* If a solution of acid fuchsin is injected under the skin of a frog it is gradually absorbed and distributed to the body without injuring the tissues. In the normal media of the body this solution remains colorless or nearly so. If now one of the legs is tetanized the muscles take on a red color, showing that an acid is produced locally. The supposition generally made is that the acidity during activity is due to an increased production of sarcolactic acid. Experiments have been made by a number of observers to determine quantita- tively the amount of lactic acid in the resting and the worked muscle respectively. Several have stated that the amount is act- ually less in the worked muscle; others have found an increase. The balance of evidence seems to show that there is an increased production, but that this increase may be obscured in the living animal by the fact that the acid is removed by oxidation or by the circulating blood. This conclusion has been confirmed in a satisfactory way by the striking experiments of Fletcher and Hopkins.f These observers have shown in the first place that injury to a muscle causes a production of lactic acid, and that, therefore, the usual method of determining the amount of this substance in supposedly resting muscle has given fallacious results owing to the injury inflicted during the process of extrac- tion. By the adoption of a new method they have avoided this error, and they find that in resting muscle lactic acid exists, in traces only (0.03 per cent.) or perhaps is absent altogether. An appreciable amount is formed when the excised muscle is well tetanized (0.22 per cent.), also after injury, and especially in the development of rigor. In heat-rigor a maximum yield of 0.3 to 0.5 per cent, is obtained in the frog's muscle. In a muscle removed from the body and deprived, therefore, of its supply of oxygen, lactic acid develops rapidly, reaching finally an amount equal to that observed in heat-rigor. As long as such a surviving muscle shows irritability toward artificial stim- * Dreser, "Centralblatt fiir Phvsiologie," 1, 195, 1887. t Fletcher and Hopkins, "Journal of Physiology," 1907, 35, 247; also 1911, 12, 43, 286, and Embden, et. al., "Biochemische Zeitschrift," 1912, 45, 45. 68 THE PHYSIOLOGY OF MUSCLE AND NERVE. ulation, lactic acid continues to form. When irritability is lost, no further production of acid can be detected and the muscle soon goes into death-rigor. On the contrary, if the muscle is supplied abundantly with oxygen, no accumulation of lactic acid can be detected. It is evident from these observations that lactic acid is formed in the muscle as a result of the chemical changes underlying contraction, and also of the changes that occur during dying. The interpretation of this fact and also of the further fact that the lactic acid does not appear when oxygen is freely supplied to the muscle is surrounded with difficulties o^^ing to our lack of knowledge of the chemical reac- tions that take place. The simplest explanation at present is that the lactic acid is an intermediary product formed from the sugar by enzyme action, and that it subsequently, in the presence of oxygen, undergoes oxidation under the influence of other enzjmies. From this point of view it is necessary to assume that when oxygen is freely supphed to an excised muscle lactic acid does not accumulate, because it is removed by oxida- tion as rapidly as it is formed. This explanation of the signif- icance and origin of the lactic acid agrees very well with the fact that in the contracting muscle glycogen disappears as the lactic acid appears. Much uncertainty, however, prevails in regard both to the immediate origin and the fate of the lactic acid. It is stated that in the juice squeezed out of a muscle or in a preparation of minced muscle the yield of lactic acid is not increased by adding sugar to the mixture. This fact is against the hypothesis that the lactic acid is produced directly from sugar under the influence of enzymes contained in the muscular substance, and suggests rather the view that the acid is formed from some as yet unknown substance. It is possible, of course, that the unknown substance may be a complex containing the sugar, Init while this suggestion meets the facts as they stand no su('h ('omi)lex has been isolated. The whole question must be left open until further facts are obtained. The attempt to refer the energy of the contraction to the Hboration l)y chemical reaction of tlie ]X)tential energy in the sugar molecule is made more difficnilt when we remember that the muscular contraction is a very rapid process. The chemical changes that take place must occur with explosive rapidity, and it is difficult to imagine that th(!y consist in a series of enzyme actions following one ui)on another. Chemical Changes during Rigor Mortis. — The chemical chang(;s dui'iiig rig(ji' have heeu referred to above, but may be summarized here in brief foini : 1. There is a coagulation of the protein material of the muscle plasma, which at present may be explained by supposing that the THE CHEMISTRY OF MUSCLE. 69 contained myosin and myogen, spontaneously, or under the action of acid products of metabolism, pass into their insoluble forms, — namely, myosin fibrin and myogen fibrin. 2. There is an increased acidity, due doubtless to a production of lactic acid. 3. There is a production of COg. Hermann, in his original ex- periments, asserts that in rigor there is, so to speak, a maximal production of COj, — that is, all of the material in the muscle capable of yielding CO2 is broken down during rigor. The amount of CO2 given off, therefore, by a resting muscle when it goes into rigor is greater than in the case of a worked muscle, since in the latter some of the material capable of yielding COj has been used up during contraction. 4. The consumption of glycogen. According to some observers, glycogen disappears during rigor as it does during contraction; but others fin d that the amount is not changed during this process. The Relation of the Chemical Changes during Contraction to Fatigue; Chemical Theory of Fatigue. — As we have seen, a muscle kept in continuous contraction soon shows fatigue ; it relaxes more and more imtil, in spite of constant stimulation, it becomes completely unirritable. We may define fatigue, there- fore, as a more or less complete loss of irritability and contractility brought on by functional activity. But even when the fatigue is complete and the muscle fails to respond at all to maximal stimulation, a very short interval of rest is sufficient to bring about some return of irritability. For a complete restoration to its normal condition a long interval of time may be necessary. If the muscle is isolated from the body and is thus deprived of its circulation and its proper supply of oxygen, fatigue appears more rapidly and is recovered from less completely. Ranke,* to whom we owe the first thorough investigation of this subject, was led to believe that as a result of the chemical changes occur- ring in the muscle during contraction certain substances are formed which depress or inhibit the power of contraction. In support of this view he found that extracts made from the fatigued muscles of one frog when injected into the circulation of another fresh frog would bring on the appearance of fatigue' in the latter. Control experiments made wath extracts of unfatigued muscles gave no such result. He designated these inhibitory products as fatigue substances and made experiments to prove that they consist of the known products of muscular metabolism, namely, lactic acid (or the lactates), carbon dioxid, and possibly also acid potassiiun phosphate (KH2PO4). These * Ranke, "Tetanus," Leipzig, 1865. 70 THE PHYSIOLOGY OF MUSCLE AND NERVE. results have been confirmed by other observers,* and we may ac- cept, therefore, the view that the products of muscular activity, if they are allowed to accumalate in the muscle, serve to diminish or suppress its contractility. We know that when muscular ac- tivity is prolonged, or is carried out under conditions which imply a lessened supply of oxygen, an accumulation of some of these products does actually occur. It is possible, of course, that other intermediary substances are formed which may have a simi- lar effect. Thus Weichardt f has stated that muscular con- tractions give rise to a definite toxin, derived from the protein material of the muscle, which, in his opinion, is the chief agent in causing fatigue. He claims to have isolated this fatigue toxin (kenotoxin) to the extent at least of having freed it from the above-mentioned fatigue substances of Ranke. When injected into the circulation of a fresh animal, it brings on fatigue or even death. Moreover, by injecting it in suitable doses, the body raa,y form an antitoxin, and this latter substance, when given to a fresh animal, may confer upon it an unusual capacity for performing muscular work. It is not advisable, however, to accept these statements until the facts have been corroborated by other observers and further experiments. At present we are justified only in laying emphasis upon the known products of mus- cular metabolism, particularly the lactic acid, or the lactates which may be formed by its reaction with the alkaline salts of the blood and lymph. When these substances accumulate in the muscle they may be carried off in the blood and thus influence other organs. On such a supposition we may explain the fact, ))rought out by ergographic experiments, that marked exercise of one set of muscles, for example, those of the legs in walking or climbing, may diminish the amount of work obtainable from other unused muscles, such as those of the arms. So also the effect of muscular exercise upon the rate of the respiratory movements and upon the heart-rate is explained, as we shall see, in a similar way. It should be addcfl that Lee, J confirming an older observation by Ranke, has published experiments which indicate that the first effect of the so-call(;(l fatigue substances is to iiK-rease the irritability of the muscle, while; the later effect is to diminish the irritability or to suppress it altogether. In this initial favoring influence Lee finds an explanation of the phenomenon of Treppe (see p. 35). *L('.(; "Arncrifan .Journ.il of Pliy.sioloKy," 1907, 20, 170, and Burridge, "Journal of I'liy.siolonv," 1911, 41, 'isn. t WcMohanl'l," An-liiv f. Anal. u. Plivsiol. (phy.siol. Abth.)," lOOrj, 219; also "Miinfhcn.T iricd. VVocliciiHchrifl," 1904, 190.'), 190(). I For diwoiissioii and cxpcriiiicnts, sco Leo, Ilarvcy Lc^clurcH, 190.5-06, Philadclpliia, 1900; also ".J(jurnal of Uic Arricfrican Mcd'utal Association," May 19, 1900, and "American Journal of Physiology," 18, 207, 1907. THE CHEMISTRY OF MUSCLE. 71 After the appearance of complete fatigue a muscle shows usually some return of irritability if given a short rest. But even in the case of a muscle in the body, with its circulation intact, an interval of some hours is required before it regains entirely its power to perform a normal amount of work. It seems probable that the loss of power to do work is referable in part to a using up of the supply of energy-yielding material, but the accumulation of the so-called fatigue-substances is doubtless the immediate cause of that gradual loss of irritabihty which we usually designate as fatigue. In what way these products depress the irritability and contractihty of the muscles is not known. theo^^o'f"^'n«l^"f'^^•^°''^^'^^''•-l^ ^' generally admitted that no means of which the shortening of the muscle is produced, the nature of the energy which is thus trans- formed into mechanical work, and the relation of this energy to the chemical reaction that takes place in the stimulated muscle. The measurable manifestations of en- ergy which are observed in the contracting muscle are the change in electric potential, the increased production of heat, and the me- chanical work. The electrical change is a fleeting phenomenon which passes rapidly over the muscle, starting from the point stimulated. Whether this electrical change is simultaneous with the chemical reaction or precedes it cannot be stated definitely, al- though simultaneous records indi- cate that the electrical change begins at least before either the mechanical or the thermal changes can be recorded. The usual point of view in physiology has been that the chemical change caused by the stimulus gives origin to all the forms of energy, electrical, mechan- ical, and thermal; which are ex- hibited by the contracting muscle. If we assume, for example, that the chemical reaction in question con- sists in the oxidation of sugar to carbon dioxid and water, then, whether this oxidation is immediate nrn^h^ P^^J}}'^''''^}' a number of stages, the final result will be that a certain proportion of the potential chemical energy in the molecule of sugar becomes converted to kinetic energy, which may take the form of heat or of heat and work or ot heat, work, and electrical energy, and the special problem has been to determine^the proportion of this energy, which mav be utilized for mechani- cal work and the mechanism through which this transformation is effected. Ihe older view was to compare the muscle to a heat engine in which the poten- rru F'S. 27.— Engelmann's artificial muscle. Ihe artificial muscle is represented by tlie catgut string, m. This is surrounded by a coil of platinum wire, w, through which an electrical current may be sent. The catgut IS attached to a lever, h, whose fulcrum is at c. The catgut is immersed in a beaker of water at 50° to 55° C, and " stimulated " by the sudden increase in temperature caused by the passage of a current through the coil. — { Atter Engelmann.) 72 THE PHYSIOLOGY OF MUSCLE AND NERVE. tial chemical energ>' of the fuel is first converted to heat by combustion, and then by appropriate mechanisms a ]Kirtion of this heat energj' is utilized to perform mechanical work. Engelmann* has furnished a specific hypothesis of this character. He assumes that tlie chemical energy set free in the muscle takes the fonn of heat, which then acts ujwn the doubly refractive particles in the dim bands of the muscular tibrilhr anti causes them to imbibe water from the adjoining light bands. If the doubly refractive particles are supposed to have a linear shape, then, by imbibition, they would tend to assume a spheri- cal form, and thus there would occur a shortening along one diameter and an increase along the diameter at right angles, such as occurs in the contracting muscle. As the muscle cools down the water passes back into the light bands and the phase of relaxation takes place. He has supported this hypothesis Fie. 28. — Curve of simple contraction obtained from an artificial muscle. The dura/- tion of the stimulus (heatinR effect caused by the current) is shown by the break in the line beneath the curve. by microscopical observations upon the relations of the dim and light bunds in the (contracted and relaxed fibrils (p. 20), and, moreover, has constructed an artificial imiscle from a string of eatgut which, working on this printiijjle, contracts when heated and relaxes when cooled. When the heating occurs Kuddenly tiiis moilel gives curves of coulraction identical witli those obt-aiiuul frf)m f)lairi muscle. The apparatus is illustrated iuid described in l"'ig. 27, and the cur\c of contraction obtained from it. is shown in l''ig. 2S. 'i'he under- lying j)rinciple of this hyi)()thesis has met with nuicli (criticism. I'^ickthas shown apparent ly that when appli(!(l (luantitatively to the work done l)y nmscle it leads to an itnpossible conclusion. If, in a ncversible j)rocess, atatempcr- ature T,„ a certain (juantity of lieat, (i,,, is converted to mechanical work, it nece,Hsitat(;s, ac,c()rding to the se(con(l law of 'I'hermodynamics, the passage of heat, Q, fnjin a higher I emperat ure, T, to a, hnvei' temperat ni'c, T^, in ac(cordancc with the erjualion, , -= (^ I , ~ ,., * F'lngelmann, "[h-})cr den Unsprung der Muskelkraft," Lcjipzig, 1893; also I'fliiger's -'Archiv," lS7:i, 7, IM. t J'K;k-Pflug(;r'H "Archiv," 1W«, r,:i, iM\. THE CHEMISTKY OF MUSCLE. 73 Since experiments have shown that the external work of a contracting muscle may be equal at a minimum to i of the total heat energy (Qj, = JQ), the equa- tion demands, if T^ = 37° C. and To = T„ that T„ the temperature to which the muscle is heated shall be 114° C. This criticism has been accepted by most authors as demonstrating that the muscle cannot work as a heat engine by transforming a part of the heat of the chemical reaction to work. A differ- ence in temperature is necessary that is not possible in the case of muscle. Other theories have been proposed, according to which the chemical energy is supposed to be converted into work either directly (Fick) or through a change in surface tension or electric potential. The muscle is supposed to act in such theories as a chemical or chemodynamic engine. The surface-tension theories have been perhaps the ones most discussed in recent years. The various forms which these theories have taken make it impossible to describe them in general terms. According to one presentation (Macallum*) the sarcous elements (dim bands) may be considered as having interfaces with the sarco- plasm along the lateral planes and with the isotropic substance (light bands) at their ends, at which surface tension exists. If the results of the chemical changes within the elements are such as to cause a diminution in surface ten- sion along the lateral walls, or an increase in this energy at the end surfaces, the elements would tend to change from a cylinder with straight to one with curved lateral walls, and this change, when multiplied by the total number of sarcous elements in the muscle, would account for the shortening. The theory is deficient_ in not explaining how the surface energy is changed, and also in failing to give an approximate quantitative determination of the total amount of mechanical energy that might be obtained in this way from the nfiuscle. According to calculations made by Bernstein,! the work energy ex- hibited by a contracting muscle is greater than can be accounted for by prob- able changes in surface tension. * Macallum, "Surface Tension and Vital Phenomena," University of Toronto Studies, Physiological Series, No. 8, 1912. t Bernstein-Pfiuger's "Archiv," 1901, 85, 271. See also Berg, "Biochemi- cal Bulletm," 1912, 2, 101. CHAPTER III. THE PHENOMENON OF CONDUCTION— PROPERTIES OF THE NERVE FIBER. Conduction. — When living matter is excited or stimulated in any way the excitation is not localized to the point acted upon, but is or may be jDropagated throughout its substance. This prop- erty of conducting a change that has been initiated by a stimulus applied localh^ is a general property of protoplasm, and is exhib- ited in a striking way by many of the simplest forms of life. A light touch, for instance, applied to a vorticella will cause a retrac- tion of its vibrating cilia and a shortening of its stalk. In the most specialized animals, such as the mammalia, this property of con- duction finds its greatest development in the nervous tissue, and indeed, especially in the axis cylinder processes of the nerve cells, the so-called nerve fibers. But the property is exhibited also to a greater or less extent by other tissues. When a muscular mass is stimulated at one point the excitation set up may be propagated not only through the substance of the cells or fibers directly affected, but from cell to cell for a considerable distance. In the heart tissue and in plain muscle it has been shown that a change of this sort may be conducted independently of the phenomenon of visible contraction. A stimulus applied to the venous end of a frog's heart, for instance, may, under certain conditions, be conducted through the auricular tissue without causing in it a visible change, and yet arouse a contraction in the ventricular muscle (Engelmann). Similarly, it can be shown that ciliary cells can convey a stimulus from cell to cell. A stinuilus ai)plied to one point of a field of ciliary epithelium may set up a change that is conveyed as a ciliary impulse to distant cells. The universality of this property of conduction in the simpler, less differentiated forms of life, and its presen(!e in some form in many of the tissues of the higher forms would justify the as- sumption that the underlying change is essentially the same in all cases. But in nerve fibers this property has become special- ized to the highest degree, and in this tissue it may be studied, thor(;forf!, with the grr;atost succ(!ss and profit. Structure of the Nerve Fiber. — The p(!rii)heral nerve fiber, as we find it in tiie nerve trunks and nerve plexuses of the body, may be either meduUated or non-meduUated. All the nerve fibers that arise histologically from the nerve-colls of the central nervous 74 THE PHENOMENON OF CONDUCTION. tO system proper — the brain and cord and the outlying sensory gangha of the cranial nerves and the posterior spinal roots— are medullated. These fibers contain a central core, the axis cylinder, which is usually regarded as an enormously elongated process of the nerve cell with which it is connected. The axis cylinder shows a differentiation into fibrils (neurofibrils) and interfibrillar sub- stance (neuroplasm). All of our evidence goes to show that the axis cylinder is the essential part of the nerve fiber so far as its property of conduction is concerned. It is further assumed that the neurofibrils in the axis cylinder form the conducting mech- anism rather than the interfibrillar substance. Surrounding the axis cylinder we have the medullary or myelin sheath, varying much in thickness in different fibers. This sheath is composed of peculiar material and is interrupted or divided into segments at cer- tain intervals, the so-called nodes of Ranvier. Outside the myelin there is a delicate elastic sheath comparable to the sarcolemma of the muscle fiber and designated as the neurilemma. Lying under the neurilemma are found nuclei, one for each intemodal segment of the myelin, surrounded by a small amount of granular proto- plasm. The non-medullated fibers have no myelin sheath. They are to be considered as an axis cylinder process from a nerve cell, surrounded by or inclosed in a neurilemmal sheath. These fibers arise histologically from the nerve cells found in the outlying ganglia of the body, the ganglia of the sympathetic system and its appendages. The Function of the Myelin Sheath. — The myelin sheath of the cerebrospinal nerve fibers is a structure that is interesting and peculiar, both as regards its origin and its composition. Much speculation has been indulged in with regard to its function, but practically nothing that is certain can be said upon this point. It has been supposed by some to act as a sort of insulator, preventing contact between neighboring axis cylinders and thus insuring better conduction. But against this view it may be urged that we have no proof that the non-medullated fibers do not conduct equally as well. The view has some probability to it, however, for we must remember that the non-medullated fibers do not run in large nerve trunks that supply a number of different organs, and therefore in them a provision for isolated conduction is not so necessary. Moreover, in the medullated fibers the myelin sheath is lost toward its peripheral end after the nerve has entered the tissue to which it is to be distributed, indicating that its function is then no longer necessary. According to the older conceptions of the process of conduction in nerve fibers, not only anatomical but also physiological continuity is necessary. Mere contact of living axis cylinders would not enable the nerve impulse to pass from one to the other. The newer views, included in the so-called 76 THE PHYSIOLOGY OF MUSCLE AND NERVE. neuron theory, assume that mere contact of hving, entirely normal nerve substance does permit an excitatory change to pass from one to the other, so that it is not impossible that the myelin sheath may serve to prevent one axis cylinder from influencing the neigh- boring axis cylinders in a nerve trunk. As some e^^dence for this view, attention has been called to the fact that in the condition known as multiple or insular sclerosis of the brain and cord the axis cj'linders of the areas affected remain intact, while the myeUn sheaths are destroj^ed. The disturbances of co-ordination accompanying this condi- tion may be an expression, therefore, of a loss of isolated conduction. Others have supposed that the myelin sheath serves as a source of nutrition to the inclosed axis cylinder, or as a regulator in some way of its metabolism. No fact is reported that would make this suggestion seem probable, except, perhaps, the statement that stimulation of a nerve, even for a brief period, causes a change in the appearance of the neurokeratin framework found in the myelin sheath. The change consists in a widening of the meshes (Stiibel*). In general, it is found that the myelin sheath is larger in those fibers that have the longest course; the size of the sheath, in fact, increases with that of the axis cylinder. It is known also that the medullated fibers in general are more irritable to artificial stimuli than the non-medullated ones, and that when induction shocks are employed, the non-medullated fibers lose their irritability more rapidly at the point stimulated. None of these facts are sufficient, however, to indicate the probable function of the myelin. The embryological development of the sheath also fails to throw light on its physiological significance. For, while it is usually supposed that the axis cylinder itself is simply an outgrowth from the nerve cell, and the myelin sheath arises from separate mesoblastic cells which surround the axis cylinder, this view, so far as the myelin is concerned, is not beyond question, and the study of the process of regeneration of nerve fibers indicates that the actual production of myelin is controlled in some way Vjy the functional axis cylinder. The axis cylinder outgrowths from the sympathetic nerve cells found in the ganglia of the sympathetic chain and in the peripheral ganglia generally of the body are usually non-medullated, although apparently this is not an invariable rule. In the birds all such fibers, on the contrary, are me(hillated (Langleyf). Nothing is known as to the conditions that determine whether a nerve-fiber process shall or shall not be surrounded l)y a myelin sheath. Chemistry of the Nerve Fiber. — Our knowledge of the chem- istry of the nerve fibers is very inconij)let,e. The myelin sheath is composed largely of borlies to which the general name of " lip- oids " has been applied. This t(!rm is used as a generic name for *.Stubel, "PfliiK(!r'H Archiv," 1912, 149, 1. *" t Langley, ".Journal of PhyHiology," 30, 221, 190:^,; 20, fyry, 1S90. THE PHENOMENON OF CONDUCTION. 77 those constituents of living cells which can be extracted by ether or similar solvents. It is a biological rather than a chemical term. By extraction of myelin with hot alcohol a complex phos- phorus-containing substance known as protagon may be obtained in crystaUine form. This substance is, however, beheved now to be a mixture rather than a definite chemical inchvidual. The most important substances isolated from the myeUn are lecithin (phosphatids), cholesterin, and the cerebrosides. Lecithin (C44H90NPO9) is a waxy hygroscopic yellowish sub- stance containing about 4 per cent, of phosphorus. When de- composed by the action of alkahes it yields as split products glycerophosphoric acid, a nitrogenous base, cholin (C5H15NO2), and some of the higher fatty acids, such as oleic, palmitic, or stearic. It is probable that there are a number of different lecithins varying somewhat in their composition, for instance, in the character of the fatty acid contained in the molecule. The lecithins constitute one member of a larger group known as phosphatids, which are characterized by the presence of both phosphorus and nitrogen. They are widely distributed in the tissues and hquids of the body, but are especially characteristic of the white matter of the nervous system. They combine easily with other substances, such as proteins, glucosides, etc., and it is probable that lecithin exists in some such combination in the myelin. The decomposition of the lecithin referred to above occurs in the body when nerves undergo degeneration. The presence of the fatty acid liberated under such circumstances is demonstrated by the well-known reaction with osmic acid used to detect degenerated nerve fibers, while the existence of cholin has been shown by Halhburton* in the liquids of the body, not only after nerve-degeneration produced by experimental lesions, but in the case of degenerative diseases of the nervous system. Cholesterin or cholesterol (C27H46O) is a white crystalline sub- stance containing, as its formula shows, neither nitrogen nor phos- phorus. It is widely distributed among the tissues of the body, and in an isomeric form, phytocholesterin, occurs also in plants. In the animal body it is especially abundant in the white matter of the nerves. The chemical nature of cholesterin has long been a matter of uncertainty, but recent work indicates that it belongs to the group of "terpenes" heretofore supposed to be confined to the plant kingdom. It is given the formula — (CH3)2 = CH - CH, - CH2 - CnH,e - CH = CH^ CHo<^^CH2 CHOH * Halliburton, "British Medical Journal," 1907, May 4 and 11. Also "Folia Neuro-Biologica," 1907, i., 38, and "Biochemistry of Muscle and Nerve," Philadelphia, 1904. 78 THE PHYSIOLOGY OF MUSCLE AND NERVE. The fact that lecithin and cholesterin usually occur together has suggested that thej' have some physiological connection. It has been supposed, for example, that they act as a check upon each other. Lecithin under certain conditions favors hemolysis of red corpuscles, or the action of lipase on fat, while cholesterin inhibits both of these activities. No application of this antagonistic rela- tionship is possible at present in the case of the myelin sheath. Cerebrosides or Cerehrogalacio sides. — This name is given to a group of bodies containing nitrogen, but no phosphorus. In the myelin they are found in connection with and possibly in com- bination with the lecithin. They belong to the group of glucosides, that is, on hydrolytic decomposition they give rise to a carbo- hydrate group, in this case galactose. Fatty acids and a nitrogenous base also result from this decomposition. The cerebroside material obtained from the white matter has been named specifically cerebrin or -phrenosin , but little is known of its exact structure. Union of Nerve Fibers into Nerves or Nerve Trunks. — The assembling of nerve fibers into larger or smaller nerve trunks re- sembles histologically the combination of muscle fibers to form a muscle. Physiologically, however, there is no similarity. The various fibers in a muscle act together in a co-ordinated way as a physiological unit. On the other hand, the hundreds or thou- sands of nerve fibers found in a nerve may form groups which are entirely independent in their physiological activity. In the vagus nerve, for instance, we have nerve fibers running side by side, some of which supply the heart, some the muscles of the larynx, some the muscles of the stomach or intestines, some the glands of the stomach or pancreas, and so on. Nerves are, therefore, anatomical units simply, containing groups of fibers which have very different activities and which may function entirely independently of one another. As a nerve-trunk is con- stituted it consists chiefly of the connective tissue binding the fibers together. It is estimattid (Ellison) that in the median nerve the connective tissue forms 63 per cent, of the whole trunk, while myelin sheaths make up 28 per cent., and the axis cylinders only 9 per cent. Afferent and Efferent Nerve Fibers. — The older physiologists believed that one and the same nerve or nerve fiber might conduct sensory impul.ses toward the central nervous system or motor im- pulses from the central nervous system to the periphery. Bell and Magendie succeeded in establishing the great truth that a nerve fiber cannot be both motor and sensory. Since their time it has been recognized that we must divide the nerve fibers connected with the central nervous system into two great groups: the efferent fibers^ which carry impulses outwardly from the nervous system THE PHENOMENON OF CONDUCTION. 79 to the peripheral tissues, and the afferent fibers, which carry their impulses inwardly, — that is, from the peripheral tissues to the nerve centers. Under normal conditions the afferent fibers are stimulated only at their endings in the peripheral tissues, in the skin, the mucous membranes, the sense organs, etc., while the efferent fibers are stimulated only at their central origin, — that is, through the nerve cells from which they spring. The difference in the direction of conduction depends, therefore, on the anatomical fact that the efferent fibers have a stimulating mechanism at their central ends only, while the afferent fibers are adapted only for stimulation at their peripheral ends. Classification of Nerve Fibers. — In addition to this funda- mental separation we may subdivide peripheral nerve fibers into smaller groups, making use of either anatomical or physiological differences upon which to base a classification. For the purpose here in view a classification that is physiological as far as possible seems preferable. In the first place, experimental physiology has shown that the effect of the impulse conveyed by nerve fibers may be either exciting or inhibiting. That is, the tissue or the cell to which the impulse is carried may be thereby stimulated to ac- tivity, in which case the effect is excitatory, or, on the contrary, it may, if already in activity, be reduced to a condition of rest or lessened activity; the effect in this case is inhibitory. Many physiologists believe that one and the same nerve fiber may carry excitatory or inhibitory impulses, but in some cases at least we have positive proof that these functions are discharged by separate fibers. We may subdivide both the afferent and the efferent sys- tems into excitatory and inhibitory fibers. Each of these sub- groups again falls into smaller divisions according to the kind of activity it excites or inhibits. In the eft"erent system, for instance, the excitatory fibers may cause contraction or motion if they ter- minate in muscular tissue, or secretion if they terminate in glandu- lar tissue. For convenience of description each of the groups in turn may be further classified according to the kind of muscle in which it ends or the kind of glandular tissue. In the motor group we speak of vasomotor fibers in reference to those that end in the plain muscle of the walls of the blood-vessels; visceromotor fibers, those ending in the muscular tissue of the abdominal and thoracic viscera; pilomotor fibers, those ending in the muscles attached to the hair follicles. The classification that is suggested in tabular form below depends, therefore, on three principles: first, the direc- tion in which the impulse travels normally; second, whether this impulse excites or inhibits; third, the kind of action excited or inhibited, which in turn depends upon the kind of tissue in which the fibers end. 80 THE PHYSIOLOGY OF MUSCLE AND XERVE. Efferent - Afferent Excitatory- Inhibitory Excitatory Motor "^ Secretory , Inhibito-mo- I lor j Inhibito-se- *• cretorv Sensory . Inhibitory ■! Reflex Inhibito-re- flex ^- s Motor. Vasomotor. Cardioinotor. Visceromotor. Pilomotor. Salivary. Gastric. Paucreatic. Sweat. Subdivisions corresponding to the varieties of mo- tor fibers above. Subdivisions corresponding to the varieties of se- cretory fibers above. Visual. Auditory. Olfactory. Gustatory. Pressure. Temperature. Paiu. Hunger. . Thirst etc. According to the efferent fibers affected. luhibitorv effects upon the conscious sensations are f iiiuiuiiorv euecui upon in J not demonstrated. J The reflex fibers that cs '^ are known to be inhibit cause unconscious reflexes ted in some cases at least. That the final action of a peripheral nerve fiber is determined by the tissue in which it ends rather than by the nature of the ner^'e fiber it.self or the nature of the impulse that it carries is indi- cated strongly by the regeneration experiments made by Langley.* For instance, the chorda tympani ners^e contains fillers which cause a dilatation in the blood-vessels of the submaxillary gland, while the cervical sympathetic contains fibers which cause a constriction of the vessels in the same gland. If the lingual nerve (containing the chorda tympani fibers) is divided and the central end is sutured to the peripheral end of the severed cervical symjjathetic, the chorda fibers will grow along the paths of the old constrictor fibers of the sympathetic. If time is given for regeneration to take place, stimulation of the chorda now causes a constriction in the vessels. The experiment can also be reversed. That is, by suturing the central end of the cervical sympathetic to the jicMiplicral entl of the divided lingual the fibers of the former grow along the jxiths of the old dilator fibers, and after regeneration has taken place stimulation of the sympathetic causes dilatation of the blood- ves.seLs in the gland. These results are ])arti('uhirly instnictive, as vasoconstriction Is an example of the excitatory efftict of the nerve impulse, being the result of a contraction of the circular muscles in the ves.scls, while vasodilatation is an example of iniiibitory action, being due to an inhil)ition of the contraction of the same muscl(;s. Yet obviously thest; two opposite effects arc determined not by the nature of the iicrvf; fibers, but by tlieir place or mode of ending in the gland. Separation of the Afferent and Efferent Fibers in the Roots of the Spinal Nerves.— Arcordiug to tlu; iicll-Magciulic discovoiy, * Langl(-y, "Journal of I'liyHioloRy," 2;i, 240, 18'.J8; ibid., iiO, WV.), 1904; " ProcecdingB Royal Society," TA, 1904. THE PHENOMENON OF CONDUCTION. 81 the motor fibers to the voluntary muscles emerge from the spinal cord in the anterior roots, while the fibers that give rise to sensa- tions enter the cord through the posterior roots. These facts have been demonstrated beyond all doubt. Magendie discovered an apparent exception in the phenomenon of recurrent sensibility. When the anterior root is severed and its peripheral end is stimu- lated only motor effects should be obtained. Magendie observed, however, upon dogs that in certain cases the animals showed signs of pain. This apparent exception to the general rule was after- ward explained satisfactorily. It was shoT\Ti that the fibers in question do not really belong to the anterior root, — that is, they do not emerge from the cord with the root fibers; they are, in fact, sensory fibers for the meningeal membranes of the cord which are on their wa}' to the posterior roots and which enter the cord with the fibers of the latter. Since the work of Bell and Magendie it has been a question whether their law applies to all afferent and efferent fibers and not simply to the motor and sensory fibers proper. The experimental evidence upon this point, as far as the mammals are concerned, has accumulated slowly. Various authors have shown that stimulation of the anterior roots of certain spinal nerves may cause a constriction of the blood-vessels, an erection of the hairs (stimulation of the pilomotor fibers), a secretion of sweat, and so on, while stimulation of the posterior roots in the same regions is without effect upon these peripheral tissues. One apparent excep- tion, however, has been noted. A number of observers have found that stimulation of the peripheral end of the divided posterior roots (fifth lumbar to first sacral) causes a vascular dilatation in the hind limb. The matter has been particularly investigated by Bayliss,* who gives undoubted proof of the general fact. At the same time he shows that the fibers in question are not efferent fibers from the cord passing out by the posterior instead of the an- terior roots. Tliis is shown by the fact that they do not degenerate when the root is cut between the ganglion and the cord, as they should do if they originated from cells in the cord. Bajdiss's own explanation of this curious fact is that the fibers in question are ordinary afferent fibers, but that they are capable of a double ac- tion: they can convey sensory impulses from the blood-vessels to the cord according to the usual type of sensory fibers, but they can also convey efferent impulses, antidromic impulses as he desig- nates them, to the muscles of the blood-vessels. In other words, for this special set of fibers he attempts to re-establish the view held by physiologists before the time of Bell, — namely, that one and the same fiber transmits normally both afferent and efferent impulses. An exception so peculiar as this to an other-wise general rule cannot be accepted without hesitation. It is possible that * Bayliss, "Journal of Physiology," 26, 173, 1901, and 28, 276, 1902. 6 82 THE PHYSIOLOGY OF MUSCLE AND NERVE. future work may give an explanation less opposed to current views than that oflfered by Bayliss. Cells of Origin of the Anterior and Posterior Root Fibers. — The efferent fibers of the anterior root arise as axons or axis cylinder processes from nerve cells in the gray matter of the cord at or near the exit of the root. The motor fibers to the voluntary muscles arise from the large cells of the anterior horn of gray matter; the fibers to the plain muscle and glands, autonomic fibers according to Langley's nomenclature, take their origin from spindle-shaped nerve cells lying in the so-called lateral horn of the gray matter.* According to the accepted belief regarding the nutrition of nerve fibers, any section or lesion involving these portions of the gray mat- ter or the anterior root will be followed by a complete degeneration of the efferent fibers. In the case of the fibers to the voluntary muscles this degeneration aaIII extend to the muscles and include the end-plates. In the case of the autonomic fibers the degenera- tion will extend to the peripheral ganglia in which they terminate, involving, therefore, the whole extent of what is called the pre- ganglionic fiber (see the chapter on the autonomic nerves and the sympathetic system). The posterior root fibers have their origin in the nerv'e cells contained in the posterior root ganglia. These cells are unipolar, the single process given off being an axis cylinder process or axon. It divides into two branches, one passing into the cord by wa}' of the posterior root, the other toward the periph- eral tissues in the corresponding spinal nerve in which they form the peripheral sensory nerve fibers. It follows that a section or lesion of the posterior root will result in a degeneration of the branch entering the cord, this branch having been cut off from its nutri- tive relationship with its cells of origin. The degeneration will in- volve the entire length of the branch and its collaterals to their terminations among the dendrites of other spinal or bulljar neurons (see the chapter on the spinal cord). After a lesion of this sort the stump of the posterior root that remains in connection with the posterior root ganglion maintains its normal stnicturc. On the other hand, a section or lesion involving the spinal nerve will be followed by a degeneration of all the fibers, efferent and afferent, lying to the peripheral side of the lesion, since the.se fibers are cut off from connection with their cells of origin, while the fibers in the central stump of the divided nerve will retain their normal structure. Afferent and Efferent Fibers in the Cranial Nerves.— The first and second cranial nerves, the olfactory and the optic, contain only afferent fibers, which arise in the former nerve from the olfac- tory epithelium in the nasal cavity, in the latter from the nerve cells in the retina. The third, fourth, and sixth nerves contain f)nl\- efferent fibers which arise from the nerve cells constituting ♦HcrrinK, " .lourn.il r,f PhyHioloKy," 2!), 2S2, !!»(«. THE PHENOMENON OF CONDUCTION. 83 their nuclei of origin in the midbrain and pons. The fifth nerve resembles the spinal nerves in that it has two roots, one containing afferent and the other efferent fibers. The efferent fibers, consti- tuting the small root, arise from nerve cells in the pons and mid- brain, the afferent fibers arise from the nerve cells in the Gasserian ganglion. This ganglion, being a sensory ganglion, is constituted like the posterior root ganglia. Its nerve cells give off a single process which divides in T, one branch passing into the brain by way of the large root, while the other passes to the peripheral tissues as a sensory fiber of the fifth nerve. The seventh nerve may also be homologized with a spinal nerve. The facial nerve proper consists of only efferent fibers, w^hich arise from nerve cells constituting its nucleus of origin in the pons. The geniculate ganglion, attached to this nerve shortly after its emergence, is similar in structure to the Gasserian or a posterior root ganglion. Its nerve cells send off processes which divide in T and constitute afferent fibers in the so-called nervus intermedins or nerve of Wrisberg. The eighth nerve consists only of afferent fibers which arise from the nerve cells in the spiral ganglion of the cochlea, cochlear branch, and from those constituting the vestibular or Scarpa's ganglion, the vestibu- lar branch. Both of these ganglia are sensory, resembling the posterior root ganglia in structure. The ninth nerve is also mixed, the efferent fibers arising from the motor nucleus in the medulla, while the sensory fibers arise in the superior and petrosal ganglia found on the nerve at its emergence from the skull. The tenth is a mixed nerve, its efferent fibers arising in motor nuclei in the me- dulla, the afferent fibers in the nerve cells of the ganglia lying upon the trunk of the nerve at its exit from the skull (ganglion jugulare and nodosum). The eleventh and twelfth cranial nerves contain only efferent fibers that arise from motor nuclei in the medulla. It will be seen from these brief statements that in all the nerve trunks of the central nervous system — that is, the spinal and the cranial nerves — the cells of origin of the efferent fibers lie within the gray matter of the brain or cord, while the cells of origin of the afferent fibers lie in sensory ganglia outside the central nervous system, — namely, in the posterior root ganglia for the spinai nerves, in the ganglion semilunare (Gasseri), the g. geniculi, the g. spirale, the g. vestibulare, the g. superius and g. petrosum of the glossopharyngeal, and the g. jugulare and g. nodosum of the vagus. These various sensory ganglia attached to the cranial nerves corre- spond essentially in their structure and phj^siology with the posterior root ganglia of the spinal nerves. Independent Irritability of Nerve Fibers. — Although the nerve fibers under normal conditions are stunulated only at their ends, the efferent fibers at the central end, the afferent at the peripheral end, yet any nerve fiber may be stimulated by artificial 84 THE PHYSIOLOGY OF MUSCLE AND NERVE. mean:^ at any point in its course. Artificial stimuli capable of affecting the nerve fiber — that is, capable of generating in it a nerve impulse which then propagates itself along the fiber — may be divided into the following groups: 1. Chemical stimuli. Various chemical reagents, when applied directly to a nerve tnmk, excite the nerve fibers. Such reagents are concentrated solutions of the neutral salts of the alkalies, acids, alkalies, glycerin, etc. This method of stimulation is not, however, of much practical value in experimental work, since it is difficult or impossible to control the reaction. 2. Mechanical stimuli. A blow or pressure or a mechanical in- jury of any kind applied to a nerve trunk also excites the fibers. This method of stimulating the fibers is also difficult to control and has had, therefore, a limited application in experimental work. The mechanical stimulus is essentially a pressure stimulus, and the difficulty lies in controlling this pressure so that it shall not actually destroy the nerve fiber by rupturing the delicate axis cylinder. Various instruments have been devised by means of which light blows may be given to the nerve, sufficient to arouse an impulse, but insufficient to permanently injure the fibers. The results ob- tained by this method have been very valuable in physiology'' as con- trols for the experiments made by the usual method of electrical stimulation. It may be mentioned also that under certain condi- tions — for instance, at one stage in the regenerjition of injured nerve fibers mechanical stimuli may be more effective than electrical, that is, may stimulate the nerve fiber when electrical stimuli totally fail to do so. 3. Thermal stimuli. A sudden change in temperature may stimulate the nerve fibers. This method of stinudation is very ineffective for motor fibers, only very extreme and sudden changes, such as may be obtained by applying a heated wire directly to the nerve trunk, are capable of so stimulating them as to produce a nmscular contraction. On the other hand, the sensory nerve fibers are quite sensitive to changes of temi)crature. If a nerve trunk in a man or animal Ls suddenly cooled, or especially if it is suddenly heated to 60° to 70° C, violent pain results from the stimulation of the sensory fibers in the trunk, wliilc the motor fibers are apj)arontly not acted upon. We have in this fact ono of several differences in reaction between motor and sensory fillers which have been noted from time to time, and which seem to indirato that there is some differcince in structure or irritability between them. 4. Electrical stimuli. Some f(jnii of tiu! electrical current is be- yond question the most effective and convenient means of stimulat- ing nerve fibers. We may employ either the galvanic current — that Is, the current taken directly from a battery — or the induced current HE PHENOMENON OF CONDUCTION. 85 from the secondary coil of an induction apparatus or the so-called static electricity from a Ley den jar or other source. In most experi- mental work the induced current is used. The terminal wires from the secondary coil are connected usually with platinum wires im- bedded in hard rubber, forming what is known as a stimulating elec- trode. (See Fig. 29.) By this means the platinum ends which now Fig. 29. — Stimulating (catheter) electrodes for nerves: b. Binding posts for attachment of wires from the secondary coil; s, insulating sheath of hard rubber; p, platinum points laid upon the ner\'e. form the electrodes, anode and cathode, can be placed close together upon the nerve trunk, and the induced current passing from one to the other through a short stretch of the nerve sets up at that point nerve impulses which then propagate themselves along the nerve fibers. The induction current is convenient because of its intensity, which overcomes the great resistance offered by the moist tissue ; be- cause of its very brief duration, in consequence of which it acts as a sharp, quick, single stimulus or shock, and because of the great ease with which it may be varied as to rate and as to intensity. On account of the very brief duration of the induced current it is dif- ficult to distinguish between the effects of its opening and closing. The Stimulation of the Nerve by the Galvanic Current. — ^When however, we employ the galvanic current, taken directly from a bat- tery, as a stimulus, we can, of course, allow the current to pass through the nerve as long as we please and can thus study the effect of the closing of the current as distinguished from that of the open- ing, or the effect of duration or direction of the current, etc. Du Bois-Reymond's Law of Stim- ulation. — ^When a galvanic current is led into a motor nerve it is found, as a rule, that with all moderate strengths of currents there is a stimulus to the nerve at the moment it is closed, the making or closing stimulus, and another when the current is broken, the breaking or opening stmiulus, while during the passage of the current through the nerve no stimulation takes Fig. 30. — Schema of the arrange- ment of apparatus for stimulating the nerve by a galvanic current : b. The battery; k, the key for opening and closing the circuit ; c, the commutator for reversing the direction of the cur- rent; + the anode or positive pole; — the cathode or negative pole. 86 THE PHYSIOLOGY OF MUSCLE AND NERVE. place: the muscle remains relaxed. We may express this fact by sajing that the motor nerve fibers are stimulated by the mak- ing and the breaking of the current or by any sudden change in its intensity, but remain luistimulated during the passage of cur- rents whose intensity does not var\-. The Anodal and Cathodal Stimuli. — It has been shown quite con- clusively that the nerve impulse started by the making of the current arises at the cathode, while that at the breaking of the current begins at the anode, or, m other words, the making shock or stimulus is cathodal, while the breaking stimulus is anodal. This fact is true for muscle as well as nerv^e, and possibly for all irritable tissues capable of stimulation by the galvanic current. This important generalization may be demonstrated for motor nerves by separating the anode and cathode as far as possible and re- cording the latent period for the contractions caused respect- ively by the making and the breaking of the current in the nerve. If the cathode is nearer to the muscle the latent period of the mak- ing contraction of the muscle will be shorter than that of the break- ing contraction by a time equal to that necessary for a nerve impulse to travel the distance between anode and cathode. If the position of the electrodes is reversed the latent period of the making con- traction will ])e correspondingly longer than that of the breaking contraction. It is very evident from these facts that when a current is passed into a nerve or muscle the changes at the two poles are different, as shown by the differences in reactions and properties of the nerve at these points. Bethe has shown that a difference may l)e demonstrated even by histological means. After the passage of a current through a nerve for some time the axis cylinders stain more deepl)^ than normal at the cathode with cer- tain dyes (toluidin blue), while at the anode they stain less deeply. Elcctrotonus. — The altered physiological condition of the nerve at the poles during the passage of the galvanic cun-ent is designated as electrotonus, the condition round the anode being known as anelectrotonus, that round the cathode as catelectrotonus. Elec- trotonus expresses itself as a change in the electrical condition of the nerve which gives rise to currents known as the eiectrotonic currents, — a brief description of these currents will be given in the next chapter, — and also ))y a change in irrital)ility and con- ductivity. The latter changes were first carefully investigated by Pfiiigei', who showcid that when the galvanic current, or, as it is usually called in this connection, the polarizing current, is not too strong there is an increase in irrital)ility and conductivity in the neighborhood of the (cathode, the so-called catelectrotonic increase of irritalMlity, while in the region of the anode there is an anelec- trotonic d(;creas(> in iiiitalMlity and conductivity. These opposite variations in the state of the nerve are represented in the accom- THE PHENOMENON OF CONDUCTION. 87 panying diagram. Between the two poles— that is, in the intrapolar region— there is, of course, an indifferent point, on one side of which the irritability of the nerve is above normal and on the other side below normal. The position of this indifferent point shifts toward the cathode as the strength of the polarizing current is increased. In other words, as the current mcreases the anelectrotonus spreads more rapidly and becomes more intense, and the conductivity in this region soon becomes so depressed as to block entirely the passage of a nerve impulse through it. The changes on the cathodal side are not so constant nor so distinct. It has been shown,* in fact, that if the polarizing current is continued for some time, the heightened irritabihty at the cathode soon diminishes and sinks below normal, so that in fact at the cathode as well as at the anode the irritabihty may be lost entirely. If the polarizing current is very strong this depressed irritability at the cathode comes on practically at once. Moreover, when a strong current that has been passing through a nerve is broken the condition of depressed irritability at the cathode persists for some time after the opening of the current. Pfliiger's Law of Stimulation. —It was said above that when a galvanic current is passed into a nerve there is a stimulus (catho- dal) at the making of the current and another stimulus (anodal) K„** ^^^" ^l-~EIectrotonic alterations of irritability caused bv weak medium nnH «trr.no. KTheTno'dl-' B fh.^r''f'^'^r''^^ P°^"*^ °^ application of Ihe efect^dtTtheL^vTI tahnftl- th»^ ' ir^ cathode. The horizontal Hne represents the nerve at normal irri- iJ^^^lUh ^'^''l^'^ r'5?^ illustrate how the irritability is altered at different part" of the nlrrK^^ currents of different strengths. Curve yi shows the effect of a weak current the part below the line indicating decreased, and that above the line increased irritabUitt at ^f ire ^nm^.n™T!f f^^ K^''^' *^'^ ^^'"^ ^^^ indifferent point at which thrcatelec[rotoS^^^^ fl^ffT^^n ^^^^"^ ^°'" ^y anelectrotonic effects; y^' gives the effect of a stron^/current and Sea e"r anVe^tefds 'farther info the fT^'^ °' the.current is increased ?heeffecrbecomes §;fftt.= r • ^ • larther into the extrapolar regions. In the intrapolar resion the in ?owrdk^eTa\h'^dl^l"(lUti:r ^'^*' ^-"^^^^^ ^'-°^^^ «^ curre^nU^or^h^e^a'L^e at the breaking of the current. This statement is true, however only for a certain range of currents. Of the two stimuli, the making or cathodal stimulus is the stronger, and it follows, therefore, * Werigo, "Pfluger's Archiv," 84, 547, 1901. See Biederraann, " Elec- trophysiology," translated by Welby, vol. ii, p. 140. 88 THE PHYSIOLOGY OF MUSCLE AXD XERVE. that when the strength of the current is diminished there will come a certain point at which the anodal stimulus will drop out. With weak currents there is then a stimulus only at the make. On the other hand, when very strong; currents are used the stimuli that act at the two poles set up nerve impulses whose passage to the muscle may be blocked by the depressed conductivity caused by the electro- tonic changes. Whether or not the stimulus will be effective in causing a contraction in the attached muscle will depend naturally on the relative positions of the electrodes, — that is, on the direction of the current in the nerve. In describing the effect of these strong currents we must distinguish between what are called ascending and descending currents. Ascending currents are those in which the direction of the current in the nerve is away from the muscle, a position of the poles, therefore, in which the anode is closer to the muscle. In descending currents the positions are reversed. Pfliiger's law of contraction or of stimulation takes account of the effect of extreme variations in the strength of the current and is usually expressed in tabular form as follows: The letter C indicates that the nerve is stimulated and causes a contraction in the attached muscle, and O indicates a failure in the stimulation (weak currents) or a failure in the nerve impulse to reach the muscle owing to blocking (strong currents) . Fig. 32. FiR. .S3. Figs. .32 and 33. — Sohorria to show the arranEcmcnt of appiinitiis for an ascc'iidinK and a d(!Mcending current: Fig. 32, ascending; Fig. 33, descending. Ahckndino CnnnENT. Making. Breaking. Vory wouk currfiits . .C Motl(;rat,(; " . . . .C Very .strong " ....() Descending CuRnrcNT. Making. Breaking. c c c c c c The effects obtained with the strong currents are readily under- stood if we bear in mind the facts stated above regarding elecitro- tonus. When the curnrnt is ascending th(! stimulus on making starts from the cathode, but cannot reach the muscle because it is blof'kod l>y a regif)n of anelectrotonus in which the conduc- THE PHENOMENON OF CONDUCTION. 89 tivity is depressed. The stimulus on breaking takes place at the anode and the impulse encounters no resistance in its passage to the muscle. With the descending current the cathode lies next to the muscle and the making or cathodal stimulus of course causes a contraction. On breaking, however, the impulse that is started from the anode is blocked by the depressed irritability in the cathodal region, which, as has been said, comes on promptly with strong currents and persists for a time after the current is broken. The Opening and the Closing Tetanus. — While the du Bois-Reymond law stated above expresses the facts as usually observed upon a nerve-muscle preparation, there are a number of observations which indicate that the excitation at the anode and the cathode during the passage of a current may give rise to a series of stimuli instead of a single stimulus. Thus with sensory nerves it is well known that the stimulation, as judged by the sensations aroused, continues while the current is passing instead of being limited to the moment of making or of breaking of the current. In this respect, as in stimulation by high temperatures, the sensory fibers differ apparently from the motor. When a galvanic current is passed through the ulnar nerve at the elbow sensations are felt during the entire time of passage of the current. But in an ordinary nerve-muscle preparation it is also fre- quently observed that at the moment of opening the current a tetanic con- traction, persisting for some time, is obtained instead of a single twitch. This phenomenon is known as the opening tetanus or Ritter's tetanus, and Pfiiiger has shown that the continuous excitation proceeds from the anode, since in the case of a descending current division of the nerve in the intrapolar region brings the muscle to rest. In the same way it frequently happens that upon closing the current through a nerve the muscle, instead of giving a twitch, goes into a persistent tetanic contraction. The tetanus in this case is designated as the closing or Pfliiger's tetanus. Both of these phenomena are observed, especially, when the irritability of the nerve is for any reason greater than normal. It should be added that the opening and the closing tetanus may be observed also in a muscle when the galvanic current is passed through it. Stimulation of the Nerves in Man. — For therapeutic as well as diagnostic and experimental purposes it often becomes desirable to stimulate the nerves, particularly the motor nerves, in man. We may use for this purpose either the induced (faradic, alternat- ing) current or the direct battery current (galvanic or continuous current). In such cases the electrodes cannot be applied, of course, directly to the nerve; it becomes necessary to stimulate through the skin, and the so-called unipolar method is employed. The unipolar method consists in placing one electrode, the active or stimulating electrode, over the nerve at the point which it is desired to stimulate, while the other electrode, the inactive or indifferent electrode, is applied to the skin at some more or less remote part, usually at the back of the neck. The indifferent electrode is made large enough to cover several square centimeters of the skin, and one may conceive the threads of current as passing from it into the moist tissues of the body, and thence to the active electrode. As the threads of current condense to this latter electrode they pass through the motor nerve which lies under it, and if sufficiently in- 90 THE PHYSIOLOGY OF MUSCLE AND NERVE. tense, will stimulate the nerve. The arrangement is represented in the accompanying schema (Fig. 34), showing the disposition of the electrodes for stimulating the median nerve. At the indifferent electrode the sensory nerves of the skin are of course stimulated, but no motor response is obtained, as no motor nerve lies immediately under the skin. Moreover, the large size of this electrode tends to diffuse the current and thus reduce its effectiveness in stimulating. The active or stimulating electrode is small in size, particularly when induction currents are employed, so that the current may be condensed and thus gain in effectiveness. The dry surface of the skin is a poor conductor of the electrical current, and to reduce the resistance at the points at which the electrodes come in contact _ FiR. 34. — Schema to show the unipolar method of stimulation in man. The anode, +, is represented as the stimulating pole, applied over the median nerve. The cathode, — , is the indififereut pole. with the skin each is covered with cotton or chamois skin kept moistomnl with a dilute saline sohition. Motor Points. — By means of the unipolar method nearly every voluntary iiiuscU; of th(! })ody may be stimulated separately. All that is necessary, wh(!n tlie induced current is used, is to bring the active electrode; as nearly as i)()ssibl(; ov(;r tlu; spot at which the muscle receives its motor branch. A diagram showing these motor points for the arm is given in Fig. .iF). In th(i same way the THE PHENOMENON OF CONDUCTION. 91 nerves of the brachial plexus and other nerve trunks may be stimulated very readily through the skin. When the induction current is used no distinction is made between the cathodic and anodic effects. When, however, the battery current is employed KL lambricalesK M. deltoideoB Iferv. musaitocutaneuM M, biceps brachii M. bractL- intarnua Xerv, medtanu$ M, supinator longus M. pronato: M, Qex. carpi radialia M. flezoT digitor. suljlim. M, flex. polUcis loDgus Nerv. mediantu M. abductor poUic. brev, M. opponens poUicia M, flex. poll, brev, M. adductor poUfa bref. Fig. 35. — Motor points in upper extremity. one may make the stimulating electrode either anode or cathode, and under these circumstances a marked difference is observed in the strength of the current that it is necessary to use to get a response. With the battery or galvanic current, in fact, one may distinguish four stimuli, the closing and the open- ing shock when the stimulating electrode is cathode and the closing and the opening shock when it is anode. The con- tractions resulting from these four stimuli are designated usually as follows: The cathodol closing contraction, C C C; the cathodal opening contraction, C C; the anodal closing contraction, A C C; and the anodal opening contraction, A C. If the minimal amount of current necessary to give each of these contractions is measured in milliamperes by means of a suitable ammeter. 92 THE PHYSIOLOGY OF MUSCLE AND NERVE. it will be found that the four stimuli are of different efficiencies. The usual relationship is expressed bj' the sequence C C C > A C C > A C >C C, although this sequence is subject to some individual variation. Pathological or traumatic lesions that cause the degeneration of the nerves may be revealed by the use of these methods of stimulation. The nerve trunk under such circimistances fails to respond to either form of stimulus, in- duced or galvanic. The muscle, on the other hand, while it may fail to respond to induction shocks, is stimulated by the gal- vanic current, and, indeed, may show an increased irritabihty toward this form of stimulus, although the contractions are more sluggish in character than in a muscle with a normal nerve supplv. Certain qualitative changes in the reaction of the muscle to the galvanic current may also be noticed, for instance, the A C C is sometimes obtained with less current than the C C C. This qualitative and quantitative change in reaction to the galvanic current, and the loss of irritability to the induced cur- rent, constitute what is known as the reaction of degeneration. 0S^ -f- A IT Fit;, ■if). — Two schemata to show the relation between the physical and the physio- lofpcal electrodes or poles. Each schema reijresents the forearm with the median nerve. Af . In / the .stimulatiiiK electrode is the cathode ; the threads of current which have started from the anode (the iiidilTereiit electrode) placed elsewhere, converRO to this pole. Where these threads enter the nerve we have a series of physioloRical anfxies, a; where they leave, a series of physioloKical cathodes, c. In // the stimulatiiiK electrode is the anode. The threads of current leave this pole to traverse the jjody toward tlie indifferent electrode (cathode). Where they enter and leave the nerve we have, as in the first case, physio- logical anodes and cathodes, now, however, on the opposite siiles of the nerve. Distinction between Physical and Physiological Poles. — The facts stated above soom to sliow, at first sight, that l)y the unipolar method wo may obtain both an opening and a ck)sing shock at cither the cathode or anode, —a result which is in apparent contradiction t(; the general law tliat the making or closing stimulus occurs only at the cathode and the breaking or opening stimulus only at the anode. This af)i)arcnt contra- diction is readily exjjlaincd when we rem(;mber that in the THE PHENOMENON OF CONDUCTION. . 93 unipolar method the active electrode rests upon the skin over the nerve, and that the threads of current radiating from this point enter the nerve at one point and leave it at another. Evidently, therefore, so far as the nerve is concerned, there will be an anode where the current is considered as entering the nerve and a cathode where it leaves it, so that under the active electrode, whether this is physically an anode or cathode, there will be, as regards the nerve, a series of what may be called physiological cathodes and anodes. The closing shock arises at these cathodes, the opening shock at the anodes. The position of the series of anodes and cathodes will vary according as the active electrode is an anode or cathode, as is indicated in the accompanying diagram (Fig. 36). CHAPTER IV. TliE ELECTRICAL PHENOMENA SHOWN BY NERVE AND MUSCLE. The Demarcation Current. — Our definite knowledge of the electrical properties of living tissue began with the celebrated in- vestigations of du Bois-Reymond* (1843). When a muscle or nerve is removed from the body, and, in the case of the muscle, when one tendinous end is cut ofT, it is found that the cut end has an electrical potential differing from that of the uninjured longi- tudinal surface of the preparation. Following the usual nomen- clature, the cut end is electronegative as regards the longitudinal surface. If, therefore, the longitudinal surface is connected by a conductor with the cut surface a current will flow from the former to the latter, as is indicated in the accompanying diagram. -f- Fig. 37. — Schema showing the course of the demarcation current in an excised nerve, when a point on the longitudinal and one on the cut surface are united by a conductor. While the direction of the current through the conductor con- necting the two points is from the longitudinal to the cut surface the current may be considered as being completed in the opposite direction within the substance of the muscle or nerve, as shown in the diagram. We may, in fact, consider an excised nerve or mu.scle as a battery, the cut end representing the zinc plate and the longitudinal surface the copper plate. Within the battery the direction of the current is from zinc to copper, from cut end to longitudinal surface; outside the battery the direction is from copper to zinc, from longitudinal to cut surface. If two wires are conneeted wifh the muscle or nerve the end of the one attached to the longitudinal surface will represent the positive pole or anode, the end of the one attached to the cut end will represent the cathode * "TIntersuchungen iiljcr tliicrische Elektricitilt," du Bf)is-Reyniond, 1848- 18G0. 1)4 ELECTRICAL PHENOMENA. 95 D or negative pole. On joining the ends of the wires a current will pass from positive to negative pole. A current of this character from an excised nerve or muscle is, of course, small in amount and to detect it one must make use of a delicate electrometer of some sort (see below). Du Bois- Reymond considered that the difference in electrical potential which gives rise to this current exists normally in the muscle, although masked by an opposite condition in the tendinous ends, and he therefore spoke of the currents as the natural muscle or natural nerve currents. It has since been shown by Hermann that this view is incorrect; that the perfectly normal uninjured muscle or nerve has the same electrical potential throughout and will therefore give no current when any two points are con- nected by a conductor. Moreover, the completely dead muscle or nerve shows no current. The difference in poten- tial that is found in the excised nerve or muscle is due, according to Hermann, to the fact that at the cut end the nerve or muscle is injured. The chemical changes that take place as a result of the injury make the tissue electronegative as regards the un- changed living substance elsewhere. For this reason Hermann described the current as a demarcation current; others have called it the current of injury. The nature of the changes at the injured end are not known. It is inter- esting to note that Bernstein * has shown that the electromotive force of the muscle current increases with the temperature, a fact which leads him to conclude that the difference in potential between the longitudinal and cut surface of the muscle depends upon a difference in concentration of the electrolytes. The muscle, in fact, acts after the manner of a "concentration cell." Such a difference in concentration may pre-exist in the normal mus- cle, or, according to the view adopted above, is developed as the result of injuring one end of the muscle. It may be supposed that the injury causes changes which result in the formation of new organic or inorganic electro- lytes and thus increases the concentration at that point. From what is known of the chemical changes in muscle it is safe to assert that there is an increased production of lactic acid at the injured end, and it is probable that other electrolytes may be liberated in diffusible form. With this increased concentration at the injured area a development of electric potential might be expected, owing to the probability that the cations (H, K, Na, Mg, Ca) will diffuse off more rapidly and thus leave the injured end with a negative charge. Experiments made by Urano and von Frey on muscle juice squeezed out of the muscle fibers under high pressure have shown that when it is diffused' against sugar solutions it loses its K and Mg more rapidly than the PO4 and SO^. * "Pfliiger's Archiv, " 1902, 92, 521. Fig. 38. — Schema showing the principle of construction of the galvanometer: M, The mag- net suspended by a thread; B, the battery, with the wires lead- ing off the current encircling the magnet. 96 THE PHYSIOLOGY OF MUSCLE AXD NERVE. Means of Demonstrating the Muscle Current. — The demarcation current and other electrical conditions to be described require especial appara- tvis for their study. To detect the existence of a current physiologists use either a galvanometer or a capillary electrometer. The galvanometers employed are of several types, the Kelvin reflecting galvanometer, the d'Arsonval foinn, and more recently the "string-galvanometer" of Einthoven. The principle of the galvanometer lies in the fact that a magnetic needle is deflected when an electrical current passes through a wire in its vicinity. If' a magnetic needle is swung by a delicate thread so as to move easily, it will come to rest in the magnetic meridian with its north pole pointing north. If now a wire is curved rountl it, as shown in the accompanying diagram (Fig. 38), and a batteiy current is sent through this wire, the needle will be deflected to the right if the current passes in one direction and to the left if it passes in the opposite direc- tion. The movement of the needle is an indication of the presence and direction of the electrical current in the wire. The extent of deflection of the needle may be used to measure the strength of the current by ascertaining FiK. 39. — D'Arsonval galvanometer as modified by Rowland. the amount of deflection caused by a standard battery. The effect of the current upon llie needle increases with the nuniber of turns of wire, so that delicate galvarujineters constructed upon tliis princiiih; are si)oken of as high re.sistance galvanometers, the great leiigtli of wire used making, of course, a liigli resistance. Instead of having the; coil througli whicli tiie current passes kept in a fi.\(;d position and tlie magnet delicately swung or poised, the reverse arrangement may be u.sed — that is, the coil may be swung between the poles of a fixf'd magnet. Under these circumstanc(\s, if a current is sent flu-ough the coil, this latter will move with rcjference to the magnet. A galvanometer con- Ktructed on this princi[)le is designated as a d'Ars(mval galvanomet.er, aft(U' tlu! pliysiologist wiio first emt)loyed this arrangement. In the d'Arsonval form the magnet is fixed while th(! coil of wire tliroiigh which th(^ current paHHcs is swung by a v(;ry delicate thread of quartz, silk fiber, or pli()Sj)lior- oronze. The principle of the arrangement is shown in the accompanying diagram CFig. 40) and one form of a complete instrument in l''ig. 39. A large horseshoe magnet (n, s) is fixed permanently and Ixitween i\u: pohis is swung a coil (c) fjf dfJlicate wirf!, the two ends of th(! wire being coimectcd with binding posts in tlie frarnf; of the instrument. The coil is held in place below by a delicate spiral. In I'"ig. 40 it will be seen that the delicate thread suspendmg ELECTRICAL PHENOMENA. 97 the coil carries just above the coil a small mirror, m, and a plate of thin mica or aluminum. The mirror is deflected with the coil, and when viewed through the telescope pictured in Fig. 39 the image of the scale above the telescope is reflected in this mirror. As the coil and mirror are twisted by the action of the current passing through the former the reflection of the scale in the mirror is displaced. By means of a cross hair in the telescope the angle of deflection may be read upon the reflected scale. The aluminum vane back of the mirror makes the system dead-beat, so that when a deflection is obtained Fig. 40. — Diagram of struc- ture of the d'Arsonval galvanom- eter, c is the coil of fine wire through which the current is passed. It is swung by a fine thread of phosphor-bronze so as to lie between and close to the poles — (ra) north pole, and (s) south pole — of the magnet. Just above the magnet the thread car- ries a mica or aluminum vane to which is attached a small mirror. The scale of the instrument is re- flected in this mirror and is observed through the telescope shown in Fig. 38. Fig. 41. — Schema of capillary electrometer arranged to show the demarcation current _ in muscle {Lombard) : a. The glass tube containing mercury and drawn to a fine capillary below; c, the receptacle containing mercury by raising which the mercury can be driven into the capil- lary of a; f, a vessel with glass sides containing mercury below, and above dilute sulphuric acid into which the capillary of a dips; E, the micro- cope for observing the mercury thread in the capillary; m, the muscle; g and h, the wires touching the longitudinal and cut surfaces of the muscle. The current flows as indicated by the small arrows ; d, the capillary thread of mercury as seen under the microscope. the system comes quickly to rest with few or no oscillations. If the coil of wire contains sufficient turns, enough to give a total resistance of two to three thousand ohms, and the poles of the magnet are brought very close to the coil, the instrument may be given a delicacy sufficient to study accurately the muscle and nerve currents. In such an instrument the effect of the earth's magnetism may be neglected and the galvanometer may be hung upon any support without reference to the magnetic meridian. The movable system of this galvanometer possesses considerable inertia, so that it will not indicate accurately the presence or extent of very brief electrical currents such as have to be studied in physiology in some cases. 7 98 THE PHYSIOLOGY OF MUSCLE AND NERVE. For purposes of this kind the string-galvanometer or the instrument known as the capillary electrometer is employed. The String-galvanometer. — In this instrument a very delicate thread of silvered quartz or of platinum is stretched between the poles of a strong magnet, as is represented in the diagrams given in Figs. 42 and 43. The Fig. 42. — One form of the string-galvanometer: E, The electromagnet; h, the projectioD microscoije; /'', a screw for varying the tension of the tliread. — (Edelmann's Catalogue. J <% Fig. 4/5. — Schema to hJiow the relation of tlie thread to tlie magnetfl in the sfring- Kalvftnrirncler : AA. 'I'lie delicate threjid of silvered <|uarl/, or of platiiiuiii, HtrettOied hi-lwec^n the polar pieeen ll'l') of an electromagnet. When a current piiMMCM through A A , tlu! thread «hoWH a moveiiietit. 'J'hu eridH of the imignctts are pierced by lioh-'H, H(!en in P\, through which the movetiientH of the thread may he watched by means of a microscope or bo pro- jected upon a photograi)hic plate.— (.After /■jinlhovcn.) metal Jjoies of tlio magnet are pierced by IkjIcs, ko tlial the tliread iiiay 1)0 illuminjitfd by an electric light (arc light j from one; Hidr;, and on the other the .shadow of the thread riiiiy bt; thrown upon a Kcrccai tift.er being tnagiiificid by a niicroHCopc (see Fig. 42j. With this arrungcdiient, tin; tliread shows a ELECTRICAL PHENOMENA. 99 —S lateral movement whenever a current is passed through it. The instrument may be made of great delicacy so as to detect very minute currents, and, moreover, it has the very great advantage of responding accurately to rapid changes in potential. If the shadow of the thread is allowed to fall upon sensitized paper properly adjusted upon a rotating surface, its movements may be photographed and a permanent record be thus obtained (see Fig. 22 for an example of such a photographic record showing the electrical changes in a contracting muscle). The Capillary Electrometer. — The principle of the construction of the capillary electrometer is illustrated in Fig. 41. A glass tube, a, is drawn out at one end into a very fine capillary, the end of which dips into some diluted sulphuric acid contained in the vessel (/). At the bottom of this vessel is a layer of mercviry connecting with a wire, g, fused into the glass vessel. The tube a is partially filled with redistilled mercury, which pene- trates for a short distance into t!ie capillary. By means of pressure applied from above c, the mercury can be forced through the capillary. Then by diminishing the pressure, the mercury can be brought back into the capillary a certain distance, drawing after it some of the dilute sulphuric acid. The mercury in tube a is connected with the other pole of the battery by a wire fused into its wall and dipping into tlie mercury. By regulating the pressure on the mercury the point of contact be- tween the thread of mercury and the sulphuric acid in the capillary, d, can be brought to any desired position. An equilibrium is then established which will remain constant as long as the conditions are not changed. If now the circuit from a battery or other source of electricity — for example, the excised nerve or muscle — is closed, the current entering by wire g, if this represents the anode, traverses the sulphuric acid and mercury in the capillary and returns by the wire h. At the moment of the establishment of the current the equilibrium of forces that holds the mer- cury at a certain point in the capillary is disturbed, the end of the mercury thread moves upward with the current for a certain distance, depending on the strength of the current and the delicacy of the capillary. If the current be passed in the opposite direction the mercury will move downward a certain distance. The meniscus of contact moves up or down with the direc- tion of the current, owing, it is supposed, to a change in the surface tension at this point. The capillary tube as used for physiological purposes is too small for the movements of the mercury to be detected with the eye. It is necessary to magnify it either with a microscope or a projection lantern. Ordinarily the electrometer is so made that it can be placed upon the stage of the microscope and the capillary be brought into focus at the meniscus, as shown in d, Fig. 41. By means of proper apparatus the movement can be photographed and thus a permanent record be obtained of the direc- tion and extent of movement of the mercury. Non-polarizable Electrodes.- — In connecting a muscle or nerve to an elec- trometer or galvanometer it is necessary that the leading off electrodes — that is, the point of contact between the wires and the muscle or nerve — shall be iso-electrical and non-polarizable. By iso-electrical is meant that the two electrodes shall have the same electrical potential, and it is obvious that the leading off electrodes must fulfil this condition approximately at least, since otherwise the current obtained from the muscle or nerve could not be attrib- uted to differences in potential in the tissue itself; it would be shown by any other moist conductor connecting the two electrodes. Two clean platinum electrodes would fulfil this condition. A more serious difficulty is found in Fia;. 44. — To show the structure of a non- polarizable electrode: 1 , The pad of kaolin or filter paper moistened with physiological sa^ hne (NaCl, 0.7 per cent.) (this is placed on the tissue) ; 2, the sat- urated solution of zinc sulphate; (3) the_ bar of amalgamated zinc. 100 THE PHYSIOLOGY OF MUSCLE AND NERVE, the polarization of metallic electrodes. "Whenever a metal conductor and a liquid conductor come into contact there is apt to be polarization. What takes place may be represented by the following diagram, in which a current is supposed to be passing + Xa Xa + Xa + Xa A CI CI CI CI — — — — between the poles A and C through a solution of sodium chlorid. During the passage of the current the cations, Xa, with their positive charges move toward the cathode: at the cathode the free sodium ion acts upon the water, HHO, forming XaOH and liberating hydrogen, which accumu- lates upon the cathode in the form of gas. The anions, CI, with their negative charges move toward the anode; there the chlorin acts upon the water, form- ing HCl and liberating oxygen. In consequence of this accunuilation of gases upon the poles a gas battery is formed, in which the direction of current is against that of the main current, that is, from C to A. It is obvious that in quantitative studies of the electrical currents of animal tissues polari- zation will destroy the accuracy of the results; the demarcation current will show a diminution due not to changes in the nerve, but to physico- chemical changes at the leading-off electrodes. To prevent polarization du Bois-Reymond devised the non-polarizable electrodes consisting of zinc terminals immersed in zinc sulphate. Theoretically any metal in a solution of one of its salts may be used, but experience sliows that the zinc-zinc sulphate electrode is most nearly perfect. Each electrode where it comes into contact with the tissue is made of one of these combinations. Various devices have been used. For instance, tlie electrode may be constructed as shown in the diagram (Fig. 44j. A short glass tube of a bore of about 4 mms. is well cleaned — one end, which is to come into contact with the nerve — is filled, as shown, by a plug of kaolin made into a stiff putty with physiological saline solution of XaCl (0.7 per cent.). The kaolin should iiave a neutral reaction and unless good kaolin is obtainable it is better to use a plug matle of clean filter paper macerated in pliysiological saline and packed tightly into the end of the tube. Above this plug the tube is filled in for a part of its length with a saturated solution of zinc sulphate into which is immersed a bar of amal- gamated zinc with a copper wire .soldered to its end. Witii a pair of sucii electrodes the conduction of tiie current througii the nerve or muscle to tiie metallic part of the circuit may be represented as follows: Zn + Zn SO. -f- Zu + Xa SO, CI + Xa 01 + Xa CI + Zn -f- Za SO, SO, Zn The liquid ])art of tlio circuit comes into r'oiifuct, willi flic motallic jiart at the junction of Zn and ZnSO,. At the cathode it may be supposed (hut the Zn cation instead of acting upon tiic water and liijerating iiydrogen, deposits itself upon tiie zinc electrode; at the anode tlic sulphion (SO,) attacLs the zinc instead of tiie water, forming ZnSO,. In lliis way polarization i.s prevented, and by the construction of tlic electroile (ho living (issue i.s brought into contact only witii the plug of kaolin moislcned with pliysio- logical saline. Such electrodes are inilis|)onsal)le in studying (he electrical phe- nomena of living tissues, and also in all investigations bearing ujion the; polar effects during the passage of an electrical current from a ba((e seen from the accompanying diagram (Fig. 40). The figure repi-esents a normal nerve hid off t(j tlie galvanometer from two points, b and c, of its longitudinal surface. As these ])()ints in the uninjured nerve have the same potential, no current is shown by the galvanometer. If the nerve is stimulated at a by a single stimulus, a negative condition or charge ])asses along the nerve. When it reaches tlu; point I), there will be a momentary current *Sl,f'inudi, "PfliiKf-r'.s Arrliiv," .W, 4S7, ]S!)4. t (Jriitzncr, "FfliiK'T's Arr;liiv," 25, 255, ISSl. t Boriittiiii, "Pflugor'H Arcliiv," S4, and 90, 1901-1902. ELECTRICAL PHENOMENA. 103 through the galvanometer from c to 6; as the charge passes on to C; this point in turn will become negative to h, and there will be a momentary current through the galvanometer in the other direction. The diphasic current that occurs under these con- ditions cannot be detected by the ordinary galvanometer, even when a series of stimuli is sent into the nerve at a, since the movable system in this instrument has too much inertia to respond to such quick changes in opposite directions. With the more mobile string-galvanometer or capillary electrometer the diphasic currents have been demonstrated successfully. In laboratory investigations one of the leading off electrodes, c, is usually placed on the cut end of the nerve. Under this con- dition the action current becomes monophasic and shows itself as a negative variation of the demarcation current. This difference is due to the fact that the negative condition accompany- ing or constituting the wave of excitation undergoes a decrement as it enters a region in which a negative condition already pre- vails. Therefore, when the leading-off electrodes are placed so that one is on the longitudinal and one on the cut surface, the change of potential accompanying the excitation will affect only the first electrode (6) and give a monophasic variation, which can now be shown by the usual galvanometer, provided a series of stimuli is thrown in at a. Fig. 46. — Schema to show the arrangement for obtaining a diphasic action current. The arrangement differs from that in Fig. 42 only in that both leading off electrodes, b and c, are placed on the longitudinal surface. No demarcation current is indicated. When the nerve is stimulated at a the negative charge reaches 6 first, causing a current through the galvanometer from c to b. Subsequently it reaches c and causes a second current in the opposite direction from 6 to c. The Positive Variation. — It happens not infrequentl^y that when one electrode is placed upon the cut end, the nerve upon stimulation with a series of induction shocks gives a positive instead of a negative variation of the demarcation current. This result is usually explained as being due to a pre- dominance of the anelectrotonic currents (see below), but Wedenski has con- tended recently that it is due to a peculiar condition of excitation in the nerve atthe cut end, a condition to which he gives the name of parabiosis. When this phenomenon occurs it can usually be avoided by making a fresh section at tJie end of the ner\'e. Detection of the Action Currents by the Rheoscopic Frog Preparation or by the Telephone. — The motor nerve of a nerve- muscle preparation from a frog is so extremely irritable to electrical 104 THE PHYSIOLOGY OF MUSCLE AND NERVE. currents that it may be used instead of a galvanometer to detect the action currents in a stimulated muscle. A nerve-muscle prep- aration used for this purpose is kno^Mi as a rheoscopic preparation. The way in which it is used is indicated in the accompanying; diagram, h represents the rheoscopic preparation, its nerve being laid upon the muscle whose currents are being investigated, a, so as to touch the cut end (x) and the longitudinal surface {g). WTien a is stimulated, either directh' or through its nerve, as represented in the diagram, the negative changes that pass along the muscle fibers of a with each stimulus cause action currents that will be led off through the nerve of b from x to g. If the nerve is in a sensitive con- dition it will be stinmlated by the action currents and thus a series of excitations will be sent into b corresponding exactly in rate with the artificial stimuli given to the nerve of a. The rheoscopic preparation may be used ver}^ beautifully to demonstrate the action current in the contracting heart muscle. If the nerve of b is laid upon the exposed beating heart of an animal, the muscle of b ■s^dll give a single twitch for each beat of the ventricle. An- other interesting method of detecting the action currents, particu- larly in nerves, is by means of the telephone. Wedenski has made especial use of this method, the telephone being connected with FJK. 47. — Schema to show the arranRement of a rheoscopic muscle-nerve preparation: 6, The rheoscopic muscle-nerve prpparation, the nerve beiiiK arranged to touch the cut sur- face anrl the longitudinal surface of the muscle, a, whose action currents are to be detected. ^yhe^ the nerve of n is stimulated each contraction of this muscle is followed by a contrac- tion of b, since each contraction of a is accompanied by an action current which passes through the nerve of b and stimulates it. the nerve in place of the galvanometer. The method has obvious advantages in the fact that it may be used with a nerve to which the muscle is also attached, so that the excitation processes in the nerve and their effect upon the muscle may be studied simul- taneously. Relation of the Action Current to the Contraction Wave in Muscle and to the Excitation Wave (Nerve Impulse) in Nerve. — The action currc-nt or, to be more accurate, the moving negative potential, which gives rise to an action current when two points of the muhclf! are led off to a galvanometer, has Ijcen shown ELECTRICAL PHENOMENA. 105 by Bernstein to precede the wave of contraction in muscle; that is, in a stimulated muscle fiber the electrical change at any point precedes the mechanical process of shortening. This relation- ship is shown in the accompanying illustration (Fig. 48) , in which the mechanical contraction (movement of the lever) is photo- graphed simultaneously with the movement of the string of the string-galvanometer which indicates the electrical change. As the figure shows the electrical change is diphasic, owing to the op- posite effects on the galvanometer of the change of potential at Fig. 48. — Simultaneous record of the mechanical and electrical change in a contracting muscle: 1, Mechanical curve of contraction, photograph of the lever; 2, movement of the string of the string-galvanometer (owing to its faintness it was necessary to retouch this curve); movement upward indicates an increase of negative potential at the upper end of the muscle; 3, time record in hundredths of a second; 4, the stimulating lever; the break in the line indi- cates the moment of stimulation; on the curve of contraction (1) this moment is indicated by X. The curve was obtained from a gastrocnemius muscle of a frog, stimulated through its nerve by a single induction shock, contraction isotonic. The leading-off electrodes were placed at the ends of the muscle; galvanometer string under tension. The electric curve is diphasic. The first phase is completed within the latent period of contrr.ction; the second phase extends into the period of shortening of the muscle, but the duration of this latter phase is complicated by the lag of the string (Snyder). the two points lead off to the galvanometer, but the first phase, which begins almost immediately on stimulation, is completed before the muscle begins to shorten. We may suppose that the electrical change is an indication of the excitation, or pos- sibly constitutes the excitation that sets up the chemical change of contraction, or else that the change in electrical potential is caused by the chemical change of contraction and precedes the mechanical result of shortening, since the latter process will have a certain latent period. It has been shown, indeed, by Demoor that a completely fatigued muscle may still con- duct an excitation (muscle impulse), although unable to con- tract, and the same fact has been demonstrated by Engelmann 106 THE PHYSIOLOGY OF MUSCLE AND NERVE. for the heart muscle. In the nerve the action current, or the negative change causing it, has been considered as simultaneous with or possibly identical with the nerve impulse. The velocity oi the two is itlentical; the action cvn'rent is given whenever the nerve is stimulated, and, so far as experiments have gone, the nerve cannot enter into activity without showing an action current, — that is, without shomng a moving electrical change. Whether this electrical change constitutes the nerve impulse or is simply an accompanying phenomenon will be discussed briefly in the paragraph upon the nature of the nerve impulse in the following chapter. The Electrotonic Currents. — In speaking of the effect of passing a gah-anic current through a nerve attention was called to the fact that the condition of the nerve is altered at each pole. At the anode there is a con- dition of decreased irritability and con- ductivity known as anelectrotonus ; a t the cathode, in the beginning, at least, a condition of in- creased irritability known as catelec- trotonus. In addi- tion to these changes in the physiological properties of the nerve there is a change also in its electrical condition at each pole, of such a character that if the nerve is led off from two points on the anode side a current will be indicated. The current can be obtained at a considerable distance from the anode, and is known as the anelectrotonic current, while the electrical condition in the nerve that makes it possible is designated as anelectrotonus. A similar current can be led off from the nerve on the cathode side for a considerable distance beyond the cathode; this is known as the catelectrotonic current, and the electrical condition leading to its production as catelectrotonus. Within the nerve these elef.-trotf)ni(; currents have the same direction as the battery or polarizing current, as is shown in the diagram (Fig. 49), The terms anelectrotonus and catelectrotonus are used, therefore, in physiology to desigriMte both the physiological and the elec- trical changes around the poles when a Ijuttery current is led Fig. 49. — Schema to .show the direction of the elec- trotonic currents in an excised nerve: P, The battery for the polarizing current sent into the nerve at +, the an- ode, and emerginK at — , the cathode; g', galvanometer arranged with leading off electrodes to detect the anelec- trotonic current, the direction of which is indicated by the arrows (in the nerve it is the same as that of the po- larizing current); g, galvanometer similarly arranged to de- tect the catejectrotonic current. The anelectrotonic and catelectrotonic currents continue as long as the polarizing current is maintained. ELECTRICAL PHENOMENA. 107 into a nerve. Whether the physiological and the electrical changes have a causal connection or are two independent phenomena is at present undecided. Bethe* has shown that during the passage of the polarizing current the neurofibrils in the axis cylinder lose at the anode their power of stain- ing with certain basic dyes (e. g., methylene blue), while at the cathode the affinity for these dyes is increased. He assumes, that in the neurofibrils there is an acid substance — -fibril acid — and that at the anode the combination with this body and the neurofibrils is loosened ; hence the loss of staining power. At the cathode the reverse change takes place. He assumes further- Fig. 50. — To show the action of the core-model: p, The polarizing current; g' and g, the galvanometers with leading off electrodes to detect the anelectrotonic and catelec- trotonic currents, respectively. more, that when the affinity between neurofibril and fibril acid is increased at the cathode an electronegative ion is liberated (anion), while at the anode at the time that the combination between fibril and fibril acid is dis- sociated an electropositive ion (cation) is liberated. In this way he constructs an hypothesis of a complex of neurofibril, fibril acid, and electrolyte which is capable of accounting for the electrotonus, both as regards the electrical and the physiological phenoinena, and which refers both phenomena to a single reaction in the nerve. Another explanation of the electrotonic currents which has been much discussed is that first developed by Hermann. t This author constructed a model consisting of a conductor surrounded by a less conductive liquid^ sheath, and showed that such a model is capable of givmg the electrotonic currents. This model may be made as represented in the accompanying diagram, of a glass tube A-B, through the middle of which is stretched a platinum wire, P, the rest of the tube being filled with a saturated solution of zinc sulphate. The glass tube is provided with vertical branches by means of which a polarizing current, p, can be sent into the solution of zinc sulphate and the electrotonic currents be led off to galvanometers, g'. g, on each side. Under these conditions a current similar to the anelectrotonic current can be detected on the side of the anode (g') and one equivalent to the catelectrotonic current on the side of the catiiode (g). The explanation given to these currents is that as the threads of current pass into the platinmn core there is a polarization at the surface between the core and the zinc sul- phate solution which extends to a considerable distance on each side of the electrodes and causes difi'usion currents from sheath to core. It is these threads of current that may be led off as electrotonic currents. Hermann suggested that m the ner\'e we have a structure essentially similar to that of the core model. He thought that the axis cylmder might be considered as representing the core and the myelin the less conductive sheath corre- sponding to the zinc sulphate solution. Others (Boruttau) have suggested that * Bethe, " AUgemeine Anatomie u. Physiol, des Nervensystems, " Leipzig, 1903. t Hermann, "Handbuch der Physiologic," vol. ii, p. 174. 108 THE PHYSIOLOGY OF MUSCLE AXD NERVE. the neurofibrils in the axis cylinder may represent the core or cores and the sur- rounding neuroplasm the sheath, thus providing for the possibility of electro- tonic currents in non-medullated fibers. As a matter of fact, the non-medul- lated fibers in mammals give A-ery slight electrotonic currents compared with the medullated fibers.* According to the "core-model" explanation, the electrotonic currents represent a purely physical phenomenon, which is dependent, however, upon a certain structure of the nerve. That is, a completely dead nerve will not show these currents, although an anesthetized ner^•e, in the mammal (Waller) at least, continues to show them, and, according to Sosnowsky, excised rab- bits' ners'es kept in a moist atmosphere may show them for several days. AVhile the core-model hy]3othesis has led to much investigation in ])hysiology and has been made the basis for a purely physical explanation of the ner\'e impulse, it is still very uncertain whether it furnishes any positive informa- tion concerning the processes that actually take place in the living nerve wheo submitted to tiie action of electrical currents or other artificial stimuli. *Alcock, ''Proceedings Royal Society," 1904, 73, p. 166. CHAPTER V. THE NATURE OF THE NERVE IMPULSE AND THE NUTRITIVE RELATIONS OF NERVE FIBER AND NERVE CELL. The question of the nature of the nerve impulse has always aroused the deepest interest among physiologists. It has consti- tuted, indeed, a central question around which have revolved vari- ous hypotheses concerning the nature of living matter. The impor- tance of the nerves as conductors of motion and sensation was apparent to the old physiologists, and the nature of the conduction or the thing conducted was the subject of many hypotheses and many different names. For many years the prevalent view was that the nerves are essentially tubes through which flows an ex- ceedingly fine matter, of the nature of air or gas, known as the animal spirits. Others conceived this fluid to be of a grosser struc- ture like water and described it as the nerve juice. With Galvani's discovery of electricity the nerve principle, as it was called, became identified with electricity, and, indeed, this view, as will be ex- plained, occurs in modified form to-day. Du Bois-Reymond, after discovering the demarcation current and action current in muscle and nerve, formulated an hypothesis according to which the nerve fibers contain a series of electromotive particles, and by this hypothesis and the facts upon which it was based he thought that he had established that "hundred-year-old dream" of phys- icists and physiologists of the identity of the nerve principle and electricity. His theory to-day has fallen into disrepute, but the facts upon which it was based remain, as before, of the deepest importance. In the middle of the nineteenth century those who were not convinced of the identity of the nerve principle with electricity believed, nevertheless, that the process of conduction in the nerve is a phenomenon of an order comparable to the trans- mission of light or electricity, with a velocity so great as to defy measurement. But in this same period a simple but complete experiment by Helmholtz demonstrated that its velocity is, as compared with light or with electrical conduction through the air or through metals, exceedingly slow, — 27 meters per second. Modern views have taken divergent directions; the movement or excitation that is conducted along the fiber has been named 109 110 THE PHYSIOLOGY OF MUSCLE AND NERVE. the nerve principle, the nerve energy, the nerve force, the nerve impulse. As the latter term is less specific regarding the nature of the movement, and emphasizes the fact of the conduction of an isolated disturbance or pulse, it seems preferable to employ it until a more satisfactory solution of its nature has been reached. The Velocity of the Nerve Impulse. — The determination of the velocity of the nerve impulse was first made by Helmholtz* upon the motor nerv^es of frogs. His experiment consisted in stimulating the sciatic nerve, first, near its ending in the muscle Fig. 51. — Record to show the method of estimating the velocity of the nerve impulse in a motor nerve. Ihe experiment was made upon a nerve-muscle preparation from the frog, the contractions bring recorded upon the rapidly moving plate of a pendidum myo- graph. Two contractions were obtained, the first (a) when the nerve wa,s stimulated near the rnuscie the second (l>) when the nerve was stimulated as far as possible from the muscle. The latent period of the second contraction was longer, as shown by the distance between the curves measurod on the line .r. The value of this distance in time is obtained by reference to the record of a tuning fork vibrating 100 times per second, which is given on the lower line. In the experiment the length of a tuning fork wave (0.01 sec.) was 21 mms., the distance between the two muscular contractions was 3.3.5 mms., and the dis- tance between the points stimulated upon the nerve was 49 mms. Hence the velocity of the ne^^'e impulse in this experiment was 49 divided by (^Wff^ Too) or 307 10 mms. (30.716 m.) per second. and, second, near its origin from the cord, and mc^asuring the time that clap.sed in each ca.se })etween the moment of stimulation and the moment of the muscular response. It was found that when the nerve was stimulated at its far end this time interval was longer, and since all other (!ondition.s remairuHl the same this dif- ference in time could only l)e due to the intcirval recjuired for the nerve impulse to trav(!l the longer stretch of nerve. In the accom- * Ilelrriliolfz, " Miiller'.s Archiv f. Aiiat. u. Pliy.siol.," 1S,'32, j). 199. NATURE OF THE NERVE IMPULSE. Ill panying figure the record of a laboratory experiment of this kind is reproduced. Knowing the difference in time and also the length of nerve between the points stimulated, the data are at hand to calculate the velocity of the impulse. The velocity varies with the temperature. According to Helmholtz, this variation lies between 24.6 and 38.4 m. per second for a range of temperature between 1 1 ° and 21° C. For average room temperatures we may say that in the motor nerves of the frog the impulse travels with a velocity of 28 to 30 meters per second. Similar experiments have been made upon man and other mammals. Helmholtz stimulated the median nerve in man at two different points and recorded the resulting contractions of the muscles of the thumb. By this means he obtained an average velocity of 34 m. per second, but others, making use of the same method, have reported varying results. Piper* has applied the string-galvanometer to the investigation of this point. Using the unipolar method, he stimulated the median nerve with induction shocks, the active electrode being applied at the elbow and at the axilla at a distance apart of from 160 to 170 mm. The muscular response was recorded not by registering the contraction, but, by means of its action current. When the stimulus was applied at the elbow the interval between the stimulation and the electrical response averaged 0.00442 second; at the axilla the interval was 0.00578 second. The difference, namely, 0.00136 second, gave the time necessary for the impulse to travel over 160 to 170 mm. of nerve, and indicated a velocity of 117 to 125 m. per second. It is interesting to recall that only six years before Helmholtz's first pub- lication Johannes Miiller had stated that we should never find a means of determining the velocity of the nerve impulse, since it would be impossible to compare points at great distances apart, as in the case of the movement of light. " The time," said he, " required for the transmission of a sensation from the periphery to the brain and the return reflex movements of the mus- cles is infinitely small and unmeasurable." The mode of reasoning by which Helmholtz was led to doubt the validity of this assertion is interesting. He says (" Miiller's Archiv," 1852, 330) : " As long as physiologists thought it necessary to refer nerve actions to the movement of an imponderable or psychical principle, it must have appeared incredible that the velocity of this movement could be measured within the short distances of the animal body. At present we know from the researches of du Bois-Reymond upon the electro- motive properties of nerves that those activities by means of which the con- duction of an excitation is accomplished are in reality actually conditioned by, or at least closely connected with an altered arrangement of their material particles. Therefore conduction in nerves must belong to the series of self' propagating reactions of ponderable bodies, such, for example, as the con- duction of sound in the air or elastic structures, or the combustions in a tube filled with an explosive mixture." One of the first fruits, therefore, of the scientific investigation of the electrical properties of the nerve fiber was the discovery of the important fact of the velocity of the nen^e impulse. * Piper, "Archiv f. d. ges. Physiologic," 1908, 124, 591. 112 THE PHYSIOLOGY OF MUSCLE AND NERVE. Xumerous efforts have been made to determine the velocity of the nen'e impulse in medullated senson' fibers. The results have not been entirely satisfactory. The end-organ in this case is the cortex of the cerebnmi, and its reaction consists in arousing a sensation, or a reflex action. Neither end-reaction can be meas- ured directly. Attempts have been made to determine it indi- rectly by noting the time of a voluntary muscle response for sensory stimuli applied to the skin at different distances from the spinal axis. In such cases the sensorj" impulse travels to the cord, thence to the brain, and the return motor impulse travels from brain to cord and then by the motor nerves to the muscle used for the re- sponse. The results of this method have been discordant, owing probably to the fact that the central paths from two different points on the skin are not identical. It is usually assumed — ^without, however, very^ convincing proof — that the velocity of the impulse in the medullated afferent nerve fibers is the same as in the efferent fibers. A large number of observations are on record which show that the velocity varies greatly in the nerves of different animals. In the mammal, according to Chauveau, the velocity for the non-medullated fibers is only 8 meters per second; in the lobster it is 6 meters per second; in the octopus, 2 meters; in the olfactory (sensory) nerve of the pike, ^ meter, and in the anodon, only y^-jj- meter per second. Relation of the Nerve Impulse to the Wave of Negativity. — A fact of great significance is that the velocity of the impulse in the motor nerves of the frog corresponds exactly to the velocity of the wave of negativity as measured by Bernstein. Evidently the two phenomena are coincident in their progress along the fiber, and physiologists generally have accepted the existence of an action cur- rent as a proof of the passage of a nerve impulse. This belief is strengthened by the fact that, as stated above, the negative wave ac- companies the nerve impulse not only when the nerve is stimulated by electrical currents, ]mt also after mechanical, chemical, or reflex stimulation. "J'he question has been raised as to whether this elec- trical phenomenon accompanies the normal nerve impulse, — that is, the nerve impulse that originates in the nerve centers, in the case of motor nerves, or in the perii)]icral sense organs in the case of sen- sory nerves. In regard to the latter relation we have positive evi- dence that when liglit falls uj)on the living retina an electrical distur- bance Ls produced Ijy the visible rays of the spectnun,* and there is every reason to believe that the passage of visual im})ulses along the optic nerve is acconipani(;(l by an electrical change. With regard to nonnal mot(jr impulses, the evidence is also positive that motor discharges from the central nervous system are accompanied * Hee Einthovon anfi JdIIv, "Qu.'irtorly Journal of Exporiiricnt.il I'liysiol- ogy," 1, :m, urn. NATURE OF THE NERVE IMPULSE. 113 by a wave of electrical potential. This fact may be shown by stimulating the motor areas in the cerebral cortex and testing the efferent nerves, such as the sciatic, for an action current; or by stimulating a posterior root on one side in the lumbar region and testing the sciatic nerve on the other side with a galvanometer.* Moreover, all influences that alter the velocity or strength of the nerve impulse affect the intensity of the action current in the same manner. It is believed generally, therefore, that the electrical change is an invariable accompaniment of the excitatory wave, and the demonstration of an action current in a nerve is tanta- mount to a proof of the passage of a nerve impulse, f Direction of Conduction in the Nerve. — The fact that under normal conditions the motor fibers conduct impulses only in one direction — i. e., toward the periphery — and the sensory fibers in the opposite direction — that is, toward the nerve center — suggests, of course, the question as to whether the direction of conduction is conditioned by a fundamental difference in structure in the two kinds of fibers. No such difference in structure has been revealed by the microscope. It is the accepted belief in physiology that any nerve fiber may conduct an impulse in both directions, and does so conduct its impulses when the fiber is stimulated in the middle of its course. An entirely satisfactory proof for this belief is difficult to furnish unless the conclusion in the preceding paragraph is ad- mitted — the con- clusion, namely, that the electrical change is a neces- sary and invariable accompaniment of the nerve impulse. Fig. 52. — Schema to show the arrangement for proving _ . ,.2j, ,, the propagation of the negative charge in both directions: it is not difficult a. The stimulating electrodes; g and g', galvanometers , I , with leading off electrodes arranged to show the negative to show by means variation on each side. of a galvanometer that when a nerve trunk is stimulated the wave of negativity spreads in both directions from the point stimulated and gives an action current on either side, as indicated in the accompany- ing diagram. This fact holds true for motor or for sensory fibers. The older physiologists attempted to settle this question in a more direct way, but by methods which later experiments have proved to be insuSicient. They attempted, for instance, to * Gotch and Horsley, "Phil. Trans., Royal Soc," London, 1891, vol. 182 (B), and Boruttau, "Pflliger's Archiv," 1901. t For a more extended discussion, see Keith-Lucas, Croonian Lecture, "Proceedings of the Royal Society," B, 85, 582, 1912. 114 THE PHYSIOLOGY OF MUSCLE AND NERVE. unite a motor and sensory trunk directly, to cut the hypoglossal (motor) and the lingual (sensory) and suture, say, the central stump of the lingual to the peripheral stump of the hypoglossal. If stimu- lation of this latter tnmk, after union had been established, gave signs of sensation it was considered as proof that the efferent hypo- glossal fibers were now conducting afferently. We now know that in such a case the old hypoglossal fibers degenerate completely, and the new ones that are eventually formed in their place are out- growths from the lingvial stump, or at least are not the old efferent fibers, and hence experiments of this kind are not so conclusive as they seemed to be at the time when it was supposed that severed nerve fibers can unite immediately, by first intention, without previous degeneration. A similar objection applies to Paul Bert's often quoted experiment. Bert implanted the tip of a rat's tail into the skin of its back. After union had taken place the tail was severed at the base, and the stump now attached to the back was tested from time to time as to its sensibility. Sensation returned slowly. At first it was indefinite, but by the end of a year was apparently normal. Modification of the Nerve Impulse by Various Influences — Narcosis — Temperature. — The strength of the impulse and its velocity may be modified in various ways: by the action of temperature, narcotics, pressure, etc. Variations of tempera- ture, as stated before, change the velocity of propagation of the impulse, the velocity increasing with a rise of temperature up to a certain point. So also the irritability as well as the con- ductivity of the nerve fiber is influenced markedly by tem- perature. If a small area of a nerve trunk be cooled or heated, the nerve impulse as it passes through this area may be increased or decreased in strength or may be blocked entirely. Different fibers show somewhat different reactions in this respect; but, speaking generally, the limits of conductivity in relation to temperature lie between 0° C. and 50° C. Cooling a nerve to 0° C. will in most cases suspend the conductivity, but this function returns promptly upon warming.* By this means we can block the nerve impulses in a nerve trunk for any desired length of time. The exact relationship between the temperature of the nerve and the velocity of the impulse has been studied carefully with the object of determining the temperature coeffi- cient. It has been shown })y van't Iloff that the velocity of chemical reactions is increased twofold or more for each rise of 10 degrees in temperature, that is, the temperature coefficient for chemical reactions lies between 2 and 3. On the other hand, with most physical processes the temperature coefficient for the * Howell, Budgett, and Ix;onanl, ".Journal of Physiology," 10, 298, 1894. NATURE OF THE NERVE IMPULSE. 115 same range of temperature lies around 1 or between 1 and 2. Snyder* finds, on comparing the velocities of the impulse at different temperatures, that they follow van't Hoff's law for chemical reactions, that is, the velocity is approximately doubled by a rise of 10° C. in temperature within physiological limits, 1- 1^ velocity at Tn - 10 o rri,- or, expressed m more general terms, — -, — t-^ — ^ V — =2. 1 his ^ ^ velocity at In effect of temperature on the velocity of the impulse is shown graphically in Fig. 53. Anesthetics and narcotics,! such as ether, Fig. 53. — Figure to show the effect of temperature on the velocity of the nerve impulse. At each temperature two contractions of the gastrocnemiu? were recorded, one when the nerve was stimulated close to tne muscle, one when it was stimulated further away (44 mm.). The horizontal distance between the cun'es as they rise can be expressed in time by refer- ence to the tuning-fork vibrations (200 per second) given below. For inter\-als of 10° C. it will be seen that the velocity, as indicated by the reciprocals of the distances between the pairs of curves, indicates a coefficient of two. — {Snyder.) chloroform, cocain, chloral, phenol, alcohol, etc., may be applied locally to a nerve trunk, and if the application is made with care the conductivity and irritability may be lessened or suspended entirely at that point, to be restored again when the narcotic is removed. It is an interesting fact that the conductivity of the nerve may be suspended also by deprivation of oxygen, J— that is, by local suffocation or asphyxia. A nerve fiber sur- rounded by an oxygen-free atmosphere will slowly lose its conductivity, and this property will be restored promptly upon the admission of oxygen. Compression of a nerve will also suspend its conductivity without permanently injuring the fibers, provided the pressure is properly graduated. Lastly, as was explained in a preceding chapter, the conductivity of the nerve may be increased or decreased or suspended entirely by the action of a galvanic (polarizing) current. This method of sus- pending conductivity temporarily has been frequently employed * Snyder, "American Journal of Physiology," 22, 179, 1908. t Frohlich, "Zeitschrift f. allgemeine Physiol.," 3, 75, 1903. J Baeyers, ibid., 2, 169, 1903. 116 THE PHYSIOLOGY OF MUSCLE AND NERVE. for experimental purposes, the arrangement being as represented in Fig. 54. The Refractory Period. — In the case of the heart, the nerve cell, and the niiiscle it has been sho^^^l that for a short period after the tissue enters into a condition of functional activity it is non- irritable toward a second stimulus. This condition of loss of excitability following upon or accompanying functional activity is designated as the refractory 'period. It is interesting to find that a tissue so irritable as a nerve fiber exhibits the same phenomenon. For a very brief period (0.002 to 0.006 of a second), after it enters into action, as indicated by the electrical response, a second stimulus throw in will be found to be ineffective. As the elec- trical change passes off, that is, as the state of activity subsides, the nerve regains its normal irritability. The refractory period of the nerve fiber may be much prolonged by conditions which slow the processes underlying activity, for example, by low tempera- tures, or by the action of certain drugs, such as yohimbine (Tait). The Question of Fatigue of Nerve Fibers. — An important question in connection with the nature of the nerve impulse has been that of the suscep- tibility of the nerve fibers to fatigue. The obvious fatigue of muscles and of nerve centers has been referred to the accumula- tion of the products of metabolism of their tis- sues or to the actual consumption of the en- ergy-yielding material in them. Functional activ- ity in these tissues im- plies the breaking down of complex organic material (catabolism) and the setting free of the so-called chemical energy. The internal energy of the compound is liberated as kinetic energy of heat, ('t(^ It has been accepted, therefore, that if the nerve fiber could be dem- onstrated to show fatigue as a result of functional activity, this fact would be probable proof that the conduction of the im- pulse is associated with a chemical change f)f a catabolic nature in the substance of the fiber. ]'iXj)erimeiital work, however, has shown that under normal conditions the nerve fiber shows no fatigue. The experiments made upon this point have been nu- merous and varied. The general idea underlying all of them has been to stimulate the nerve c(jntinu(jusly, but to interpose a block Fig. 54.— Schema to show the method of block- ing the nerve impulse by means of a polarizing cur- rent: a. The stimulating electrodes; 6, the battery, the current of which is led into the nerve. The de- pressed irritability at both anode, +, and cathode, ; — , prevents the nerve impulse started at a from reaching the mu;^cle. NATURE OF THE NERVE IMPULSE. 117 somewhere along the course of the nerve so that the unpulses should not reach the end-organ. This precaution is necessary because the end-organ — muscle, gland, etc. — is subject to fatigue, and must therefore be protected from constant activity. From time to time or at the end of a long period of stimulation the block is removed and it is noted whether or not the end-organ — for in- stance, the muscle — gives signs of a stimulation. The removable block has been obtained by the action of a polarizing current, by cold, by narcotics, by curare, etc. Using curare, for instance, Bowditch* found that the sciatic nerve might be stimulated continu- ously by induction shocks for several (four to five) hours without complete fatigue, since as the curare effect wore off the muscle whose contractions were being recorded (M. tibialis ant.) began to respond, at first with single and finally with tetanic contractions. The curare in this case may be supposed to have blocked the nerve impulse at the motor end-plate and thus protected the muscle from responding until the lapse of several hours, although the nerve was under stimulation during this entire time. This experiment has since been repeated by Durig,t who has made use of the fact that the effects of curare can be removed within a few minutes by the salicylate of physostigmin, Durig stimulated the nerve for as much as ten hours and then upon removing the curare block found from the contraction of the muscle that the nerve was still conducting. EdesJ and others have shown that the same result is obtained when the nerve is tested by a capillary electrometer instead of by the response of an end-organ. Under such conditions the nerve exhibits an undiminished action cur- rent, although constantly stimulated by tetanizing shocks from an induction apparatus. Brodie and Halliburton § have found that the non-medullated fibers in the splenic nerve can also be stimulated for many hours without losing their power of conduction, — that is, without showing fatigue. Many other observers have obtained similar results, which have confirmed physiologists in the belief that the nerve fibers may conduct impulses indefinitely, or, in other words, that their normal functional activity may be carried on continuously without fatigue. If this belief is entirely correct it would place the nerve fibers in a class by themselves, since all other tissues that have been studied show evidence of fatigue when kept in continuous functional activity. Moreover, if this belief is entirely correct it would imply that the conduction of an impulse in the nerve fiber is not associated with a consumption of material, * Bowditch, "Journal of Physiology," 6, 133, 1885. t Durig, "Centralblatt f. Physiol.," 15, 751, 1902. t Edes, "Journal of Physiology," 13, 431, 1892. § Brodie and Halliburton, "Journal of Physiology," 28, 181, 1902. 118 THE PHYSIOLOGY OF MUSCLE AND NERVE. a metabolism, and in this respect also the functional activity of the nerve would be placed in contrast with that of other organs. It must be remembered, however, that, although the above ex- periments demonstrate the practical " unfatigueableness " of nerve fibers under ordinary conditions of stimulation, there are some reasons to make us hesitate in supposing that in these structures functional activity is entirely without a depressing effect upon irritability. Garten has showTi that one nerve, the olfactory of the pike, when stimulated by induction shocks, with an interval between the stimuli of as much as 0.27 sec, gives evidence of fatigue, since its action current, as measured by the capillary electrometer, diminishes in extent quite rapidly, and recovers after a short rest.* So also it has been found that while a nerve deprived of oxygen, by keeping it in an atmosphere of nitrogen, loses its irritability after a certain time, this event occurs much more rapidly if the nerve is stimulated constantly, f This fact would suggest that some oxygen is consumed during functional activity, and that the ability of the nerve under normal circum- stances to escape the results of fatigue may be due possibly to the fact that the supply of oxygen is sufficiently abundant to oxidize promptly the fatigue substances formed during activity. Does the Nerve Fiber Show Any Evidence of Metabolism During Functional Activity? — The functional part of a nerve fiber in conduction is the axis cylinder, and, indeed, probably the neurofibrils in the axis cylinder. The mass of this material, even in a large nerve trunk, is small (al)out 9 per cent.), and its chemistry is but little known. The efforts that have been made to prove a metabolism in the nerve fiber during activity have been directed along the linos indicated by what is known of muscle metabolism. In a muscle during contraction heat is produced, the substance of the muscle shows an acid reaction, and among tlie products formed carbon dioxid gas is perhaps the most prominent. Efforts to show similar reactions in stimulated nerves have been only partially successful. RollestonJ investigated the question of heat produc- tion with the aid of a dcHc-atc btjlometer (•ai)al)le of indicating a difference of temperature of 7to'oo° CJ. The frog's s(aatic was used, but no increase in temperature during stimulation could be demonstrated. Making use of a more sensitive instrument. Hill has obtained the same negative result. If any heat is I)roduc(Hl by the transmission of a nerve impulse it must be less, according to his measiircincnts, th.m ;i huiuh-ed-millionth ♦Quoted from liiciicriii.-iriii, "ErgcbniHSc dcr I'liysiolo^iic," vol. ii, |)!irt ii, p. 129. tThorncr, "Zcilschrifl f. ullji. I'liv.sioIoKic," S, ry.H), 19()S. t Roliestoti. "Journal of PhyHJoloKy," 11, 20H, 1S9(). NATURE OF THE NERVE IMPULSE. 119 of a degree centigrade.* On the other hand, Tashirof reports that, by means of a new method which is capable of detecting as little as 0.0000001 gm. of carbon dioxid, he has been able to show that the resting nerve produces carbon dioxid and that this pro- duction is increased about two and a half times when the nerve is stimulated. Additional evidence for the occurrence of a nerve metabolism during activity is found in the fact, already alluded to, that oxygen plays a part in maintaining the irritability of nerves. An excised frog's nerve loses its irritability in an atmos- phere deprived of oxygen, and regains it promptly when oxygen is again supplied. When stimulated in an atmosphere free from oxygen the nerve shows signs of fatigue, while in the presence of oxygen activity is maintained, one may say indefinitely, under continuous stimulation. These facts warrant the belief that oxygen is used by the nerve during activity, and presumably it is used in this as in the other tissues to produce physiological oxidations. Another fact which points in the same direction is the high value of the temperature coefficient for nerve conduc- tion, which has been referred to above. Bearing these two general considerations in mind, we can hardly escape the con- viction that the functional activity of the nerve fiber is connected with a chemical reaction of some kind, most probably a reaction in which some material in the nerve undergoes oxidation. Views as to the Nature of the Nerve Impulse. — The older con- ceptions of the nerve principle, while they varied in detail, were based upon the general idea that the nervous system contains a matter of a finer sort than that visible to our senses. This matter was pictured at first as a spirit (animal spirits), and later as a mate- rial comparable to the luminiferous ether or to electricity. Since the discovery that the nerve impulse travels with a relatively slow velocity and is accompanied by a demonstrable change in the electrical condition of the nerve, many different views regarding its nature have been proposed. In discussing the matter it is evident that two perhaps different phenomena have to be consid- ered, namely, the act of excitation by natural or artificial stimuli and the act of propagation or conduction. Formerly, it was held in a general way that the nerve impulse depends upon the breaking down of some unstable substance within the axis cylinder. It was assumed that this sensitive and unstable material is upset by the energy of the stimulus at the point stimulated, and that the energy thus liberated acts upon contiguous particles, and so the disturb- ance is propagated along the nerve as a progressive chemical *Hill, "Journal of Physiology," 43, 433, 1911-12. t Tashiro, "American Journal of Physiology," "Proc. of Am. Physiologi- cal Soc," 31, 22, 1913. 120 THE PHYSIOLOGY OF MUSCLE AND NERVE. change which in a very general way may be compared to the pas- sage of a spark along a line of gunpowder. A fundamental ob- jection to such a view is the uncertainty of the proof regarding the consumption of material in a nerve during activity, as has been ex- plained in the preceding sections. Quite the opposite point of view has also been held, namely, the idea that the nerve impulse is a purely physical process, which involves no chemical change and no using up of material. Various suggestions have been offered as to the character of this physical change, but the one that is perhaps most worthy of consideration identifies the nerve im- pulse with the negative electrical change that is known to pass along the fiber. It is assumed that this electrical change consti- tutes the nerve impulse, and to explain its occurrence and propaga- tion from a physical standpoint it has been supposed that the nerve fiber has a structure essentially similar to the '' core conduc- tor " (see p. 107), in that it contains a central thread surrounded by a liquid sheath of less conductive material. The central thread may be supposed to be the axis cylinder and the less conductive sheath the surrounding myelin, or, perhaps, to follow another sug- gestion that fits the non-medullated as well as the medullated fibers, the central threads are represented by the neurofibrils within the axis cylinder and the surrounding sheath by the perifibrillar substance. That the axis cylinder is a better conductor than the myelin sheath has been indicated by the microchemical researches of Macallum. This observer has shown that in the axis cylinder the chlorids exist in greater concentration than in the surrounding sheath.* The point of importance is that, with a core model (see Fig. 50), consisting of a glass tube with a core of platinum wire and a sheath of solution of sodium chlorid, 0.6 per cent., electrical phenomena can be obtained similar to those shown by the stimulated nerve. If an induction current, serving as a stimulus, is sent into one end of such an artificial nerve and from the other end two leading off electrodes are connected with a galvanometer, then we can demonstrate by means of the galvanometer that an electrical charge is propagated along the model at each application of the stiirmlus. And, as such a moving electrical disturbance is the only objective phenomenon known to occur in the stimulated nerve, it has been assumed that it constitutes the nerve impulse. When this electrical disturbance reaches the end-organ, — the nmscle, for instance, — it initiate's the; chemical changes that characterize the activity of the organ. This kind of tluiory makes the nerve impulse an electrical phenomenon, and assumes that the nerve * Macallum, " Proceed ingH of the Royal Society/' l\H)('>, B. Ixxvii., 105. NATURE OF THE NERVE IMPULSE. 121 fibers have become differentiated to form a specific kind of conductor, the efficiency of which depends upon its having a structure similar to that of a " core conductor." Other theories of a physico-chemical character have been proposed especially to explain the initial excitation caused by a stimulus and the electrical phenomena responsible for the action current. Nernst has supposed that the electrolytes contained in the axis cylinder lie within membranous partitions which are impermeable to the passage of certain ions. When an electrical current is passed through a nerve, it is conveyed of course by the dissociated elec- trolytes, and in consequence of the impermeable character of the septa, there will be a concentration of positively charged ions at one face of the membranes and of negatively charged ions at the other. When the concentration of the ions reaches a certain point, excitation occurs. The nature of the excitation under such circumstances has been further imagined by Hill, who suggests that some sensitive substance, presumably a colloid, exists in the nerve in combination with certain ions. This combination is in an unstable or critical state, and when, in consequence of a stimulus of any kind, the concentration of ions in combination with it is increased, it breaks down and this act constitutes the excitation, which is then propagated along the nerve. This author has treated his assumption mathematically to ascertain how far it accords with the known facts of the stimulation of nerves with electrical currents. It should be added that these and, indeed, all specific theories of the nature of the nerve impulse are, at present, matters for discussion and experiment among specialists. We are far from having an explanation of the nerve impulse resting upon such an experimental basis as to command general acceptance.* Qualitative Differences in Nerve Impulses and Doctrine of Spe- cific Nerve Energies. — Whether or not the nerve impulses in vari- ous nerve fibers differ in kind is a question of great interest in physi- ology. The usually accepted view is that they are identical in character in all fibers and vary only in intensity. According to this view, a sensory nerve — the auditory nerve, for instance — car- ries impulses similar in character to those passing along a motor nerve, and the reason that in one case we get a sensation of hearing and in the other a contraction of a muscle is found in the manner of ending of the nerve, one terminating in a special part of the cortex * For a summary of the literature upon the nature of the nerve impulse consult Boruttau, "Zeit. f. allg. Physiologie," 1, 1, Sammelreferate, 1902; Biedermann, "Ergebnisse der Physiologie," vol. ii, part ii, 1903; Hering, "Zur Theorie der Nerventhatigkeit." 1899; Hill, "Journal of Physiology," 40, 190, 1910; Lucas, ibid., p. 224; and Croonian Lecture, "Proceedings Royal Society," B. 85, 582, 1912. 122 THE PHYSIOLOGY OF MUSCLE AND NERVE. of the cerebrum, the other in a muscle. From this standpoint the nerve fibers may be compared to electrical wires. The current conducted by the wires is similar in all cases, but may give rise to very different effects according to the way in which the wires ter- minate, whether in an explosive mixture, an arc light, or solutions of electrolytes of various kinds. We have in physiology what is known as the doctrine of specific nerve energies, first formulated by Johannes Miiller. This doctrine expresses the fact that nerve fibers when stimulated give only one kind of reaction, whether motor or sensory, no matter in what way they may be stimulated. The optic nerve, for instance, gives us a sensation of light, usually because light waves fall on the retina and thus stimulate the optic nerve. But if we apply other forms of stimulation to the nerve they will also, if effective, give a sensation of light. Cutting the optic nerve or stimulating it with electrical currents gives visual sensations. On the identity theory of the nerve impulses the specific energies of the various nerves — that is, the fact that each gives only one kind of response — is referred entirely to the charac- teristics of the tissue in which the fibers end. If, as has been said, one could successfully attach the optic nerve to the ear and the auditory nerve to the retina then we should see the thunder and hear the lightning. The alternative theory supposes that nerve impulses are not identical in different fibers, but vary in quality as well as intensity, and that the specific energies of the various fibers depend in part at least on the character of the impulses that they transmit. On this theory one might speak of visual impulses in the optic nerves as something different in kind from the auditory impulses in the auditory fibers. With our present methods of investigation the question is one that can not be definitely decided by experimental investigation; most of the discussion turns upon the applicability of the doctrine to the explanation of various conscious reactions of the sensory nerves. So far as experimental work has been carried out on efferent nerves, it is undoubtedly in favor of the identity theory. The action current is similar in all nerves examined; the reactions to artificial stimuli are essentially similar. Moreover, nerves of one kind may be sutured to nerves of another kind, and, after re- generation has taken place, the reactions are found to be deter- mined solely by the place of ending (see p. 80). The Nutritive Relations of the Nerve Fiber and Nerve Cell. — In recent times in accf)rdance with the so-called neuron doctrine (see p. 128) (^vcry axis cylinder has bc^en considered as a process of a nerve cell, and therefore as a part, morphologically speaking, of that cell. However this may be, there is excellent experimental NATURE OF THE NERVE IMPULSE. 123 evidence to show that the physiological integrity of the axis cylinder depends upon its connection with its corresponding nerve cell. This view dates from the interesting work of Waller,* who showed that if a nerve be severed the peripheral stump, containing the axis cyl- inders that are cut off from the cells, will degenerate in a few days. The process of degeneration brought about in this way is known as secondary or Wallerian degeneration. The central stump, on the contrary, remains intact, except for a short region immediately contiguous to the wound, for a relatively long period, extending perhaps over years. Waller, therefore, spoke of the nerve cells as forming the nutritive centers for the nerve fibers, and this belief is generally accepted. In what way the cell regulates the nutrition of the nerve fiber throughout its whole length is unknown. Some of the cells in the lumbar spinal cord, for instance, give rise to fibers of the sciatic nerve which may extend as far as the foot, and yet throughout their whole length the nutritive processes in these fibers are dependent on influences of an unknown kind, emanating from the nerve cells to which they are joined. These influences may consist simply in the effect of constant activity; that is, in the conduction of nerve impulses, or there may be some kind of an actual transferal of material. This latter idea is supported by the interesting fact, which we owe to Meyer, that tetanus and diph- theria toxins may be transmitted to the central nervous system by way of the axis cylinders of the nerve fibers. By means of his method Waller investigated the location of the nutritive centers for the motor and sensory fibers of the spinal nerves. If an anterior root is cut the peripheral ends of the motor fibers degenerate throughout the length of the nerve, while the fibers in the stump attached to the cord remain intact; hence the nutritive centers for the motor .fibers must lie in the cord itself. Subsequent histo- logical work has corroborated this conclusion and sho\vn that the motor fibers of the spinal nerves take their origin from nerve cells lying in the anterior horn of gray matter in the cord, the so-called motor or anterior root cells. If the posterior root is cut between the ganglion and the cord, the stump attached to the cord degener- ates ; that attached to the ganglion remains intact, and there is no degeneration in the nerve peripheral to the ganglion (Fig. 55). If, however, this root is severed peripherally to the ganglion degenera- tion takes place only in the spinal nerve beyond the ganglion. The nutritive center, therefore, for the sensory fibers must lie in the pos- terior root ganglion, and not in the cord. This conclusion has also been abundantly corroborated by histological work. It is known that the sensory fibers arise from the nerve cells in these ganglia. * Waller, "Muller's Archiv," 1852, p. 392; and "Comptes rendus de I'Acad. de la Science," vol. xxxiv., 1852. 124 THE PHYSIOLOGY OF MUSCLE AND NERVE. By the same means it has been shown that the motor fibers in the cranial nerves arise from nerve cells (nuclei of origin) situated in the brain, while the sensory fibers of the same nerves, with the exception of the olfactory and optic nerves ■s^'hich form special cases, arise from sensory ganglia lying outside the nervous axis, such, for Fig. 55. — Diagram to show the direction of degeneration on section of the anterior and the posterior root, respectively. The degenerated portion is represented in black. instance, as the spiral ganglia of the cochlear nerve, or the gan- glion semilunare (Gasserian ganglion) of the fifth cranial nerve. Nerve Degeneration and Regeneration. — When a nerve trunk is cut or is killed at any point by crushing, heating, or other means all the fibers peripheral to the point of injury undergo de- generation. This is an incontestable fact, and it is important to bear in mind the fact that the definite changes included under the term degeneration are exhibited only by living fibers. A dead nerve or the nerves in a dead animal show no such changes.* The older physiologists thought that if the severed ends of the nerves were brought together by sutures they might unite by fir.st intention without degeneration in the peripheral end. We know now that this degeneration is inevitable once the living continuity of the fibers has been interrupted in any way. Any functional union that may occur is a slow process involving an act of regeneration of the fibers in the peripheral stump. The time required for the degeneration differs somewhat for the different kinds of fibers found in the animal body. In the dog and in other mammalia the degeneration begins in a few (four) days; in the frog it may require from thirty to one hundred and forty days, depending upon the .season of the year, although if the frog is kept at a liigh temperature (30° C.) degeneration may proceed as rajjidly as in the mammal. In the dog it proceeds so quickly that the process seems to bo simultaneous thi'oughout the whole peripheral stump, while in the frog, and, jiccording to Bethe, •Sec Van (iohuchtcn, "I.o N6vriixc." VM)',. vii., 2iY.i. Fig. 56. — Histology of a degenerating nerve fiber. Fig. 57. — Embryonic fibers in a regenerating nerve. Fij{. 58. — A newly d«!Velopu(i libcT in ii ri;Kt;norutinK nerve fiber. NATURE OF THE NERVE IMPULSE. 125 in the rabbit, it can be seen clearly that the degenerative changes . begin at the wound and progress peripherally. The fibers break up into ellipsoidal segments of myelin, each containing a piece of the axis cylinder, and these segments in turn fragment very irregu- larly into smaller pieces which eventually are absorbed* (Fig. 56). The central stump whose fibers are still connected with the nerve cells undergoes a similar degeneration in the area immediately contiguous to the wound, but the degenerative processes extend for only a short distance over an area covering a few internodal segments. Although the central ends of the fibers remain sub- stantially intact, it is interesting to find that the nerve cells from which they originate undergo distinct changes, which show that they are profoundly affected by the interruption of their norma) connections (see p. 127). In the peripheral end the process of regeneration begins almost simultaneously with the degenerative changes, the two proceeding, as it were, hand in hand. The regen- eration is due to the activity of the nuclei of the neurilemmal sheath. These nuclei begin to multiply and to form around them a layer of protoplasm, so that as the fragments of the old fiber disappear their place is taken by numerous nuclei and their surrounding cytoplasm. Eventually there is formed in this way a continuous strand of protoplasm with many nuclei, and the fiber thus produced, which has no resemblance in structure to a normal nerve fiber, is described by some authors as an "embryonic fiber"; by others as a "band fiber" (Fig. 57). In the adult animal the process of regeneration stops at this point unless an anatomical connection is established with the central stump, and, indeed, such a connection is usually established unless special means are taken to prevent it. The central and peripheral stumps find each other in a way that is often remarkable, the union being guided doubtless by intervening connective tissue. Forsmanns f has emphasized this peculiar attraction, as it were, be- tween the peripheral and the central ends, giving some reason to believe that it is a case of chemotaxis or chemotropism. When the ends of the nerves were given very unusual positions by means of coUodium tubes into which they were inserted they managed to " find" each other. Moreover, he states that a central stump, if given an equal opportunity to grow into two coUo- dium tubes, one containing liver and the other brain tissue, will chose the latter, a fact which would indicate some underlying chemical attraction or affinity in nerve tissue for nerve tissue. A directive influence of this kind depending upon some property connected with chemical relationship is desig- nated as " chemotaxis." If the central and peripheral stumps are brought together by *See Howell and Huber, "Journal of Physiology," 13, 335, 1892; also Mott and Halliburton, " Proceedings Royal Society," 1906, B. Ixxviii., 259, and Cajal, " Trabajos del laboratorio de investigaciones biologicas (Univ. of Madrid)," vol. 4, 119, 1906. t Forsmanns, "Zeigler's Beitrage," 27, 216, 1902. 126 THE PHYSIOLOGY OF MUSCLE AND NERVE. suture or grow together in any way, then, under the influence of the central end, the " band fiber " gradually becomes transformed into a normal nerve fiber, with myelin sheath and axis cylinder (Fig. 5S). It is possible that this result is due to local processes in the band fiber stimulated by nutritive influences of some kind from the central stump, but more probablj' there is an actual down- growth of the axis cylinders from the central ends. In support of this latter view, it may be said that the outgrowth of the new axis cylinders from the old ones present in the fibers of the central stump has been followed more or less successfully by a number of histologists. Betho* ha.s throwTi some doubt upon this view, for he has shown appar- ently that in young manunals (eight flays to eight weeks) the regeneration of the fibers in the peripheral stuni]) tloes not stop at the stage of "band fibers," but jjrogresses until p(>rfeetly normal nerve fibers are produeed, even though no connection is made with the central stumi). It should be added, however, that the fibers so formed do not persist indefinitely unless they become con- nected with the central stump. If this connection fails to take place, the newly formed fibers will degenerate after an interval of some months. Still, the fact, if true, that in the young fiber the regeneration is complete seems to indicate that the axis cylinder may arise independently of the fibers in the central stump. Whether or not Bethe's observations upon the autoregeneration of the axis cylinders in the severed nerves of young animals can be accepted is doubtful, the balance of evidence at j^resent seems to indicate that what he took for autoregenerated fibers were really fibers which grew into the de- generated trunk from the surrounding tissue. Degenerative Changes in the Neuron on the Central Side of the Lesion. — According to the Wallerian law of degeneration, as originally stated, the nerve fiber on the central side of the injury and the nerve cell itself do not imdergo any change. As a matter of fact, the central stump immediately contiguous to the lesion undergoes typical degeneration and regeneration similar to that described for the fibers of the peripheral sttimp. The immediate degenerative changes in the fibers in the central stump were supposed to extend back only to the first node of Ranvier, — to affect, there- fore, only the internodal segment actually injured. Later it was found that the degeneration may extend back over a distance of several internodal segments. This limited degeneration on the central side must be considered as traumatic, — that is, it involves only those portions directly injured by the lesion. The central end of the fil)cr in general was supposed to remain intact as long as its cell of origin was normal. It was thought at first tliat after simple section of a nerve trunk, in amputation, for instaiu-e, the nerve cells and central stumps remain nonn.ii throughout the life * Bet he, "Aligemeine Anat. u. i'hyHiologie des NervensyHteniK," HKW. NATURE OF THE NERVE IMPULSE. 127 of the individual. Dickinson, however, in 1869 * showed that in amputations of long standing the motor cells in the anterior horn of the cord decrease in number and the fibers in the central stump become atrophied. This observation has been corroborated by other observers, and it is now believed that after section of a nerve chronic degenerative changes ensue in the course of time in the central fibers and their cells, resulting in their permanent atrophy. We have, in such cases, what has been called an atrophy from disuse. A fact that has been discovered more recently and that is perhaps of more importance is that the nerve cells do undergo certain definite although usually temporary changes immediately after the section of the nerve fibers arising from them. It has been shown that when a nerve is cut the corresponding cells of origin may show distinct histological changes within the first twenty-four hours. These changes consist in a circumscribed destruction of the chromatin material in the cells (chromato lysis), which in a short time extends over the whole cell, so that the primary staining power of the cell is lost (condition of achromatosis) (see Fig. 63). The cell also becomes swollen and the nucleus may assume an excentric position. These retrogressive changes continue for a certain period (about eighteen days). After reaching their maxi- mum of intensity the cells usually undergo a process of restitution and regain their normal appearance, although in some cases the degeneration is permanent. According to other observers a number of the cells in the spinal cord and spinal ganglia undergo simple atrophy after section of their corresponding nerves, and some of the nerve fibers in the central stumps may also show atrophy, while others undergo a genuine degeneration, which, however, comes on much later than in the peripheral stumps. It seems evident that the behavior of the cells and fibers on the central side of the section is not uniform; atrophy rather than degeneration is the change that is prominent, and this atrophy in some neurons occurs early, while in others it is apparent only after a long interval of time. An explanation of this variation in the reaction of the nerve cells and their disconnected central stumps cannot yet be given. On the peripheral side of the section, as stated above, the de- generative changes are complete and affect all of the fibers. t * " Journal of Anatomy and Physioloogy," 3, 176, 1869. t Nissl, "AUgemeine Zeitschrift f. Psychiatrie," 48, 197, 1892. Also Bethe, loc. cit., and Ranson, " Retrograde Degeneration in the Spinal Nerves," The Journal of Comparative Neurology and Psychology, 1906, xvi., 265. SECTION II. THE PHYSIOLOGY OF THE CENTRAL NERVOUS SYSTEM. CHAPTER VI. STRUCTURE AND GENERAL PROPERTIES OF THE NERVE CELL. The Neuron Doctrine. — Since the last decade of the nineteenth century the physiology of the nervous system has been treated from the standpoint of the neuron. According to this point of view, the entire nervous system is made up of a series of units, the neurons, which are not anatomically continuous with each other, but communicate by contact only. It has been taught also that each neuron represents from an anatomical and physiological standpoint a single nerve cell. The typical neuron consists of a cell body with short, branching processes, the dendrites, and a single axis cylinder process, the axon or axite, which becomes a nerve fiber, acquiring its myelin sheath at some distance from the cell. According to this view, the peripheral nerve fibers are simply long processes from nerve cells. Within the central nervous system each neuron connects with others according to a certain schema. The axon of each neuron ends in a more or less branched " terminal arborization," forming a sort of end-plate which lies in contact with the dendrites of another neuron, or in some cases with the body of the cell itself, the essentially modern point of view being that where the terminal arborization of the axon meets the dendrites or body of anotlior neuron the communication is by contact, the neurons being anatomically independent imits. It is usually ac- cepted also as a part of the neuron docitrine that the conduction of a nerve impulse through a neuron is always in one direction, that the dendrites are receiving organs, so to speak, receiving a stimulus or impulso from the axon of another unit and conveying this impulse toward the cell body, while the axon is a discharging 128 PROPERTIES OF THE NERVE CELL. 129 process through which an impulse is sent out from the cell to reach another neuron or a cell of some other tissue. The neuron, so far as conduction is concerned, shows a definite polarity, the conduction in the dendrites being cellulipetal, in the axons, cellulifugal. The neuron doctrine, so far as the name at least is concerned, dates from a general paper by Waldej^er,* in which the newer work up to that time was summarized. The main facts upon which the conception rests were furnished by His (1886), to whom we owe the generally accepted belief that the nerve fiber (axis cylinder) is an outgrowth from the cell, and secondly by Golgi, Cajal, and a host of other workers, who, by means of the new method of Golgi, demonstrated the wealth of branches of the nerve cells, particularly of the dendrites, and the mode of connection of one nerve unit with another. The view that these units are anatomically independent and on the embryologicaJ Fig. 59.- -Motor cell, anterior horn of gray matter of cord. From human tetus (Lenhos' sek): * marks the axon; the other branches are dendrites. side are derived each from a single epiblastic cell (neuroblast) has proved acceptable and most helpful; but tlie valichty of this hypotliesis lias been called into question from time to time. As was stated on p. 126, Bethe has claimed that in young animals the nuclei of the neurilemmal sheath may regenerate a new nerve fiber containing axis cylinder and myelin sheath, and this fact, if true, at once brings into question the hitherto accepted belief " Deut. med. Wochenschrift," 1891, p. 50. 130 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. that the axis cylinder can be formed only as an outgroAvth from a nerve cell. Some histologists— Apathy, Bethe, Nissl — have also attacked the most fundamental feature of the neuron doctrine — tlie view, namely, that each neuron represents an independent anatomical element. These authors contend that the neurofibrils of the axis cylinder pass through the nerve cells and enter bj'' way of a network into direct connection with the neurofibrils of other neurons (see Fig. 64). The neurofibrils form a contimuim through whicli nerve impulses pass without a break from neuron to neuron. Ac- cording to this conception, the ganglion cells play no tlirect part in the con- duction of the impulse from one part of the nervous system to another; the neurofibrils alone, and the intracellular and pericellular networks with whicli they comiect, form the conducting paths that are everywhere in con- tinuity. In tlie explanation given below of the activities of the nervous system, the author, following the usual custom, makes use of the neuron doctrine. The Varieties of Neurons. — The neurons differ greatly in size, shape, and internal structure, and it is impossible to classify them ^^ith entire success from either a physiological or an anatomical standpoint. Neglecting the unusual forms whose occurrence is limited and whose structure is perhaps incompletely kno^^^l, there are three distinct types whose form and structure throw some light on their functional significance: I. The bipolar cells. This cell is fovmd in the dorsal root gan- glia of the spinal nerves and in the ganglia attached to the sensory fibers of the cranial nerves, the ganglion semilunare (Gasserian) for the fifth cranial, the g. geniculi for the seventh, the g. vestibu- lare and g. spirale for the eighth, the g. superius and g. petrosum for the ninth, the g. jugulare and g. nodosum for the tenth. The typical cell of this group is found in the dorsal root ganglia. In the adult the two processes arise as one, so that the cell seems to be unipolar, but at some distance from the cell this process divides in T, one branch passing into the spinal cord via the posterior root, the other entering the spinal nerve as a sensory nerve fiber to be distributed to some sensory surface. Both processes become modullated and form typical nerve fibers. That these apparently unipolar cells are really bipolar is shown not only by this division into two distinct fibers, but also by a study of their development in the embryo. In early embryonic life the two processes arise from different poles of the cell, and later become fused into an ap- parently simple proc(!ss (Fig. 60). The striking characteristics of this cell, therefore, arc that it gives rise to two nerve fibers, and that it possesses no dendritic processes. On the physiological side these cells might be designated as sensory cells, since they appear to be associated always with sensory nerve fibers. The nerve cells found in the sensory (ganglia exhibit, as a matter of fact, a number of difTer(;nt types, some of which possess short dendritic processes. T\\cs<: hisfoiogicai variations cannot as yet be given a i)]iysiologi(;al signifi- cance, but their occurrence certainly .seems to indicate a po.ssibility that the sensory ganglia may have a much more varied physiological activity PROPERTIES OF THE NERVE CELL. 131 than has been attributed to them heretofore. For a description of these gangUa and a classification of their cells under eight different types con- sult Cajal in "Ergebnisse der Anat. u. Entwickelungsgeschichte," vol. xvi., 1906, and Dogiel, "Bau der Spinalganglien, etc.," Jena, 1908. So far as the sensory fibers of the spinal and cranial nerves are concerned, it is worth noting also that all of them arise from cells lying outside the main axis of the central nervous system. It has been a question whether the sensory impulses brought to the ganglion cells through the peripheral process (sensory Fig. 60. — Bipolar cells in the posterior root ganglion. Section through spinal gan- glion 9f newborn mouse {Lenhossek) : a. The spinal ganglion ; b, the spinal cord ; c, the posterior, d, the anterior root. fiber) pass into the body of the cell before going on to the cord or brain, or whether at the junction of the two processes they simply pass on directly to the cord. According to the histo- logical structure there is no apparent reason why an impulse should not pass directly from the peripheral to the central process at the junction, but whether or not this realh' occurs and the relation of the ganglion cell to the conducting path are questions that must be left unsettled at present. II. The multipolar cells. The processes of these cells fall into two groups: the short and branching dendrites with an inner structure resembling that of the cell body, and the axon or axis cylinder process (Fig. 59). According to the structure of this last process, this type may be classified under two heads : Golgi cells of the first and the second type. The cells of the first type are charac- terized by the fact that the axon leaves the central gray matter and becomes a nerve fiber. This nerve fiber within the central nervous system may give off numerous collaterals, each of which ends in a 132 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. terminal arborization. Bj- this means the neurons of this tj^De may be brought into physiological connection with a number of other neurons. This kind of nerve cell is frequently described as the t3^pical nerve cell. Golgi supposed that it rep- resents the motor type of cell, and this view is, in a measure, borne out by sub- sequent investigation. The distinctly motor cells of the central nervous system — such, for instance, as the pyramidal cells of the cere- bral cortex, the anterior horn cells of the spinal cord, the Pur kin je cells of the cere- bellum — all belong to this a' ^ Fig. 61. — Golgi cell (.second type). The axon, a, divides into a number of fine branches. — (From Oberateiner, after Andriezen.) FiK- *i2. — Normal anterior horn cdl (Warrington') , tihowinR the Nissl granules in the cell and dendrites : o. The axon. type. But within the nerve axis must of the conduction from neuron to neuron, along sensory as well as motor paths, is made with the aid of such sti'uctures, the deiidrit(^s Innng the receptive or sensory organ an(i the axon the motor apparatus. The (jolgi colls of the second type (Fig. 61) are relatively less numerous and important. They are characterized by the fact that the axon proc(!Ss instead of forming a nerve fiber splits into a great nurnbci- of branches within llic gray matter. Assuming PROPERTIES OF THE NERVE CELL. 133 that in such cells the distinction between the axon and the den- drites is well made and that as in the other type the dendrites form the receiving and the axon the discharging apparatus, these cells would seem to have a distributive function. The impulse that they receive may be transmitted to one or many neurons. They are sometimes spoken of as intermediate or association cells. Internal Structure of the Nerve Cell. — Within the body of the nerve cell itself the striking features of physiological signifi- cance are, first, the arrangement of the neurofibrils, and, second, the Fig. 63. — Anterior horn cell fourteen days after section of the anterior root (Warring- ton) : To show the change in the nucleus and the Nissl granules, beginning ehromatolysis. presence of a material in the form of granules, rods, or masses which stains readily with the basic anilin dyes, such as methj'lene blue, thionin, or toluidin blue. This latter substance is spoken of as the "chromophile substance," tigroid, or more frequently as Nissl's granules, after the histologist who first studied it success- fully. These masses or granules are found in the dendrites as well as in the cell, but are absent from the axon (see Fig. 62). Little is known of their composition or significance, but their presence or ab- sence is in many cases characteristic of the ph3^siological condition of the cell. After lesions or injuries of the neuron the material may become dissolved and diffused through the cell or may decrease in amount or disappear, and it seems probable, therefore, that it repre- sents a store of nutritive material (Fig. 63). The non-staining material of the cell, according to most recent observers, contains neurofibrils which are continued out into the processes, dendrites as well as axons. These fibrils may be regarded as the conducting structure along which passes the nerve impulse. The arrangement of these fibrils within the cell is not completely known, the results obtained varying with the methods employed. A matter of far- reaching importance on the phj'siological side is the question of 134 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. the existence of an extracellular nervous network. Most recent histologists agree in the behef that there is a dehcate network surrounding the cells and their protoplasmic processes. This pericellular net or Golgi's net is claimed by some to be a ner- vous structure connecting with the neurofibrils inside the cell and forming not only a bond of union between the neurons, but possibly also an important intercellular nervous structure that ma}' play an important role in the functions of the nerve centers. This view is represented schematically in Fig. 64. According to others, this network around and outside the cells is a supporting tissue simply that takes no part in the activity of the nerve units. Fig. 64. — Bethe's schema to indicate the connections of the pericellular network: Rz, A sensory cell in the posterior root Kanglion; the fibrils in the branch that runs to the cord are indicated as connecting directly with the pericellular network of the motor cells. 6z. General Physiology of the Nerve Cell. — Modem physiologists have considered the cell body of the neuron, including the den- drites, as the source of the energy displayed by the nervous system, and it has been assumed that this energy arises from chemical changes in the nerve cell, as the energy liberated by the muscle arises from the chemical changes in its substance. It would follow from this standf)oint that evidences of chemical activity should bo obtained from the cells and that these elements should exhibit the phenomenon of fatigue. Regarding this latter point, it is believed in physiology that the nerve cells do show fatigue. The nerve centers fatigue as the result of continuous activity, as is evident from our personal experience in prolonged intellectual or emo- tional activity and as is implied in the necessity of sleep for re- cuperation and by the rapidity with which functional activity is- PROPERTIES OF THE NERVE CELL. 135 lost on withdrawal of the blood supply. Objectively, also, it has been shown in the ergographic experiments (see p. 49) that the well-knowTi fatigue of the neuromuscular apparatus possibly affects the nerve centers as well as the muscle. Assuming that the nerve cells are the effective agent in the nerve centers, such facts indicate that they are susceptible to fatigue under what may be designated as the normal limits of activity. But we have no very direct proof that this property is possessed universally by the nerve cells nor any indication of the probable differences in this regard shown by nerve cells in different parts of the central nervous system. It seems probable that under normal conditions — that is, under the influence of what we may call minimal stimuli — some portions of the nerve centers remain in more or less constant activity during the day without showing a marked degree of fatigue, just as our muscles remain in a more or less continuous state of tonic con- traction throughout the waking period at least. Doubtless when the stimulation is stronger the fatigue is more marked, because the processes of repair in the nerve centers can not then keep pace with the processes of consumption of material. In general, it may be held that every tissue exhibits a certain balance between the processes of consumption of material associated with activity and the processes of repair. If a proper interval of rest is allowed, the tissue will function without exhibiting fatigue, as is the case with the heart and the respiratory center. If, however, the stimu- lation is too strong or is repeated at too rapid an interval, then the processes of repair do not keep pace with those of consumption, or the products of functional activity are not completely removed, and in either case we have the phenomenon of fatigue, that is to say, a depression of normal irritability. The point of importance is to determine the differences in this respect between the different tissues. Our actual knowledge on this point as regards nerve cells is quite incomplete. Evidence of a probable chemical change in the nerve cells during activity is found also in the readiness with which the gray matter of the nervous system takes on an acid reaction.* In the fresh resting state it is prob- ably alkaline or neutral, but after death it quickly shows an acid reaction, due, it is said, to the production of lactic acid. Its resemblance to the muscle in this respect leads to the inference that in functional activity acid is also produced. Mosso states that in the brain increased mental activity is accompanied by a rise in the temperature of the brain, f His experiments were made upon individuals with an opening in the skull through which a * Langendorff, "Centralbl. f. d. med. Wiss.," 1886. See also Halliburton, "The Croonian Lectures on The Chemical Side of Nervous Activity," 1901. t Mosso, "Die Temperatur des Gehirns," 1894. 136 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. delicate thermometer could be inserted so as to lie in contact with brain. So also the facts briefly mentioned in regard to the Nissl granules give some corroborative evidence that the activity of the nerv'ous system is accompanied by and probably caused b}' a chemical change within the cells, since the excessive activity of the nerve cells seems to be accompanied by some change in these granules, and in abnormal conditions associated with loss of func- tional activity the granules undergo chromatolysis, — that is, they are disintegrated and dissolved. Obvious histological changes which imply, of course, a change in chemical structure, have been observed by a number of investigators.* All seem to agree that activity of the tissue, whether normal or induced by artificial stimulation, may cause visible changes in the appearance of the cell and its Fig. 65. — Spinal ganclion cells from English sparrows, to .show the daily variation in the appearance of the cells due to normal activity: A. Appearance of cells at the end of an active day; B, appearance of cells in the morning after a night's rest. The cytoplasm is filled with clear, lenticular ma.s.ses, which are much more evident in the rested cells thaa in those fatigued. — {Hodye.) nucleus. Activity within normal limits may cause an increase in the size of the cell together with a diminution in the stainable (Nissl) substance, and excessive activity a diminution in size of the cell and the nucleus, the formation of vacuoles in the cell body, and a markcid effect upon the stainable material. Ilodgc has shown that in Ijirds, for instance, the spinal ganglion cells of a swallow killed at nightfall after a day of activity exhibit a marked lo.ss of su})stance as com])ared with similar cells from an animal kill(!d in the early irujruing fFig. (if)). Dollcyf also .states that in * S(;c especially HoiIk'', ".Journui of Morpholoi^y," 7, Df), 1S92, and 9, 1, 1894. t Dollcy, "American .Journal of J'hy.siolof^y," 2.'j, 1.51, 1909. PROPERTIES OF THE NERVE CELL. 137 the dog the cerebellar cells exhibit a definite series of changes in the chromatic substance, both that within the nucleus and that within the cytoplasm (Nissl's granules) following upon prolonged muscular activity or after such conditions as shock or anemia. If these conditions are extreme, the chromatin material may be entirely removed from the cells, and this he interprets as an indica- tion of a functionally exhausted cell. It must be remembered, however, that our knowledge of the nature of the chemical changes that occur in the cell during activity is very meager. Presumably carbon dioxid and lactic acid are formed as in muscle, and we know that oxygen is consumed. Enough is known perhaps to justify the general view that the energy exhibited by the nervous system is derived, in the long run, from a metabolism of material in the nerve cells, a metabolism which consists essentially in the sphtting and oxidation of the complex substances in the protoplasm of the cell. Summation of the Effects of Stimuli. — In a muscle a series of stimuli will cause a greater amount of shortening than can be obtauied from a single stimulus of the same strength. In this case the effects of the stimuli are summated, one contraction taking place on top of another, or to put it in another way, the muscle while in a condition of contraction from one stimulus is made to contract still more by the following stimulus. In the nerve fiber such a phenomenon has not been demonstrated. In the nerve cell it is usually taught that the power of summation is a charac- teristic property. It is pointed out that, while a single stimulus applied to a sensory nerve may be ineffective in producing a reflex response from the central nervous system, a series of such stimuli will call forth a reaction. In this case it is assumed that the effects of the succeeding stimuli are summated within the nerve cells through which the reflex takes place, and, generally speaking, it is assumed in physiology that the nerve centers are adapted by their power of summation to respond to a series of stimuli or to continuous stimulation. The best examples of this kind of action are obtained perhaps from sensory nerves, in which case we judge of the intensity of the cell activity by the concomitant sensation, or by a reflex response. Response of the Nerve Cell to Varying Rates of Stimula- tion. — The various parts of the neuromuscular apparatus — namely, the nerve cell, the nerve fiber, and the muscle fiber — have different degrees of responsiveness to repeated stimuli, and this responsiveness varies, moreover, for the different kinds of mus- cles and of nerve fibers, and, probably for the different kinds of nerve cells. The motor cells of the brain and cord discharge their impulses under normal stimulation at a certain rhythm 138 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. which was formerly supposed to average about 10 per second, but is now estimated as varying between certain wide limits, perhaps from 40 to 100 per second (p. 46). For any particular group of these motor cells the e\ddence indicates that it has a prac- tically constant rate whatever may be the intensity of the stimulus — and, indeed, when artificial stimulation is used and the rate is varied, the evidence that we have so far appears to show that the nerve cells do not discharge in a one to one correspondence with the rate of stimulation, as is the case, within limits, for muscle and nerve fibers. On the contrary, under such circum- stances the discharge from the nerve cells takes place in a rhythm characteristic of the cells and independent of that of the stimula- tion.* From this point of view we must look upon these nerve cells as possessing fundamentally a rhythmic activity, as in the case of the heart. There is no doubt, however, that some at least of the motor cells of the spinal cord can be stimulated by a single stimulus so as to respond with a single cUscharge instead of a rhyth- mical series of discharges. As will be described below, the knee- kick is a simple muscular contraction, not a tetanus, which is aroused b}^ reflex stimulation of the corresponding motor cells in the spinal cord. The Refractory Period of the Nerve Cell. — It will be recalled that the nerve fiber exhibits what is called a refractory period for a brief interval (0.002 to 0.006 sec.) after it is stimulated. During this period it is not irritable to a second stimulus. The same phenomenon is exhibited to a marked degree by the heart muscle and like^\^se by many nerve cells. In the motor nerve cell which shows the property of chscharging a series of impulses with rhythmic regularity it may be supposed that the refractory period is marked, and indeed is connected probably with the rhythmic character of the cell's activity. But in this as in other properties it is certain that there are great differences in the many varieties of nerve cells found in the central nervous system. While those that act rhyth- mically have probably a relatively long refractory period, others may exhibit a period of unirritability but little longer than that shown by the nerve fibers. In the case of the reflex motor centers in the lumbar spinal cord of the frog it is stated (Langendorff) that a second stimulus falling at an int(!rval of 0.04 sec. after the first is effective. The refractory period of these cells is less, therefore, than this interval. * Horsley and Schafer, "Journal of Physiology," 7, 90, 1886. CHAPTER VII. REFLEX ACTIONS. Definition and Historical. — By a reflex action we mean the involuntary production of activity in some peripheral tissue through the efferent nerve fibers connected with it in consequence of a stimulation of afferent nerve fibers. The conversion of the sensory or afferent impulse into a motor or efferent impulse is effected in the nerve centers, and may be totally unconscious as well as invol- untary, — ^for instance, the emptying of the gall-bladder during digestion, or it may be accompanied by consciousness of the act, as, for example, in the winking reflex when the eye is touched. The appUcation of the term reflex to such acts seems to have been made first by Descartes* (1649), on the analogy of the reflection of light, the sensory effect in these cases being reflected back, so to speak, as a motor effect. The attention of the early physiologists was directed to these involuntary movements and many instances were collected, both in man and the lower animals. Their invol- untary character was emphasized by the discover}^ that similar movements are given by decapitated animals, — frogs, eels, etc. Some of the earlier physiologists tliouglit that the reflex might occur in the anastomoses of the nerve tninlcs, but a convincing proof that the central nervous system is the place of reflection or turning-point was given by Whji^t (1751) . He showed that in a de- capitated frog the reflex movements are abolished if the spinal cord is destroyed. Modern interest in the subject was excited by the numerous works of Marshall Hall (1832-57), who contributed a number of new facts with regard to such acts, and formulated a view, not now accepted, that these reflexes are mediated b}' a spe- cial set of fibers — the excitomotor fibers. In describing reflexes the older physiologists had in mind only reflex movements, but at the present time we recognize that the reflex act may affect not only the muscles, — voluntary, involuntary^, and cardiac, — but also the glands. We have to deal with reflex secretions as well as reflex movements. The Reflex Arc. — It is implied in the definition of a reflex that both sensory and motor paths are concerned in the act. Ac- * See Eckhard, " Geschichte der Entwickelung der Lehre von den Reflex- erscheinungen," "Beitriige zur Anatomie u. Physiologie," Giessen, 1881, voL ix 139 140 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. cording to the neuron theory, therefore, the simplest reflex arc must consist of two neurons: the sensory neuron, whose cell body lies in the sensory ganglia of the posterior roots or of the cranial nerves, and a motor neuron, whose nerve cell lies in the anterior horn of gray matter of the cord or in the motor nucleus of a cranial nerve. The reflex arc for the spinal cord is represented in Fig. 66. The arc may, however, be more complex. The sensory fibers entering through the posterior roots may pass upward through the entire length of the cord to end in the medulla, and on the way give off a number of collaterals as is represented in Fig. 67, or they may make connections with intermediate cells which, in turn, are con- nected with one or more motor neurons (Fig. 68). According Fig. 66. — Schema to show the connection between the neuron of the posterior root and the neuron of the anterior root, — the reflex arc. to these schemata, one sensory fiber may establish reflex connections with a number of different motor fibers, or, a fact which must be borne in mind in studying some of the well-known reflex activities of the cord and medulla especially, a sensory fiber carrying an impulse which eventually reaches the cortex of the cerebrum and gives rise to a conscious sensation may, by moans of its collaterals, connect with motor nuclei in the cord or medulla and thus at the same time give origin to involuntary and even unconscious re- flexes. Painful stimulation of the skin, for example, may give us a conscious sensation of pain and at the same time reflexly stimulate the vasomotor center and cause a constriction of the small arteries. The fact that in this case two distinct events occur does not necessitate the assumption that the impulses from the skin are carried to the cord by two different varieties of fibers. KEFLEX ACTIONS. 141 It may well be that one variety of sensor}^ neuron, the so-called pain fibers, effects both results, because of the opportunities in the cord for connections with different groups of nerve cells. The Reflex Frog. — The motor reflexes from the spinal cord can be studied most successfully upon a frog in which the brain has been destroyed or whose head has been cut off. After such an operation the animal may for a time suffer from shock, but a vigorous animal wall usually recover and after some hours will Fig. 67. — KoUiker's schema to show the direct reflex arc. It shows the pos- terior root fiber (black) entering the cord, dividing in Y, and connecting -ndth motor cells (red) by means of collater- als. Fig. 68. — Kolliker's schema to show the reflex arc with intercal- ated tract cells. Posterior root fiber, black; intercalated tract cell, blue; motor cells, red. exhibit reflex movements that are most interesting. The funda- mental characteristics of reflex movements in their relations to the place, intensity, and quality of the stimulus can be studied with more ease upon an animal whose cord is thus severed from the brain than upon a normal animal. In the latter case the connec- tions in the nervous system are more complex and the reactions are therefore less simple and less easily kept constant. Spinal Reflex Movements. — The reflex movements obtained from the spinal cord or from other parts of the central nen^ous system may be divided into three groups by characteristics that are physio- logically significant. These classes are: (1) Simple reflexes, or those in which a single muscle is affected. The best example of 142 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. this group is perhaps the winking reflex, in which only the orbic- ularis palpebrarum is concerned. (2) Co-ordinated reflexes, in which a number of muscles react with their contractions so grad- uated as to time and extent as to produce an orderly and useful movement. (3) Convulsive reflexes, such as are seen in spasms, in which a number of muscles — perhaps all the muscles — are con- tracted convulsively, without co-ordination and with the pro- duction of disorderly and useless movements. Of these groups, the co-ordinated reflexes are by far the most interesting. They can be obtained to perfection from the reflex frog. In such an animal no spontaneous movements occur if the sensory surfaces are entirely protected from stimulation. A sudden stimulus, however, of sufficient strength applied to any part of the skin will give a definite and practically invariable response in a movement which has the appearance of an intentional effort to escape from or remove the stimulus. If the toe is pinched the foot is withdrawn — in a gentle manner if the stimulus is light, more rapidly and violently, but still in a co-ordinated fashion, if the stimulus is strong. If the animal is suspended and various spots on its skin are stimulated by the application of bits of paper moistened with dilute acetic acid the animal will make a neat and skillful movement of the corresponding leg to remove the stimulating body. The reactions may be varied in a number of ways, and in all cases the striking features of the reflex response are, first, the seemingly purposeful character of the movement, and, second, the almost mechanical exactness with which a definite stimulus will give a definite response. This definite relationship holds only for sensory stimulation of the external integument, the skin and its organs. It is obvious, in fact, that a muscular response can be effective only for stimuli originating from the external surface. Stimuli from the interior of the body exert their reactions, for the most part, upon the plain musculature and the glands. The convulsive reflexes may be produced by two different means : (1) By very intense sensory stimulation. The reflex response in this case overflows, as it were, into all the motor paths. A variation of this method is seen in the well-known convulsive reaction that follows tickling. In tiiis case the stimulus, although not intense from an objective standpoint, is obviously violent from the standpoint of its effectiveness in sending into the central nervous system a series of maximal sensory impulses. (2) P>y heightening the irritability of the (central nervous system. Upon the reflex frog this effect is obtained most readily by the use of strychnin. A little strychnin injected under the skin is soon absorbed and its effect is shown at first by a greater sensitiveness to cutaneous stimulation, the sliglit(!st touch to the foot causing its withdrawal. Soon, howc.vor, the nisponse, instead of being orderly and adapted to a useful cud, becomes REFLEX ACTIONS. 143 convulsive. A mere touch of the skin or a current of air will throw every muscle into contraction, and the extensors being stronger than the flexors the animal's body becomes rigid in extension at every stimulation. The explanation usually given for this result is that the strychnin, acting upon some part of the nerve cells, increases greatly their irritability, so that when a stimulus is sent into the central nervous system along any sensory path from the skin it apparently radiates throughout the cord and acts upon all the motor cells. This latter supposition leads to the interesting con- clusion that all the various motor neurons of the cord must be in physiological connection, either direct or indirect, with all the neurons supplying the cutaneous surface. The further fact that under normal conditions the effect of a given sensory stimulus is manifested only on a limited and practically constant number of the motor neurons seems to imply, therefore, that normally the paths to these neurons are more direct and the resistance, if we may use a somewhat figurative term, is less than that offered by other possible paths. Muscular spasms are observed under a number of pathological conditions, — for instance, in hydrophobia. We are at liberty to assume in such cases that the toxins produced by the disease affect the ii'ritability of the cells in much the same way as the strychnin. Theory of Co-ordinated Reflexes. — The purposeful character of the co-ordinated reflexes in the frog gives the impression to the observer of a conscious choice of movements on the part of the brainless animal. Most physiologists, however, are content to see in these reactions only an expression of the automatic activity of a mechanism. It is assumed that the sensor}^ impulses from any part of the skin find, on reaching the cord, that the paths to a certain group of motor neurons are more direct and offer less resistance than any others. It is along these paths that the reflex ^^^ll take place, and we may further assume that these paths of least resistance, as they have been called, are in part preformed and in part are laid doMTi by the repeated experiences of the indi- vidual. That is, in each animal a definite structure may be sup- posed to exist in the cord; each sensory neuron is connected A^ith a group of motor neurons, to some of them more directly than to others, and we may imagine, therefore, a system of reflex apparatuses or mechanisms which when properly stimulated will react always in the same way. And, indeed, in spite of the adapted character of the reflexes under consideration their automaton-like regularity is an indication that their production is due to a fixed mechanical arrangement. Whether or not the reactions of the nervous system in such cases are accompanied by any degree of consciousness can not be proved or disproved, but the assumption of such an accom- paniment does not seem necessary to explain the reaction. 144 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. Spinal Reflexes in the Mammals. — Experiments upon the lower mammals show that co-ordinated reflex movements may be ob- tained from the cord after severance of its connections with the brain. Sherrington* has described a simple operation by which the head may be removed from an anesthetized cat and the animal be kept alive for a number of hours. Stimulation of the skin in such an animal calls forth numerous definite reflexes, such as flexion or extension of the legs, the scratching movements of the hind legs, stretching movements, etc. Or the spinal cord may be severed in the thoracic region, below the origin of the phrenic nerves, and the animal, with care, can be kept alive for months or years. In such an animal reflex movements of the hind legs or tail may be ob- tained readily from slight sensory stimulation of the skin. The knee-jerk and similar so-called deejD reflexes are also retained. But it is evident that these movements are not so complete nor so distinctly adapted to a useful end as in the frog. The muscles of the body supplied by the isolated part of the cord retain, however, a normal irritability and exhibit no wasting. In man, on the contrary, it is stated that after complete section of the cord the deep reflexes, such as the knee-jerk, as well as the skin reflexes, are very quickly lost. The muscles undergo wasting and soon lose their irritability. t The monkeys exhibit in this respect a condition that is somewhat intermediate between that of the dog and man. It seems evident from these facts that in the lower animals, like the frog, a much greater degree of independent activity is exhibited by the cord than in the more highly developed animals. According to the degree of development, the control of the muscles is assumed more and more by the higher ]3ortions of the nervous system, and the spinal cord becomes less important as a series of reflex centers, its functions being more dependent upon its connections with the higher centers. Dependence of Co-ordinated Reflexes upon the Excitation of the Normal Sensory Endings. — It is an interesting fact that when a nerve trunk is stimulated directly in a reflex frog — the sciatic nerve, for instance — the reflex movements are disorderly and quite unlike those obtained by stimulating the skin. It is said that if the skin bo loosened and the nerve twigs arising from it ))e stimulated, an operation that is quite possible in the frog, the re- sponse is again a disorderly reflex, whereas the same fibers stimu- lated through the skin give an orderly, co-ordinated movement. The difl"erenco in response in these cases is proba])]y not due to any peculiarity in the nature of the sensory imj)ulses originating in the nerve endings of the skin, but more likely to a difference in their strength anrl arrangement. When one stimulates a sensory nerve *8horririKtf)n, ".lournal of F'hysioIoKy," 38, 375, 1909. t See CollicT, " Jirain," 1904, p. 'SH. REFLEX ACTIONS. 145 trunk directly, — the ulnar nerve at the elbow in ourselves, for in- stance, — the resulting sensations are markedly different from those obtained by stimulating the skin areas supplied by the same nerve; we have little or no sensations of touch or temperature, only pain and a pecuUar tingling in the fingers. In such an experiment the stimulus applied to the trunk affects more or less equally all the contained fibers, whereas in stimulation of the skin itself the effect upon the cutaneous fibers of pressure, temperature, or pain pre- dominates and presumably it is these fibers that normally are con- nected in an efficient way with the reflex machinery in the nerve centers. Reflex Time. — Since nerve centers are involved in a reflex movement, a determination of the total time between the appli- cation of the stimulus and the beginning of the response gives a means of ascertaining the time needed for the processes within the nerve cells. Helmholtz, who first made experiments of this kind, stated that the time required within the nerve centers might be as much as twelve times as great as that estimated for the conduction along the motor and sensory nerves involved in the reflex. Most observers state that the time within the center varies with the strength of the stimulus, being less, the stronger the stimulus. It varies also with the condition of the nerve centers, being lengthened by fatigue and other conditions that depress the irritability of the nerve cells. By reflex time or reduced reflex time we may designate the time required for the processes in the center, — that is, the total time less that required for transmission of the impulse along the motor and sensory fibers and the latent period of the muscle con- traction. For the frog this is estimated as varying between 0.008 and 0.015 sec. In man the reflex time usually quoted is that given by Exner for the winking of the eye. He stimulated one lid electrically and recorded the reflex movement of the lid of the other eye. The total time for the reflex was, on an average, from 0.0578 sec. to 0.0662 sec. He estimated that the time for transmission of the impulse along the sensory and motor paths, together with the latent period of the muscle, amounted to 0.0107 sec. So that the true reflex time from his determinations varied between 0.0471 and 0.0555 sec. Mayhew,* using a more elaborate method, obtained for the total time a mean figure equal to 0.0420 sec. If Exner's correction is applied then the true reflex time according to this de- termination is equal to 0.0313 sec. In a series of experiments made upon frogs, in which the efferent response to stimulation of the afferent fibers of the sciatic nerve was measured by the electrical variation in the muscle involved, Buchanan finds that the delay in the cord, when the reflex was on the same side, was * Mayhew, "Journal of Exp. Medicine," 2, 35, 1897. 10 146 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. equal to 0.01 to 0.02 sec. If the reflex was on the crossed side about double this time was consumed in the cord. This delay of the velocity of transmission of an impulse in the nerve centers is a factor which must vary somewhat in different parts of the nervous system. It has been shown that, in certain cases at least, when strong stimuli are used the latent period of a reflex is not greater than would be accounted for by transmission through the nerve fibers and by the latency of the muscular contraction. Thus Frangois Frank, in an experiment in which the gastrocnemius muscle of one side was made to contract reflexly by stimulation of the afferent root of a lumbar nerve on the other side, records a latent period of only 0.017 sec. Evidently in such a case there was no perceptible delay in passing through the nerve centers of the lumbar cord. Inhibition of Reflexes. — One of the most fundamental facts regarding spinal reflexes is the demonstration that they can be depressed or suppressed entirely — that is, inhibited — by other im- pulses reaching the same part of the spinal cord. The most sig- nificant experiment in this connection is that made by Setschenow.* If in a frog the entire brain or the cerebral hemispheres are re- moved, then stimulation of the exposed cut surface — for instance, by crystals of sodium chlorid — will depress greatly or perhaps inhiVjit entirely the usual spinal reflexes that may be obtained by cutaneous stimulation. On removal of the stimulating substance from the cut surface by washing with a stream of physiological saline (solution of sodium chlorid, 0.7 per cent.) the reflex activities of the cord are again exhibited in a normal way. This experiment accords with many facts which indicate that the brain may inhibit the activities of the spinal centers. In the reflex from tickling, for instance, we know that by a voluntary act we can repress the muscular movements up to a certain point; so also the limited control of the action of the centers of respiration and micturition is a phenomenon of the same character. To explain such acts we may assume the existence of a definite set of inhibitory fibers, arising in parts of the brain and distributed to the spinal cord, whose function is that of controlling the activities of the spinal centers. In view of the fact, however, that there is no independent proof of the existence of a separate set of inhibitory fibers within the central nervous system — that is, a set of fibers whose specific energy is that of inhibition — it is preferable to speak simply of the inhibitory infiuence of the brain upon the cord, leaving unde- cided the (question as to whether this influence is exerted through a special set of fibers, or is brought about by some variation in * Sefsrhenow, " PhysioloKisclie Studieii iiher d. Ilemmungs-Mechanismen f. (1. Reflexthiitigkeit im Geliirn d. Frosches," Berlin, 1803. REFLEX ACTIONS. 147 the time relations, intensity, or quality of the nerve impulses. Regarding the fact, however, there can be no question, and it constitutes a most important factor in the interaction of the dif- ferent parts of the nervous system. It is probable that this factor explains why a normal frog gives reflexes that are so much less constant and less predictable than one with its brain removed. A similar inhibition of spinal reflexes may be obtained by simul- taneous stimulation of two different parts of the skin. The usual reflex from pinching the toe of one leg may be inhibited in part or completely by simultaneous stimulation of the other leg or by direct electrical stimulation of an exposed nerve trunk. A similar interference is illustrated, perhaps, in the well-known device of inhibiting an act of sneezing by a strong sensory stimulation from some part of the skin — for instance, by pressing upon the upper lip. The importance of the process of inhibition in the normal movements of the body is illustrated strikingly by the phenomenon known as reciprocal innervation, which has been investigated chiefly by Sherrington.* This observer has found that when a flexor muscle is stimulated reflexly there is at the same time a relaxation or loss of tone in its antagonistic extensor, which is explained as being due to an inhibition of the motor cells of the extensor in the cord. Reflex stimulation of the extensor is accompanied similarly by an inhibition of the tone of the antagonistic flexor. This phenomenon has been demonstrated not only for reflex stimulation of the cord but also for voluntary movements (Athanasieu) and for electrical stimulation of the cortical centers. The motor centers of the muscles surrounding the joints are apparently so connected in pairs that when one is excited the center of the corresponding antagonist is inhibited. This reciprocating mechanism dis- appears under conditions, such as strychnine-poisoning, in which, according to the usual belief, the irritability of the centers is greatly increased. A relationship quite comparable to the reciprocal innervation, although working in only one direction, is exhibited by the peripheral nerve plexuses in the intestinal canal in the so-called law of the intestines (see p. 714). A brief statement of the more or less unsatisfactory theories of inhibition is given in connection with the inhibitory action of the vagus nerve on the heart beat (see p. 579). It should be added, however, in this connection, that stimulation of the cord, and probably of other parts of the nervous system, from two different sources may result not only in an inhibition of the reflex normally occurring from one of the stimuli, but under some circumstances ♦Sherrington, "The Integrative Action of the Nervous System," 1906, p. 84. 148 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. may give an augmentation or reinforcement of the reflex. A striking example of this augmenting effect is given below in the paragraph upon the knee-kick. Influence of the Condition of the Cord on its Reflex Ac- tivities. — The time and extent of the reflex responses may be altered greatly by various influences, particularly by the action of drugs. The effect in such cases is usually upon the nerve centers, — that is, upon the cells themselves or upon the synapses, that is to say, the connections between the terminal arborization and the dendrites — the process of conduction within the sensory and motor fibers being less easily affected. A convenient method of studying such influences is that employed by Tiirck. In this method the reflex frog is suspended, and the tip of the longest toe is immersed to a definite point in a solution of sul- phuric acid of a strength of 0.1 to 0.2 per cent. If the time between the immersion and the reflex withdrawal of the foot is noted by a metronome, or by a record upon a kymograph, it will be found to be quite constant, provided the conditions are kept uniform. If the average time for this reflex is obtained from a series of observations it is possible to inject various substances — such as strychnin, chloroform, potassium bromid, quinin, etc. — under the skin, and after absorption has taken place to determine the effect by a new series of observations. So far as drugs are concerned the results of such experiments belong rather to pharma- cology than to physiology. The method in some cases brings out an interesting difference in the effects of various kinds of stimulation. Strychnin, for instance, as was stated above, increases greatly the delicacy of the reaction to pressure stimulation. At one stage in its action before the convulsive responses are obtained the threshold stimulus is greatly lowered, — mere contact with the toes causes a rapid retraction of the leg; whereas in the normal reflex frog a relatively large pressure is necessary to obtain a similar response. At this stage in the action of the strychnin the effect of the acid stimulus, on the contrary, may be markedly weakened so far as the time clement is concerned. If the action of the strychnin is not too rapid, it is usually possilile to find a point at which the time for the reflex is diminished, but this effect quickly disappears and the period between stimulus and response becomes markedly lengthened at a time when the slightest mechanical stimulation gives a rapid reflex mov(!ment. Tliis paradoxical result may depend pos- sibly upon the variety of nerve fib(!r stimulated by the two kinds of stimuli or may be connected with the fact that the acid stimuli may bring about inhibitory as well as excitatory processes in thf; conl. Reflexes from Other Parts of the Nervous System. — Nu- merous typical reflexes are known to occur in tlu; brain. The REFLEX ACTIONS. 149 reflex effects upon the important centers in the medulla, such as the vasomotor center, the respiratory center, and the cardio- inhibitory center, the winking of the eye, sneezing, the light reflex upon the sphincter muscle of the iris, and many other similar cases might be enumerated. All of these reactions will be described and discussed in their proper places. The conscious reactions of the brain are not included among the reflexes by virtue of the defi- nition which lays stress upon the involuntary characteristic of the reflex response, but it should be remembered that, so far as the nervous mechanism is concerned, these conscious reactions do not differ from the true reflexes. When we voluntarily move a Hmb the movement is guided and controlled by sensory impulses from the muscles put into action. The fibers of muscle sense from these muscles convey sensory impulses through a chain of neurons to the cortex of the brain and there the impulses doubtless affect and set into action the motor neurons through which the movement is effected. So far as we know, the discharges from the efferent neurons of the brain do not arise independently within these cells, they are conditioned or originated by stimuli from other neurons; so that the activities of the brain are carried on by a mechanism of one neuron acting on another, just as in the case of the reflex arc. The added feature of a psychical factor, a reaction in consciousness, enables us to draw a fine of distinction between these activities and those of so-called pure reflexes ; but the distinction is perhaps one of convenience only, for, although the extremes may be far enough apart to suit the definition, many intermediate instances may be found which are difficult to classify. All skilled movements, for in- stance, such as walking, singing, dancing, bicycle riding, and the like, — although in the beginning obviously effected by voluntary co-ordination, nevertheless in the end, in proportion to the skill ob- tained, become more or less entirely reflex, — that is, involuntary. In learning such movements one must, as the saying goes, establish his reflexes, and the result can hardly be understood otherwise than by supposing that the continual adjustment of certain sensory im- pulses to certain co-ordinated movements results in the formation of a more or less complex reflex arc, a set of paths of least resistance. Reflexes through Peripheral Ganglia — Axon Reflexes. — • Many attempts have been made by physiologists to ascertain whether or not reflexes can occur through the peripheral nerve ganglia, lying outside the central nervous system. With regard to the posterior root ganglia, it has usually been supposed that they cannot exhibit reflexes. When the posterior root con- necting such a ganglion to the cord is severed, then, according to our usual conception, the cells in the ganglia are cut off from all connections with the peripheral tissues by efferent 150 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. paths. This usual view may not, however, be correct. On the physiological side we have the fact (see p. 81) that stimu- lation of certain of the posterior root ganglia under such cir- cumstances does give peripheral effects ^ on the blood-vessels, causing a vascular Y dilatation in a certain region. On the histological side Cajal* and others have shown that some of these cells are provided with a pericellular nerve network, which is an afferent path so far as the cell is con- cerned, while the axon of the cell con- stitutes an efferent path. Whether these cells form a special group of efferent cells lying within the sensory ganglion, or whether they are sensory cells discharging into the cord and stimulated reflexly through the nerve network as well as through the peripheral process of the axon, cannot be said. The subject is one full of interest to physiology. In the ganglia of the sympathetic nerve and its appen- dages and in the similar ganglia contained in many of the organs the nerve cells have dendritic processes, and, so far as their histology is concerned, it would seem possi- ble that in any ganglion of this type there might be sensory and motor neurons so connected as to make the ganglion an independent reflex center. Numerous experiments have been made to determine experimentally whether reflexes can be o])tained through such ganglia. Perhaps the most successful of these experiments have been made upon .the inferior mesenteric ganglion. This ganglion may be isolated from all connections with the central nervous system and left attached to the bladder through the two hypogastric nerves (see Fig. 287). If now one of these nerves is cut and the central stump is stimulated, a contraction of the bladder follows. Obviously in this case the impulse has traveled to the ganglion anrl down the other hy- pogastric nerve; the reactif)n has every appearance of ])eing a true reflex. Nevertheless, Langley and Anderson, f who have studied the matter with especial care, are convinced that in this * Cajal, "ErKobnissn der Anat . u. Entwirrkolungsgeschichte," vol. xvi., 1900; Dogifl, "Ilau (Jcr Spiriti!ti;:in>j;licri, etc.," 190S. f Langley and Anderson^ "Journal of Pliy.siology," 16, 410, 1894. Fig. 69. — Schema to show idea of an a.xon re- flex: The preganglionic fiber, a, sends branches to two postgangUonic fibers, b, c. If .stimulated at X the imijulse pa.sses backward in a direction the reverse of normal and falling into 6 and c gives a pseudoreflex efifect. REFLEX ACTIONS. 151 and similar cases we have to do with what they call pseudo- reflexes or axon reflexes. The idea underlying this term may be explained in this way: Every sympathetic ganglion is connected with the central nervous system, brain and cord, by efferent spinal fibers, preganglionic fibers, which terminate by arborization around the dendrites of the sympathetic cells. The efferent fibers arising from the latter may be designated as post- ganglionic fibers. These authors give reasons to believe that any one preganglionic fiber, a, Fig. 69, may connect by collaterals with several sympathetic cells. If such a fiber were stimulated at x, then the impulse passing back along the axon in a direction the reverse of normal would stimulate cells h and c, giving effects that are apparently reflex, but which differ from true reflexes in that the stimulating axon belongs to a motor neuron. Under normal circumstances it is not probable that an effect of this kind can be produced. The Tonic Activity of the Spinal Cord. — In addition to the definite reflex activities of the cord, each traceable to a distinct sensory stimulus, there is evidence to show that many of its motor neurons are in that state of more or less continuous activity which we designate as tonic activity or tonus. There is abundant reason for this belief in regard to many of the special centers of the cord and brain, such as the vasomotor center, the center for the sphinc- ter muscle of the iris, the centers for the sphincter muscles of the bladder, the anus, etc. But the evidence includes the motor neurons to the voluntary as well as the involuntary musculature. In a decapitated frog the muscles take a definite position, and Brondgeest showed that if such an animal is suspended, after cut- ting the sciatic plexus in one leg, the leg on the uninjured side takes a more flexed position. The explanation offered for this result is that the muscles on the sound side are being innervated by the motor neurons of the cord. Inasmuch as a result of this kind cannot be obtained from a frog whose skin has been removed, or in one in which the posterior roots have been severed it seems evident that this tonic discharge from the motor neurons is due to a constant inflow of impulses along the sensory paths. The muscle tonus, in other words, is really a reflex tonus, which differs from ordinary reflex movements only in the absence of a sudden, visible contraction and in the more or less continuous character of the innervation. In the section on animal heat the importance of this constant innervation of the muscles as a source of heat is further emphasized. The idea of a more or less continuous but varying activity of the centers in the brain and cord in consequence of the continuous inflow of impulses along the sensory paths fits in very well with many facts observed in the peripheral organs, — 152 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. facts that will be referred to from time to time as the physiology of these organs is considered. Effects of Removal of the Spinal Cord. — Numerous investi- gators have sectioned the cord partly or completely at various levels. The general results of these experiments as regards loss of sensation or voluntary movement are described in the next section treating of the cord as a path of conduction to and from the brain. But attention may be called here to some of the gen- eral results obtained by Goltz* in some remarkable experiments in which the entire cord was removed with the exception of the cervical region and a small portion of the upper thoracic. In making this experiment it was necessary to perform the operation in several steps. That is, the cord was first sectioned in the upper thoracic region and then in successive operations the lower tho- racic, lumbar, and sacral regions were removed completely. Very great care was necessary in the treatment of the animals after these operations, but some survived and lived for long periods, the digestive, circulatory, and excretory organs performing their functions in a normal manner. The muscles of the hind limbs and trunk, however, underwent complete atrophy, owing to the destruction of their motor nerves. The blood-vessels also were paralyzed after the first operations, but gradually their muscu- lature again recovered tone, showing that, although under normal conditions the tonic contraction of the vessels is under the in- fluence of nerves arising from the cord, this tone may be re-estab- lished in time after the severance of all spinal connections. Some of the specific results of these experiments, bearing upon the re- flexes of defecation, micturition, and parturition, will be described later. Attention may be called here to the general results illustrating the general functions of the cord. In the first place, there was, of course, a total paralysis of volun- tary movement in the muscles innervated normally through the parts of the cord removed, and a complete loss of sensation in the same regions, particularly of cutaneous and muscular sensibility. In the second place, the visceral organs, including the blood-vessels, were shown to be much more independent of the direct control of the central nervous system. While these organs in the experiments under consideration were still in connection with the sympathetic ganglia and in part with the brain through the vagi, still their connections with the central nervous system, particularly as regards their sensory paths and the innervation of the blood-vessels, were in largest part destroyed. The immediate effect of this destruction would have been the death of the animal if the care * (johz and Ewald, "rfliiger'H Arcliiv fiir die gesammte Physiologic," 63, 362, 1896. REFLEX ACTIONS. 153 of the observer had not replaced, in the beginning, the normaJ control exercised by the nervous system through the spinal nerves; but later this careful nursing was not required. While these organs, therefore, are capable of a certain amount of independent activity and co-ordination, they are normally controlled through the various reflex acti\ities of the brain and cord. In the third place, it is noteworthy that the adaptabiUty of the cordless portion of the animal was distinctly less than normal. Its power of preserving a constant body temperature was more limited than in the normal animal, and the susceptibility to inflammatory disturbances in the visceral organs was greatly increased. It seems evident, from these facts, that, although the animal was living, its power of adaptation to marked changes in the external or internal environment was greatly lessened, and this fact illustrates well the great general importance of the spinal cord and brain as reflex centers controlling the nutri- tion and co-ordinated activities of the body tissues and organs. This control is necessary under normal conditions for the success- ful combination of the activities of the various organs. A large part of this control is doubtless dependent upon the regulation of the blood supply to the various organs. The mechanism by which this is effected and the parts played by the cord and the brain (medulla oblongata), respectively, will be described in the section on Circulation. Knee-jerk. — Knee-jerk or knee-kick is the name commonly given to the jerk of the foot when a light blow is struck upon the patellar ligament just below the knee. The jerk of the foot is due to a contraction of the quadriceps femoris muscle. Accord- ing to Sherrington, the parts of this muscular mass chiefly concerned are the m. vastus medialis and m, vastus intermedins. In order to obtain the muscular response it is usually neces- sary to put the quadriceps under some tension by flexion of the leg. This end is achieved most readily by crossing the knees or by allowing the leg to hang freely when sitting on the edge of a bench or table. Under such circumstances the jerk is obtained in the great majority of normal persons, and this fact has made it an important diagnostic sign in many diseases of the spinal cord. The importance of the reaction for such purposes was first brought out by the work of Erb and Westphal * in 1875. Reinforcement of the Knee-jerk.— It was first shown by Jendrassik (1883) that the extent of the jerk may be greatly aug- mented if, at the time the blow is struck upon the tendon, a strong voluntary movement is made by the individual, such as squeezing the hands together tightly or clenching the j aws. This phenomenon * Erb and Westphal, " Archiv f. Psychiatric," 1875, vol. v. 154 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. was studied carefully in this country by Mitchell and Lewis,* who ascertained that a similar augmentation may be produced by giving the individual a simultaneous sensory stimulation. They desig- nated the phenomenon as a reinforcement, and this name is gen- erally employed by English writers, although occasionally the term "Bahnung," introduced by Exner to describe a similar phenom- enon, is also used. It is found that by a reinforcement the knee- jerk may be demonstrated in some individuals in whom the ordi- nary blow upon the tendon fails to elicit a response. Bowditch and Warren t studied the phenomenon of reinforcement and brought out a fact of very great interest. They studied especially the time interval between the blow upon the tendon and the reinforcing act and found that if the latter preceded the blow by too great an inter- val then, instead of an augmentation of the jerk, there was a dimi- nution which they designated as negative reinforcement or inhi- bition. This inhibiting effect began to appear when the reinforcing act (hand-squeeze) preceded the blow by an interval of from 0.22 to 0,6 sec, and the maximum inhibiting effect was obtained at an 40- 30- Fig. 70. — ShowiriK in millimeters tiie amount by which the " reinforced " knee-kick varied from the normal, the level of which is represented by the horizontal line at 0, "nor- mal." The time intervals olapsiiiji; betw(u;ii the clenching of the hands (which constituted the reinforcement) and tlie taj) on the tendon are marked below. The reinforcement is KreateHt when the two eventH are nearly simultaneous. At an interval of 0.4 .sec. it amounts to nothing; during the next (J. 6 .sec. the height of the kick is actually diminished, while after an interval of 1 sec. the negative reinforcement tends to disapi)ear; and when 1.7 .sec. is allowed to elapse the height of the kick ceases to be affected by the clenching of the hand-t. — {Bowditch and Warren.) interval of from 0.6 to 0.0 sec. Beyond this point the effect became less noticeable, and at an interval of 1 .7 to 2.5 sec. the reinforcing act had no influence at all upon the jerk. These relations are shown in the accompanying curve (Fig. 70). These autliors con- * Mitclicll ami Lewis, " .VrncTicun .Jcjurna,! of Mod. Sciences," 92, ;}G3, 1886. t Bowditcli and Warren, "Journal of Pliy.siology, " 2, 25, 1890. REFLEX ACTIONS. 155 firmed also the fact that a sensory stimulus, such as a gentle blast of air on the conjunctiva or the knee, may reinforce the jerk. The physiological explanation of the reinforcement, negative and posi- tive, is a matter of inference only, but the view usually held is that it is due to "overflow." That is, many facts, such as strychnin tetanus, indicate that the neuromuscular machinery of the entire central nervous system is more or less directly connected and that functional activity at one part may influence the irritability of the remainder, either in the direction of reinforcement or inhibi- tion. We may conceive, therefore, that when the hands are squeezed, the motor impulses sent down from the cortex of the brain to the upper portion of the cord overflow to some extent, sufficient at least to alter the irritability of the other motor neurons in the cord. Experimental stimulation of the cortex has given similar results, Exner* found that when the motor center for the foot in the cortex of a rabbit was stimulated, the stimulation, even if too weak to be effective itself, caused an increase in the contraction brought about reflexly by a simultaneous stimulation of the skin of the paw, and furthermore if these stimuli were so reduced in strength that each was ineffective, then when applied together a contraction was obtained. In this case an ineffective stimulus from the cortex reaching the spinal cord increased the irritability of the motor centers there so that a simultaneous reflex stimulus from the foot, ineffective in itself, became effective. Is the Elnee-jerk a Reflex? — The most interesting question in this connection is whether the jerk is a true reflex act or is due to a direct mechanical stimulation of the muscle. Opinions have been divided upon this point. Those who beheve that the jerk is p reflex lay emphasis upon the undoubted fact that the integrity of the reflex arc is absolutely essential to the response. The quad- riceps receives its motor and sensory fibers through the femoral nerve, and pathological lesions upon man as well as direct experimental investigation upon monkeys prove that if either the posterior or anterior roots of the third and fourth lumbar spinal nerves are destroyed the knee-jerk disappears entirely. The oppo- nents of the reflex view explain this fact by the theory that in order for the quadriceps to respond it must be in a condition of tonus. This tonus depends upon the reflex arc, the sensory impulses from the muscle serving to keep it in that condition of subdued contraction known as tone. On this view destruc- tion of the reflex arc renders the muscle less irritable, so that it will not respond by a contraction to the sudden mechanical exten- sion or pull caused by the blow on the tendon. The adherents of this view lay emphasis upon two facts: First, the knee-jerk is a * Exner, "Archiv f. die gesammte Physiologie," 27, 412, 1882. 156 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. simple contraction, and not a tetanus, and, generally speaking, the motor centers of the cord discharge a series of impulses when stimulated. In answer to this objection it may be said that while muscular contractions produced reflexly are usually tetanic, it does not follow that this is invariably the case. Sher- rington* has shown, for instance, that an undoubted reflex designated by him as the "extensor thrust," which also involves the extensor muscles of the hind leg, is very short lasting, requir- ing perhaps only 4- sec, and judged by this standard is as much of a simple contraction as the knee-jerk. The "extensor thrust" is a sharp contraction of the extensor muscles of the hind leg aroused by pressure upon the plantar surface of the hind foot. On the frog also a single stimulus applied to the central end of the divided sciatic nerve will call forth a reflex contraction, which is a twitch, and not a tetanus. Second, the time for the jerk — that is, the interval between the stimulus and the response — is too short for a reflex. The determination of this time has been attempted by many observers for the purpose of deciding the controversy, but unfortunately the results have been lacking in uniformity, although the best results from man indicate a latency between stimulus and response of 0.02.3 sec. after deducting the latent period of the mus- cle icself. Applegarth, making use of a dog with a severed spinal cord, obtained for the time of the knee-jerk an interval of 0.014 to 0.02 sec. ; Waller and Gotch, using the rabbit, found the time to be only 0.008 to 0.005 sec. Other figures would appear to indicate that the latent period is shorter the smaller the animal, a fact which in itself would imply that some factor other than the latency of the muscle itself enters into the time required. And if we accept the newer figures in regard to the velocity of the nerve impulse in mammalian nerves at the body temperature (see p. Ill), there would seem to be sufficient time in all cas(>s for the impulse to get to the cord and back. Several observerst have attempted to determine the time intervening between stimulus and response by using the string galvanometer to indicate the electrical response in the muscle, instead of attempting to record the contraction itself. According to Snyder, the time interval hes between 0.01 13 and 0.015 sec, while Hoffmann's results give an interval of 0.019 to 0.024 sec. The calculations of })oth observers indicate that the time is sufficient for a reflex, and iriuch too long for a direct excita- tion. In the case of the Achilles jerk, Hoffmann finds that it may be liberated by electrical stimulation of the n. tibialis and that under these circumstances there is first a deflection of the galvano- meter, due to dir(!ct stimulation of the gastrocnemius through * .ShorrinRlon, "The Int,(iKra1.ivo Acl'um of tin; N(5rvouH 8yHt,om," 1906. fSnydor, "American .jDiirnal of Physiology," 26, 474, 1910. Hoflfmann, "Archiv f. Physiologic," 1910, 223. REFLEX ACTIONS. 157 its motor nerve, and this is followed later by a second deflection, due to reflex stimulation. This latter accords in time interval with the Achilles jerk, and gives a new proof that the phenomenon is a genuine reflex. In view of these facts it would seem to be safe to conclude that the knee-kick and similar phenomena are reflexes, but reflexes in which a single nerve impulse is sent out from the cord, causing a simple contraction in the muscle affected. Conditions Influencing the Extent of the Knee-jerk.— The effect of various normal conditions upon the knee-jerk has been studied by a number of observers, particularly by Lombard.* The results are most interesting in that they indicate very clearly that the irritability of the spinal cord varies with almost every marked change in mental activity. During sleep the jerk disappears and in mental conditions of a restful character its extent is relatively small. In conditions of mental excitement or irritation, on the contrary, the jerk becomes markedly increased. Lombard ob- served also, in his own case, a daily rhythm, which is represented in the chart given in Fig. 71. It would seem from his experiments Fig. 71. — Lombard's figure to indicate the daily rhythm in the extent of the knee- jerk and the effect of mental stimuli. The ordinates (0-110) represent the extent of the kick in millimeters. Each dot represents a separate kick, while the heavy horizontal line gives the average extent for the period indicated. that the extent of the knee-jerk is a sensitive indicator of the relative state of irritability of the nervous system: "The knee- * Lombard, "The American Journal of Psychology," 1887, p. 1. See also article "Knee-jerk" (Warren), "Wood's Ref. Handbook of Med. Sci- ences," second edition, 1902, 158 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. jerk is increased and diminished by whatever increases and di- minishes the activity of the central nen'ous system as a whole." This general fact is supported, especially as regards mental activity, by observ'ations on other similar mechanisms, — such, for instance, as the condition of the nervous centers controlling the bladder. Use of the Knee-jerk and Spinal Reflexes as Diagnostic Signs. — ^The fact that the knee-jerk depends on the integrity of the reflex arc in the lumbar cord has made it useful as a diagnostic indication in lesions of the cord, particularl}^, of course, for the lumbar region. It is mainly on account of its practical value and the ease with which it is ordinarily obtained that the phenom- enon has been studied so extensively. In the disease known as progressive locomotor ataxia the posterior root fibers in the pos- terior columns in the lumbar region are affected, and, as a con- secjuence, the jerk is diminished or abolished altogether according to the stage of the disease. So also lesions affecting the anterior horns of the gray matter will destroy the reflex by cutting off the motor path, while in other cases lesions in the brain or the lateral columns of the cord affecting the pyramidal S3^stem of fibers may be accompanied by an exaggeration of this and similar reflexes. This latter fact agrees with the experimental results (see p. 146) upon ablation of the brain. After such operations in the frog and lower mammals at least the spinal reflexes may show a marked increase. Interruption of the descending connections between brain and cord at any point, therefore, may be accompanied by a strik- ing increase in sensitiveness of the spinal reflexes. The explana- tion usually given is that the inhibitory influences of the brain centers upon the cord are there)3y weakened or destroyed. Other Spinal Reflexes. — Various other distinctive reflexes through the spinal cord may be obtained readily, and since the motor cells concerned lie at different levels in the cord the presence, absence, or modified character of these reflexes has been used frequently for diagnostic purposes. In the first place there are a number of so-called deep reflexes which may be aroused by sensory stimulation of parts beneath the skin, such as the tendons, ligaments, and periosteum. Almost any tendon if stiinulutod iiiechanically may give a jerk of the cor- responding muscle, just as in the case of the knee-kick. Such reactions have l^een described and used in the case of the wrist- jerk, the jaw-jerk, the Achilles-jerk, etc. The last named is ol)tained by f)utting the foot into a position of dorsiflexion and then tuf)[>ing the tendo calcaneus (Achillis). The result is a contraction of the gastrocnrunius, causing i)hintar flexion of the foot. A variation of this reflex is the phenomenon known as ankle clonus. This is obtained by giving a (|uick forcible Fig. 72. — Diagrammatic representation of the lower portion of the human bulb and spinal cord. The cord is divided into its four regions: 1, Medulla cervicalis; 2, medulla dorsalis; 3, medulla lumbalis; 4, medulla sacralis. Within each region the spinal segments bear Roman numbers. On the left side of the diagram the locality supplied by the sensory (afiFerent) neurons is indicated by one or more words, and the.se latter are connected with the bulb or the segment* of the cord at the levels at which the nerves enter. The afferent character is indicated by the arrow tip on the Unes of reference. On the right-hand side the names of muscles or groups of muscles are given, and to thern are diawn referetice lines which start from the segments of the cord in which the cell-bodies of origin have been located. Within the cord itself, the fiesignations for several reflex centers are inscribed in the segment where the mechanism is localized. For e.\am|)Ie, Reflexus scapularis, Centrum «;ili(>-H()inale, Reflexus e()igastri(us, Reflexus abdominalis, Reflexus crema.stericus, Reflexus i»at«llaris, Heflexus tendo Achiilis. Centrum vesicale. Centrum anale (tlie la.st two on the left fide of the diagram). (Donaldson, "Amer. Text-book of Physiology," from "Icoies Neurologic*," Strumpeli and Jakob.) Pharynx Oesophagus Larj'nx, Trachea Mm. pharyngis, palati Mm. laryngis Oesophagus Sternocleidofnastoiileus Musculi colli et I Regio occipitalis Regie colli Regio nuchae Regio Nervi rarfialis Regio N. meijiani Regio N. ulnaris Regio feinoris Regio cruris Fig. REFLEX ACTIONS. 159 dorsiflexion to the foot thus putting the tendon and muscle under a sudden mechanical strain. In some cases there results a rhythmical series of contractions of the gastrocnemius. A second group of reflexes may be obtained by stimulation of special points on the skin, the cutaneous reflexes. For example, the plantar reflex, which consists in a flexion of the toes when the sole of the foot is stimulated by tactile or painful stimuli. Under pathological conditions which involve a lesion of the pyramidal tracts in the cord this reflex is altered, the great toe being extended instead of flexed (Babinski's phenomenon). The cremasteric reflex consists in a contraction of the cremasteric muscle which raises the testis. It follows from stimulation of the skin on the inner side of the thigh at the level of the scrotum. The location of the motor centers of these and other similar reflexes is shown in the accompanying illustration (Fig. 72). CHAPTER VIII. THE SPINAL CORD AS A PATH OF CONDUCTION. In addition to the varied and important functions performed by the cord as a system of reflex centers controlling the activities of numerous glands and visceral organs as well as the so-called voluntary muscles, it is physiologically most important as a path- way to and from the brain. All the fibers, numbering more than half a million, that enter the cord through the posterior roots of the spinal nerves bring in afferent impulses, which may be continued upward by definite tracts that end eventually in the cortex of the cerebrum, the cerebellum, or some other portion of the brain. On the other hand, many of the efferent impulses originating reflexly or otherwise in different parts of the brain are conducted downward into the cord to emerge at one or another of the anterior roots of the spinal nerves. The location and extent of these ascending and descending paths form a part of the inner structure of the cord, which is most important practically in medical diagnosis and which has been the subject of a vast amount of experimental inquiry in physiology, anatomy, pathology, and cUnical medicine. In working out this inner architecture the neuron conception has been of the greatest value, and the results are usually presented in terms of these interconnecting units. The Arrangement and Classification of the Nerve Cells in the Gray Matter of the Cord. — Nerve cells arc scattered throughout the gray matter of the cord, but are arranged more or less distinctly in groups or, considering the longitudinal aspect of the cord, in columns the character of which varies somewhat in the different regions. From the stand]:)oint of physiological anatomy these cells may be grouped into four classes: (1) The anterior root cells, clustered in the anterior column of gray matter (1, Fig. 73). The axons of these cells pass out of the cord almost at once to form the anterior or motor roots of tlie spinal nerves. (2) The tract cells, so called because their axons instead of leaving the cord by the spinal roots enter the white matter and, passing upward or downward, help to form the tracts into which this white matter may bo dividcid (2 and 3 of Fig. 73). These tract cells arc found throughout the gray matt(!r, and, according to the side on which the axon ent(Ts into a tract, tlu^y maybe divided into three subgroups: IGO SPINAL CORD AS A PATH OF CONDUCTION. 161 (a) Those whose axons enter the white matter on the same side of the cord, the tautomeric tract cells of Van Gehuchten. (&) Those whose axons pass through the anterior white commissure and thus reach the tracts in the white matter of the other side. These are known as commissural cells or the heteromeric tract cells of Van Gehuchten. They form one obvious means for crossed conduction in the cord, (c) Those whose axons divide into two, one passing into the white matter of the same side, the other pass- ing by way of the anterior commissure to reach the white matter of the opposite side — the hecateromeric tract cells of Van Gehuch- ten. (3) The Golgi cells of the second type — that is, cells whose i/entral Fig. 73. — Schema of the structure of the cord. — After Lenhossek.) On the right the nerve cells; on the left the entering nerve fibers. Right side: 1, Motor cells, anterior column, giving rise to tlie fibers of the anterior root; 2, tract cells whose axons pass into the white matter of the anterior and lateral funiculi; 2, commissural cells whose axons pass chiefly througli the anterior commissure to reacli the anterior funiculi of the other side; 4, Golgi cells (second tj'pe), whose axons do not leave the gray matter; 5, tract cells whose axons pass into the white matter of the posterior funiculi. Left side: 1, Entering fibers of the posterior root, ending, from within outward, as follows: Clarke's column, posterior column of opposite side, anterior column same side (reflex arc), lateral column of same side, posterior column of same side; 2, collaterals from fibers in the anterior and lateral funiculi, 3, collaterals of descending pyramidal fibers ending around motor cells in anterior column. axons divide into a number of small branches like those of a dendrite. The axons of these cells, therefore, do not become medullated nerve fibers; they take no part in the formation of the spinal roots or the tracts of white matter in the cord, but terminate diffusely within the gray matter itself. (4) The pos- terior root cells l5ang toward the base of the anterior columns. These cells have been demonstrated in some of the lower verte- brates (petromyzon — chick embryo), but their existence in the mammal is still a question in some doubt; their axons pass out from the cord bj^ the posterior root and they form the anatomical evidence for the view that the posterior roots may contain some 11 162 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. efferent fibers. Some of the groups of tract cells have been given special names — such, for instance, as the dorsal nucleus (Clarke's column). This group of cells lies at the inner angle of the posterior column of gray matter (5, Fig. 76), and forms a column usually described as extending from the middle lumbar to the upper dorsal region. The axons from these cells pass to the dorsal margin of the lateral funiculi on the same side to con- stitute an ascending tract of fibers known as the tract of Flechsig, or the fasciculus cerebellospinalis. General Relations of the Gray and White Matter in the Cord. — Cross-sections of the cord at different levels show that the relative amounts of gray and white matter differ considerably at different levels, so that it is quite possible to recognize easily from what region any given section is taken. At the cervical and the lumbar enlargements the amounts of both gray and white matter — that is, the total cross-area of the cord — show a sudden -- — White maffer. Gray matter. —Entire secHon. xoo 80 60 .^ - '^^NComposile curves based on 4 Cases. -— "^ \ 1 --._ \ 40 SO _^_^^- 10O JU lU IV T VI VII nu 1 D in iv IT Vl YU BU iX X XI Xll 1 11 JunrYi uiuurl Fig. 74. — Curves to show the relative areas of the gray and white matter of the spinal cord at diflferent levels. — (Donaldson and Davis.) The Roman numerals along the abscissa represent the origin of the different spinal nerves. increase owing to the larger number of fibers arising at these levels. The white matter, and therefore the total cross-area, shows also a constant increase from below upward, due to the fact that in the upper regions many fibers exist that have come into the cord at a lower level or from the brain, those from the latter region being gradually distributed to the spinal nerves as wc proceed downward. In the accompanying figure a curve is presented showing the cross- area of the cord and the relative amounts of gray and white matter at each segment. Tracts in the White Matter of the Cord, Methods of Deter- mining.— 'I'lio sf;parati()n of the m(!(liillat(ul Jibcirs of the cord into distinct tracts of fibers possessing (liffciront functions has been accomplished in part by the combined results of investiga- tions in anatomy, physiology, and pathology. The two methods that have boon employed most fr(!f|u(!ntly and to the best advan- tage are the method of secondary degeneration (Wallerian degen- SPINAL CORD AS A PATH OF CONDUCTION. 163 eration) and the method of myelinization. The method of second- ary degeneration depends upon the fact that, when a fiber is cut ofif from its cell of origin, the peripheral end degenerates in a few days. If, therefore, a lesion, experimental or pathological, is made in the cord at any level, those fibers that are affected undergo degeneration: those with their cells below the lesion degenerate up- ward, and those with their cells above the lesion degenerate down- ward. According to the law of polarity of conduction in the neuron a descending degeneration in the cord indicates motor or efferent paths as regards the brain, and ascending degeneration indicates sensory or afferent paths. It is obvious that locaUzed lesions can be used in this way to trace definite groups of fibers through the cord. If, for instance, one exposes and cuts the posterior roots in one or more of the lumbar nerves, the portions of the fibers entering the cord will degenerate, and the path of some of these fibers may be traced in this way upward to the medulla. The degenerated fibers may be revealed histologically by the staining methods of Weigert or of Marchi. The latter method (preservation in Miiller's fluid, staining in osmic acid and MiiUer's fluid) has proved to be espe- cially useful; the degenerated fibers during a certain period give a black color with this liquid, owing probably to the splitting up of the lecithin in the myelin and the liberation of the fat from its combination with the other portions of the molecule.* The mye- linization method was introduced by Flechsig. It depends upon the fact that in the embryo the nerve fibers as first formed have no myelin sheath, and that this easily detected structure is in the central nervous system assumed at about the same time by those bundles or tracts of fibers that have a common course and func- tion. By this means the origin and termination of certain tracts may be worked out in the embryo or shortly after birth. The well-known system of pyramidal fibers, for instance, is clearly differentiated in the embryo late in intra-uterine life or at birth, owing to the fact that the fibers composing it have not at that time acquired their myelin sheaths. Flechsig assumes that the development of the myelin marks the completed structure of the nerve fiber and indicates, therefore, the time of its entrance into full functional activity. General Classification of the Tracts. — ^The tracts that have been worked out in the white matter of the cord have been classified in several ways. We have, in the first place, the division into as- cending and descending tracts. This division rests upon the fact that the axon conducts its impulses away from the cell of origin, and consequently those neurons whose axons extend upward toward the * See Halliburton, "The Chemical Side of Nervous Activity," Londcm, 1901; "Croonian Lectures." 164 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. higher parts of the cord or brain are designated as ascending, since normally the impulses conducted by them take this direction. They constitute the afferent or sensory paths, and in case of injury to the fiber or cell the secondarv' degeneration also extends upward. The reverse, of course, holds true for the descending or motor paths. The tracts may be divided also into long and short (or segmental) tracts. The latter group comprises those tracts or fibers which have only a short course in the white matter, extending over a dis- tance of one or more spinal segments. Histologically the fibers of these tracts take their origin from the tract cells in the gray matter of the cord and after running in the white matter for a distance of one or more segments they again enter the gray matter to terminate around the dendritic processes of another neuron. These short tracts may be ascending or descending, and the impulses that they conduct are conveyed up or down the cord by a series of neurons, each of whose axons runs only a short distance in the white matter, and then conveys its impulse to another neuron whose axon in turn extends for a segment or two in the white matter, and so on. These tracts are sometimes described as association or short associa- tion tracts, because they form the mechanism by which the activi- ties of different segments of the cord are brought into association. This method of conduction by segmental relays involving the par- ticipation of a series of neurons may be regarded as the primitive method. It indicates the original structure of the cord as a series of segments, each more or less independent physiologically. The short tracts in the mammalian cord he close to the gray matter, forming the bulk of what is known as the anterior and lateral proper fasciculi. The long tracts, on the contrary, are com- posed of those fibers, ascending or descending, which run a long distance, and, in fact, extend from the cord to some part of the brain. It is known, however, that, although the tracts as tracts extend from })rain to cord, many of their constituent fibers may begin and end in the cord or in the brain, as the case may be. Some of the fibers of the long tracts are, there- fore, so far as the cord is concerned, simply long association tracts which connect different regions — e. g., cervical and lum- bar — of the cord by a single neuron, as the short asso- ciation tracts connect different segments of the same region. It is said that in these long tracts those fibers that have the shortest course lie to the inside — that is, nearest to the gray matter.* From the results f)f corni)arative studies of the different vertebrates we may conclude that the long tracts arc a j-elatively late development in their phylogenetic history, and that in the most highly developed animals, man and the anthropoid apes, ♦Sherrington and Laslett, "Journal of PhyHiology," 29, 188, 1903; and Sherrington, ihi/L, 14, 25.5. SPINAL CORD AS A PATH OF CONDUCTION. 165 these long tracts are more conspicuous and form a larger per- centage of the total area of the cord. A physiological corollary of this conclusion should be that in man the independent activity of the cord is less marked than in the lower vertebrates, and this deduction is borne out by facts (see p. 144). Specific Designation of the Long Spinal Tracts. — The tracts that are most satisfactorily determined for the human spinal cord are indicated schematically in Fig. 75. They are named as follows: In the posterior funiculus, 1. The fasciculus gracilis (column of Goll). 2. The fasciculus cuneatus (column of Burdach). Fig. 75. — Schema of the tracts in the spinal cord (Kolliker) : g, Fasciculus gracilis ; b, fasciculus cuneatus ; pc, fasciculus cerebrospinalis lateralis ; pd, fasciculus cerebrospinalis anterior ; /, fasciculus cerebellospinalis ; gr, fasciculus anterolateralis superficialis. In the lateral funiculus, 1. The fasciculus cerebrospinalis lateralis, known also as the lateral or crossed pyramidal tract. 2. The fasciculus cerebellospinalis, known also as Flechsig's tract. 3. The fasciculus anterolateralis superficialis, known also as Gower's tract. 4. The lateral ground bundle (fasciculus lateralis proprius), made up chiefly of short association fibers. In the anterior funiculus, 1. The fasciculus cerebrospinalis anterior, known also as the direct or anterior pyramidal tract. 2. The anterior ground bundle (fasciculus anterior proprius). 166 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. Of these tracts, the fasciculus gracilis, fasciculus cuneatus, fasciculus cerebellospinalis, and fasciculus anterolateralis super- ficialis represent ascending or sensory paths, while the lateral and anterior cerebrospinal or pyramidal fasciculi form a related descending or motor path. It will be convenient to describe first the connections and physiological significance of these tracts and then refer briefly to the other less definitely estab- lished ascending and descending paths. The Termination in the Cord of the Fibers of the Posterior Root. — All sensory fibers from the limbs and trunk enter the cord through the posterior roots. Inasmuch as these roots are superfi- cially connected with the posterior funiculi, the older observers naturally supposed that this portion of the white matter of the cord forms the pathway for sensory impulses passing to the brain. That this sup- position is not entirely cor- rect was proved by experi- mental physiology. Sec- tion of the posterior fu- niculi causes little or no obvious loss of sensations in the parts lielow the lesion. Histological inves- tigation has since shown that only a portion of the fibers entering tlirough the posterior root continue up the cord in the posterior funiculi; some and indeed a largo proportion of the whole nuiiibor enter into Fig. 76. — Schema to show the terminations of the entering fibers of the posterior root: 1, Fibers enterinj? zone of Lissauer and terminating in posterior column; 2, fiber terminating around a tract ceil whose axon passes into wliite matter of same side; '.i, fiber terminating around a tract cell whose axon passes to opposite side (commissural cell); 4, fiber terminating around motor cell of anterior column (reflex arc); 5, fiber terminating .in tract cell of dorsal nucleus; 6, fiber (exog- lenous) passing upward in posterior funiculus to terminate in the medulla oblongata. the gray matter and end around tract cells, whence the path is continued upward by the axons of these latter cells, mainly in the lateral or anterolateral funiculi. The several ways in which the posterior root fibers may end in the cord are indicated in Fig. 70. The posterior roots contain fibers of different diameters, and those of smallest size (1) are found collected into an area known SPINAL CORD AS A PATH OF CONDUCTION. 167 as the zone of Lissauer, lying between the periphery of the cord and the tip of the posterior column. These fibers enter the gray matter chiefly in the posterior column of the same side and end around tract cells. The larger fibers of the root lying to the median side fall into two groups: Those lying laterally (2, 3, 4) enter the gray matter of the posterior column and end in tract cells (2) whose axons are distributed to the same side of the cord, or in tract cells whose axons (3) pass to the other side through the anterior white commissure, or (4) in the motor cells of the anterior column, thus making a typical reflex arc. Some of the fibers of this group may also pass through the posterior commissure, to end in the gray matter of the opposite side. The larger fibers lying nearest to the median line enter the fas- ciculus cuneatus and run forward in the cord, some of them (6) continuing upward to the medulla, and some of them (5), after a shorter course, turning into the gray matter to end in the cells of the dorsal nucleus. The axons of the cells in the dorsal nucleus in turn pass out of the gray matter to constitute the ascending path in the lateral funiculus, known as the cerebello- spinal fasciculus. This general outline of the mode of ending in the cord of the fibers of the posterior root is complicated further by the fact that these fibers are supposed to give off collaterals after entering the cord. The course of the typical fiber in the posterior root is represented in Fig. 67. According to this diagram, the root fiber, after entering the cord, makes a Y or T division, one branch passing downward or posteriorly for a short distance, the other, longer division, passing upward or anteriorly. Each of these main stems may give off one or more lateral branches, sensory collaterals. A main stem, therefore, which runs upward in the fasciculus cuneatus (6) to terminate in the medulla oblongata may give off collaterals at various levels which terminate in the gray matter of the cord, either around tract cells or around the anterior root cells, forming in the latter case a simple reflex arc. The existence of collaterals upon the root fibers within the cord has been demonstrated in the human embryo, but we have little exact information concerning their numerical value in the adult. The schema given in Fig. 76 must, therefore, be accepted as an entirely diagrammatic representation of the chief possibilities of the mode of ending of the fibers of the posterior root by way of their collaterals as well as by way of the main stems. Ascending (Afferent or Sensory) Paths in the Posterior Funiculi.- — The posterior funiculi are composed partly of fibers derived directly from the posterior roots (6 in schema) and arising, therefore, from the cells in the posterior root ganglia, and partly 168 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. from fibers that arise 4^ Ceruical y^-'^Dorsal Z'^ Lwnbar Fij?. 77.— DiaKram.s fo flhow courHC of upward tle- Keneration of fibers of poHte- rior funiculi aftor section of a numVjer of pONtcrior rootH of the nervr-M frjrrninK the lumbfvsacral picxuH.- - (Mott.) It will be noted that in the cervical roRionH the degener- ated area Ih confined to the faMciculuH gracilis. from tract cells in the gray matter of the cord itself. It is convenient to speak of the former group as exogenous fibers, using this term to designate nerve fibers which arise from cells placed outside the cord; and the latter group as endo- genous fibers — that is, fibers that have their cells of origin in the gray matter of the cord. If we omit a consideration of their collaterals the course of the exogenous fibers is easily understood. They come into the cord at every pos- terior root, enter into the fasciculus cuneatus, and pass upward. The fibers of this kind that enter at the lower regions, sacral and lumbar, are, however, gradually pushed toward the median line by the exogenous fibers entering at higher levels, so that in the upper tho- racic or cervical regions the fasciculus gracilis is composed mainly of exogenous fibers that have entered the cord in the lumbar or sacral region. These fibers continue upward to end in two groups of cells that lie on the dorsal side of the medulla ol)longata, and are known, respectively, as the nucleus of the fasciculus gracilis (or nucleus of Goll) and the nucleus of the fasciculus cunea- tus (or nucleus of Burdach). Their patli forward from the medulla is con- tinued by new neurons arising in these nuclei, and will be described later. The course of these fibers in the cord may be shown beautifully l)y the metliod of secondary degeneration. If one or more of the posterior roots of the lumbar spinal nerves are cut or, better still, if the posterior funiculi are severed in this region, the degeneration will affect tlie exogenous fibers throughout their course to the medulla, and it will be seen that in the cervical region the degen- erated fii)ers are grouped in the area of the fasciculus gracilis (see Fig. 77). The SPINAL CORD AS A PATH OF CONDUCTION. 169 endogenous fibers, so far as they are ascending, represent afferent paths in which two or more neurons are concerned. The pos- terior root fibers concerned in these paths end in the gray matter of the cord, and thence the conduction is continued by one or more tract cells. The conduction by this set of fibers may be on the same side of the cord as that on which the root fibers entered, or it may be crossed, or, using a convenient terminology, it may be homolateral or contralateral. The physiological value of the ascending fibers in the posterior funiculi has been investigated by a large number of observers. The physiologists have employed the direct method of cutting the funiculi in the thoracic or lumbar region and observing the effect upon the sensations of the parts below the lesion. The positive results of these experiments have been difficult to discover. Most of the older observers found- that there was no detectable change in the sensations of the parts below, but they paid attention only to cutaneous sensations, and, indeed, chiefly to the sense of pain. Later observers* have differed also in their description of the effects of this operation; but most of them state that the animal shows an awkwardness or lack of skill in the movements of the hind limbs, especially in the finer movements, and this effect is interpreted to mean that there is some loss of muscle sense. This conclusion is strength- ened by the results of pathological anatomy. In the disease known as tabes dorsalis the posterior funiculi of the cord in the lumbar region are affected and the striking symptom of this condition is an interference with the power of co-ordinating properly the movements of the lower limbs, particularly in the act of maintaining body equilibrium in standing and walking, — ■ a condition known as locomotor ataxia. So far as the cutaneous sensations are concerned, — that is, the sensations of touch (pressure), pain, and temperature, — all observers agree that the two latter are not affected by section of the funiculi, while regarding touch, opinions have differed radically. Schiff contended that touch sensations are detectable as long as these funiculi are intact, and are seriously interfered with when they are sectioned ; but most of the results, pathological and experimental, indicate that when the continuity of these fibers is destroyed, the sense of touch is still present in the parts supplied by the cord below the lesion. An explanation of the confusion in the reported results may be found perhaps in the fact reported below (see p. 174) that fibers conveying the impulses necessary to tactile discrimination pass upward in these funiculi, while other touch (pressure) impulses cross in the cord and pass upward in the anterior funiculi. To * Borchert, "Archiv f. Phj^siologie," 1902, 389. See also Sherrington, "Journal of Physiology," 14, 255, 1893. 170 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. summarize, therefore, we may say that the evidence at hand proves that the ascending fibers of the posterior funicuU do not conve}' impulses of pain or temperature, that if they convey any touch (pressure) impulses, they certainly do not form the only path of conduction for this sense, and that most probably their chief function is the conduction of impulses of muscle sense, — that is, they consist of those deep sensory fibers from the volun- tary muscles, the tendons, and the joints, which give us an idea of the position of the Umbs and the state of contraction of the mus- cles. The muscle sensations thus aroused in the higher parts of the brain are necessary to the proper co-ordination of the movements of the muscles. Injury to these funiculi, therefore, while it does not cause paralysis, is followed by disorderly — that is, ataxic — move- ments. On the histological side it has been shown, as stated above, that the fibers, particularly the exogenous fibers, end in nuclei of the medulla, and thence are continued forward by the great sensory tract known as the " lemniscus," to end eventually in that part of the cortex of the cerebrum designated as the area of the body senses. Ascending (Afferent or Sensory) Paths in the Lateral Funic- uli. — The two best known ascending tracts in these funiculi are those of the cerebellospinal and the superficial anterolateral fasciculi. The former takes its origin in the lower thoracic region, and is composed of axons connected with the tract cells of the dorsal nucleus. The impulses which its fibers convey are brought into the cord through those fibers of the posterior root that end around the cells of the dorsal nucleus. A number of the fibers in this funiculus end doubtless in the gray matter of the upper regions of the cord, but most of them continue upward on the same side, enter the inferior peduncle of the cerebellum (restiform body), and terminate in the posterior and median portions of the vermiform lobe, mainly on the same side, but partly also on the opposite side. The superficial anterolateral fasciculus, situatful ventrally to tiic cero])cll()spinal fas- ciculus (gr, Fig. 75), may ex- tend forward into the anterior funiculi along the periphery of the cord. The two bun- dles may be more or Uiss intermingled at the points of contact. This tract begins in the lumbar region, its fibers arising on the yl^e/ve Fig. 78. — To hIiow the course of the fibcra of the ctfrcl)fll;ir tracts of tlie cord (Moll): v.a.c. Ventral tract (Hiiperficial antcrolatciral); d.a.c, dornal tract (cerebellospinal); a.v., superior vermis; P.C.Q., inferior colliculuH. SPINAL CORD AS A PATH OF CONDUCTION. 171 same side from tract cells situated in the intermediate portions of the gray matter, or, according to Bruce,* in the lower cells of the column of Clarke. This author states also that fibers belonging to this tract in the lower thoracic region may pass over into the tract of Flechsig at higher levels. Many of the fibers in this tract possibly terminate in the cord itself, since the bundle does not in- crease regularly in size as it passes up the cord. Most of the bundle continues forward, however, along the ventral side of the pons, gradually shifts more to the dorsal side, and at the level of the superior peduncles of the cerebellum turns backward, for the most part, at least, and passes to the cerebellum by way of the superior peduncle (brachium conjunctivum) and the anterior medullary velum, to end in the vermiform lobe chiefly on the same side, but to some extent on the opposite sidef (Fig. 78). The area of dis- tribution of these fibers lies anterior or headward of those arising in the dorsal cerebellospinal tract (Flechsig). Where this tract separates from the cerebellospinal fasciculus it is stated t that it gives off a number of fibers which enter the restiform body with the cerebellospinal fasciculus to end in the cerebellum. This and other facts indicate that the two tracts constitute a com- mon system. Regarding the physiology of these two tracts there is little experimental and not much clinical evidence. Some observers have cut the cerebellospinal fasciculus in ani- mals, but with no very obvious effect except again a slight degree of ataxia in the movements below the lesion and some loss of muscular tone.§ This result, together with the fact that the bundle ends in the cerebellum, gives reason for be- lieving that the fibers convey afferent impulses from the muscles. As we shall see, much evidence of various kinds connects the cere- bellum with the co-ordination of the muscles of the body in the complex movements of standing and locomotion. This power of co-ordination in turn depends upon the afferent impulses from the muscles and the joints and other so-called deep sen- sory parts, and since the fibers of the cerebellospinal fasciculus end in the cerebellum, and since experimental lesion of them gives no loss of cutaneous sensibility, but some degree of ataxia, it seems justifiable to conclude that these fibers are physiolog- ically muscle-sense fibers. The similar fibers in the posterior funiculi end eventually in the cortex of the cerebrum, and may be supposed, therefore, to mediate our conscious muscular sensa- * Bruce, "Quarterly Journal of Exp. Physiology," 3, 391, 1910. t For the literature upon these tracts see Van Gehuchten, "Le Ne\Taxe," 3, 157, 1901; Horsley and Macnalty, "Brain," 1909, 237, and Bruce, loc. cit. t Schafer and Bruce, "Journal of Physiology," 1907 ("Proc. Phj^siol. See"). § Bing, "Archiv fiir Physiologie," 1906, 250; also Horsley and Macnalty, loc. cit. 172 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. tions, but these fibers in the cerebellospmal tract end in the cere- bellum, an organ which, so far as we know, gives rise to no con- scious sensations. To speak of them, therefore, as muscle-sense fibers may be somewhat misleading, and it may be better to follow the plan of designating them as the non-sensory afferent fibers arising from tissues beneath the skin, such as the muscles, the tendons, and the ligaments round the joints. The superfi- cial anterolateral fasciculus has been the subject of some ex- perimental study from the physiological side, but the results have been negative. Clinically, the tract may be involved in pathological or traumatic lesions of the lateral funiculi. Cow- ers* gives a history of some such cases, which lead him to be- lieve that this tract constitutes a pathway for pain impulses, and this view or the view that it conducts the impulses of both pain and temperature has been more or less generally accepted. Entire confidence, however, cannot be placed in this conclusion, since the lesions in question were not strictly confined to the fasciculus in question, although clinical evidence indicates that the fibers conveying impulses of pain or of pain and temperature lie in the neighborhood of this tract. The only positive indication that we have concerning the physiological value of this specific tract of fibers is given by their histology in the fact that they end, for the most part, in the cerebellum. The cerebellum, we know, msLy be removed in dogs and monkeys without loss of the sensation of pain, temperature, or touch, and this fact speaks strongly against the view that either the cerebellospinal or the superficial anterolateral fasciculus is concerned in the conduction of these cutaneous sen- sations. From a physiological standpoint we should be inclined to believe that both of these tracts conduct afferent impulses from the tissues lying under the skin, particularly from the muscles, tendons, and joints. It would seem, therefore, that all the long ascending tracts in the posterior and lateral funi(;uli of the cord may be made up of fibers of muscle sense, using this term in a wide sense to include the deep sensibility of the joints, tendons, and muscles. The immense importance of muscular control in the maintenance of life and in defense against enemies may explain, upon the doctrine of the struggle for existence, why the long paths should have been developed first in connection with this sense. The Spinal Paths for the Cutaneous Senses (Touch, Pain, and Temperature). — From the facts stated in the last two para- graphs it would seem probable that the spinal paths for touch, pain, and temperature must be along the short association tracts of the i)roper fasciculi of the lateral and anterior funiculi. There is evidence frotn the clinical side; that the paths of con- * Gowers, "Lancet," 1S86. SPINAL CORD AS A PATH OF CONDUCTION. 173 duction for these senses are separate. In the pathological condition known as syringomyelia, cavities are formed in the cord affecting chiefly the central gray matter and the contiguous portions of the white. In these cases a frequent symptom is what is known as the dissociation of sensations; the patient loses, in certain regions, the sensations of pain and temperature (analgesia and thermo-anesthesia), but preserves that of pressure (touch). Facts of this kind indicate that the paths of conduc- tion for touch are separate from those for pain and temperature, but little that is positive is known regarding the exact location of these paths. The fibers of pain and temperature probably end in the gray matter of the cord (posterior column) soon after their entrance, and the path is continued upward by tract cells whose axons enter the proper fasciculi in the anterolateral funiculi,* but the number of such neurons concerned in the conduction as far as the medulla is not known. Regarding the path for the touch impulses a singular amount of uncertainty has prevailed. This sense is not lost or, at least, is rarely lost in cases of syringomyelia in which the other cutaneous senses are affected. On the other hand, the posterior funiculi, as we have seen, may be completely sectioned in lower animals without destroying the sense of touch and in the case of man extensive pathological lesions of the same funiculi are reported in which the sense of touch was not lost. Some authors, therefore, have been led to believe that the touch impulses may be conveyed up the cord by several paths: by the long association fibers of the posterior funiculi, and by the short association fibers of the lateral funiculi. Such a view receives little support from the experimental work on the lower mammals. In these animals the evidence tends to show that the conductirn is by way of the lateral or anterolateral funiculi, by means of tract cells and short association tracts. The fact that in man the chnical evidence seems to point to the posterior funiculi as a pos- sible or, indeed, probable path for these fibers may serve to ex- emplify the fact that in these matters the various mammalia differ more or less according to the degree of their development. It seems possible that, so far as man is concerned, an explanation of the difference of opinion regarding the spinal paths of the sense of touch is found in the distinction made by Head and Thompson f between tactile discrimination and cutaneous sensibility to touch. By the former is meant the ability to discriminate between two stimuli applied simultaneously to the skin at a certain distance apart, by the latter, the ability to perceive and locate accurately a light pressure stimulus applied to the skin. These two forms of *For discussion, see Bertholet, "Le Nevraxe," 1906, vii., 283, for the lower animals and Head and Thompson, "Brain," 1906, p. 537, and Thomp- son "Lancet," 1909, for man. t Head and Thompson, "Brain," 1906. 174 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. cutaneous touch sensations are mediated according to these authors by separate systems of fibers. As the result of a spinal lesion the power of discrimination may be lost over a given area of skin which other-^dse is complete^ sensitive to all cutaneous stimuli. They find that the fibers of tactile discrimination travel up the cord uncrossed in the posterior funiculi, together with the fibers of muscle sense — ^that is, the fibers which give us a sense of posi- tion and movement of the hmbs. The fibers of cutaneous touch sensations in general, on the contrary, cross to the other side be- fore reaching the medulla, and pass upward in the anterolateral ground-bundles. Homolateral and Contralateral Conduction of the Cutaneous Impulses. — Great interest, from the medical side, has been shown in the question of the crossed or uncrossed conduction of the cutaneous impulses in the cord. The matter is naturally one of importance in diagnosis. In human beings it was pointed out by Brown-Sequard* that unilateral lesions of the cord are followed by muscular paralysis below on the same side, and loss of cutaneous sensibility on the opposite side. This syndrome has been held clinically to establish the diagnosis of a unilateral lesion, and has led to the view that, while the conduction of the motor impulses is homolateral, that of the cutaneous sen- sory impulses is contralateral. Experimental work on lower animals, on the contrary, has not supported this view. While results in this direction have varied, as would be expected from the intrinsic difficulties connected with the interpretation of the sensations of an animal, the general outcome has been to show that the sensory conduction is bilateral, but mainly on the same side. That is, if the cord is cut on one side only (hemisected) in the thoracic region, the cutaneous sensibility of the parts below the lesion is impaired upon the same side, but not completely abolished, showing that some crossing has taken place. f It is probable that this crossing is more com- plete in man than in the lower animals, although later studies in man of unilateral lesions of the cord (Brown-Sequard paraly- sis) indicate that the contralateral loss of cutaneous sensibility affects completely the senses of pain and temperature, and in part the sense of touch, while nmscular sensibility is affected only on the same side. Head and Thompson, in the paper previously referred to, conclude, upon the basis of extensive clinical studies, that in man all the filx^rs of cutaneous sense cross in the cord except those rn(!(liating tactile discrimination. As stated above, these latter pass upward in the posterior funiculi together with * Brown-S«';quanl, ".lournul do PhysioloKie," fi, 124, 232, 581, 18G3. t Mott, "Brain," 18%, 1, and iicrtliolr't, "Le N(jvraxe," 1900, vii., 283. SPINAL CORD AS A PATH OF CONDUCTION. 175 some of the fibers of muscle sense, and do not cross until after they reach the medulla. These authors in studying the sensory paths in the spinal cord make a distinction, in the first place, be- tween cutaneous sensibility and deep sensibility. By the latter term they designate the senses of pressure, of pain, and of position resident in the muscles, tendons, and other parts beneath the skin. Fig. 79. — Diagram of the afferent nerve-fibers and their course in the spinal cord: a. Specific receptor for painful impulses; 6, specific receptor for heat impulses; c, specific receptor for cold impulses; d, specific receptor for tactile impulses; e, specific receptor for impulses of passive position and tactile discrimination; /, specific receptor for non-sensory afferent impulses; 1, sensory fibers of the second order for pain, heat, and cold; 2, sensory fibers of the second order for touch; 3, sensory fibers of the second order for passive position and tactile discrimination; 4, long fibers (uncrossed) in the posterior column of the cord; 5, spinocerebellar tracts (lateral columns) for non-sensory afferent impulses (from Thompson, slightly modified). Cutaneous sensibility they divide further into epicritic sensibility (touch, cold, heat) and protopathic sensibility (cold, heat, pain), see p. 273. The fibers of these three general varieties are re- grouped in the cord in such a way that the epicritic and proto- pathic temperature fibers are brought together into a common tract, 176 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. to their which is contralateral; the deep and cutaneous pain fibers are likewise united into a common tract, which is contralateral, and cutaneous pressure fibers, except those mediating tactile discrim- ination, unite with the deep pressure fibers to form a common tract which crosses the mid-line less promptly. This conception is indicated in the accompanying schema (Fig. 79). According interpretation, a complete unilateral lesion of the cord in the cervical region would be followed by a homolateral loss of motion in the parts below, and also of tactile discrimination and muscle sense, using the latter term to cover the deep sensibility in regard to position and movements of the limbs. On the contralateral side there would be a loss of pain, temperature, and pressure. The Descending (Efferent or Motor) Paths in the Antero-lateral Column. — The main descending path in the cord is the pyramidal or cerebrospinal system of fibers. In man, as shown in Fig. 75, there are two fasciculi belonging to this system — the anterior and the lat- eral pyramidal tracts. Both tracts arise from the anterior pyramids on the ventral face of the medulla, whence the name of the pyramidal system. At the junction of the medulla and cord the fibers of the pyramids decussate in part, form- ing a conspicuous feature of the internal structure at this point, known as the pyramidal decussa- tion. According to the general schema of this decussation (see Fig. 80), the larger number of the fibers in the pyramid of on(! side pass over to form the lateral pyramidal fasciculus of tlu; other side of the cord (4, 5), while a smaller part (3) continues down on the same side to form the anterior pyra- midal fasciculus. Eventually, however, these latter fibers also cross the mid-line in the anterior white commissure, not, however, all at once, as at the pyramidal decussation, but some at the level Fig. 80.--,S(l, the course of tlie ■ma rf'presnnf itiK iljiTH of the pyra- midal or cerebnj^pitiai .system: 1, Fibers to the nuclei f)f the cranial nerve; 2, uncroMwed fibers to the lateral pyramidal fasciculuw; 3, fibers to the anterior pyramidal fa.sciculus CTC)»H\ng in the cord; 4 and .5, fibers that croHM in the pyramidal decuwsa- tion to make the lateral pyramidal fasciculus of the opposite side. SPINAL CORD AS A PATH OF CONDUCTION. 177 of each spinal nerve. These pyramidal fibers have their origin in the cortex of the cerebral hemispheres in large pyramidal cells ; some of them cross the mid-line before reaching the medulla to end around the cells of origin of the cranial nerves, but the greater number continue into the cord and, after crossing the mid- line in the pyramidal decussation or in the anterior white com- missure, terminate around the motor cells of the anterior columns which give rise to the motor roots of the spinal nerves. Both fasciculi, the l9,teral and the anterior, continue throughout the length of the cord, diminishing in area on the way as some of their fibers terminate in each segment. This system of fibers is supposed to represent the mechanism for effecting voluntary movements, and according to the general schema the voluntary motor path from cerebrum to muscle comprises two neurons, — the pyra- midal or cerebrospinal neuron and the spinal or the cranial neuron. Moreover, as represented in the schema, the innerva- tion is crossed, the right side of the brain controlling the mus- culature of the left side of the body and vice versa. As we shall see, however, when we come to study the motor areas of the brain, this rule has important exceptions, and histologically there is proof that some of the fibers in each pyramid (2 in Fig. 80). continue into and terminate in the cord on the same side. The pyramidal system varies, in an interesting way, in the extent of its development among the different vertebrates. It reaches its highest development in man and the anthropoid apes. In the other mammalia it is relatively less important and the anterior fasciculus in the anterior funiculus is lacking altogether. In the birds what represents the same system is found in the anterior funiculus (Sandmeyer), while in the frog the system does not exist at all. The relative importance of the system in the different mammalia is indicated in the accompanying table taken from Lenhossek,* in which the area of the pyramidal system is given in percentage of the total cross-area of the cord : Mouse 1.14 per cent. Guinea pig 3.0 " Rabbit 5.3 " Cat 7.76 " Man 11.87 " Evidently, therefore, the importance of the pyramidal system varies in different animals, and it is necessary to bear this fact in mind in applying the results of experiments on the lower animals to man. In the lowest vertebrates there are undoubtedly motor paths between the brain and cord through which so-called voluntary * Lenhossek, "Bau des Nervensystems," second edition, 1895. 12 178 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. movements are effected, but these are probably short paths in- volving a number of neurons. The higher the position of the animal in the phylogenetic scale, the more complete is the develop- ment of the long pyramidal system; but even in the higher mam- mals it is probable that motor paths, other than the pyramidal system, connect the cortex and subcortical centers with the motor nuclei in the cord. In the dog, for example, section of the pyramids is not followed by complete paralysis, and, indeed, after such sections stimulation of the motor areas of the cortex still causes definite muscular movements.* One such indirect motor path is referred to below in connection with the rubrospinal tract (Monakow's bundle) . Less Well-Known Tracts in the Cord. — In addition to the tracts just described there are a number of others — mainly, descend- ing tracts — concerning which our anatomical knowledge is less complete, and the physiological value of which is entirely un- known or at best is a matter of inference from the anatomical relations, t Descending Tracts in the Posterior Funiculus — Comma Tract; Oval Field. — In the posterior funiculi several tracts of descending fibers have been described. The comma tract of Schultze is found in the cervical and the upper thoracic cord. The bundle lies at the border-line between the fasciculus gracilis and the fasciculus cuneatus. In the lower regions of the cord, lumbar and sacral, similar small areas of descending fibers are found — oval field (Flechsig), median triangle (Gombault and Philippe) — • which represent possibly different systems. It is probable that these fibers belong to the group of long association fibers connecting distant portions of the cord. Nothing is known regarding their physiology. Descending Tracts in the Anterolateral Funiculus. — The pre- pyramidal tract, known also as Monakow's bundle, the fasciculus intermediolateralis, or the rubrospinal tract, is a conspicuous bundle forming a wedge-shaped or triangular area in the lateral columns between the lateral pyramidal fasciculus and the superficial anterolateral fasciculus (Gower's), or, perhaps, more correctly speaking, forming the anterior portion of the lateral pyi-aniidal fasficulus; the two systems Ijeing more or less inter- mingled. Tiic fibers composing this bundle are descending fibers that take their origin in the midbrain in the cells of the red nucleus. .Shortly after their origin they cross to the opposite * Rothrnann, "Zcilsohrift f. klin. Mod.," vol. xlviii., 1903; Schafer, "Q>iari(;rly .Journal of ]*]xp. Pliysiolof^y," 3, 35.5, 1910. t Collier and liuiczard, "li'rain," 1901, 177; Fraser, ".Journal of Physi- ology," '2.''^, 3W), 1902. For wurnrnary and Iit(Tat,ur(! consult Van Gchuchten, "Anatomic; du Hy.st< inc riervoux do i'hornrno," 4ih ed., 1906. SPINAL CORD AS A PATH OF CONDUCTION. 179 side and, passing through the pons and medulla, enter the spinal cord in the lateral funiculi, in which they may be detected as far as the sacral region. These fibers terminate around cells lying in the posterior part of the anterior column of gray matter, whose axons, in turn, probably emerge through the anterior roots. This tract, therefore, constitutes a crossed motor path from midbrain to the anterior roots, and, since the red nucleus, in turn, is con- nected with the cerebrum, either directly or by way of the cere- bellum, it represents a cerebrospinal motor path in addition to that offered by the pyramidal system. The vestibulospinal fibers lie anterior to the preceding tract in the anterolateral funiculus; they may extend into the anterior funiculus as far as the anterior pyramidal fasciculus. It is stated that they arise in cells of the nucleus of Deiters and the nucleus of Bechterew, and similar cells lying in the region of the pons. In the cord these fibers end around cells in the anterior column. Since the Deiters nucleus forms a termination for the sensory fibers of the vestibular branch of the eighth cranial nerve, and since these fibers are believed to give us a sense of the position of the body and to be concerned in the reflex adjustment of the muscles in the movements used to maintain equilibrium, their connection in Deiters' nucleus with a spinal motor path becomes very significant as furnishing a reflex arc- through which sensory impressions from the vestibular apparatus in the ear may automatically control the musculature of the body. A number of other descending paths in the anterior and lateral funiculi have been described, such as Helweg's bundle or the olivospinal tract, lying on the margin of the cord at the junction of the anterior and the lateral funiculi and supposed to arise in the olivary bodies; the anterior and the lateral reticulospinal tracts arising from cells in the reticular formation of medulla, pons, and midbrain; and the continuation into the cord of the important medial longitudinal fasciculus (post. long, bundle), which extends from the midbrain through to the cord and connects the motor nuclei of the cranial nerves with the motor centers of the cord. Concerning these and similar tracts our physiological knowledge is scanty, and it is not possible at present to employ them with certainty in explaining the activity of the neuromuscular apparatus. CHAPTER IX. THE GENERAL PHYSIOLOGY OF THE CEREBRUM AND ITS MOTOR FUNCTIONS. From the time of Galen in the second century of the Christian era the cerebrmn has been recognized as the organ of inteIHgence and conscious sensations. Galen established this view not only by anatomical dissections, confirming the older work of the Alexandrian school (third century B.C.) in regard to the origin from the brain of the cranial nerves, but also by numerous vivisection experiments upon lower animals. All modern work has confirmed this belief and has tended to show that in the cerebral hemispheres and, indeed, in the cortex of gray matter lies the seat of consciousness. It is perhaps still an open question as to the existence of a conscious or psychical factor in the activities of other parts of the nen^ous system, but there is no doubt that the highest develop- ment of psychical activity in man is associated with the cortical mat- ter of the cerebrum. In the young infant the dawn of its mental powers is connected with and dej^endent on the development of the normal cortical structure, while in extreme age the failure in the mental faculties goes hand in hand with an atrophy of the elements of the cortex. If this cortex were removed all the intelligence, sen- sation, and thought that we recognize as characterizing the highest psychical life of man would be destroyed, and abnormalities in the structure of this cortical material are accepted, as the immediate causal factor of those perversions in reasoning and in character which are exhibited by the insane or the degenerate. The cortical gray matter, therefore, is the chief organ of the psychical life, the tissue through whose activity the objective changes in the external world, so far as they affect our sense organs, are converted into the subjective changes of consciousness. The nature of this reac- tion constitutes the most difficult pro])lom of physiology and psy- chology, a problem which it is generally believed is beyond the possibility of a satisfactory scientific explanation. For it is held that the methods of science are api)licjil)l(! only to the investiga- tion of the o})j(!ctive — that is, tlic physical and chemical — changes within tlif; ncsrvous matter, while tlu; j)syf!hical reaction is of a nature that cannot be approached through the conceptions or methods of physical science. In other words, there is a physicochcmical mechanism in the brain matter which is capable of giving us a 180 GENERAL PHYSIOLOGY OF THE CEREBRUM. 181 reaction in consciousness. The methods of physiology are adapted to the investigation of the nature of this mechanism, but the reac- tion in consciousness deals with a something which so far as we know is not matter or energy, and which, therefore, is not within the scope of physiological or, indeed, scientific explanation. In what follows, therefore, attention is called only to the mechanical side, — the facts that have been discovered regarding the anatomical structure and the physical and chemical properties of the nervous mechanism. The Histology of the Cortex. — The finer structure of the different regions of the cortex has been the subject of much investi- gation, but in this connection it is only necessary to recall the elementary facts so far as they are useful in physiological explana- tions. Leaving aside differences in the shape and stratification of the cells, it is an interesting fact that the cortex everywhere has a similar structure. It consists of four or five layers more or less clearly distinguishable (see Fig. 81). 1. The superficial, plexiform, or molecular layer, lying imme- diately beneath the pia mater, and having a thickness of about 0.25 mm. In this layer, in addition to the supporting neuroglia, there are found a number of very small nerve cells of several types lying with their processes parallel to the surface of the brain. The axons and dendrites of these small cells terminate within the layer, so that they take no direct part in the formation of the white matter of the brain, but have, probably, a distributive or associa- tive function. In this layer, also, end many of the dendrites of the larger nerve cells of the deeper layers and the terminal arboriza- tion of entering nerve fibers (axons) from other regions. 2. The layer of pyramidal cells. This layer is characterized by the presence of numerous pyramidal cells (see D, Fig. 84), which in general increase in size in passing from the upper to the lower strata. The apices of these cells are directed toward the external surface. The dendrites from the apical process terminate in the molecular layer, while the axon arising from the basal side of the cell passes inwardly to constitute one of the nerve fibers of the medullary portion of the cerebrum. This thick lamina of cells is sometimes subdivided into three layers of small, medium, and large pyramidal cells. 3. The granular or stellate layer composed of many small cells, some of which are pyramidal and some stellate in form, with short branching axons. These latter belong to Golgi's second type of nerve cell. 4. The deep pyramidal layer or layer of large or medium-sized pyramidal cells, similar in form to those in layer two, and the axons of which pass into the medulla or white matter of the cerebrum as nerve fibers. 182 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. 5. The layer of fusiform or polymor- phic nerve cells. A layer of cells whose form is more irregular than that of the pyramidal cells, but whose axons also pass into the medullary portion of the cerebrum, while their dendrites stretch externally into the layers of pyramidal cells. In this layer are found also some cells belonging to the second type of Golgi (Martinotti cells). The medulla of the cerebrum. The white matter of the cerebrum begins immediately below the last-named layer, and consists (1) of nerve fibers which originate from the pyramidal and poly- morphic cells immediately exterior to it, and which carry outgoing impulses from that part of the cortex, and (2) of fibers arising elsewhere in the cortex or in the lower portions of the brain, which termi- nate in the cortex and carry the incoming impulses — impulses which are afferent as regards that part of the cortex. The fibers in this white matter may be classi- fied under three heads: First, the projec- tion system {A, B, C, D, and E of Fig. 82), comprising those fibers, afferent and efferent, which connect the cortex with underlying parts of the central nervous system, — the spinal cord, medulla, pons, midbrain, or thalamus. This great pro- jection system emerges, for the most part, through the internal capsule and the peduncles of the cerebrum. Second, the (issociation system, ('ertain parts of the cortex are seemingly lacking in a projection system; the fibers arising from these parts do not (mter the capsule to make connection with the motor and s(^ii- sory ])aths below, but pass to other parts of the cortex, forming a part of the system of association fibers. This sys- FiR. 81. — Section throuKli ttn; r<>rU:\ of tho third frontal convolution (Broru'H convolu- tion) to Hhow tho Htnitificjilion of I In- rir:rv(! (:)■]]»: 1, Tiio pl<:xiforiii or iiiolnculiir luy<'r; 2, th or inner i)yniniidal layer; .'5, the fuwform or poiyniorpfiic layer (from a camera lucida drawing hy Melius). w i<.' _j GENERAL PHYSIOLOGY OP THE CEREBRUM. 183 oere&^^Utlfl^'^^e^'oflir^^^^^^^ l^Vr^ef [Z Tyf" ?' ^^^e peduncles of the nuclei, and so to the cerebelliim f,r,,ftoi u' ^'^^'^^ "°m the frontal gyr to the pons (pyrainidal) tract; cf the sen oo ( IZJsluswt^^^^^^^ *'he nfotS tract -^F, the fibers of thesuperiorpeSe of the cerebellum r*fih ^'^%K\ ^' t^ea^ditoiy cle uniting with A in the pons ; //fibers of Hie inferf™H^ ' i ' ^^f '"^ °^ the middle pedun- between tlie auditory nucleus knd the inf^ri^l „;?ir T P^'auncle of the cerebellum ; J, fibers n the bulb; Vt. ioirtrventncte VheZume^^^^^^^ horn Starr.) ^ucuumerais reier to the cranial nerves. — (Modified ^fA~Tl%t7ee°r!.',^^^^^^^^ bundles of association 'een frontal and temporal Jen7 cinLlunf: Tll^^^^^^^^ areas; C. fibers (Starr) : A, A, Between adjacent gvrBb^tWeenfrnn/V'' ''T'^^^? 9^ association between frontal and temporal areas rinm.ln'm-' n k f ^ron/al and occipital areas ; C, sciculus uncinatus ; ^T between occioUa and tfm^orT''" ^'"°"/^' -^^^ temporal arks :erior :C.iV, caudate nucleus -OrtlXmus^ ^^^^^' fasciculus longitudinalia tern may be defined as comprising those fibers which connect one part of the cortex with another (Fig. 83). There are short associ- 184 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. ation tracts (.4, A) connecting neighboring convolutions and long tracts passing from one lobe to another. Third, the commissural system, consisting of association fibers that cross the mid-line and connect portions of one cerebral hemisphere ^^'ith the cortex of the other. These fibers make up the commissural bands, known in gross anatomy as the corpus callosum, anterior white commissure, fornix, etc. Physiological Deductions from the Histology of the Cortex. — Cajal* especially lays stress upon some anatomical features which seem to justify certain generalizations of a physiological nature. In the first place, ever}' part of the cortex receives incoming impulses and gives rise to outgoing impulses. Every part of the cortex is, therefore, both a termination of some afferent path and the begin- ning of some efferent path; it is, in other words, a reflex arc of a greater or less degree of complexity. We may suppose that everv^ efferent discharge from any part of the cortex is occasioned by afferent impressions reaching that point from some other part of the nervous system. Whether or not there is such a thing as absolutely spontaneous mental activity cannot be determined by physiology, but on the anatomical side at least all the structures exhibit connections that fit them for reflex stimulation, and many of our apparently spontaneous acts must be of this character. Secondly, all parts of the cortex exhibit an essentially similar structure. Modern physiology has taught that different parts of the cerebrum have different functions, but the differentiation in structure which usually accompanies a specialization in func- tion is not at first very evident. Definite differences in the thickness of the layers, in the size or shape of the cells, or in the character of the fibrillation, have been pointed out (see p. 225), but it is perhaps something of a disappointment to find so little of an anatomical distinction between structures whose reaction in con- sciousness may be separated so widely. Numerous special studies made upon the lamination of different parts of the human cortex (see p. 225), and comparative observations upon the cerebral cor- tex in different vertebrates, have served to give an anatomical foundation for various interesting speculations which subsequent work may or may not confirm, f It is pointed out that if we omit the outer or molecular layer the other cells of the cortex fall into three groups, nanudy, the (jranular layer (3 in Fig. 81), the supra- granular layer (2j, comprising the pyramidal cells external to the granular layer, and the infragranular layer (4 and 5), comprising * Oijal, "Los nouvc'IlcK \(\6x'.n Hur hi stTucturc du .syst6mo norvoux, cto.," • Paris, 1H94. t For a summary of ihcHc views consult Bolt-oii, "Brain," 1910 and 1912, or "Further y^dvanees in FFiysif)h)Ky," Hill, London and New York, 1909; Van V'alkenhurK, "FoHa neiirohioloKiea," 1910, 4, '.i'.iry. GENERAL PHYSIOLOGY OF THE CEREBRUM. 185 the pyramidal and fusiform cells internal to the granular layer. Comparison of the cerebral cortex in the brains of the different vertebrates indicates that the supragranular cells have appeared relatively late in the phylogeny of the vertebrates, and have reached their greatest development in the human brain. The suggestion occurs, therefore, that these cells have a different func- tional significance from those in the infragranular layer. It has been supposed that the supragranular cells mediate the so-called Fig. 84. — A-D, Showing the phylogenetic development of mature nerve cells in a series of vertebrates : a-e, the ontogenetic development of growing cells in a typical mam- mal (in both cases only pyramidal cells from the cerebrum are shown) ; A, frog; B, lizard; C, rat; D, man; a, neuroblast without dendrites; b, commencing dendrites; c, dendrites further developed; d, first appearance of collateral branches; e, further development of collaterals and dendrites. — (From Ramon y Cajal.) higher psychical processes, which characterize man and the related mammalia as compared with the lower vertebrates. The infra- granular cells, on the other hand, constitute a primitive layer which has obvious connections, through projection fibers, with the under- lying parts of the brain and of the body at large. These cells form, therefore, a mechanism through which the brain is connected directly with the rest of the body, and through which the older instinctive reactions are controlled. In the matter of lami- nation and distinct variations in size and appearance of the 186 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. strata of cells and fibers the human cortex shows a greater dif- ferentiation than in the lower animals, and it is especially characterized by a large development of what are known as associational areas (p. 219), particularly in the frontal lobe. In the third place, the central nervous system throughout the vertebrates is constructed upon the same lines, a mechanism of intercomiecting neurons. There is a vast difference in the men- "1 A >■'' ■:'M^d ',>\' './.('».' %%■:■/' • ' « • ^' 1;ivi>M^| ••'^•hvVf?^^ Fig. 85. — Sections throufch corresponding parts of the cortex in: n, Man; 6, dog; b:kJ c, mole, to hIiow the greater separation of tne nerve cells in the higher animals. — ■ (liethe, after Nisal.) tal activity of a frog and a man, but the cortex of the cerebrum show.s a fundamental similarity in structun; in the; two cases. In addition to the variations in stratifi(;ation or lamination referred to above on(! general distinction that comparative anatomy is able to make is that in the higher animals the greater mental develop- ment is associated with a greater complexity and ricliiuiss in the con- nections of the neurons. As shown in Figs. 84 and 85, the number of processes, particularly the dendritic process(!S, is much gn^ater in the cortical cells of the higher animals; or, to put this fact in another GENERAL PHYSIOLOGY OF THE CEREBRUM. 187 way, the number of cells in the cortex of the higher animals is much less for an area of the same size than in lower animals. The amount of in-between substance or the richness of the network of processes is increased. This anatomical fact would indicate that the greater mental activity in the higher animals is dependent, in part, upon the richer interconnection of the nerve cells, or, expressed physiologic- ally, our mental processes are characterized by their more numer- ous and complex associations. A visual or auditory stimulus that, in the frog, for instance, may call forth a comparatively simple motor response, may in man, on account of the numerous associa- tions with the memory records of past experiences, lead to psychi- cal and motor responses of a much more intricate and indirect character. Extirpation of the Cerebrum. — One of the methods used in physiology to determine the general functional value of the cerebral hemispheres has been to remove them completely, by surgical operation, and to study the effect upon the psychical responses of the animal. Upon the cold-blooded animals and the birds the operation may be perfonned with ease, but in these animals the positive results are not striking and the experiments are valuable chiefly for their negative results. If the cerebral hemispheres are removed from the frog, for example, the animal after recovering from the immediate effects of the operation — that is, the effects of the anesthetic and the shock — shows surprisingly little difference from the normal animal. It maintains a normal posture and shows no loss at all in its power of eciuilibration. When placed on its back it quickly regains its usual position. If thro\Mi into water it swims to a solid support and crawls out like a normal animal. It jumps when stimulated and is careful to avoid obstacles placed in its way, showing that its \dsual reflexes are not impaired. It is said, however, that the more complicated reactions that depend upon the memory of past experiences or the instincts are absent or imperfect. This latter peculiarity is manifested most impressively in birds (pigeons) after removal of a part or all of the cerebnim. As a result of such an operation, the nervous, active animal is changed at once to a stupid, lethargic creature which reacts only when stimulated. It sits in a drowsy attitude, with its head drawn in to the shoulders, its eyes closed, and its feathers slightly erected; occasionally it will open its eyes, stretch the neck, gape, preen its feathers perhaps, and then sink back into its somnolent attitude. The animal in this condition maintains its equilibrium perfectly, flies well if throAvn into the air and perches comfortably upon a narrow support. It may be kept alive apparently indefinitely by appropriate feeding and so long as it is well fed retains its stupid and impassive appearance. If allowed to starve for a while it 188 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM. becomes restless from the effects of hunger, may walk to and fro, and peck aimlessly at the ground. If surrounded by grain it may peck at the separate grains, but never actuall}- seizes one in its beak and swallows it. The striking defect in these animals is the loss of those responses that depend upon memory of past or in- herited experiences. Its motor reactions are all of a simple kind. If placed upon a hot plate it will, for a time, lift first one foot, then the other, and finally squat, but never flies away. When dosing a loud noise awakens it, but it exhibits no signs of fear, and quickly relapses into somnolence when the auditory stimulus ceases. The one positive conclusion that we may draw from the behavior of these animals is that in them the cerebrum is the organ in which the memory associations are mediated, and that when it is removed the actions of the animal become much more direct and predictable, since the stimulus awakens no associations with past experiences. The complete removal of the cerebrum in mam- mals is attended with more difficulty. When taken out at once by a single operation, the animal survives but a short time and the permanent effects of the operation cannot be detected. Goltz,* however, has succeeded, in dogs, in removing by a peculiar opera- tion all of the cerebral cortex. The operation was performed in several successive stages with an interval of several months between.. In the most successful experiment the animal was kept alive for a year and a half and the postmortem examination showed that all of the cortex had been removed except a small portion of the tip of the temporal lobe, and this latter, since its connection with the other parts of the brain had been destroyed, was, of course, functionless. In addition, a large part of the corpora striata and the thalami and a small portion of the midbrain had been re- moved. The behavior of this animal was studied carefully. After the immediate effects of the operation — paralysis, etc. — had disap- peared the animal moved easily; in fact, showed a tendency to keep moving continually. There was no permanent paralysis of the so- called voluntary movements. He answered to sensory stimuli of various kinds, but not in an intelligent way. If, for instance, a painful stimulus was applied to the skin, he would growl or bark, and turn his head toward the place stimulated; Ijut did not attempt to bite. No caressing could arouse signs of pleasure, and no- threatening signs of fear or anger. Like the pigeon, the most con- spicuous defect in the animal was a lack of intelligent response, — that is, the responses to sensory stimuli were simple, and evidently did not involve complex associations with past experiences. His memory records, for the most ])art, had lieen destroyed. Goltz records that when starved he showed signs of liuiigcr, and that * Goltz, "Arfhiv f.