The Integrative Action of the Nervous System

ELECTRICITY AND MATTER. By Joseph John Thomsok, d.sc.ll.d., PH.D., F.R.8., Fellow of Trinity College and Cavendish Professor of Experimental Physics, Cambridge University. {FouHh Printing.) THE INTEGRATIVE ACTION OF THE NERVOUS SYSTEM. By CHABLK8 S. Sherrington, d.sc, m.d.. hon. ll.d. tor., f.r.s., Holt Pro- fessor of Physiology, University of Liverpool. {Sixth Printing.) RADIOACTIVE TRANSFORMATIONS. By Ernest Rutherford, d.sc, LL.D., F.R.S. , Macdonald Professor of Physics, McGill University. (Second Printing.)

MODYNAMICS TO CHEMISTRY. By Dr. Walther Nernst, Pro- fessor and Director of the Institute of Physical Chemistry in the University of Berlin. PROBLEMS OF GENETICS. By William Batesov, m.a., f.r.s.. Director of the John Innes Horticultural Tnstitution, Merton Park, Surrey, England. {Second Printing.) STELLAR MOTIONS. With Special Reference to Motions Determined by Means of the Spectrograph. By William Wallace Campbell, sc.d., LL.D., Director of the Lick Observatory, University of California. {Second Printing.)

THEORIES OF SOLUTIONS. By Svante Arrhenius, ph.d., sc.d., m.d.. Director of the Physico-Chemical Department of the Nobel Institute, Stockholm, Sweden. {Third Printing.) IRRITABILITY. A Physiological Analysis of the General Effect of Stimuli in Living Substances. By Max Verworn. m.d., ph.d., IYo- fessor at Bonn Physiological Institute. (Second Printing.) PROBLEMS OF AMERICAN GEOLOGY. By William North Rice, Frank D. Adams, Arthur P. Coleman, Charles D. Walcott, Waldemar LiNDGREN, Frederick Leslie Ransome, and William D. Matthew. {Second Printing.)

THE PROBLEM OF VOLCANISM. By Joseph Paxson Iddings, ph.b., BCD. {Second Printing.) PHYSIOLOGY OF BREATHING. By John Scott Haldane, m.d.. LL.D., F.R.S., Fellow of New College, Oxford University. {Second Printing.) A CENTURY OF SCIENCE IN AMERICA: WITH SPECIAL REFER- ENCE TO THE AMERICAN JOURNAL OF SCIENCE. 1818-1918. By Edward Salisbury Dana, ph.d., Charles Schuchert, ll.d.. Herbert E. Gregory, ph.d., the Late Joseph Barbell, ph.d., sc.d., George Otis Smith, vh.d.. Director of the United States Geological Stirvey, Richard SwANN Lull, ph.d., Louis V. Pirsson, m.a., William E. Ford, ph.d., R. B. SosMAN, PH.D., Physicist at the Geophysical Laboratory of the Carnegie Institution, Horace L. Wells, sc.d., Harry W. Foote, ph. D., Leigh Page, ph.d., Wesley R. Coe, ph.d., and George L. Goodale,

HoU Prqfessor qf Physiology in the University qf Liverpool, Honorary Member qflke American Physiological Society, etc. In the year 1883 a legacy of eighty thousand dollars was left to the President and Fellows of Yale College in the city of New Haven, to be held in trust, as a gift from her children, in memory of their beloved and hon- ored mother Mrs. Hepsa Ely Silliman. On this foundation Yale College was requested and directed to establish an annual course of lectures de- signed to illustrate the presence and providence, the wisdom and goodness of God, as manifested in the natural and moral world. These were to be designated as the Mrs. Hepsa Ely Silliman Memorial Lectures. It was the belief of the testator that any orderly presentation of the facts of nature or history contributed to the end of this foundation more effectively than any attempt to emphasize the elements of doctrine or of creed ; and he therefore provided that lectures on dogmatic or polemical theology should be excluded from the scope of this foun- dation, and that the subjects should be selected rather from the domains of natural science and history, giving special prominence to astronomy, chemistry, geology, and anatomy.

It was further directed that each annual course should be made the basis of a volume to form part of a series constituting a memorial to Mrs. Silliman. The memo- rial fund came into the possession of the Corporation of Yale University in the year 1902; and the present volume constitutes the second of the series of memorial lectures. The first volume in this series was "Electricity and Matter," by Prof. J. J. Thomson, of Cambridge University. The pressure of varied work has prevented my forward- ing the text of these lectures for publication so early as I could have wished, and I take this occasion of express- ing my regret at the delay. The circumstance that thus impels me to preface with a few words their issue affords me also the opportunity of recording how much I am indebted to President Hadley and the authorities of Yale University for their kindness during a visit which I shall ever remember with pleasure. To Pro- fessor Chittenden, Director of the Sheffield Scientific School of the University, I owe further a debt of grati- tude for unstinted assistance open to me from him on all occasions.

Argument : The nervous system and the integration of bodily reactions. Characteristics of integration by nervous agency. The unit mechanism in integration by the nervous system is the reflex. Co-ordination of reflexes one with another. Co- ordination in the simple reflex. Conduction in the reflex-arc. Function of the receptor to lower for its reflex-arc the threshold value of one kind of stimulus and to heighten the threshold value of all other kinds of stimuli for that arc : it thus confers selective excitability on the arc. Differences between con- duction in nerve-trunks and in reflex-arcs respectively. These probably largely referable to the intercalation of synaptic mem- branes in the conductive mechanism of the arc. Latent time of reflexes. Reflex latency inversely proportional to intensity of stimulation. Latency of initial and incremental reflexes. None of the latent interval consumed in establishing connec- tion between the elements of a resting arc. After- discharge a characteristic of reflex reactions. Increase of after-discharge by intensification of the stimulus, or by prolongation of short stimuH. " Inertia " and " momentum " of reflex-arc reactions.

CO-ORDINATION IN THE SIMPLE REFLEX {continued) 36 Argument : Reflex-arcs show high capacity for summing excita- tions. Irreversibility of direction of conduction in reflex-arcs. Reversibility of direction of conduction in certain nerve-nets, e. g. that of Medusa. Independence between the rhythm of the reflex-discharge and the rhythm of the external stimulus exciting it. Refractory phase in reflexes ; in the eyelid-reflex ; in the scratch-reflex. The neuronic construction of the reflex- arc of the scratch-reflex. Long descending proprio-spinal tracts revealed by the method of "successive degeneration." The "final common path" and the "afferent arc." Intra- spinal seat of the refractory phase of the scratch-reflex. The value of refractory phase in the co-ordination of the swimming of Medusa. Its value in the co-ordination of the scratch-reflex. Significance of the intraspinal situation of the refractory phase of the scratch-reflex. Other instances of "central" refractory phase.

Argument: Correspondence between intensity of stimulus and intensity of reflex reaction. Differences between different re- flexes in this respect. Functional solidarity of the intraspinal group of elements composing a reflex "centre." Sensitivity of reflexes, as compared with nerve-trunks, to asphyxial and anaemic conditions, and to anaesthetic and certain other drugs. Functional significance of the neural perikarya. Reflexes of double-sign. Reflexes of successive double-sign, and of simultaneous double-sign. Evidence of reciprocal innervation in reflexes. Reflex inhibition of the tonus of skeletal muscles. Reflex inhibition of the knee-jerk. Time-relations and other characters of reflex inhibition as exemplified by the flexion- reflex. Other examples of inhibition as part of reflex recipro- cal innervation. The seat of this reflex inhibition is intraspinal. Conversion of reflex inhibition into reflex excitation by strych- nine and by tetanus toxin. Significance of the **' central " situation of reflex inhibition in the cases here dealt with.

Argument: The "simple reflex" a convenient but artificial ab- straction. Compounding of reflexes. The principle of the common path. Relative aperiodicity of the final common path. Afferent arcs which use the same final common path to dif- ferent effect have successive but not simultaneous use of it *•' Allied " reflexes. Allied reflexes act harmoniously, are capable of simultaneous combination, and in many cases reinforce one another's action on the final common path. " Antagonistic " reflexes. AlHance or coalition occurs be- tween (i) individual reflexes belonging to the same "type- reflex," (2) certain reflexes originated by receptors of different species but situate in the same region of surface, (3) certain reflexes belonging to proprio-ceptive organs secondarily ex- cited by reflexes initiated at the body-surface (the three fields of reception, extero-ceptive, intero-ceptive, and proprio- ceptive), (4) certain reflexes initiated from widely separate but functionally interconnected body-regions. Alliance between reflexes exemplified in inhibitory actions as well as in excitatory. Antagonistic reflexes interfere, one reflex deferring, intemipt- ing, or cutting short another, or precluding the latter altogether from taking effect on the final common path. Intraspinal

Page seat of the interference. Compound reflexes may interfere in part. The place ( ? synapse) where convergent afferent paths impinge on a common path constitutes a mechanism of co- ordination. The convergence of afferent paths to form com- mon paths occurs with great frequency in the central nervous system. A question whether any reflexes are in the intact organism wholly neutral one to another. Argument: Combination of reflexes simultaneously proceeding. Spread of reflex-response about a focus. Gray matter and lines of reflex resistance. " Short " reflexes and " long " re- flexes. Rules decipherable in the spread of reflex reaction. Pfliiger's "laws" of spinal irradiation. The "reflex figure." Variability of reflex result. Irradiation of a reflex attaches itself to the problem of the simultaneous combination of reflexes. Co-ordination of reflex result obtains even when large mixed afferent nerve-trunks are stimulated. The move- ment excited by stimulation of the motor spinal nerve-root does not really resemble a movement evoked reflexly or by the will. Extent of simultaneous combinations of reflexes. Simultaneous stimuli arrange themselves naturally in constel- lations in which some component is usually of pre-eminent intensity. The resulting compound reaction has both positive and negative sides.

Argument: Co-ordination of reflex sequences. Chain-reflexes (Loeb). Overlapping of successive stimuli in time. The sequence of allied reflexes. Spread of bahnung, '* immediate induction." Sequence of antagonistic reflexes. The role of inhibition in this transition. Views of the nature of inhibition : Rosenthal, Wundt, E. Hering, Gaskell, Verworn, J. S. Mac- donald. The " interference " of reflexes. " Alternating re- flexes." W. Macdougall's view of "drainage of energy." " Compensatory reflexes." Factors determining the issue of the competition between antagonistic reflexes. " Successive induction." Rebound-effects in spinal reactions; tend to restore reflex equilibrium. Fatigue in reflexes. Relative high resistance to fatigue possessed by the final common path, /. e. motor neurone. Intensity of reaction a decisive factor in

Page the competition of afferent arcs fpr possession of the final common path. Noci-ceptive nerves. Prepotency of reflexes generated by receptors that considered as sense organs initiate sensations with strong affective tone. Resistance of tonic reflexes to fatigue. All these factors render the conductive pattern of the central nervous system mutable between certain limits. Argufne?it : Reflexes as adapted reactions. The purposes of various type-reflexes. Shock a difficulty in deciphering the purpose of reflexes. Characters of spinal shock. Its inci- dence confined to the aboral side of the transection. Its difference in severity in different reflexes and in different animals. Shock referable not to the irritation of the trauma but to the cutting off by the trauma of some supra-spinal influence.

Pseudaffective reflexes afford opportunity for determining the pain-path in the spinal cord. This ascends both lateral columns, chiefly the one crossed from side of stimulation. The " chloroform cry " in decerebrate animals. Mimesis of pleasure as compared with mimesis of pain. The bodily res- onance of the emotions. The theory of James, Lange, and Sergi. Emotional expressions in dogs deprived of visceral and largely of bodily sensation. Argument: Remarkable that electrical stimuli applied to the organ of mentality yield with regularity certain localized movements from certain restricted areas of its surface. Func- tional topography of " motor " cortex in the chimpanzee, orang-utan, and gorilla. The cerebral fissures, not functional boundaries. The anthropoid ape has a direct pyramidal tract like that of man. Recovery of function not due to symmetrical part of opposite hemisphere taking on supplemental work. Inhibition as elicitable from the cortex. Reciprocal innervation of antagonistic eye-muscles. Reciprocal inhibition in other muscular groups. Seat of the inhibition subcortical in these cases. Reciprocal innervation in willed movements. Pre- ponderant representation in the " motor " cortex of the same movements as are preponderantly elicitable as local reflexes

om the cord and bulb. Scanty representation of certain movements as cortical and local spinal reactions alike. Ap- pearance under strychnine and tetanus toxin of movements reversing the normal direction of the preponderance. This due to these agents transmuting reciprocal inhibition into excitation. Decerebrate rigidity, A system of tonic innerva- tion in action. Strychnine and tetanus toxin augment this innervation. Hughlings Jackson's '* co-operative antagonism " of paired systems of innervation, one tonic, the other phasic. Decerebrate rigidity and hemiplegic rigidity. The relation of the cortex to receptor organs ; the pre-eminent representation in it of the " distance-receptors."

Argument: The primitive reflex arc. The diffuse nervous sys- ^ tem and the gray-centred nervous system ; the central nervous ] system a part of the latter. Nervous integration of the seg- j ceptive field. Special refinements of the receptor-organs of 1 receptors " ; the projicience of sensations. Extensive inter- j nuncial paths belonging to " distance-receptors." " Distance- \ receptors " initiate precurrent reactions. Consummatory reactions ; strong affective tone of the sensations adjunct to

physiologically conceived. Proprio-ceptive arcs excited sec- I ondarily to other arcs. Close functional connection between \ the centripetal impulses from muscles and from the labyrinth. I Tonic reflexes (of posture, etc.) and compensatory reflexes are characteristic reactions of this combined system. Nervous \ integration of the segmental series. Restriction of segmental I distribution a factor in bodily integration. The cerebellum _ { Argument: Nervous integration in relation to bodily movement j

and to sensation compared. Sensual fusion in a relatively \ simple instance of binocular vision. The rotating binocular lantern. Flicker sensations generated at "corresponding retinal \ Page points " ; absence of evidence of their summation or interfer- ence either with synchronous or asynchronous flicker of similar frequency. Their interference when the flicker is of dissimilar frequency. Talbot's law not applicable to "corresponding points.'* Fechner's paradox. Prevalence of contours under Weber's law and under binocular summation compared. The physiological initial stages of the reaction generated in either of a pair of corresponding retinal points proceeds without touching the apparatus of the twin point. Only after the sen- sations initiated from the right and left " points " have been elaborated so far as to be well amenable to introspection does interference between the reactions of the two (right and left) eye-systems occur. The convergence of nerve-paths from the right and left retinae respectively toward one cerebral region is significant of union for co-ordination of motor reaction rather than for synthesis of sensation. Resemblances between motor and sensual reactions. The cerebrum pre-eminently the organ of and for the adaptation of reactions.

Argument: The nervous system and the integration of bodily reactions. Characteristics of integration by nervous agency. The unit mechan' ism in integration by the nervous system is the reflex. Co-ordination of reflexes one with another. Co-ordination in the simple reflex. Conduction in the reflex-arc. Function of the receptor to lower for its reflex-arc the threshold value of one kind of stimulus and to heighten the threshold value of all other kinds of stimuli for that arc: it thus confers selective excitabiHty on the arc. Differences between conduction in nerve-trunks and in reflex-arcs respectively. These probably largely referable to the intercalation of synaptic mem- branes in the conductive mechanism of the arc. Latent time of reflexes. Reflex latency inversely proportional to intensity of stimu- lation. Latency of initial and incremental reflexes. None of the latent interval consumed in establishing connection between the elements of a resting arc. After- discharge a characteristic of reflex re- actions. Increase of after-discharge by intensification of the stimulus, or by prolongation of short stimuli. " Inertia " and " momentum " of reflex-arc reactions.

Nowhere in physiology does the cell-theory reveal its presence more frequently in the very framework of the argument than at the present time in the study of nervous reactions. The cell- theory at its inception depended for exemplification largely on merely morphological observations ; just as these formed origi- nally the almost exclusive texts for the Darwinian doctrine of evolution. But with the progress of natural knowledge, biology has passed beyond the confines of the study of merely visible form, and is turning more and more to the subtler and deeper sciences that are branches of energetics. The cell-theory and the doctrine of evolution find their scope more and more, there- fore, in the problems of function, and have become more and

more identified with the aims and incorporated among the methods of physiology. The physiology of nervous reactions can be studied from three main points of view. In the first place, nerve-cells, like all other cells, lead indi- vidual lives, — they breathe, they assimilate, they dispense their own stores of energy, they repair their own substantial waste ; each is, in short, a living unit, with its nutrition more or less centred in itself. Here, then, problems of nutrition, regarding each nerve-cell and regarding the nervous system as a whole, arise comparable with those presented by all other Hving cells. Although no doubt partly special to this specially differentiated form of cell-life, these problems are in general accessible to the same methods as apply to the study of nutrition in other cells and tis^sues and in the body as a whole. We owe recently to Verworn and his co-workers advances specially valuable in this field.

Secondly, nervous cells present a feature so characteristically developed in them as to be specially theirs. They have in ex- ceptional measure the power to spatially transmit (conduct) states of excitement (nerve-impulses) generated within them. Since this seems the eminent functional feature of nerve-cells wherever they exist, its intimate nature is a problem co-extensive with the existence of nerve-cells, and enters into every question regarding the specific reactions of the nervous system. This field of study may be termed that of nerve-cell conduction.

But a third aspect which nervous reactions offer to the physi- ologist is the integrative. In the multicellular animal, especially for those higher reactions which constitute its behaviour as a social unit in the natural economy, it is nervous reaction which par excelleiice integrates it, welds it together from its compo- nents, and constitutes it from a mere collection of organs an animal individual. This integrative action in virtue of which the nervous system unifies from separate organs an animal possess- ing solidarity, an individual, is the problem before us in these lectures. Though much in need of data derived from the two previously mentioned lines of study, it must in the meantime be carried forward of itself and for its own sake.

The integration of the animal organism is obviously not the result solely of any single agency at work within it, but of several. Thus, there is the mechanical combination of the unit cells of the individual into a single mass. This is effected by fibrous stro- mata, capsules of organs, connective tissue in general, e. g, of the liver, and indeed the fibrous layer of the skin encapsulating the whole body. In muscles this mechanical integration of the organ may arrive at providing a single cord tendon by which the tensile stress of a myriad contractile cells can be additively

ncentrated upon a single place of application. Integration also results from chemical agency. Thus, repro- ductive organs, remote one from another, are given solidarity as a system by communication that is of chemical quality; lactation supervenes post pat turn in all the mammary glands of a bitch subsequent to thoracic transection of the spinal cord severing all nervous communication between the pectoral and the inguinal mammae (Goltz). In digestive organs we find chemical agency co-ordinating the action of separate glands,

d thus contributing to the solidarity of function of the diges- ive glands as a whole. The products of salivary digestion on reaching the pyloric region of the stomach, and the gastric secretion on reaching the mucosa of the duodenum, make there substances which absorbed duly excite heightened secretion of gastric and of pancreatic juice respectively suited to continue the digestion of the substances initiating the reaction (Bayliss and Starling, Edkins). Again, there is the integrating action effected by the circulation of the blood. The gaseous exchanges at one limited surface of the body are made serviceable for the life of every living unit in the body. By the blood the excess o1 heat produced in one set of organs is brought to redress the loss of heat in others; and so on.

But the integrative action of the nervous system is different from these, in that its agent is not mere intercellular material, as in connective tissue, nor the transference of material in mass, as by the circulation ; it works through living lines of stationary cells along which it despatches waves of physico-chemical dis- turbance, and these act as releasing forces in distant organs where they finally impinge. Hence it is not surprising that nervous integration has the feature of relatively high speedy a feature peculiarly distinctive of integrative correlation in animals as contrasted with that of plants, the latter having no nervous system in the ordinary sense of the word.

The nervous system is in a certain sense the highest expres- sion of that which French physiologists term the milieu interne. With the transition from the unicellular organism to the multi- cellular a new element enters general physiology. The phe- nomena of general physiology in the unicellular organism can be divided into two great groups ; namely, those occurring within the cell, intracellular, and those occurring at the surface of the cell, in which forces that are associated with surfaces of separa- tion have opportunity for play at the boundary between the organism and its environment But in the multicellular organ- ism a third great group of phenomena exists in addition ; namely, those which are interceWulsLV, occurring in that complex material which the organism deposits in quantity in the intercellular inter- stices of its mass as a connecting medium between its individual living units.

When the intercellular substance is solid, e» g. in many con- nective tissues, the physiological agencies for which it afifords a field of operation are mechanical rather than chemical. The organism obtains from it scaffolding for supporting its weight, levers for application of its forces, etc., and in this degree the intercellular material performs an integrative function. Where the intercellular material is fluid, as in blood, lymph, and tissue juice, it constitutes a field of operation for agencies chemical rather than mechanical. The intricacy of the chemistry of this milieu interne is shown by nothing better than by the specificity of the precipitins, etc., the intercellular media for each separate animal species yielding its own particular kinds. The cells of a multicellular organism have therefore in addition to an environ- mental medium in which the organism as a whole is bathed, and to which they react either directly or through the medium of surface cells, an internal medium created by their organism itself, and in many respects specific to itself.

But the internal interconnection of the multicellular organism is not restricted to intercellular material. Intercellular material is, after all, no living channel of communication, delicately re- sponsive to living changes though it may be. An actually living internal bond is developed. When the animal body reaches some degree of multicellular complexity, special cells assume the ex- press office of connecting together other cells. Such cells, since their function is to stretch from one cell to another, are usually elongated ; they form protoplasmic threads and they intercon- nect by conducting nervous impulses. And we find this living bond the one employed where, as said above, speed and nicety of time adjustment are required, as in animal movements, and also where nicety of spatial adjustment is essential, as also in animal movements. It is in view of this interconnecting func- tion of the nervous system that that field of study of nervous reactions which was called at the outset the third or integrative, assumes its due importance. The due activity of the intercon- nection resolves itself into the co-ordination of the parts of the animal mechanism by reflex action.