The Integrative Action of the Nervous System

inhibition effect into excitation effect by the hypothesis of reflex antagonistic sets of fibres, oppositely poisoned centrally, com- mingled in these afferent nerves. Moreover, when a hamstring muscle is taken as the test muscle, a similar conversion of inhibition into excitation (contraction) by strychnine is seen under the crossed extension-reflex. . This reflex, elicitable through the skin or various afferent nerves of the contralateral hind limb, normally excites the knee-extensor to contraction and inhibits the hamstrings, the knee-flexors. Under strychnine its reflex inhibition of the hamstring muscle is converted into reflex excitation (contraction) of that muscle. The observations, as they stand at present, incline me to the inference that the action of the alkaloid is to convert in the spinal cord the process of inhibition — whatever that may essentially be — into the process of excitation — whatever that may essentially be.^ The reflex nexus was pre-existent, but the effect across it was signalized by a different sign, namely minus prior to the strychnine or tetanus toxin, instead oipliis, as afterward (See Fig. 37).

The action of the toxin in respect to inhibition resembles that of strychnine closely in several ways. Thus, in the stages of the disease in which the tetanus is still ** local " and manifested in one limb, namely that (^e. g., the hind limb) which received the toxin injection, the toxin early converts into excitation the reflex inhibition of the extensor muscles, normally obtainable from the internal saphenous nerve, but that obtainable from the peroneal and popliteal nerves, and from the hamstring nerve, remains unreversed, though the strength of the inhibitory effect of these nerves may be very distinctly less than normal. Later, as the condition progresses, the inhibitory effect normally be-

1 From the predominance of extension as a reflex in the hind limb of the * spinal * frog under strychnine, flexion predominating normally, Cushny has recently (3d Edition of Textbook of Pharmacology and Therapeutics, Philadelphia, 1903) argued much as I did (Joum. of Physiology, vol. xiii, 1892), also from experiments on the frog, that strychnine acts as a destroyer of reciprocal innervation. The hind limb of the frog, owing to the number of double-joint muscles, is, as said in the text, not a preparation wherewith it seems possible to definitely test this argument or inference. But the evidence obtained from more suitable preparations fully bears out, as the text shows, the earlier inferences drawn by Cushny and myself regarding the frog. [October, 1905. C. S. S.]

longing to the peroneal and popliteal nerves becomes actually reversed into excitation. Finally, even that of the hamstring nerve itself is reversed. This is the same sequence of effect pursued by progressive increase of dosage of strychnine. One difference that seems apparent between the action of the tetanus toxin and the strychnine in these observations is that in the relatively slow progress of the tetanus it is easy to note the stage in which the conversion of the inhibition effect into excitation effect has occurred, while there is yet none of that obvious lowering of the threshold of reflex reaction which early marks the course of strychnine poisoning, and has been drawn attention to by many observers.

In experiments on the hind limb, I have usually introduced the toxin into the sciatic trunk well below the hamstring branch, more rarely into the hamstring nerve as well, or alone. I have found the inhibitory effect of the internal saphenous nerve (stimulated in its course below the knee) converted to excitation in forty-eight hours from the time of inoculation. In the gradual progress of the condition, I have several times found the ham- string nerve produce slight inhibition of the extensor if the initial posture taken at the knee be extension, and yet produce distinct excitation of the extensor if the initial posture taken at the knee be flexion. This recalls the results of v. Uexkiill in Ophioglypha and Echinus.*-®^*

The conversion of inhibition into excitation by tetanus toxin is demonstrable, as is that by strychnine, with the reflexes of the fore limb as well as with those of the hind limb, and in the ** decerebrate " animal as well as in the merely ** spinal. " We can understand what havoc such a change must work in the co-ordinative mechanisms.^^ The observed difference between the facility with which strychnine and tetanus toxin convert the in- hibition by the hamstring nerve into excitation, and that with which they convert the inhibition of the other limb-nerves mentioned, does not seem referable to a different action on muscular affer- ents and cutaneous afferents respectively. Stimulation of the central end of the vasto-cnireus nerve evokes normally inhibition of the hamstrings of the opposite limb, but under strychnine it

evokes their contraction. In that case, therefore, the strychnine converts with facility the inhibition by a muscular afferent into excitation, just as with the skin nerves mentioned. That strychnine and tetanus can convert a central inhibition into an excitation, and that the various normal reflex spinal in- hibitions show differences one from another in the ease with which they undergo conversion into excitation makes the syn- chronous excitation of antagonistic muscles in certain willed actions less difficult to understand. Vasodepressor reflexes under chloral (v. Cyon), chloroform (Bayliss),^*^ etc., change into vasoconstrictor under curare, morphia, etc. But the re- versal does not appear to occur with equal facility in all afferent nerves alike. It is stated to be impossible to obtain any vascular reflex, but a depressant one from the " depressor " nerve. This nerve, arising in the heart (v. Cyon)*^ and aorta (Koster and A. Tschermak),^^^ may in a sense be considered the afferent nerve of the muscle antagonistic to the ring muscu- lature of the arteries, namely, the muscle whose tonus it reflexly depresses. It is in that way comparable with the afferent nerve of the hamstring muscles in relation to the extensors of the knee. The depressor action of the hamstring nerve on the knee-extensor seems, as just said, in my experience, particu- larly resistant to conversion from inhibition into excitation by strychnine.

In examples of reciprocal innervation drawn from lowlier organisms and visceral organs we find the inhibition a periph- eral phenomenon, that is, with its seat outside the central nervous system. On the other hand, in examples drawn from higher organisms and skeletal movements, the inhibition is a central phenomenon, e.g.^ intraspinal. The same considerations which traced the line of adaptation in placing the seat of the refrac- tory phase of spinal reflexes intraspinally between the ending of receptive neurone and the commencement of motor neurone, apply here to central inhibition. The significance of the cen- tralization of these processes of refractory phase and reciprocal inhibition seems the same as we may infer for the centrality of the central nervous system itself {vide infi-a^ Lecture IX).

Argument: The "simple reflex" a convenient but artificial abstraction. Compounding of reflexes. The principle of the common path. Rela- tive aperiodicity of the final common path. Afferent arcs which use the same final common path to different 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. Alliance or coalition occurs between (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 propriocep- tive organs secondarily excited 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 re- flexes exemplified in inhibitory actions as well as in excitatory. An- tagonisitc reflexes interfere, one reflex deferring, interrupting, or cutting short another, or precluding the latter altogether from taking effect on the final common path. Intraspinal seat of the interference. Compound reflexes may interfere in part. The place ( ? synapse) where convergent afferent paths impinge on a common path consti- tutes a mechanism of co-ordination. The convergence of afferent paths to form common 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.

We have hitherto dealt with reflex reactions under the guise of a convenient but artificial abstraction, — the simple reflex. That is to say, we have fixed our attention on the reaction of a reflex-arc as if it were that of an isolable and isolated mechanism, for whose function the presence of other parts of the nervous system and of other arcs might be negligible and wholly indif- ferent. This is improbable. The nervous system functions as a whole. Physiological and histological analysis finds it con- nected throughout its whole extent. Donaldson opens his

description of it with the remark: "A group of nerve-cells dis- connected from the other nerve-tissues of the body, as muscles and glands are disconnected from each other, would be without physiological significance.** A reflex reaction, even in a " spinal animal " where the soHdarity of the nervous system has been so trenchantly mutilated, is always in fact a reaction conditioned not by one reflex-arc but by many. A reflex detached from the general nervous condition is hardly realizable.

The compounding together of reflexes is therefore a main probleni in nervous co-ordination. For this problem it is im- portant to recognize a feature in the architecture of the gray- centred (synaptic) nervous system which may be termed " t/te principle of the common path^^^ If we regard the nervous system of any higher organism from the broad point of view a salient feature in its scheme of construction is the following. At the commencement of every reflex-arc is a receptive neurone extending from the receptive surface to the central nervous organ. This neurone forms the sole avenue which impulses generated at its receptive point can use whithersoever be their destination. This neurone is therefore a path exclu- sive to the impulses generated at its own receptive point, and other receptive points than its own cannot employ it. A single receptive point may play reflexly upon quite a number of differ- ent efl*ector organs. It may be connected through its reflex path with many muscles and glands in many different regions. Yet all its reflex-arcs spring from the one single shank or stem, i. e.^ from the one afferent neurone which conducts from the receptive point at the periphery into the central nervous organ.

But at the termination of every reflex-arc we find a final neurone, the ultimate conductive link to an effector organ, (muscle or gland). This last link in the chain, e. g, the motor neurone, differs obviously in one important respect from the first link of the chain. It does not subserve exclusively impulses generated at one single receptive source, but receives impulses from many receptive sources situate in many and various regions of the body. It is the sole path which all impulses, no matter

whence they come, must travel if they are to act on the muscle- fibres to which it leads. Therefore, while the receptive neurone forms a private path exclusively serving impulses of one source only, the final or efferent neurone is, so to say, a public path, common to impulses arising at any of many sources of reception. A receptive field, e, g.y an area of skin, is analyzable into receptive points. One and the same effector organ stands in reflex connection not only with many individual receptive points but even with many various receptive fields. Reflexes generated in manifold sense- organs can pour their influence into one and the same muscle. Thus a limb-muscle is the terminus ad quem of many reflex- arcs arising in many various parts of the body. Its motor- nerve is a path common to all the reflex-arcs which reach that muscle {cf. infra^ Fig. 44, p. 148).

Reflex-arcs show, therefore, the general features that the initial neurone of each is a private path exclusively belonging to a single receptive point (or small group of points) ; and that finally the arcs embouch into a path leading to an effector organ ; and that their final path is common to all receptive points whereso- ever they may lie in the body, so long as they have connection with the effector organ in question. Before finally converging upon the motor neurone the arcs converge to some degree. Their private paths embouch upon internuncial paths common in various degree to groups of private paths. The terminal path may, to distinguish it from internuncial common paths, be called the final common path. The motor nerve to a muscle is a collection of final common paths.

Certain consequences result from this arrangement. One of these seems the preclusion of essential qualitative difference between nerve-impulses arising in different afferent nerves. If two conductors have a tract in common, there can hardly be essential qualitative difference between their modes of conduc- tion ; and the final common paths must be capable of respond- ing with different rhythms which different conductors impress upon it. It must be to a certain degree aperiodic. If its dis- charge be a rhythmic process, as from many considerations it

appears to be, the frequency of its own rhythm must be capable of being at least as high as that of the highest frequency of any of the afferent arcs that play upon it ; and it must be able also to reproduce the characters of the slowest.^ A second consequence is that each receptor being dependent for final communication with its effector organ upon a path not exclusively its own but common to it with certain other recep- tors, such nexus necessitates successive and not simultaneous use of the common path by various receptors using it to different or opposed effect. When two receptors are stimulated simultane- ously, each of the receptors tending to evoke reflex action that for its end-effect employs the same final common path but em- ploys it in a different way from the other, one reflex appears without the other. The result is this reflex or that reflex, but not the two together. ^^^ Excitation of the central end of the afferent root of the eighth or seventh cervical nerve of the monkey evokes reflexly in the same individual animal sometimes flexion at elbow, sometimes extension. If the excitation be preceded by excitation of the first thoracic root the result is usually extension : if preceded by excitation of the sixth cer- vical root it is usually flexion. Yet though the same root may thus be made to evoke reflex contraction of the flexors or of the extensors, it does not, in my experience, evoke contraction in both flexors and extensors in the same reflex-response. Of the two reflexes on extensors and flexors respectively, either the one or the other results, but not the two together. Thus, in my experience, excitation of the seventh or eighth root never causes simultaneously with reflex contraction of the flexors of elbow a contraction of that part of the triceps which extends the elbow. The flexor-reflex when it occurs seems therefore to exclude the extensor-reflex, and vice versa. If there resulted a com- promise between the two reflexes, so that each reflex had a share in the resultant, the compound would be an action which was neither the appropriate flexion nor the appropriate exten- sion.

Were there to occur at the final common path algebraical summation of the influence exerted on it by two opposed re- 1 Baglioni's results 288 support this inference. ceptive arcs, there would result in the effector organ an action adapted to neither and useless for the purposes of either. In the Coelenterate, Carmarina^ a mechanical stimulus ap- plied to the subumbrella causes, as in another Geryonid, Tiar- opsis indicansp a reflex movement that brings the free end of the manubrium to the spot touched. Bethe reports ^63 that if two stimuli are applied simultaneously to opposite points of the discoid subumbrella, the points chosen being such that the manubrium is midway between them, the manubrium is moved toward the point at which the stimulus applied was the stronger. He adds that if both stimuli are of exactly equal strength the manubrium remains unmoved and uncontracted. To obtain such a result as this last with antagonistic spinal reflexes in the vertebrate would obviously be more difficult, because the more complex the preparation and the nervous system involved, the more difficult it will be at any moment to exactly balance the two reflexes. But, apart from that, the observation on Carmarina is an analogue of that in the monkey's arm. £|

This dilemma between reflexes would seem to be a problem of frequent recurrence in reflex co-ordination. We note an orderly sequence of actions in the movement of animals, even in cases where every observer admits that the co-ordination is merely reflex. We see one act succeed another without con- fusion. Yet, tracing this sequence to its external causes, we recognize that the usual thing in nature is not for one exciting stimulus to begin immediately after another ceases, but for an array of environmental agents acting concurrently on the animal at any moment to exhibit correlative change in regard to it, so that one or other group of them becomes — generally by in- crease in intensity — temporarily prepotent. Thus there domi- nates now this group, now that group in turn. It may happen that one stimulus ceases coincidently as another begins, but as a rule one stimulus overlaps another in regard to time. Thus each reflex breaks in upon a condition of relative equilibrium, which latter is itself reflex. In the simultaneous correlation of reflexes some reflexes combine harmoniously, being reactions that mu- tually reinforce. These may be termed allied reflexes, and

the neural arcs which they employ allied arcs. On the other hand, some reflexes, as mentioned above, are antagonistic one to another and incompatible. These do not mutually reinforce, but stand to each other in inhibitory relation. One of them inhibits the other, or a whole group of others. These reflexes may in regard to one another be termed antagonistic ; and the reflex or group of reflexes which succeeds in inhibiting its opponents may be termed " prepotent " for the time being.

Figure 38. — Summation effect {immediate spinal induction) between the arcs Ra and R3of Fig. 39 B. FC the flexor muscle of the hip. Sa the signal line marking the period of stimulation of the skin belonging to arc Ra (Fig. 39 B) of the shoulder skin. The strength of stimulus is arranged to be subminimal, so that a reflex-response in fc is not obtained. S^ the signal line marking the period of stimulation, also subminimal of a point of shoulder skin 8 centimeters from Ra. Though the two stimuli applied separately are each unable to evoke the reflex, when applied contemporaneously they quickly evoke the reflex. The two arcs Ra and R/5, therefore, reinforce each other in their action on the final common path FC. Time in fifths of seconds. Read from left to right.

Allied reflexes. The action of the principle of the final com- mon path may be instanced in regard to " allied arcs " in the scratch-reflex as follows. If, while the scratch-reflex is being elicited from a skin point at the shoulder, a second point distant, e. g. lO cent, from the other point but also in the re- ceptive field of skin, be stimulated, the stimulation at this second point favours the reaction from the first point. This is well seen when the stimulus at each point is of subminimal in- tensity. The two stimuli, though each unable separately to invoke the reflex, yet do so when applied both at the same time (Fig. 38). This is not due to overlapping spread of the feeble currents about the stigmatic poles of the two circuits used. Weak cocainization of either of the two skin points annuls it Moreover, it occurs when localized mechanical stimuli are used. It therefore seems that the arcs from the two points, e. g. Ra and RyS (Fig. 39 B) have such a mutual relation that reaction of one of them reinforces reaction of the other, as judged by the effect on the final common path.

It is obvious that such reinforcement — immediate spinal I induction may occur in either of two ways. The diagram (Fig. 39 B) treats the final common path as if it consisted of a single individual neurone. The single neurone of the dia- gram stands for several thousands. It may be (i) that when the reflex is excited from Ra only a particular group of the motor neurones composing the final common path is thrown into action, and similarly another particular group when the reflex is excited from R/S. If the two groups in the final common path are separate groups, the explanation of the reinforcement shown in the muscular response may be by me- chanical summation of contraction occurring in two separate fields of muscular tissue, the contraction of each too slight to cause perceptible movement by itself without the other. In other words, the reinforcement would be due not to the response in the set of neurones comprising the final common path (FC Fig. 39 B), being neurone for neurone more intense under the combined stimulation of Ra and R/S than under stimulation of either singly, but the result would arise from the number of

Figure 39. — A. The "receptive field," as revealed after low cervical transection, a saddle- shaped area of dorsal skin, whence the scratch-reflex of the left hind limb can be evoked. Ir marks the position of the last rib. B. Diagram of the spinal arcs involved. L, receptive or afferent nerve-path from the left foot; r, receptive nerve-path from the opposite foot; Ra, r/3, receptive nerve- paths from hairs in the dorsal skin of the left side; FC, the final common path, in this case the motor neurone to a flexor muscle of the hip ; Pa, p/3, proprio-spinal neurones.

neurones in action in FC being simply greater under the stimu- lation of the two skin points than under stimulation of one of them only. On the other hand, it may be (2) that all the neurones com- posing the final common path constitute together one almost unitary apparatus, so that stimulation at Ka excites or can excite them all, and similarly stimulation at RyS excites or can excite them all. The question, therefore, regarding the mode of the reinforcement is a question between intensity and extensity. The scratch-reflex affords some opportunity for ex- amining this question. The rhythm of the reflex has practically the same frequency whether the reflex be excited strongly or feebly : thus, whether the amplitude of the contractions be great or small, they recur with practically the same frequence. Sup- pose the reflex be excited by stimulation of the skin point R a (Fig- 39 B), and suppose the stimulus is weak, producing only a feeble reflex. Then let another skin point R^ (Fig. 39 B) be stimulated while Ra is being stimulated, and let the stimuli at RyS be timed so as to fall alternately with those applied at Ra. Then if the two paths impinge on two different sets of units in the compound group of motor neurones composing the final common path, evidence of two rhythms should appear, for the muscle-fibres (of the flexors of the hip) can respond to a much quicker rhythm than four per second. But, in fact, the result is that the rhythm appears unquickened and unaltered (Figs. 18, 19, 20, 21). There is not even a break or interference in it. It might be thought, therefore, that for some reason the stimu- lation of the second point, R/S, is remaining ineffective alto- gether. But that is not so, because the stimulation at R/S has often the effect of increasing the amplitude (Fig. 18) of the individual beats of the rhythmic reflex, though it does not alter the rhythm. This change in amplitude proves that the reflex is also in action from the second skin point as well as from the first. But there is no interference of the rhythms of the two reflexes.

Evidently the central mechanism on which R/^ acts is subjected by Ra to a refractory state which the stimulation at R/3 does not break through. That is, the refractory state obtaining in the central mechanism under action from Ra obtains at the same moment for excitation reaching it from RyS. The central mechanism acted on by Kff must therefore belong in common to the reflexes from Ra and Ry8 respectively. And since the experiment can be repeated with a great number of different pairs of points in the receptive field, practically the whole of the

neurones of FC are common to all the receptive points in the receptive field. Similarly it is shown by Zwaardemaker ^^2 that the refractory phase demonstrated by him in reflex deglutition spreads to the whole of the reflex centre, both right and left. Again, it was shown above, under the heading of summation, that although a single-induction shock, even though strong, does not in my experience ever evoke a scratch-reflex, a series of even feeble shocks does so by summation. But in order to act by summation the individual shocks must follow each other at not too long an interval of time, the interval being caeteris pari- bus shorter the less intense the shocks. Suppose an induction shock be applied to Ra at such a frequence, e, g. once a second, that at the intensity chosen they fail to evoke the reflex. Sup- pose that a series of induction shocks be applied to R/S similarly unable to evoke the reflex. Then suppose that while the stimuli are being applied to Ra and fail to evoke the reflex, the other series of stimuli are applied to R^S, and are so ap- plied that each stimulus at RyS falls at a moment of time mid- way between the moments of application of the stimuli at Ra. The stimuli thus conjoined suffice to evoke the reflex. Evi- dently the internal excitatory change is not confined to the arcs to whose receptive ends the external stimulus is actually applied. It spreads to other arcs belonging to the same " type-reflex," especially to those arising near to those actually stimulated in the receptive field. A subminimal stimulus at one point in the field favours response to a subsequent stimulus at a second point in the field even 8 centimeters distant — so long as the second stimulus follows within summation time; but the summation time is shorter than when stimuli follow each other at one and the same spot, and is especially so when the points stimulated lie distant from one another.

Hence we may draw some sort of picture of the extent of the excitatory internal change in- duced in this reflex mechanism by a single momentary stimu- lus: as to distribution in time the change fades off" gradually from an early maximum to a trace just detectable after 14000-, if the stimulus be strong : as to distribution in space it spreads from the peripherally stimulated arcs A A themselves as centre to the intraspinal parts of other arcs of the same type-reflex, but among these it affects those starting in the skin as neighbours to A A more than ones more distant in origin, and it endures less long in these than in its own arcs ; hence the shorter sum- mation time. Exner early insisted on the close connection between " facilitation " (bahnung) and summation. The above immediate spinal induction illustrates it well.

The mutual reinforcement of action exercised by the two scratch-reflexes one upon another appears therefore to be an affair of intensity. This does not, however, exclude the exist- ence of extensity as a factor also in some degree. There is evidence, adverted to above (p. ^6^ Lect. Ill), that makes it likely that in very weak reflexes not all the individual neurones composing the final common path are in action, although in stronger reflex reactions all may be in action.

In the scratch-reflex the mutual reinforcing power between the reflexes falls as the distance between the receptors of the arcs increases. The nearer the skin points of Ra and R/3 lie together the greater the mutual reinforcement between the action of their arcs on FC. This suggests an explanation by physical diff'usion of the stimulating currents applied to Ra and R/3 ; but for the reasons above mentioned this overlap of stimulus can, I consider, be excluded. Light is however thrown on this propor- tion between the degree of reinforcement and the degree of nearness of the receptive points by another feature of the re- flex. The scratch-reflex in the spinal dog carries the foot ap- proximately toward the place of stimulation. In the spinal dog the reflex does not succeed in bringing the foot actually to the irritated skin point, yet when the irritation lies far forward the foot is carried further forward, and when the irritation is far back the foot is carried further back. A scratch-reflex evoked by a stimulus applied far back and high up in the dorsal skin is therefore not wholly like a scratch-reflex evoked from far forward and low down. These diff*erences are easily registered in graphic tracings of the movement at hip (Fig. 40). It is found that the greater the likeness between the two scratch-reflexes which two separate skin points initiate, the