The Integrative Action of the Nervous System

chiefly or at all due to an interaction of cortical neurones one with another. Exner drew from his observations on the rabbit a similar in- ference that the inhibitory phenomena had their chief seat in the spinal mechanisms though elicited from the cortex. My own inference has been that the seat of inhibition in these reactions from the " motor " cortex Hes probably at the place of confluence of conducting channels in a common path, likely enough at their confluence upon the '^ final common path,'' the motor neurone, that is at the ultimate synapse. But it may well be, indeed is in the highest degree Hkely, that in other fields of action one corti- cal element inhibits another cortical element.

In '^willed'' movements of the eyeballs of the monkey the same kind of co-ordination was revealed in some observations I ob- tained on this point. When the III and IV cranial nerves had been resected intracranially and the animals in ten days or so had recovered completely from the surgical interference, the eye movements were examined. In these animals if the gaze was attracted to an object, e. g. food, held level with the eyes and to the right of the median plane (left III and IV nerves cut) the left eye looked straight forward, the right looked to the right. If the object was then shifted more to the right or less to the right, the right eye fol- lowed it, moving as the object was moved, while the left eye remained motionless, looking straight forward all the time. But when the object was held to the left of the median plane both eyes were directed upon it, apparently quite accurately, When the object was shifted farther and farther to the left both eyes followed it with a steady conjugate movement not detectably different from the normal. When the object was carried from the left-hand verge of the field back toward the median plane both eyes followed it as accurately as before. If the object was moved suddenly from the extreme left-hand edge of the field up to the median plane both eyes immediately and apparently equally quickly reverted to parallelism with that plane. Or, if the object were suddenly brought back from the left edge of the visual field to some point intermediate between that and the

median plane both eyes at once shifted apparently equally to a correspondingly diminished deviation from the primary posi- tion. These actions must mean that in the left eye relaxation of rectus externus kept accurate time and step with contraction of rectus externus of right eye. And the action of the left rectus externus gives presumably a faithful picture of a synchronous process going forward in the right rectus internus. It is interesting to recall that in the seventeenth century Descartes in his De Homine,^ discussing willed movements,

Figure 74. — A. Figure from the De Nomine of Descartes, edit, of 1662^ in which he illus- trates his conception of the co-ordination of the antagonistic muscles of the eyeball by the above drawing from his own hand. B. Figure illustrating the same text in De Homine, edit, of 1677*; in this the sketch by Descartes has been much elaborated. suggested for the mechanism of the lateral movements of the eyeball, with which he deals in some detail, a co-ordination much resembling reciprocal innervation. He urged that the vital spirits were conducted into the external rectus by valved channels in that muscle, and at the same time were from the internal rectus led out by valved channels, so that as the one

muscle became tense by distension the other became flaccid by emptying. He furnished with his own pencil a figure illus- trating the mechanism as he conceived it (Fig. 74). There is an essential resemblance between his scheme and that of '* recip- rocal innervation," except that he imagined the mechanism a peripheral one, that is to say that the " inhibition," as we now term it, had its seat in the muscle, not in the nerve-centres themselves. Again, early last century (1823) Charles Bell, in a footnote to a paper in the Philosophical Transactions,^^ argued a similar kind of co-ordinate mechanism in the execution of willed movements. He wrote : " The nerves have been considered so generally as instruments for stimulating the muscles, without thought of their acting in the opposite capacity, that some additional illustration may be necessary here. Through the nerves is established the connection between the muscles, not only that connection by which muscles combine to one effort but also that relation be- tween the classes of muscles by which the one relaxes and the other contracts. I appended a weight to a tendon of an ex- tensor muscle which gently stretched it and drew out the muscle ; and I found that the contraction of the opponent flexor was attended with a descent of the weight, which indicated the relaxa- tion of the extensor." " If such a relationship be established, through the distribution of the nerves, between the muscles of the eyelids and the superior oblique muscles of the eyeball, the one will relax while the other contracts." But like Descartes he pictured a peripheral inhibition, for he says : " If we suppose that the influence of the 4th nerve is, on certain occasions, to cause a relaxation of the muscle to which it goes, the eyeball must be then rolled upwards." Descartes and Bell, therefore, with remarkable prescience imagined the existence of an action of nerve on muscle just such as was later actually discovered by the Webers^^ in the vagal inhibition of the heart — an inhibition which Volkmann ^'* previous to the Webers met in the course of experiment, but unevpectant of it, rejected ^^ as illusory and due to some experimental error.

As for salient objective differences observable between move* \ ments elicited from the so-called " motor " cortex and thos# ^ of spinal reflexes, these are for the most part less clear than l might at first be supposed. The general statement that the co- i ordination is of a " higher " kind in the former has doubtless truth, but it proves vague when details are demanded. A co- ordination though simple may yet be perfect. The co-ordination ; by which the leg is drawn up in the spinal ** flexion-reflex " seems as perfect as when the limb is drawn up by stimulation of the ' cortex. It is true that in the dog's scratching movement elicited i as a spinal reflex after transection of the cord the foot in my experience practically never attains accurately the site of the i stimulation, although broadly directed toward it. Were the movement elicited from the cortex one would expect it to be ■ more accurate in this respect. But I have never succeeded in ; eliciting this action from the cortex, and so am unable to insti- tute the comparison. ;

If by higher co-ordination it be meant that larger groups of reflex systems are simultaneously thrown into — or out of — ' action under cortical excitation than in merely spinal reflexes, that is more than probable. Yet we must admit that the field of musculature thrown into action by a focal stimulation of the ] cortex seems in some cases extremely limited. Thus A. S. Griinbaum and myself have seen that in the chimpanzee and gorilla any single manual digit can be moved isolatedly by stimulation of the cortex. We must not forget, however, that with even a small movement the field of inhibition may yet be \ wide, for I have on occasion noted inhibition of muscles of the shoulder when the thumb was moved under cortical excitation, the shoulder previously being unrelaxed.

There is the well-known clonic after-discharge following | cortical stimulation. But a marked after-discharge is also | usual in spinal reflexes, rhythmic in rhythmic reflexes, tetano- | clonic in tetanic reflexes e. g, in the " flexion-reflex," and is \ sometimes enormously prolonged (Figs. 49 and 57). So that \ even this difference is less marked than is customarily thought. I Certain other differences appear to me more significant. When a spinal reflex is prolonged under strong stimulation its dis- charge spreads, developing what Dr. Hughlings Jackson ^ has termed a " march." The ** march " of the spinal reaction tends to transgress the mediajt line more than does that of a cortical reaction, which tends rather to spread unilaterally. Also the progress of the spinal ** march" runs a more rapid course than does the cortical.

In the synthesis of movement in the animal it is obvious that these reactions elicitable from the motor cortex fall into three groups, like the three groups above distinguished in spinal reflexes (Lect. IV). In one group the movement evoked from the cortex of one hemisphere seems a fraction of a natural movement, the natural movement requiring in its completeness the co-operation of the symmetrical area of the cortex of the opposite hemisphere. Opening of the jaw as elicited from one hemisphere, e. g. the left, is seen after the jaw is split at the symphysis to be executed by the muscles of the crossed, i. e. right, half of the jaw, the muscles of the left half being very slightly activated or not at all. This cortical movement is evidently incomplete and fractional. The inference is unavoid- able that in the natural undeviated opening of the mouth the actions of symmetrical areas of the right and left cortices are coupled as ''allied'' reactions. In a second group, instanced by conjugate lateral deviation of the eyeballs toward the opposite side, it is equally obvious that the reactions of symmetrical areas of the right and left cortices are related one to another as ** antago- nistic " reactions. Such reactions have inhibitory relation one to another (151, 304). They must have this inhibitory relation even when combined, as Mott and Schafer showed they can be, to yield convergence of the ocular axes under bilateral excita- tion of the right and left hemispheres. In a third group of cases the reactions of symmetrical cortical areas right and left seem neutral one to another. Thus, with the area which yields movement of the thumb that reaction seems neither to reinforce nor to interfere with the similar reaction evoked from the twin area of the opposite hemisphere. That the reactions are really wholly neutral one to another is of course difficult to say

because the experimental observations are carried out under narcosis, and the narcosis probably sets in abeyance many co- ordinating mechanisms of the brain itself. It is clear, however, that the same broad groups of interrelationship (alliance, inter- ference, neutrality) as were traced in bulbospinal reflexes re- appear also between motor reactions of symmetrical areas of the cortex of the hemispheres. It is striking that the complete, /. e, perfectly balanced, bilaterality of motor representation with which the Broca motor speech centre is credited, no doubt justly, is exceptional in the motor cortex. Beevor and Horsley pointed out that move- ments of perfectly balanced bilaterality are of much rarer dis- tribution in the cortex of the hemisphere than was generally supposed. I incline to think that even the small category of such movements which they admit will have to be reduced further by the removal from it of " mastication." Certain it is that for a group of movements to be perfectly bilaterally repre- sented in an area of one hemisphere and not equally in the corresponding area of the other hemisphere, the state of things generally supposed for the Broca centre, is an arrangement wholly unknown in the motor cortex. It shows how different must be the operations of the Broca area from those of the areas of the so called motor cortex. Griinbaum and myself in excitation experiments could get no evidence of a Broca centre in the anthropoid apes.

One broad resemblance between the movements elicited from the motor cortex and spinal reflexes is striking, and yet is, I think, not insisted on by writers. We have seen that the movements elicitable in the various regions as local reflexes by stimulation of the afferent paths of those regions present regular and characteristic quality. Thus stimuli to a fore limb induce lifting of that limb with flexion at elbow and retraction- flexion at shoulder; stimuli to a hind limb induce drawing up of that limb with flexion at knee, hip, and dorsi-flexion at ankle ; stimuli to the mouth induce opening of the jaws, and so on. While these movements are emphatically evidenced as local spinal reactions the overwhelming predominance of their

occurrence equally emphasizes the scarcity of occurrence of certain other movements as local spinal reactions. Extension of the hind limb can, it is true, be evoked from that limb as a spinal reflex by a certain special form of stimulus, but that stimulus has to be applied to a special part of the foot and is successful only after " spinal shock " has passed off; while the flexion-reflex can be evoked by various forms of stimuli applied practically to any point of the limb surface, and is elicitable almost from the very hour of spinal transection onward. So also I have occasionally succeeded in evoking closure instead of opening of the jaw by stimulation of a certain part of the Hp in the decerebrate animal — but even then the reflex is not regularly elicitable. On the other hand reflex opening of the jaws is easily and regularly elicitable from various points of the oral surface. Similarly extension of the elbow as a local reflex elicitable by stimuli applied to the fore limb itself is a reflex practically unknown to me.*

Now those movements that are practically wanting as local bulbo-spinal reflexes and strike the observer of the spinal or decerebrate animal by their default, are likewise practically absent, comparatively infrequent, or only limitedly and irregu- larly elicitable from the motor cortex itself.^^ On the other hand, the movements regularly and widely elicitable as local reflexes are liberally represented in the motor cortex.^^ In the light of the observations mentioned above, which show that reciprocal innervation is a mode of co-ordination widely exhibited in the reactions elicitable through the motor cortex, this sparse occurrence of certain movements, e, g. extension of the knee or closure of the jaw, does not mean that the ex- tensor muscles of the knee or the muscles which close the jaws are unrepresented in the cortex. It does not mean that this cortex is in touch with the flexors alone and not with the extensors. It means that the usual effect of the cortex on these latter is inhibitio7t. It means not that the extensors and the

* Extension of elbow and of knee are of course easily obtainable as crossed reflexes and as parts of reflexes evoked from distant points. Such reflexes I do not include as local reflex reactions. jaw-closers are unrepresented cortically, but that their normal representation in the cortex under the ordinary conditions of experiment has the form of inhibition, not excitation, and thus unless specially sought escapes observation. Since, as above shown, strychnine and tetanus toxin trans- form certain inhibitions into excitations, we have a means of further testing this point. It is in my experience quite ex- ceptional to obtain primary extension of the opposite knee as a motor reaction from the cerebral cortex of the cat — or even, indeed, as a secondary movement. In exploring the cortex with unipolar faradization I have often failed to elicit the movement at all throughout a series of observations. Flexion, on the other hand, is regularly obtainable. After exhibition of strychnine the extension of knee can be regu- larly excited from the cortex, and from the very points of it that yielded flexion previously. This conversion is not so facile as the conversion of the spinal reflex. The dose of strych- nine has to be larger, or to operate longer. With doses addi- tively given, there seems, early in the experiment, a period when reflex spinal inhibition of the extensors has been converted into excitation, but the cortex of the brain still yields knee-flexion, not knee-extension. The cortical reversal has required in my hands doses that evoke convulsive seizures from time to time. I have seen, immediately after a severe convulsion, the cortex either unable to evoke any movement of the knee or produce knee-flexion, though a short while before it gave knee-extension.

Tetanus toxin likewise converts the cortical flexion into extension. The efl*ect is in its case the more marked, because, if the cortical examination be at an early stage of the progressive malady ensuing on inoculation by a moderate dose, or where the dose has been quite small, the tetanus is " local ". and con- fined to the inoculated limb, and then, if the tetanus be " local" in one hind limb, e. g. the left, the appropriate area of the right hemisphere yields knee-extension, whereas the corresponding of the left hemisphere yields knee-flexion.

But these effects are better studied in the monkey. There, in my experience, to obtain primary extension of the crossed knee from the cortex is, as in the cat, extremely unusual. A number of experiments can be made without obtaining it at all. Even as a secondary movement it is extremely poorly repre- sented in the cortex. For twenty instances of flexion at knee it is, in my experience, often difficult to find one of extension at that joint. But after tetanus toxin or strychnine the whole " leg- area " of the cortex, from all points of its surface, may yield nothing but leg-extension, in which extension of knee is prominent as an evident part of a primary combined movement. This is espe- cially striking when the tetanus is still merely ** local," and con- fined to one hind limb, e. g. left. The ** leg-area " of the right cortex then yields knee-extension everywhere; the " leg-area " of the left cortex yields the normal flexion results. The " leg- area " of the right cortex provokes moreover from many of its points extension of right knee and ankle, as well as of left, though less strongly. The " leg-area " of left hemisphere does this little, if at all. Under moderate faradization the " leg-area " in the monkey, in my experience, moves the homonymous hind limb, in addition to the crossed, very slightly and rarely, much less easily than in the cat, though in both the movement is the same, namely, " extension." So localized may be the toxic influence in its early stage that reversal of the usual cortical eflect at knee may obtain while in the same hemisphere that on hip and ankle still remain flexion as usual.

Similarly with the " arm-area." In the cat, it is in my expe- rience quite infrequent to obtain primary extension of the crossed elbow from the cortex. Flexion is readily and regularly obtained. Strychnine changes this : the very surface that yielded flexion then provokes extension, and strongly. But the dose of strych- nine seems to be larger than for conversion of the spinal reflex, and the conversion shows the phases before mentioned in regard to the knee-inhibition, and its conversion in the case of the ham- string nerve. In the monkey, in my experience, the effect of strychnine and of tetanus toxin when pushed to the general convulsive stage is often contrary to the effect in that stage in so many other animals. I have seen them, though producing extension at elbow at first, later produce flexion at elbow.

In one case, in a monkey, in which the tetanus had become general in the sense that only one limb was unaffected, thJ|, affected arm was strongly extended and rigid at elbow with some retraction at shoulder. But in all my instances, where by introduction of the toxin into the trunk of the median or ulnar a " local " tetanus of the arm has been produced, the limb has been extended rigidly at elbow and retracted at shoulder. In these cases faradic examination of the cortex showed that the small field of the " arm-area" to which extension at elbow is restricted, was enlarged so as to include the whole " arm-area." Under the toxin the cortex that normally in the cat yields flexion of the crossed fore limb and extension of the uncrossed, will yield extension of both when there is local tetanus in the crossed limb. Extension at elbow sometimes alone, more often with retraction at shoulder, or with extension at wrist or fingers, sometimes as a leading movement, sometimes rapidly ensuent on retraction at shoulder or extension in the hand, according as higher or lower points in the area were stimulated, was prominently exhibited at all points of the entire surface of the " arm-area." That area, with this as its salient reaction, seemed particularly in evidence, for its extreme limits appeared traceable further than usual, and to encroach on or overlap more than is usual under the feeble or moderate stimu- lation employed, the " leg-area " above and the ** face-area " below, and to run exceptionally far forward above the pre- central sulcus, though remaining undemonstrable in the free surface of the ascending parietal convolution. From no point in all this extensive " arm-area " was, despite repeated trials, any flexion at elbow or shoulder or hand obtained (Fig. 75).

Various intensities of faradization were employed, and points known normally to yield it most regularly were tried : but ex- tension, not flexion, always resulted. This condition of the " arm-area " can in tetanus exist in one hemisphere or even in both hemispheres and the "leg-area" of each hemisphere yet yield flexions at knee and hip and ankle, and its other normal forms of reaction. Tetanus produced by introduction of the toxin into the arm (js. g. median or

ulnar trunk) affects subsequently to the inoculated limb, the fellow fore limb first, and the jaw before the hind limbs, although the knee-jerk on the homonymous side to the inoculation may be brisk. Under decerebrate rigidity, e, g. in the cat, the closing muscles of the jaw are kept in tonic action, holding the mouth somewhat shut.^^ By stimulation of any point of a large ** skin- area " appropriate for the reflex, reflex opening of the mouth, including depression of the lower jaw, is easily and regularly elicited, or by faradization of an afferent twig of the trigeminus; or as was shown by Woodworth and myself,^"^ even by stimula- tion of distant afferent nerves, e, g. plantar or saphenous. Here the action of the powerful closing muscles is reflexly inhibited while the weaker opening muscles are reflexly excited — it seems, in fact, a case of Astacus claw, except that the inhibi- tion is central, not peripheral. This reflex ** opening " is in the decerebrate animal converted into reflex closure by tetanus toxin and by strychnine, the inhibition of the predominantly powerful closing muscles being converted into excitation of them.

Similarly, when the " face-area " of the monkey's cortex is tested by faradization after exhibition of strychnine the points of surface that previously yielded regularly the free opening of the jaw, yield strong closure of the jaw instead. Now closure of the jaw is a movement of very limited representation in the cor- tex of the monkey, even of the anthropoid. On the other hand, opening of the jaw is always readily and regularly elicitable from a large field of the " face-area." And adjoining and overlapping this large area whence steady opening of the jaw is obtained, is found an area whence, as Ferrier '^ first pointed out, " rhythmic alternating opening and closing of the jaws," as in feeding, can be evoked. Under tetanus toxin (Fig. 75) and strychnine the whole of this combined area not only ceases to yield opening of the jaws, either maintained or rhythmic, but yields closing of them instead — often with visible retraction of the tongue. For this conversion larger doses of strychnine have, in my hands, been required than for conversion of knee-flexion into extension.

With tetanus toxin the conversion appears the more striking when examined early in the progress of the intoxication, because it may be found at a stage preceding altogether the occurrence ■ of any general convulsions, and also because it can then some- times be found to be unilateral, that is, to be present in the " face-area " of one hemisphere * without or almost without any affection of the " face-area " of the other hemisphere. The reactions of the normal field thus remain for comparison in the same individual with the reactions of the abnormal field.

Tetanus toxin shows marked predilection for the closure l mechanism of the jaw. After inoculation in the hind leg, even before the " local " tetanus has obviously invaded the fellow limb of the opposite side, a slight tightness of jaw and an ] immobile pursing of the lips has several times given warning i that general tetanus had really set in, before any trace of general convulsive seizures or any involvement of the arms i was detected. Tetanus toxin has also certainly intensified the | reactions of the cortical areas that give retraction of the neck ; and retraction of the abdominal wall (Fig. 75).

The progress of the change wrought by these agents in con- verting these reactions of the cortex from their usual form to j the diametrically opposed seems to involve the same kind of ' steps as that noted above in their conversion of the inhibitory ; hamstring nerve effect on the knee-extensor. Stages can be found in which the inhibitory effect is less than normal, yet is not replaced by excitatory. With the cortical opening of jaw, in early tetanus a grade is discoverable when faradization of the cortex produces a slight opening of the jaw — a mere *' loosen- ing" of the jaws, so to say — distinctly less than normal, and j hardly effectively opening the mouth. Also with the " leg-area " of the cortex, at an early stage of the tetanus it would seem that ';j an undue but far from exclusive preponderance of plantar exten- sion at ankle over dorsal flexion at that joint exists, while the ! symptomatic knee-extension is as yet not excitable though knee-

* The hemisphere, the " face-area " of which is earlier affected, is, in the case of inoculation in a limb, the hemisphere contralateral to the limb inoculated! .| Pig. 75 . — Outline to illustrate the changes produced by tetanus-toxin in the functional topog- raphy of the motor-cortex of the monkey, Cercopithecus callithrix. CF = the central fissure. F indicates hip-knee flexion, E indicates hip-knee extension ; / indicates elbow flexion, e indicates elbow extension ; < indicates jaw opening, = indicates jaw closing ; prosthotonic indicates in regard to "body " ventral bending, opisthotonic indicates dorsal bending. The distribution of these symbols in the drawing indicates broadly the field whence could be elicited the movements that the symbols respectively stand for, in A before and in B after development of lockjaw. In B at the lowest part of the face-area a place still yielded opening of the mouth. In the experiment which furnished the specimen figured the site of inoculation had been the leg, hence the toxic action reached the jaw comparatively late. Had the exploration of the cortex been deferred even longer the open ing of the jaw might perhaps have been transformed to closure throughout the cortex.

flexion is almost in abeyance. Neither under tetanus toxin or strychnine have I at present observed conversion of the abducens inhibition into excitation. The foregoing observations appear to give an insight into at least a part of the essential nature of the condition brought about by tetanus and by strychnine poisoning. These disorders work havoc with the co-ordinating mechanisms of the central nervous system because in regard to certain great groups of musculature they change the reciprocal inhibitions, normally as- sured by the central nervous mechanisms, into excitations. The sufferer is subjected to a disorder of co-ordination which, though not necessarily of itself accompanied by physical pain, inflicts on the mind, which still remains clear, a disability inexpressibly distressing. Each attempt to execute certain muscular acts of vital importance, such as the taking of food, is defeated because from the attempt results an act exactly the opposite to that intended. The endeavour to open the jaw to take food or drink induces closure of the jaw, because the normal inhibition of the stronger set of muscles — the closing muscles — is by the agent converted into excitation of them. Moreover, the various reflex- arcs that cause inhibition of these muscles not only cause exci- tation of them instead, but are, periodically or more or less constantly, in a state of super-excitement, and yet attempt on the part of the sufferer to restrain, to inhibit, their reflex reaction, instead of relaxing them, only heightens their excitation further, and thus exacerbates a rigidity or a convulsion already in progress.

It seems to me not improbable that the virus of rabies may similarly upset reciprocal innervation, though its field of opera- tion, at least in man, lies not in the same group of mechanisms as are affected by strychnine and tetanus toxin but in an allied one, namely, that inter-regulating (by co-ordinations in- volving inhibition, as Meltzer and Kronecker showed) the acts of deglutition and respiration. Little has met me in the course of observations on the re- actions of the cortex under strychnine or tetanus toxin to indi- cate that the transformation of the motor effects of the reactions

is due to action of these agents on the cortex itself. The change of result seems quite explicable by alteration produced in lower centres, e. g. spinal and bulbar, on which the cortex acts. This seems especially shown by the toxin when injected into the right arm and producing extensor rigidity at that elbow and rigid torticollis to the right, converting the flexion of arm-area of the left hemisphere into extension under arm-area excitation, and in the right hemisphere torticollis movement to the right.

The vast role of inhibition in cerebral processes as evidenced by mental reactions, and the slightness of mental disorder in strychnine poisoning or tetanus indicates a difference between inhibition as it occurs in the bulbo-spinal arcs and in the arcs of purely sensual and perceptual level, a difference presumably of physicochemical nature. We find, therefore, these reactions changed in a like manner by strychnine and tetanus whether we excite them from the cortex or from reflex spinal arcs. And a further similarity be- tween the representation of movement in the motor cortex and in the bulbo-spinal axis as a mechanism for local reflexes is the following. When the induced movement embraces both hind limbs or both fore limbs it is in an opposite sense in the two limbs. Thus the crossed accompaniment to the flexion-reflex of the limb is extension : and so also when cortical stimulation evokes [e.g. in cat) flexion e.g. of the right fore limb, not rarely it evokes movement, weaker it is true, in the left, and that move- ment, as Exner^ noted in the rabbit, is extension.

The local reflex movements obtainable from the bulbo-spinal animal and the reactions elicitable from the motor cortex of the narcotized animal fall into line as similar series. Both consist of the same group. But in striking contrast to this group stands the motor innervation active in " decerebrate rigidity." Decerebrate rigidity ^^^ is a condition which ensues on remo- val of the fore-brain by transection at any of the various levels in the mesencephalon or the thalamencephalon in its hinder part.