The Integrative Action of the Nervous System

Figure 51. — Effect of overlapping in time of the stimuli for the flexion- reflex and the scratch-reflex. The top signal shows the stimulus for the scratch -reflex, the lower signal that for the flexion-reflex. Time in seconds below. The scratch-reflex seems to displace the flexion-reflex ; had it fused with it the combined lift of the lever would have been much higher than it is (spinal dog). Compare the scratch-reflex above in the figure to left.

If the reflexes are closely similar, it is difficult to say at what moment the transition under overlapping stimuli occurs, since the initial reflex on discontinuance of the first stimulation is maintained unaltered by the second. But if the reflexes are recognizably dissimilar, e. g. a low scratch-reflex and a high scratch-reflex, the moment of transition is obvious, for the reflex then takes the form of the response which the second stimulation would excite, and, on discontinuing the first stim- ulation, is continued in that form (Fig. 50). In my experience the transition does not, in the case of this reflex at least, in- clude a period of summation of the two reflexes in the sense that the reflex under the two stimulations A and B consists of the response to stimulation A summed with that to stimula- tion B. So also in the transition from one reflex to another of even greater dissimilarity. ^Hiere is the same absence of any period of fusion of the two reflexes. Such fusion might be appropriately termed confusion. The rule seems that such confusion is avoided in the transition. In the hind limb a scratch-reflex of the high form presents a certain degree of resemblance to a simple flexion-reflex, inasmuch as there can be distinguished in the former a marked tonic flexion on which the clonic is, so to say, superposed. When a scratch- reflex of this foMn supervenes on the flexion-reflex the result is commonly that which is seen in Fig. 51. The transition occurs without confusion; even in regard to the tonic con- traction, an element possibly common to the two reflexes, there is in the transition no period at which the tonic con- traction of the flexion-reflex has added to it that of the scratch-reflex. In the instance figured the amplitude of the tonic contraction of the scratch-reflex was about equal to that of the flexion-reflex; if these summed, therefore, their joint am- plitude would be much greater than that of either reflex singly.

But the record shows a smooth continuity of flexion-reflex with scratch-reflex in which there is no stage of summated amplitude of the two contractions. This is what I mean by saying that the transition from one reflex to another takes place without confusion. Not that the onset of one reflex is uninfluenced by the exist- ence of the other — its interval of latency is, for instance, liable to be greatly influenced. In the example furnishing Fig. $1,

Figure 52. — The displacement of the stepping-reflex by the scratch-reflex during the con- tinuance of the stimulation appropriate for the former. The upper signal indicates the stimulus for the scratch-reflex, namely, 75 break shocks delivered (unipolar faradization) at rate of 30 per second. The lower signal gives the stimulus for the stepping-reflex — a crossed reflex, the stimulus (unipolar faradization) being delivered to the opposite foot. The scratch-reflex, after a considerable latency, displaces the stepping-reflex. The crossed stepping-reflex reappears only in modified and imperfect form, though its stimulus is continued unaltered for some seven seconds after the end of the stimulus for the scratch- reflex. Time marked below in seconds.

the scratch-reflex, though its intensity is not increased, shows a hesitancy about the opening of its clonus not present in the reflex when elicited singly. Again, in Fig. 52, which shows transition from the crossed stepping-reflex to the scratch-reflex, though no period of confusion occurs in the transition from the former reflex to the latter, there is yet, on cessation of the latter, evidence of modification of the former. The crossed stepping- reflex returns, but considerably modified and after a longer latency than before. The amount of modification is greater than would in my experience be ascribable with probability to the effect of mere fatigue for the period during which the stim- ulus was at work, although the movement itself was in abeyance; the rhythm is present but weakened.

If it is advantageous for the transition from one reflex to another of like type to occur without a period of confusion, it is still more advantageous that it should be so in the case of tran- sitions from one reflex to another of converse type. Confusion in the literal sense above would in that case involve not merely inaccuracy at the outset of each new reflex, but would mean mutual destruction of the two reflex effects ; an interval of impo- tent mutual self-hindrance would disadvantageously intervene between successive motor acts of opposite direction. In the transition from one reflex to another of antagonistic kind the avoidance of confusion of the two reflexes emphasizes at the same time the impossibility of co-ordinating them in a simul- taneous combination.

Though the stimulus exciting the reflex that is displaced continues while the new reflex is introduced, the displacement of the former reflex occurs without confusion. Taking the flexion-reflex and the scratch-reflex, the one may temporarily interrupt the other in mid career (Figs. 43, 53) or may cut it short or may defer its onset; in all these cases it does so without a phase of confusion in the transition, although the stimuli belonging to both reflexes continue in contemporary operation (Figs. 43, 51, 52, etc.) all the time. And the same holds between other antagonistic reflexes, e. g. flexion-reflex and crossed extension-reflex (Figs. 30, 32, 33), extension-reflex and scratch-reflex (Figs. 42, 54), etc.

And the direction of the interference is reversible. The flexion-reflex may be made to interrupt the scratch-reflex (Fig. 43) or the scratch-reflex to interrupt the flexion-reflex (Fig. 51). The scratch-reflex may be made to interrupt the crossed step- ping-reflex (Fig. 52) or the crossed stepping-reflex to interrupt Figure 53. — A. Scratch-reflex interrupted by a brief flexion-reflex. The time of applica- tion of the stimulus evoking scratch-reflex is shown by the lowest signal line; that of the stimulus of the flexion-reflex in the signal line immediately above the other. Time marked in fifths of seconds at top of the record. The scratch-reflex returns with in- creased intensity after the interruption.

B. Similar to A, but the scratch-reflex is interrupted later and returns more slowly and with marked irregularity in its beat. the scratch-reflex (Fig. 55); and similarly with other pairs of antagonistic reflexes. Inhibition. The process in virtue of which this transition from one antagonistic reflex to another occurs is obviously one of active intervention. In many cases the form which the in- tervention takes is inhibition. For instance, where a crossed extension-reflex is interrupted by a brief flexion-reflex, two transitions occur, the first at a moment a from the E-reflex to the F-reflex, the second at a moment /3 from the F-reflex back to the E-reflex (Fig. 33, p. loi). Although stimuli for the two reflexes are both in operation continuously from a to y8, there is a clean transition from one reflex to the other. The tracing is taken from the extensor muscle of the knee. The flexion- reflex expresses itself by inhibition of the reflex contraction in progress in that muscle at that time under the combined in- fluence of the crossed extension-reflex and of the tonic extensor

Figure 54. The scratch-reflex cut short by excitation of the skin of a digit of the opposite hind foot. Below, the upper signal marks the period of application of the stimulus to the opposite hind foot, the lower signal marks the period of application of the stimulus exciting the scratch-reflex. Time above in .2 seconds. rigidity due to the animal being decerebrate. It causes the contraction due to these conjoined reflexes to cease. In such a case the transition from the extension-reflex to the flexion- reflex evidently occurs by inhibition. So also in the transition from the flexion-reflex to the extension-reflex when the ham- string muscles are examined (Fig. 32, p. 98).

We do not yet understand the intimate nature of inhibition. In the cases before us now, its seat is certainly central, and in all probability is, as argued above, situated at points of synapsis. I have urged that a prominent physiological feature of the synapse is a synaptic membrane. It seems therefore to me that inhibition in such cases as those before us is probably referable to a change in the condition of the synaptic membrane causing a block in conduction. But what the intimate nature of the inhibitory change may be we do not know.

of the nature of inhibition may be cited here, both for their in- trinsic interest and the suggestion of lines of investigation. One view has been that, as the process of conduction along nerve- fibres is an undulatory one in the sense that the nerve-impulse travels as a disturbance with wave-like configuration of inten- sity, inhibition is due to a mutual suppression of two wave-like disturbances impinging on the same point of the conductor but in opposite phases of disturbance.

In those cases where stimulation through one nerve inhibits the action of a tissue acting under another nerve we can imagine a process which leaves the tissue unaffected but simply inter- feres with another stimulus, as in the physical interference of vibrations. Rosenthal's ^ resistance theory of the action of the afferent vagus-fibres upon the respiratory centre is a supposition of this kind. It recognizes during the inhibition no change of total output of energy in the particular function inhibited. The alteration of a hypothetical resistance only distributes the discharge of the nerve-centre over an altered time-rhythm, — smaller and more frequent discharges representing the same lib- eration of energy as larger and less frequent. Such a view of the nature of inhibition is that which Gaskell ^^ termed the " neutra/" one ; according to it the inhibition leaves the tissue in the same ultimate condition as that in which it found it, neither exhausted nor surcharged. " As far as the central nervous system is con- cerned, there exists a strong general tendency to look upon the inhibitory processes occurring there as * neutraV in their character. " ^^

This view, originally put forward by v. Cyon,^ has been abandoned by him, although it has since been supported by Lauder Brunton ^^' and others. It was expressly dissented from by Wundt.^^ And the grounds of Wundt's objection are valid, the kernel of them being that though in a certain sense of the word the nerve-impulse can be described as wave-like it is not an undulatory disturbance at all in the sense in which those reactions are which show physical interference. It is therefore to physical interference that in this view of inhibition the analogy is drawn, but the similarity between the process of

Figure 55. — The scratch-reflex interrupted by the crossed stepping-reflex. The upper signal of the two below the myograph trace shows the period of application of the stimu- lation (unipolar faradization of shoulder skin) evoking the scratch-reflex. During the ; continuance of this stimulation a fairly strong stimulation of the crossed foot was applied, as marked by the lower signal at bottom of the record. The inhibition outlasts the application of this second stimulus by some 3 seconds ; the scratch-reflex then returns, and only ceases on cessation of its own stimulus. Time marked in fifths of seconds • above.

nerve-conduction and conduction of light and electrical waves \ or sound, etc., is not real enough to strictly justify such analogy. ; Moreover, as we shall see presently, central inhibition is not a : neutral process, for, at least in many cases, it leaves the reflex ■ The most striking thing that we know of inhibition is that it i is a phenomenon in which an agent such as in other cases excites \ or increases an action going on in this case stops or diminishes ^

an action going on. Now, the activity of a tissue can be low- ■ ered or abolished by production in it of deleterious changes \ such as exhaustion or, in the highest degree, death. But there \ is no evidence that inhibition of a tissue is ever accompanied by \ the slightest damage to the tissue ; on the contrary, it seems to \ predispose the tissue to a greater functional activity thereafter. ' We can imagine that a material continuously produced by a tissue, and yielding on decomposition the particular activity which is inhibited, may by an inhibition be checked in its decomposition, and accumulate, so that at the end of the period of inhibition the tissue contains more of the particular decom- posable material than before. This molecular rearrangement would diminish activity for the time being, but lead to increase of activity afterwards. There would ensue a rebound effect. This is, as is well known since Gaskell's ^* researches, what actually happens in the pure vagus action on the heart. A similar rebound-effect is perfectly obvious in many instances of inhibition in the central nervous system.^^ It constitutes a point of resemblance between central and peripheral inhibition.

Such an explanation as this second one may take the chem- ical structure of the living material, the bioplasnty of the cell as the field of operation for the decomposition and the synthetic process that it pictures. The living cell is constantly liberating energy in its function, and rebuilding its complex structure from nutrient material. Its life is therefore an equilibrium of balanced katabolism and anabolism ; at any given moment the one process or the other may predominate in the cell. At a moment when the cell is vigorously discharging some function which involves conversion of internal energy into external energy it is in a katabolic phase. In subsequent relative repose from the discharge of that function the replenishment of its store of potential energy by assimilation may predominate and the cell be in an anabolic phase. Katabolism and activity of external function, anabolism and rest from external function, come on this view to be almost synonymous terms. But Hering, Gaskell, Verworn, and others have taught us to attach important external functions to the assimilatory (anabolic) phase. The first men- tioned has dealt with the visual sensations in assimilation-dis- similation pairs. Black-white sensation is thus traced to a pair of reactions affecting the trophism of the cell in exactly opposite directions. Gaskell relates vagus inhibition of the heart to the throwing of the cardiac muscle-cell into a phase predominantly anabolic. Verworn in his " Biogen-hypothese " has developed

this trophic theory with further elaboration still. These views all take the actual nutritive activity of the cell as the direct and immediate field in which inhibition has its seat. The tendency to rebound after-effect in the opposite direction is in this view a natural trophic result. Hence Gaskell expressively speaks of the vagus as the "trophic nerve of the heart." And Hering*^ (1872)^^2 formulated his experience somewhat as follows: The action of a stimulus affects the cell's autonomic trophic equilibrium ; it may increase or lessen either the cell's asssimi- lation or the cell's dissimilation; in whichever of these ways the stimulus acts the excitation of the cell, owing to a self-regulation proper to it, dwindles for that stimulus and for all stimuli produc- ing a similar change, while the excitability increases for stimuli that produce an opposite effect. On all these views inhibition is in its intimate and essential nature a trophic process.

An hypothesis not built immediately on views of the nutri- tive processes of the cell has recently been put forward by Mac- donald.®^ Dealing with nerve and muscle fibres, he does not take the purely chemical structure of the living framework of the cell as the field of operation for either excitation or inhibi- tion. The explanation he offers of these two latter processes is as follows. From study of the part played by inorganic salts in the function of nerve, he sees in the attachment of these salts to the proteids present, and in their partial detachment from the proteids, normal occurrences underlying the conditions of rest and excitation respectively. He assumes the connection be- tween salt and proteid involved in this matter to be of purely physical nature. The axis-cylinder, for example, is composed of a colloid solution in which there are present minute particles of colloid proteid. These may increase in size — indeed so much as finally to become visible — under the influence of factors determining a tendency towards coagulation. Upon the surface of these particles the major portion of the inorganic salts present is held restrained in a condition of condensed solution. An increase in the size of the particles is accompanied by a diminution in the total surface separating the particles from the

solvent in which they lie. Such a diminution in surface is equivalent to a diminution in the forces restraining the motion of the inorganic salts. It occasions the liberation of salt mole- cules in a state of free motion into the surrounding aqueous solution. This release of hitherto restrained molecules is the cause of alterations in osmotic pressure, of new processes of diffusion, of resultant electrical phenomena, and thus of the phenomena of excitation.

Macdonald thus considers a stimulus as an agency determin- ing an approach to the condition of coagulation. He regards as the important characteristic of the excited state the release of inorganic salts resulting from this change. According to him inhibition is a condition in which the inorganic salts are more securely packed away upon the surface of the " colloid particles " than usual by reason of diminution in the individual size of the particles and an increase in the surface they present to the sur- rounding solution. He supposes the communication of a nega- tive electrical charge to be a stimulus provoking a tendency to coagulation with all the just-mentioned dynamic consequences of the enlargement of the colloid particles. So he considers that conversely the communication of a positive charge produces a change of an exactly opposite kind in which inorganic salts hitherto in motion are brought to a static condition of rest.

It does not seem at once clear that the condition of greater subdivision of particles should also be a condition of greater stability, although it is clear that such a conception might ex- plain the greater store of potential energy possessed by an inhibited tissue. Macdonald, in fact, does not, I take it, assume this to be the case. To explain this separate fact he appeals to the evidence upon which the conception is based and points out a distinction between the amount of inorganic salt involved in changes above (inhibition) and changes below (excitation) the equilibrium line of the normal resting state. Thus there is quantitative evidence to show that the amount of salt remaining for withdrawal from the resting colloid solution is only a small fraction of the total amount of salt present ; the major portion is already withdrawn, and is, so to speak, in reserve in this large

quantity for such changes of excitation as occur below the base line of rest. Changes from the normal to the hypernormal, and from the hypernormal to the normal, cannot therefore involve a redistribution of salt comparable in quantity to those taking place down from, and up to, the normal. It is in this way con- ceivable that the application of a stimulus to an inhibited tissue — although productive of an effect akin to the phenomenon un- derlying the process of excitation — might yet lead only to such a subminimal change in the amount of inorganic salt in motion as to determine no externally appreciable manifestation of its occurrence. Imagine a tissue which has been placed in a con- dition of inhibition by the communication of a positive electrical charge. The application of a negative charge to such a tissue would produce no visible effect, although productive of an in- ternal change. The application of a second negative charge would give rise to a characteristic excitation, its efficiency deter- mined by " summation." Let us on the other hand suppose that the tissue has not only been inhibited, but is maintained in a continuous state of inhibition by the steady arrival of positive charges. In this case the application of a succession of stimuli would result in nothing more than a series of subminimal, and therefore unnoticed, changes.

In an excited tissue, summarizing this conception, an unusual quantity of inorganic salts is in motion. Excitation is ended by the reduction of this excessive motion. Inhibition is the condi- tion in which the possibilities of free motion are most reduced. This view is fertile in suggestion for further experiment. Based on examination of the physical structure of nerve by electrical methods irreproachably employed, and on the revela- tion, under the microchemical test which we owe to Macallum,^' of potassium appearing in quantity at injured points of nerve- fibres, and explaining naturally as it does the injury-current of nerve as similar in production to the current of a " concentra- tion " battery 2^* the concentrations of which can be known from the current, it merits very careful consideration. The features and conditions of occurrence of inhibition harmonize strikingly with what on Macdonald's view we should expect them to be.

^m Interference. Whatever the intimate nature of the inhibition, ^Ht is, however, only one part of the processes involved in transi- ^Hon from one antagonistic reflex to another. In the transition ^Brom the crossed extension-reflex to the flexion-reflex the in- hibition of previous excitation in the extensor neurone is accom- panied by excitation of the previously inhibited flexor neurone. And conversely in the transition from flexion-reflex to extension- reflex. Transition from one form of reciprocal innervation to another will obviously involve such changes wherever the transi- tion is from one reflex of simultaneous double-sign to an antago- nistic of simultaneous double-sign. There will be inhibition at one set of points and excitation at another. The process of transition, therefore, in many cases is one half of it inhibitory, one half excitatory. It seems advisable, therefore, to avoid em- ploying the term "inhibition" for the displacement in general of one reflex by another. To avoid confusion, some expression of broader scope, including excitation as well as inhibition proper, seems required. The term " interference " already used by Wundt®^ and by A. Tschermak^^ in an almost similar way seems to me well suited for this purpose. In employing it Wundt expressly stipulated that it had in this use no reference to its technical employment by physicists for the mutual interaction of vibrations, as in light and sound. The term " interference " as applied to reflexes would mean simply the interaction between antagonistic reflexes, that is, reflexes which are incapable of simultaneous combination. These reflexes are capable of sue- . cessive combination, and in that process the influence of one reflex replaces that of another upon a common path potentially belonging to each.

The replacement may take place by inhi- bition succeeding excitation, or by excitation succeeding in- hibition, or by excitation of one kind succeeding excitation of another kind, as when the steady tonic flexion of the flexion- reflex is succeeded by the rhythmic clonic flexion of the scratch-reflex. In all these cases the process of displacement of one reflex action by the other may be termed interference. We thus get a comprehensive convenient term for embracing the whole series of cases.

The frequency with which, in co-ordination of reflexes by successive combination, the reflex which succeeds to another is antagonistic to this latter is very great. Two important classes of such sequence are especially common. One is that which forms what are known as ''alternating reflexes;" the other is the class of " compensatory reflexes." Alternating reflexes are seen very clearly in cyclic reversals of direction of movement; thus, when extension succeeds flexion in the stepping-reflex. Here antagonistic reflexes suc- ceed one another alternately at two final common paths. In the motor neurones for the knee, in the stepping-reflex, excita- tion and inhibition alternately ensue in the flexor neurones, while synchronously with that, inhibition and excitation alternately ensue in the extensor neurones.

The essence of an alternating reflex is that excitation and inhibition ensue in succession at two (or more) final common paths, a sequence of antagonistic reflexes possessing them in turn. In an ordinary rhythmic reflex a periodic excitation (and a periodic refractory or inhibitory state) is recurrently produced in the reflex-arc at rhythmic intervals. Every alter- nating reflex, therefore, is a rhythmic reflex, but not every rhythmic reflex is an alternating reflex. The movements of the vertebrate limb in locomotion give instances of alternating re- flexes ; probably the movement of the tail of fishes in swimming is a similar instance, but has not yet been analyzed as to its reflex composition. Alternating reflexes form an excellent field for examination of reciprocal innervation of antagonistic muscles.

It is particularly by the case of " alternating reflexes " that Macdougall illustrates his view of the central process in re- ciprocal innervation. His scheme also offers an explanation for the transition from one antagonistic reflex to another. Based more immediately on the behaviour of visual images, it is applied by Macdougall specifically to the case of the reciprocal innervation of antagonistic muscles. "Let us," he writes,^®* "imagine each arc in a simple schematic form as a chain of three neurones afferent (^j), central (^a^, efferent (^3), and let us call them a^, a^, and ^3, and ^j, b^, and ^3, in