The Integrative Action of the Nervous System

Figure \^ (opposite). — Cross-sections of the spinal cord of the dog, revealing the position of the nerve-tracts descending to the hind-limb region from origin in the foremost three thoracic segments, by the method of " successive degeneration." The 8th cervical segment had been exsected, and 568 days later a crosscut was made at the hindmost level of the 3d thoracic s^ment. The transverse extent of this lesion, as determined by microscopical sections afterwards, is shown in diagram i of the figure. The greater part of the right lateral column is seen to have been spared from injury. Three weeks subsequent to this second lesion the animal was sacrificed. Preparations made with the Marchi method for reveal- ing degenerate nerve-fibres showed the degeneration indicated by diagrams 2, 3, 4 and 5 in the figure. After the second injury to the cord the scratch-reflex remained elicitable from the right shoulder, but was lost from the left shoulder in its anterior scapular region. The degeneration of these proprio-spinal fibres descending from the shoulder segments went, therefore, hand in hand with disappearance of the scratch-reflex from a region of skin of the shoulder whence it was elicitable previously.

fibres it is desired to examine. It becomes once more a clean slate on which a new degeneration can be written. The proprio- spinal fibres are revealed by making a transection between the fourth and fifth thoracic segments. Four weeks after this second lesion the proprio-spinal fibres descending from the third and fourth thoracic segments are degenerate. They can be studied (Fig. 17) throughout their course from the fourth thoracic segments backwards along the cord by any of the ordinary methods, such as the Marchi method, for studying de- generate fibres. Many of these proprio-spinal fibres pass from the shoulder segments to end in the hind-limb segments. The existence of the neuroglial scar, left by old degeneration that has cleared up, far from complicating the tracing of the new degeneration assists by forming a contrast background to it, the sharpness of which leaves nothing to be desired.

From the results obtained by this method the following reflex-chain can be inferred ^^ as possible and probable for the scratch-reflex. 1. The receptive neurone (Fig. 13 B, Ra) from the skin to the spinal gray matter of the corresponding spinal segment in the shoulder. 2. The long descending proprio-spinal neurone (Fig. 13 B, Pa) from shoulder segment to the gray matter of the leg segments. 3. The motor neurone (Fig. 13 B, F C) from the spinal seg- ment of the leg to a flexor muscle.

This chain thus consists of three neurones. It enters the gray matter twice ; that is, it has two neuronic junctions, two synapses. It is a disynaptic arc. In venturing to thus schematically express the construction of this arc as disynaptic, I am influenced by the desire to ex- press its construction as simply as possible so far as consistent with the ascertained data of the case. I therefore omit from the scheme the possible Schalt-Zellen (v. Monakow) between Ra and Pa, and between Pa and F c. Much of what I intend to express by " disynaptic " would be as clearly though not as concisely expressed by saying that gray matter is inter- calated in the arc twice i. e., at two separate places. That,

however, is not expressible by a single adjective, and since synapses occur so far as we know only in gray matter, disynap- tic does include that idea. But it also implies somewhat more. I venture upon it in spite of the assumptions it includes because, in my opinion, much in those further assumptions seems justi- fiable and useful as a working hypothesis, and because it lays stress on the importance of the synapse in reflex conduction, — an importance which for reasons given before seems considerable.

The reflex-arc consists, therefore, of at least three neurones. It is convenient to have a term distinguishing the ultimate neu- rone F C from the rest of the arc. For reasons to be given later it may be spoken of as the final common path^ The rest of the arc leading up to the final common path is conveniently termed the afferent arc. The morphological components of this reflex mechanism include, in addition to the above neural elements, the muscle- fibres of the flexor muscle at one end, and possibly a receptive cutaneous organ at the other end probably in the root-sheath of a hair. Somewhere in this chain of structures the property of refractory phase has its seat, and refractory phase is a pivot on which the whole co-ordinating mechanism of this reflex turns.

In attempting to locate the seat of the refractory state, con- siderations that arise are the following. The muscle involved is one which neither when excited directly nor through its motor- nerve exhibits this refractory period. We can exclude the phenomenon, therefore, from it, and from its motor-nerve, and from the link between it and its motor-nerve, — the end-plate. Further, this refractory state is not exhibited when the motor neurones of this muscle are excited to activity by various other channels ; for instance, by the afferent neurones coming in from the receptive organs of the leg itself, or by the palliospinal pyramidal neurones descending to them from the cortex of the cerebral hemisphere. We are free, therefore, to exclude the motor neurone F c supplying the flexor muscle itself as the source of the refractory state characterizing the scalptor-reflex. Again, the elicitation of the reflex typically (Fig. 14) by all the various above-mentioned forms of artificial (electrical) stimuli

applied through a needle electrode inserted in the skin suggests that it is the commencement of the receptive nerve-fibres in the skin rather than any specialized cutaneous sense-organ therein that are the seat of stimulation when the reflex is thus artificially excited. We have no knowledge of the existence of a refractory phase of such duration as this as a property of any afferent fibre passing from the skin to the spinal cord. There is indeed con- clusive evidence that the seat of this refractory phase lies neither in the skin nor in the afferent neurone itself. When the reflex is in progress under stimulation of the skin at one point, e. g., Ka (Fig. 13, B), stimulation at some other, even remote, point also producing the reflex — as can be proved in various ways — does not break the rhythm of the reflex ^^s 300 or complicate it in any way. The reflex elicited from spot R/3 may be initiated while that elicited from Ra is in progress, and may then be carried on while A is allowed to cease, or vice versa; but in neither case is the rhythm of the reflex broken or reduplicated. And this although, from other evidence, we know that the flexor muscle and the motor neurone F C can respond rhythmically to stimuli with a rate of rhythm more than twice as high as that of the stimuli applied to produce the reflex. Or the reflex from a spot B may be introduced into the middle of one from a spot A, and although its reflex (B) impresses characters of its own as to amplitude, direction of the foot, etc., it does not reduplicate or break up the already exist- ing rhythm. The result does not differ whether the individual stimuli of the two series of stimulations at spots A and B are alternate or not. Figures 18, 19, 20, 21 illustrate these points.

The refractory phases obtaining in the reflex arising from spot A are respected by the stimuli delivered at B also and are not broken down by them. Figure 18 (opposite). — Tracing of the flexion of the hip in the " scratch-reflex." The reflex is evoked by two separate stimulations (unipolar faradization) at points ten centimeters apart on the skin surface. The upper signal shows the time of application of the first stimulation, and the line immediately below that the frequency of repetition of the double-induction shocks of that stimulation. The lowest line signals the time of application of the second stimulation : the frequency of repetition of the double shocks in this stimulation was much greater than in the other stimulation and is not shown. At the top the time is marked in

fifths of seconds. The moment of commencement of the first stimulation is marked by an abscissa on the base line. The periods of the two separate stimulations overlap, the second beginning a full second before the first ends, but no interruption or increase of the rate of rhythmic reflex-response appears. Figure 19. — Similar to the preceding, but with different points of stimulation and with longer overlappmg in time of the two separate stimulations.

Figure 20. — Similar to the preceding, but with different skin points and slower series of in- duction shocks, the moments of delivery of the shocks at one skin point being midway be- tween those of delivery at the other. The sequence of the stimulations at the two points in B is the reverse of that in A. The top line marks the time in fifths of seconds ; the next line below that shows the frequency of repetition of the weak double shocks, the rate being the same for both stimuli ; below, the two signal lines showing the time of applica- tion of each of the two separate stimulations.

is common to impulses started both at A and at B. And this holds when spots A and B lie even ten centimetres apart. It is Figure 21. — Records of scratch-reflex as before, evoked by separate unipolar stimulation of two skin points 8 centimeters apart. In A the second stimulation commences during the after-discharge of the first reflex and causes no interruption or alteration in the rhythm of the reflex-response. In B the second stimulation of the above pair evokes the reflex, and during its progress the stimulation which comes first in A is introduced ; and conversely in C. In none of the three cases is there interruption of or alteration in rate of the rhythmic reflex-resp>onse. Rate of delivery of the exciting shocks is shown on separate lines.

against what we know of the receptive neurones to suppose that there is between them any collateral nexus beyond their impinge- ment directly or indirectly on other neurones more or less common to them both. The seat of the refractory phase seems therefore to lie somewhere central to the receptive neurones in the affer- ent arcs. The refractory phase induced in some element of the arc by the reflex from A extends to some element which is also concerned in the conduction of the reflex induced from B. This element must be some neurone common to the two arcs from A andB respectively. Neurone FC (Fig. 13), the final common path, is such an element. But neurone FC as tested by other reflexes, e. g., the flexion-reflex shows no such refractory period. The common mechanism sought for seems therefore to lie some- where between FC and Ra, R/3. It may well be that neurone Pa

is partly common to Ra and R/S, for these R neurones are well known to split intraspinally into headward and tailward stem- fibres, each carrying many collaterals, and probably by them con- nected with the gray matter in not only one spinal segment but in a series of segments. Collaterals from Rff as well as from Ra may reach Pa, therefore ; and similarly with Py3. The scratch-reflex has instructive points of likeness to that of the swimming-beat of Medusa. The arrangement of its response is quite like that of the muscular response of the swimming-bell of Medusa under stimulation of two points of the subumbrella or two of the marginal receptor organs. We can compare each lateral half of the saddle-shaped receptive area of the dog's back in regard to the scratch-reflex quite strictly to the marginal surface of Rhizostoma in regard to its swimming-beat reflex.

In Medusa a second stimulus following close upon a first does not prolong the contraction ; ^^ it finds the bell in refractory phase. The beat induced by the first stimulus has no second contraction fused with it in consequence of the second stimulus. The principles of the co-ordination thus obtained in the rela- tively simple swimming of Medusa seem as follows. One condition of the co-ordination of the swimming-beat, as said above, is the unpolarized nature of the nerve-channels allowing free flow of nervous impulses in either direction from conductor to conductor along the nerve-net. Another condition is the continuity mediate or immediate of every conductor with every other. These conditions of the nervous system allow a single stimulus given at any single point to evoke a co-ordinate contraction of the whole musculature, to evoke, in short, a full and perfect swimming stroke or beat. But they do not insure that under a series of stimuli delivered in irregular and varied sequence and at various points in perhaps rapid succession a series of co-ordinate strokes or beats shall result.

Romanes '^ showed that the receptor organs at the edge of the bell were the source of the natural beats of the bell, and that so long as even one of these remained the swimming-bell con- tinued to beat spontaneously. There therefore exist in this case quite a number of points which all tend under natural circum- stances to initiate the beats of the bell. Suppose that shortly after a stimulus has occurred at A, and before the contraction induced by it has passed off, another stimulus is delivered at B, and then similarly at C. All these stimuli are, taken singly, similarly provocative of locomotion, and the only locomotive act of the creature is the systolic stroke of its bell. Each reaction is therefore aimed at incitement of locomotion only for a propulsive movement of the bell. But the two conditions, /. ^., unpolarized conduction and end-to- end continuity obtaining in the nerve-net, though they insure that result for one stimulus, defeat it in the case of a series of stimuli quickly following either at one and the same point or at several, — and for the following reason. The series of stimuli would, were those two conditions all, merely immobilize the bell. The second stimulus following during the contraction excited by the first would be conducted, as was the former, to all the musculature of the movement, and would simply accentu- ate and prolong the systolic condition already in progress. But that would interrupt locomotion, not promote it. The con- traction of the muscular disc to produce the stroke must be immediately preceded by diastole, enabling it to embrace the proper volume of water for re-expulsion.

An essential feature of the co-ordination is therefore due to alternation of the two converse phases of contraction and relax- ation, in the one muscle; these execute the locomotion of this simple animal. This necessary condition is insured, even under irregular series of stimuli, by refractory phase. When the bell is replying or has just replied to a stimulus, it remains inexcitable to further stimuli for a period which outlasts its phase of contraction. This prevents disharmony occurring in the rhythmic movement under multiple stimulation.

It is on conditions like these governing Medusa's swimming- bell that the co-ordination of the heart's action is based, except that in the heart there is but one initiatory spot, prepotent per- manently, as in Vertebrates, or temporarily, as in Tunicates. In Medusa presumably any one of various specialized points (border organs) becomes prepotent at different times, by reason of stimu- lation from the environment. In this Medusa more closely re- sembles the scratch-reflex, where any one of many points in a large receptive field becomes temporarily prepotent under stim- ulation, e. g., puncture by a flea or other parasite, and then initiates and leads a series of beats which can be prolonged or intensified by concurrent stimulation by parasites at other points, but cannot by their concurrence be upset as regards rhythm. In the action of scratching it is as necessary as in the swimming of Medusa, or the beating of the heart, that relaxa- tion follow contraction.

Refractory phase is obviously an essential condition in the co-ordination of the scalptor-reflex. The scratching-reflex, in order to secure its aim, must evidently consist of a succession of movements repeated in the same direction, and intervening between the several members of that series there must be a complemental series of movements in the opposite direction. Whether these two series involve reflex contractions of two antagonistic muscle-groups respectively in alternate time, I would leave for the present. The muscle-groups or their reflex-arcs must show phases of refractory state during which stimuli can- not excite, alternating with phases in which such stimuli easily excite. Evidently this is fundamental for securing return to the initial position whence the next stroke shall start. The refrac- tory phase secures this. By its extension through the whole series of arcs it prevents that confusion which would result were refractory phase in some of the arcs allowed to concur with ex- citatory phase in others.

But there is one significant difference between refractory state in the scratch-reflex and in the swimming mechanism of Medusa. In the latter, as in the heart, the refractory state is a property not relegated to a central nervous organ remote from the peripheral tissue in whose function it finds expression. It is located in intimate connection with the peripheral organ itself. From observations of Bethe it seems likely that refractory phase in Medusa is a function of the nerve-net. Magnus^®* has re- cently shown that the refractory phase of the beat of the isolated

intestine is referable to the local nerve-plexus (Auerbach's) lying [ in the gut wall. In these cases the refractory state seems to ,: belong to the nervous elements, but to nervous elements diffused | through the peripheral tissue. But in the scratch-reflex the | site of the refractory state is central, intraspinal. | The centrality of seat of the refractory state of the scratch- | reflex is significant of the difference of the conditions under which | the scratch-reflex and the swimming of Medusa respectively go 5 forward. In the case of the locomotor action of the swimming- I bell of Medusa, we have a simple musculature which can execute '] practically but one movement It is in fact a single muscle, that ;j is to say, comparable with what in the more complex muscula- I ture of higher organisms — e. g.^ vertebrates — is regarded as a i unit of musculature, a single muscle, such as the gastrocnernuis, \ tibialis, etc., in the frog. Each and every receptor organ which ■ under stimulation produces locomotion is therefore connected by nerve with that single muscle of locomotion, and when impelled by each or any of them, the muscle effects practically the same action as it does when impelled by any other of the sister receptor organs. The movement of locomotion which is provoked through each receptor is practically the same as that provoked through any of the rest. The mechanical organ in this case can perform but one movement, and its performance of that movement is, so to say, the one purpose demanded from it by each of all the receptor channels playing upon it.

But with the mechanical organ which the scratch-reflex employs the case is different. That organ is the hind limb, a complex structure built of parts, many of them spatially op- posed, and able as a whole to execute movements of various kinds. Thus it can reflexly not only scratch, but stand, walk, run, or gallop, squat in defaecation, abduct and flex in mic- turition, etc. In the swimming-bell of Medusa there is no opportunity for antagonism between the motor end-results of the reflexes that employ it, save in respect to the possible confusion of successive contractions which would destroy the rhythmic pulse, and that confusion is avoided by refractory phase. The swimming-bell of Medusa is at the behest of but

one type-reflex. The scratch-reflex possesses the same safe- guard against destruction of its rhythmic character. But in the case of the scratch-reflex that reflex is but one of several re- flexes that share in a condominium over the efl"ector organ — the limb. It must therefore be- possible for the scratch-reflex, taken as a whole, to be, as occasion demands, replaced in exer- cise of its use of the limb by other reflexes, and many of these do not require clonic action from the limb, — indeed, would be defeated by clonic action. It would not do, then, for the peripheral organ itself to be a clonic mechanism. The clonic mechanism must lie at some place where other kinds of reflex can preclude the clonic actuator from affecting the peripheral organ. Now such a place is obviously the central organ itself; for that organ is, as its name implies, a nodal point of meeting to which converge all the nervous arcs of the body, and among others all those which for their several ends have to employ the same mechanical organ as does the scratch-reflex itself. It is therefore only in accord with expectation that the seat of the refractory phase of the scratch-reflex lies where we traced it, in the central nervous organ itself, and somewhere between the motor neurone to the muscle and the receptive neurone from the skin. For it is upon the motor neurone that other arcs impinge.

The refractory state is obviously akin to a state of inhibition, and just as there are well-known examples in which the inhibi- tory state is peripheral (e.g.t the heart), and others in which the inhibition is central, so undoubtedly phases of refractory state are in some instances peripheral, but also in numerous instances are central, — and this is so in certain reflex actions. The reflexes of which refractory phase constitutes a promi- nent feature are those concerned with cyclic actions occurring in rhythmic series ; such as the scratch-reflex, reflexes of swal- lowing and blinking, and probably the rhythmically recurring reflexes concerned in the stepping of the Hmbs.

Nothnagel (1870),^* following up an observation by Sets- chenow,^^ studied a periodic and rhythmic reflex of the crossed hind limb in the spinal frog. He found that if some days after the frog's cord had been transected at the fourth vertebra, the central end of the sciatic is faradized, a rhythmic alternating flexion and extension of the opposite hind limb is evoked. He noted that no intensity of stimulation makes the rhythmic move- ment alter from clonic to tonic. A reflex of this kind is, I find, elicitable in the spinal dog's hind leg by unipolar faradiza- tion of the opposite foot, and, as Nothnagel noted in the frog, no mere increase of intensity of stimulation converts its clonic character into maintained tonic. It is rhythmic (Fig. 22), and has a refractory period which no ordinary increase of inten- sity of stimulation suffices to break down. The frequency of its rhythm averages 2.3 per second, but varies somewhat in different observations. This is about twice as slow as the frequency of the scratch-reflex, which averages 4.5 per second. The average rhythm of the scratch-reflex is almost exactly the same as that ascertained by Gotch and Burch ^^* for reflex-discharge from i the electric cell of Malapterurus, but the rate in Malapterurus I appears to vary much more than that of the scratch-reflex. >;

Figure 22. — Crossed stepping-reflex (spinal dog) elicited by unipolar faradization of the opposite foot. The flexions of the limb succeed each other at a rate of about five times in two seconds — about half the frequence they exhibit in the scratch-reflex. The "after- discharge" of the reflex includes four "steps," the last being of small amplitude and slow, as with the final beats of the scratch-reflex. Time marked below in seconds. Above the time line is the signal line, showing the period of application of the stimulus.

^IGURK 23. — The " extensor-thrust *' ; spinal dog. Time below in seconds. There is a peculiar brief extension-reflex of the dog's hind leg which I term^ the "extensor-thrust" Baglioni 288 has more recently noted an analogous reflex in the frog. This reflex is elicited by mechanical stimuli applied to the planta. In the spinal dog, where well marked, it is often elicitable by even lightly stroking with the edge of a piece of paper the skin behind the plantar cushion. It is more certainly evoked by pushing the finger-tip between the plantar cushion and the toe- pads, especially when the hip and knee, not necessarily the ankle, are resting, passively flexed.

The ** extensor-thrust " I have never succeeded in prolonging to a full half-second — none of my records exhibit it as long as that Usually the duration as recorded is about a fifth of a second (Fig. 23.). Possibly its muscular contraction may be a simple twitch, though reflexly excited. Its muscular field involves the muscles of the " knee-jerk." The myogram of the extensor thrust is shorter than that of tetanic contraction of the dia- phragm (Head's slip) ^^^ caused by two successive stimuli to the

phrenic nerve when the muscular responses of the two just fuse J (Fig. 24). Immediately after its elicitation this reflex, in my experience, f remains in the spinal dog for nearly a second relatively inelicit- FiGURB 24. — Myogram of the contraction of the diaphragm of the rabbit (Head's slip) elicited by two break shocks applied to the phrenic nerve. The moments of application of the two shocks are indicated by abscissae on the myograph curve. Time below in hun- dredths of a second (Macdonald and Sherrington).

able. Its reflex-arc exhibits after its phase of activity a refrac- tory phase. The refractory phase is here far longer than that of the scalptor-reflex. It may last six times as long as the period of activity ; thus the extensor-thrust may last only 1 70 a while the succeeding refractory phase may endure a full second. The extensor-thrust is probably an important element in the reflex mechanism of the dog's locomotion.^ One peculiarity it has as compared with other spinal reflexes of the limb is the considerable force which it exerts. In the locomotion of the animal it provides much of the propulsive power required. 1 Compare on this the recent paper by M. Philippson.^**®