The Integrative Action of the Nervous System

Reflex latency. A dissimilarity between nerve-trunk con- duction and reflex-arc conduction which has often been stressed is the slowness of the latter as measured by the latent interval between application of stimulus and appearance of end-effect In nerve-trunks the interval between the moment of stimulation and the appearance of response (electrical) at any distant point is strictly proportional to the distance of that point from the seat of stimulation. There is in the nerve-trunk no measurable delay or latent interval for the response at the seat of excitation. The latent time for nerve-trunk response is therefore entirely a propagation time. The speed of propagation in frog's nerve at 15° C. is about 3 cm. per sigma ((t = .ooi second). We may compare with this the latent period of the flexion-reflex of the " spinal " dog's hind leg. The movement of this reflex is a flexion at knee, hip, and ankle. It is easily and regularly evoked by nocuous or electrical stimuli applied to the skin of the limb or to any afferent nerve of the limb. For measure- ments of the reflex latency I have stimulated with break or make shocks of regular but varied frequency. Assuming that in warm-blooded nerves the conduction is the same (Helmholtz found it faster) as in the frog, and that the length of the reflex- arc of the dog's knee is two thirds of a metre, and assuming that we may add 5 a- for mechanical latency of the flexor con- traction of the limb, we should have about 27 <t as the latent time for the flexion-reflex, supposing its conduction proceeded as does nerve-trunk conduction. But, as a fact, a period double that is common enough for this reflex under ordinary moderate intensities of stimulation.

But with intenser stimuli the latent period of this reflex is much less. A period of 300- from commencement of stimu- lus to commencement of mechanical response is not then un- common. I have met, at shortest, with 22 a. There is here little difference between speed of reflex conduction and speed of nerve-trunk conduction. Similarly Francois Franck"^ has recorded latent periods for reflex action differing little from those of simple nerve-trunk conduction. Thus, 17 a were ob- tained for a reflex contraction of the crossed gastrocnemius evoked by stimulation of the afferent root of the first lumbar nerve. These short latencies Franck obtained with strong stimuli.

It would seem, therefore, that the more intense the stimulation Figure 2. — A, B. Scratch-reflex. The tracings show the usual lengthening of latency on reducing the intensity of the stimulation. The two tracings are in reproduction unequally reduced, but the frequency of repetition of the double-induction shocks used as stimuli was the same in both shocks of weaker intensity in B than in A. The reflex movement began after delivery of three stimuli in A, after delivery of nine in B. The greater intensity of the stimuli in A is also evidenced by the greater amplitude of the movement and by the longer " after-discharge." Time marked in fifths of seconds below.

the more the conduction along the reflex-arc comes to resemble in speed the conduction along simple nerve-trunks. It is with mild stimuli that the difference in speed between reflex conduction and nerve-trunk conduction becomes most obvious. The latent period for the flexion-reflex, then, lies usually between 60 a and 1200-. I have met with it as long as 200 0-. There is no good evidence that the speed of propaga- tion in nerve-trunk conduction is in response to weak stimuli appreciably slower than to strong. This slackening of propa- gation speed under weak stimuli (Fig. 2) is, I would urge, a more significant difference between reflex-conduction and nerve-trunk conduction than is the mere greater slowness of the former than of the latter. Another difference between the two in regard to conduction-speed is that in the various cerebrospinal nerve- trunks of the same animal species the conduction-speed ap- pears to be practically the same. But reflex conduction-speed as measured by the latent period differs greatly in the various type-reflexes of even one and the same limb. The latent time of the scratch-reflex is, on the average, much longer than that of the flexion-reflex or extensor-thrust, although the spatial dis- tance of the nerve-fibre conduction is not greater. The latency of the former usually in my experience lies between 140 a- for intenser stimulation and 500 <t for weaker, and I have seen it ex- tend to 24400- and even to 3540 o-. So that although a weakly provoked flexion-reflex may have a lengthier latency than a strongly provoked scratch-reflex, the latency of the scratch- reflex is nevertheless on the average very characteristically longer than that of the flexion-reflex. Now there is no evidence that this is referable to a difference in the conduction rate along the nerve-trunks of the two reflexes ; indeed, the efferent nerve- trunks for the two reflexes are the same.

The speed of travel of nervous impulses along nerve-trunks is fairly known. On the not improbable assumption that their velocity along the myelinate fibres of the white tracts of the central nervous system is about the same as along the myelinate fibres of nerve-trunks, the latent period of reflex-actions of moderate intensity is obviously greater than can be accounted for by travel along such conductors of the same length as the reflex-arc itself. The delay in speed occurs whenever the impulses pass through gray matter. This has been especially clearly shown by Exner."^ The delay in the gray matter may conceivably be due to slower conduction in the minute, branched, and more diffuse conducting elements — perikarya, dendrites, arborizations, etc. — found there; or it may be referable to a fresh kind of transmission coming in there, a process of trans- mission different in nature to conduction along nerve-fibres. The neurone itself is visibly a continuum from end to end, but continuity, as said above, fails to be demonstrable where neurone meets neurone — at the synapse. There a different kind of trans- mission may occur. The delay in the gray matter may be refer- able, therefore, to the transmission at the synapse.

And if the delay occur at the synapse, the possibility sug- gests itself that the time consumed in the latent period may be spent mainly in establishing active connection along the nervous-arc, which connection once established, the conduction in the arc then proceeds perhaps as speedily as does conduction in a simple nerve-trunk. The latent time would then be com- parable with time spent in closing a key to complete an electric circuit or in setting points at a railway junction. The key once closed, the points once set, the transmission is as expeditious there as elsewhere. Measurements of reflex times deal custom- arily, so far as I am aware, with the latent time of reflexes initiated in arcs not in action at the moment when the exciting stimulus is applied to their afferent end. How the latent time is spent can receive some light from observation on the latent time of an increase of action in an arc already active in the same direction as the incremental action.

To examine this the flexion-reflex was excited by a sub- maximal stimulus, and after its appearance the intensity of the exciting stimulus was abruptly increased by short-circuiting a definite resistance from the primary circuit. The stimulus was a series of break shocks of regular interval given by a key rotating at constant speed in the primary circuit of the induc- torium. An electromagnet marked the interruptions of the Figure 3. — Flexion-reflex. Spinal dog. Latent time of incremental reflex compared with that of initial reflex. Unipolar faradization by break shocks. Kathode at needle- point in plantar skin of outermost digit. A weak initial stimulus is delivered and main« tained, and then when the resulting reflex movement has become steady the stimulus is increased in intensity by short-circuiting 5 ohms from the primary circuit. The rate and intensity of the break shocks is marked above by a recording electromagnet ; the armature is arranged to have an ampler excursion when the current is increased at the point marked B. The latent time of the incremental reflex is seen to the right hand, and is distinctly shorter than that of the initial reflex. Time below is written in iJ^ sec. and in seconds. Abscissae on the myograph line show the moment of first delivery of the initial (A) and of the incremental ( B) stimuli.

primary current; the electromagnet was arranged to show by more ample excursion of its armature the point of time from which onward the primary current was increased. The shocks were applied by a needle-point (kathode) to the skin of a digit : the other electrode, large and diffuse, was wrapped round a fore- foot, /. e., head ward of the spinal transection. In these experi- ments the earlier reflex elicited may be termed the initial reflex. Its sudden increase on sudden intensification of the stimulus may be termed the incremental reflex. The latent times of the initial reflex and incremental reflex, when compared, showed almost always that the latency of the latter was rather the shorter. But the difference often was not great (Figs. 3 and 4). The average for 30 of the initial reflexes was 48 tr, and for the 30 corresponding incremental reflexes was 38 c This difference seems too small to support the supposition that the latent time of the initial reflex is chiefly consumed by " setting " the synapse, which, once set, conducts in much the same way as regards speed of transmission as does the rest of the arc. It might be that the incremental reaction involved the " setting " of other additional synapses. But such an explanation demands that none of the augmentation occur through the synapses already in action, for the latent time is measured to the first beginning of the steplike incremental ascent of the curve.

In the incremental stage of the reaction the reflex is usually a relatively intense one. Now the length of reflex latency is caeteris paribus inversely as the intensity of the reflex. If the reflex as produced in two stages be compared with the reflex produced by delivery of the stimulus in its full strength at the outset, the latent time of this latter is found shorter than that of either the initial or incremental reaction of the other reflex (Fig. 4). The latent time under the same external stimulus is thus less in circumstances that ex hypothesi involve building a bridge and then sending impukes across it, than when the bridge already having been built the impulses have merely to pass. This argues against an amoeboid movement of the protoplasm of the cell being the step which determines its conductive com- munication with the next (Demoor, Cajal, Renaut, Monti, Duval,

Figure 4. — Same as preceding (Fig. 3), but with somewhat stronger initial stimulus and reflex. At the extreme right hand of the figure is shown the beginning of the " total " re» flex, that is, the reflex when the intensity of stimulus used incrementally in the left-hand observation is thrown in at outset. There is little difference between the latent times of the "initial" and "incremental" reflexes; the latent time of the "total" reflex is shorter than that of either the initial or incremental reflex. Electromagnet above records break shocks as before ; at A the initial^ at B the incremental^ at y the total stimulus. The time below is given in ^j^ sec. and in seconds.

Lugaro). It also seems conclusive against any major portion of the latent period being consumed at the synapse in a process which sets the synapse ready to conduct, — a process of preparation for transmission as distinguished from a process of transmission. It argues that the delay is inherent in the process of transmis- sion itself, and that therefore the actual nervous transmission at these points has, when the stimuli are weak, a different order of speed to that in nerve-fibres. The shorter latent time of the reflex induced by the stimulus delivered in full at the outset is in

harmony with the reflex, being under that mode of excitation rather more intense {e, g.^ of greater ampHtude) than when excited as an increment to a foregoing reflex of less strength. The shorter latent times given by intenser stimuli seem readily explicable by the minimal quantity of transmitted influence nec- essary to give detectible effect, being necessarily earlier reached with copious transmission than with weaker transmission. The observations indicate, therefore, that the latent time belongs to some process which is the same in nature, both in initiating a reflex from a resting arc and in increasing a reflex through an arc already in submaximal activity, — and probably therefore in maintaining a reflex in unaltered continuance in an arc. It argues that any " setting " process in the nerve-centre, if it occur at all, is negligible in regard to the time it consumes- It suggests that even while at rest the reflex apparatus is just as prepared for immediately transmitting impulses as when actually engaged in reflex activity in the very direction the new impulses would require. It therefore suggests the greater need for active inhibition in the co-ordination of activity of arcs which have a final path in common and yet use that path to different effects. If resting paths all lie open for conduction, prevention of confusion must depend not on the path excited being the only one open for conduction, but on its excitation being accom- panied by inhibition of others that, did they enter into action, would detrimentally confuse the issue of events.

Reflex after-discharge. Another characteristic difference be- tween conduction in nerve-trunks and in reflex-arcs is the less close correspondence in the latter between moment of cessation of stimulus and moment of cessation of end-effect. The reflex- arc shows marked " after-discharge ** ; the nerve-trunk does not. Tetanic contraction of the knee-flexor muscles of the dog in- duced by brief faradization of the motor-nerve usually ceases within 1500- of the cessation of the stimulation of the nerve, if crude condition of fatigue, etc., be avoided. The contraction of those same muscles, when induced reflexly by a similar brief stimulation, often persists for ^Q00(t after cessation of the stimu- lus (Fig. 5).

Figure 5. — Flexion-reflex. Effect of increase of intensity of stimulation. Stimulus con- sisted of 45 break shocks delivered at frequency of 42 per second for each reflex. Clonus is seen in the after-discharge. The measure of intensity of stimulus is given from the units of the Kronecker coil; the measure of the reflex is from the area included between myograph curve and base line. Reflex IV not in the figure. We must subtract from the period of after-discharge a period equal to the latent time. But usually the latent time is quite insignificant in length as compared with the after-discharge. The after-discharge in flexion-reflex VI (Fig. 6) was more than five hundred times longer than the latent time.

The after-discharge increases with increase of intensity of the stimulus, not only absolutely, but relatively to the whole reflex — when the stimulation is not long lasting. Taking the flexion- reflex for example, the increase of after-discharge with increas- ing intensity of stimulation is more marked than the increase of contraction-height (Fig. 7). With stimulation lasting not more than 1000 <T the maximum amplitude of the reflex arrives, as the intensity of the stimulus is increased, later and later, so that with weaker stimuli it falls within the excitation period, but with stronger stimuli it is reached only after the application of the stimulus has ceased. Very marked in the after-discharge of this, the flexion-reflex, is a clonus (Figs. 5, 6) with a rate in my records varying between 7.5 and 12 per second. Undulations of similar kinds are clear in the reflex movement even from the outset in weak intensities of the reflex.

Figure 6. — Flexion-reflex. Stimulus for each reflex was 72 break shocks at the rate of 40 per second. This stimulus is registered above by electromagnet in the primary. Ab- scissae on the myograph curve show its delivery and cessation on that curve. The curve marked V is the actual record of its observation ; the other curves are tracings of the records obtained in the consecutive series of which curve V was the fifth member; the record is thus condensed and contrasted.

Intensity 0/ stimulus. Measure 0/ reflex. Measure 0/ after-dischargt. The clonus of the after-discharge is well seen. Time below in seconds. Under short-lasting application of rather weak serial stimuli at slow frequency of repetition (break shocks at 20 per second), increase of the number of stimuli, without alteration of their in- tensity or rate, in other words mere prolongation of the stimula- tion, increases the after-discharge (Fig. 8). The reflex induced by nine stimuli has an after-discharge three times as great as the reflex from three similar stimuli. The maximum amplitude in this case may remain practically the same, the later stimuli simply prolonging the maximum without increasing it. They prolong it for a far greater time than their own delivery pro- longs the stimulation time.

In the scratch-reflex, likewise, intensity increases the after- discharge (Fig. 9). Its after-discharge is rhythmic, a clonus like the rest of the reflex, with the slight lengthening of duration and sequence of the terminal beats that is characteristic of this reflex. The after-discharge from the scratch-reflex is not usually so prolonged as that from a flexion-reflex produced by a stimulus of like length and intensity (Fig. 10). Six to nine beats usually complete the after-discharge.

In the spinal dog there is a reflex of the hind limb in which a movement of extension at knee, ankle, and hip is caused by stimulation of the skin of the contralateral hind limb — the "crossed extension-reflex." When this reflex is provoked with more than a certain intensity its after-discharge becomes a feature of extraordinary prominence, both as regards degree of contraction and duration. This after-discharge may then be more intense than any other part of the reflex, and may persist, gradually decHning for 10 or 15 seconds (Fig. 27). Wundt®^ and Biedermann ^^ have noted that in the cooled frog the dura- tion of the reflex after-discharge is prolonged.

FiGURB 7. — Flexion-reflex. Elicited by lo break shocks at rate of 20 per second, «.#., stimulation Isisting .5". Intensity of stimuli increased by bringing secondary coil toward primary. The intensity of stimulus is given in units of the Kronecker inductorium. The amount of reflex is measured by the area between the myograph curve and the base line. Figure 8. — Flexion-reflex; " spinal " dog. Effect of prolongation of the exciting stimuu- i tion. The circular key rotating at constant speed interrupted the primary circuit of an \

inductorium the break shocks of which were delivered through a needle electrode (kath- ode) to the plantar skin of the outermost digit. An adjustible spring rheotome allowed the desired number of interruptions in the primary, and therefore the desired number of break shocks in the exciting circuit when that was unshortcircuited. Three of the suc- cessive stimuli elicited the uppermost reflex, four the next, five the next, six the next, and nine the lowest. The " af ter-discharge " is seen to be increased by mere prolonga- tion of the stimulus within these limits. The frequency of the stimuli remained in all cases 20 per second, and their intensity was the same for all the reflexes.

Figure 9. — Effect of intensity of stimulus on scratch-reflex. Stimulus is 9 break shocks at rate of 25 per second delivered to a point in the scapular skin by unipolar faradization, the stigmatic electrode being the kathode. A, the stimulus is very weak : one small beat of characteristic slowness is evoked after a long latent period ; B, increase in intensity of shocks with resulting shorter latent time and a reflex movement of two feeble beats ; C, further increase of intensity of stimulus : the latent time is shorter, and a reflex of ten fairly quick and ample beats ensues. The stimulus lasted less than a half second ; the reflex is not completed for more than two seconds after cessation of the stimulus.

There is no feature of the conduction of a reflex-arc which distinguishes its mechanism more universally from that of a mere nerve-fibre tract or trunk than lengthy after-discharge. Richet^^ has paradoxically applied to this feature the old adage modified : '* Sublata causa, non tollitur efifectus." The after-discharge can, however, be cut short sharply by " inhibi- tion" \ it seems also to remanifest itself sometimes after a passing interruption by inhibition.

The long latency and the marked after-discharge of reflex- conduction easily explain a phenomenon often met when study- ing reflexes provoked by stimuli that are brief, especially if they Figure io. — Scratch-reflex and flexion-reflex provoked by similar stimulation in the same animal in quick succession. Stimulation was unipolar faradization with 45 break shocks ; the kathode was stigmatic and applied, to the shoulder skin for scratch-reflex, to the fourth toe for flexion-reflex; diffuse electrode on forefoot. Frequency of shocks, 18 per second. The after-discharge of the scratch-reflex lasted barely one second ; that of the flexion, nearly eight seconds. Time is marked in seconds below each record ; above, an electromagnet in the primary circuit records the interruptions giving the shocks.

be also weak. The stimulus, thaugh it may last for a good many sigmata, is over and past ere the reflex-response appears (Fig- 9)' That response, when it appears, may nevertheless endure for looo a or more. There is nothing closely compar- able with this in the conduction of nerve-trunks. The after-discharge of a reflex may be considered analogous to 2i positive after-image left by a visual stimulus. The analogy is suggestive in connection with others to be drawn between spinal and visual phenomena.

Conduction along reflex-arcs presents in contrast to that along nerve-trunks characters that may be figuratively described as indicating inertia and momentum. It is as though in the case of a weight to be pulled from a position of rest the tractive force were applied through a rigid rod in nerve-trunk conduc- tion, but through a relatively yielding elastic band in reflex-arc conduction. But there are other differences between the two forms of conduction which this simple simile does not figure. We have to enter on such at our next meeting.

Argument: Reflex-arcs show high capacity for summing excitations. Irreversibility of direction of conduction in reflex-arcs. Reversibility of direction of conduction in certain nerve-nets, e. g. that of Medusa. Independence between the rhythm of the reflex-discharge and the rhythm of the external stimulus exciting it. Refractory phase in re- flexes ; in the eyelid-reflex ; in the scratch -reflex. The neuronic construction of the reflex-arc of the scratch-reflex. Long descend- ing propriO'Spinal tracts revealed by the method of "successive degeneration." The "final common path" and the "afferent arc." Intraspinal seat of the refractory phase of the scratch-reflex. The value of refractory phase in the co-ordination of the swimming of Medusa. Its value in the co-ordination of the scratch-reflex. Signifi- cance of the intraspinal situation of the refractory phase of the scratch- reflex. Other instances of " central " refractory phase.

Summation. Summation of subliminal stimuli so that by repe- tition they become effective is practically unknown in nerve- trunk conduction. But it is a marked feature of reflex-arc conduction (vSetschenovir,^^ Stirling^''). Nor is it attributable to the muscles whose contraction may serve as index of the reflex- response, since summation of this extent is not known for vertebrate skeletal muscle, though found by Richet^ in the claw-muscle of the crayfish.

We find striking instances of the summation of subliminal stimuli given by the scratch-reflex. The difficulty in excit- ing a reflex by a single-induction shock is well known. A scratch-reflex cannot in my experience be elicited by a single- induction shock, or even by two shocks, unless as physiological stimuli they are very intense and delivered less than 600 a apart. Although the strongest single-induction shock is therefore by itself a subminimal stimulus for this reflex, the summating power of this reflex mechanism is great. Very feeble shocks, each

ucceeding the other within a certain time — summation time — sum as stimuli and provoke a reflex. Thus long series of sub- minimal stimuli ultimately provoke the reflex. I have records where the reflex appeared only after delivery of the fortieth suc- cessive double shock, the shocks having followed each other at a frequency of 1 1.3 per second, and where the reflex appeared only after delivery of the forty-fourth successive make shock, the shocks having followed at 18 per second. A momentary stimulus, e.^.,a, break shock of fair physiological strength applied by a stigmatic pole (needle point) to a skin-spot in the receptive field of this reflex, produces in the nervous arc a change which though, as just said, unable of itself alone to produce the reflex movement, shows its facilitating influence {bahnung) on a subsequent stimu- lus applied even 1400 <r later. The duration of the excitatory change induced by a momentary stimulus is therefore in this mammalian arc (scratch-reflex) almost as long as that noted in the frog by Stirling, namely, 1 500 (t.