The Integrative Action of the Nervous System

The form in which this central inhibition occurs may be best gathered from illustrative examples. bell of Medusa gives little evidence of an arrangement for a ; form of spatial co-ordination which is very prevalent in more | of it, can be actively moved, not merely in one direction but j in two or more, opposed or partially opposed. The muscula- ^ ture is then usually divided into various discrete pieces called 1 ** muscles." The contraction of one muscle, or set of muscles, ;]

produces movement in one direction; the contraction of an- • other produces movement in another direction. Instances of '; this are common in the limbs, neck, tail, etc., of Vertebrates ; Reflex co-ordination makes separate muscles whose contrac- : tions act harmoniously, e. g. on a lever, contract together, although • at separate places, so that they assist toward the same end. In ; other words, it excites synergic muscles. But it in many cases ;

does more than that. Where two muscles would antagonize ; each other's action the reflex-arc, instead of activating merely one of the two, causes when it activates the one depression of ^ the activity (tonic or rhythmic contraction) of the other. The j latter is an inhibitory effect. Classical examples of inhibition are those of the vagus nerve [ on the heart, and of the corda tympani on the blood-vessels of '\ the submaxillary region. In these cases the stimulation of the \

distal end of a peripheral nerve quells the existing contraction ■ of the muscles of the heart and blood-vessel respectively. \ When the submaxillary gland is called into activity reflexly, \ depression of the tonic contraction of the muscular coat of j its arteries accompanies the heightened secretory activity of \ gland cells simultaneously evoked. The two reflex actions — the \ one depressing the activity of one tissue, the other heightening \

that of the other tissue — are mutually co-operative, and are ^ combined in the one reflex action, and are instances of a reflex • co-ordination quite comparable with that in which one muscle \ of an antagonistic couple is thrown out of action when the other \ is brought into action. And as in this case, so in some cases \ of mutual co-operation of inhibition with pressor action in the \ nervous regulation of antagonistic muscles, the inhibition is peripheral; that is to say, stimulation of the distal piece of the divided peripheral nerve itself suffices to produce it. Instances of this occur in the claw of Astacus, and in the muscles opening the shell of the bivalve Anodon. In Astacus, as is well known, (Richet,*^ Biedermann,^^ Piotrowski ^*^) stimulation of the distal end of the cut peripheral nerve causes, under suitable condi- tions, relaxation of the closing muscle at the same time as contraction of the opening muscle. This is comparable with the stimulation of the distal end of the cut corda tympanic which produces relaxation of the muscular coat of the arteries of the submaxillary gland at the same time as it causes secretion by the gland cells.

The muscles of the claw of Astacus are striate, and the case is interesting as one in which the co-ordination of action of two antagonistic muscles of skeletal type is effected by peripheral inhibition of one through the same nerve-trunk that induces active contraction of the other. But the similar co-ordination in the taxis of the skeletal musculature of vertebrates exerts its inhibition not at the periphery but in the nerve-centres. It occurs within the gray matter of the central nervous system.

When the spinal cord has been transected headward of the lumbar region, reflex movements of the hind limb can, after the period of shock has passed, be studied with much uniformity of result. Electric stimuli apphed to the skin of the limb, especially of the foot, evoke practically uniformly a drawing up of the limb. This flexion-reflex, as presented by the spinal dog, consists in flexion at knee, hip, and ankle. The afferent fibres from each even small area of the skin of the foot do not enter together as a tiny group into the spinal cord in any single filament of a single afferent root, but scatter and make their entrance into the cord via a. number of root- lets,^^^ belonging not merely to one but to two or even three adjacent afferent spinal roots. These afferent fibres having entered the cord, severally subdivide in the manner well known since the researches of Nansen, Ramon, Van Gehuchten, v. Lenhossek, and others ; and their collaterals and terminals must,

as it were, seek out the motor cells of the above-cited flexor muscles, and, as it might appear from the above evidence, leave the motor cells of other muscles, for instance, of the extensors, alone. Increase of intensity of the stimulation of the plantar skin does not in my experience make the spinal reflex action flow over, so to say, from the flexor muscles to the extensors. As the strength of the stimulus is increased from minimal, the number of the flexor muscles obviously thrown into action in the limb is increased, and the reaction irradiates to other regions of the body ; for instance, to the extensor muscles of the contra- lateral hind leg. In the muscles already implicated in the weaker response the contraction becomes, as the stimulus is in- creased, stronger, but I have not found it involve the muscles, causing extension of the homolateral hind limb itself. This flexor-reflex of the limb therefore appears, although able to excite to various degrees of activity the flexor musculature of the limb, unable to excite the extensor musculature.

It would be a mistake, however, to suppose that it is without any direct influence on the latter musculature. It might appear from the statement that the distribution of the aflerent con- ductors of the reflex was to the motor neurones of flexion only, and not to those of the extensor muscles. But the motor neurones of the extensor muscles are not inaccessible to im- pulses arriving by this afferent path. On the contrary, they can be shown to be easily and habitually accessible to them.

To examine this we may turn to the " knee-jerk," and to the tonus of the extensor muscles of the knee. In the spinal animal, for instance in the dog and cat, after transection of the spinal cord in the thoracic region, it is easy to satisfy one's self that, after the shock has passed off" the extensor muscles of the knee still possess considerable tonus. The spinal tonus is reflex, and it has been shown ^* that in the crureus and vastus medialis muscles of the cat, the reflex tonus of those muscles is traceable to aff"erent nerves arising in those very muscles themselves.

The reflex-arc through which the tonus is produced and maintained arises in those muscles themselves and returns to them again. The knee-jerk is easily elicited in the spinal cat and dog. The muscles which contract when the patellar tendon is struck are in these animals the vastus medialis and crtirens}^ The knee-jerk seems, however, only obtainable in them when their reflex spinal tonus is present. Its briskness varies pari passu with the degree of this tonus. Severance of the affer- ent nerves of these muscles destroys their tonus, and renders at the same time the knee-jerk inelicitable, just as also does the severance of their motor-nerves.

The knee-jerk is, therefore, Hke the spinal tonus itself, de- pendent on the integrity of the reflex spinal arc of the muscles. But it is customary to regard the knee-jerk not as a reflex action (Westphal, Waller, and others) ; hence it is termed " knee- phenomenon," " knee-jerk," etc. The main ground for denying its claim to be really reflex is that its latent period is shorter than that of other indubitable reflexes. The latency for the knee-jerk has been shown (Waller,^^^ Gotch,^^"^ and others) to be about 10 <r, whereas the shortest latency found by Exner^ for reflex eyelid-closure was 45 o- and by Fr. Franck ^" for a spinal reflex about i/o". The latency for the knee-jerk is but little longer than that for direct excitation of the extensor muscle itself.

If we regard the knee-jerk not as a true reflex but as a "direct" response of the muscle, we have to suppose that the reflex tonus of the muscle, which is admittedly a conditio siiie qua non for the jerk, so raises the direct excitability of the muscle that the muscle responds by a contraction to a sudden slight stretch of itself due to a tap on its tendon. No experi- menter has, however, satisfactorily succeeded by artificial stimula- tion of the motor-nerve in similarly raising the direct excitability of the muscle. Moreover, Gotch^^^ found the muscle in its state of tonus gave no other indication of increased excitability than simply that it then yielded ** the jerk." It has been urged against the reflex nature of the jerk that the contraction given by the muscle to the jerk is a simple twitch. The " jerk " con- traction lasts no longer, or hardly longer, than the twitch given by the muscle in response to a single stimulus, e.g.^ an induction shock. All reflex contractions are usually considered as tetanic.

That is in the main doubtless true. It is what might be inferred from the great part played by summation of stimuli in the elici- tation of reflexes. Yet the extensor-thrust reflex, which is undoubtedly a true reflex, appears on measurement (p. ^j) to be as brief as the knee-jerk. Its time-relations have been re- ferred to. It is interesting that this brief-lasting reflex also has, as has the knee-jerk itself, the extensor muscles of the hind limb for its seat of expression. The mere brevity of the period of contraction of the knee-jerk is therefore no good evidence that it is not reflex.

The knee-jerk, whether reflex or not, furnishes, since it is an index of the reflex tonus of the extensor muscles, a gauge for the effect, if any, exerted by the flexion-reflex on the extensor muscles of the limb. It was said above that the extensors are not thrown into contraction by this flexion-reflex. The reflex reaction may therefore either be neutral to them and leave them and their condition untouched, or it may inhibit them and depress their reflex activity, even if that activity have at the time only the form of tonus.

If the hamstring muscles (flexors of the knee) be separated from their attachments at their distal (knee) end, and then while the knee joint is passively held in approximate or full extension the flexor-reflex be elicited, e. g. by electric stimulation of the foot, the extensor muscles above the knee are easily felt by pal- pation to at once lose their tonus and relax.^^ At the same moment the exposed and freed flexor muscles are seen to enter contraction. That is to say, the same exciting stimulus that reflexly throws the flexors into contraction interrupts reflexly the reflex tonus of the extensor muscles. If the knee-jerk be elicited at regular short intervals, signalled for instance by a metronome, and while it is in progress the flexor-reflex be elic- ited after the flexor muscles have been detached from their knee attachments and the knee thus left free, the knee-jerk is found inelicitable or much diminished directly the reflex contraction of the hamstring muscles sets in (Fig. 29). This inhibition of the jerk sometimes seems to set in even before the reflex contraction of the flexors is apparent. It occurs

sometimes when the stimukis is not even strong enough to evoke obvious contraction of the flexors. In the " flexion-reflex," therefore, the reflex excitation of the flexor muscles is accom- panied by reflex inhibition of the antagonistic extensor muscles both as regards their reflex tonus which is in progress when the flexor-reflex is excited, and as regards their response to a stim- ulus (tap on tendon or muscle) that otherwise excites them. Figure 29. — Tracing from preparation of the extensor muscles of the knee, recording a series of knee-jerks elicited at each alternate beat of a metronome. Weak faradization of the central end of the hamstring nerve was applied during the time marked by the signal line below. The tonus of the extensor preparation at once fell, and with it the knee-jerk was temporarily abolished. After cessation of the inhibiting stimulus the tonus and the knee-jerk quickly returned, and the latter became more brisk than previous to the inhibition. The lowest line marks the time in seconds.

A corresponding reaction is seen also after ablation of the cerebral hemispheres and thalamencephalon. After removal of those organs, there ensues " decerebrate rigidity." *^» ^^ One feature of this condition is a heightened tonus of the extensor muscles of the knee. The knee is maintained rigidly extended. At the same time the knee-jerk is elicitable in unusual degree. When the knee is under these circumstances freed from the flexor muscles, and the flexor-reflex is then induced by appro- priate excitation, e.g.y of the plantar skin, the knee joint at once drops loose, and if the knee-jerk be tested, it is found to be inelicitable, or elicitable only very faintly (Fig. 29).

Similarly, if instead of the knee-jerk or the reflex rigidity of the decerebrate animal, we take the reflex termed the ex- tensor-thrust as a guide to the condition of the extensor arcs during the flexion-reflex, we get similar evidence that those arcs are temporarily out of action. While the flexion-reflex is in progress the extensor-thrust is less elicitable. If the flexion- reflex is quite weak, the extensor-thrust can be obtained and breaks through it ; but it cannot if the flexion-reflex be of fair or of considerable intensity. The reflex called the extensor- thrust is an extremely powerful one ; it can in the spinal dog lift the whole body from the ground and push it forward. Yet none of the devices normally evoking it can elicit it during a fair flexion-reflex. It becomes elicitable again when the flexion-reflex is over.

It seems, therefore, that in the flexion-reflex and in the other above-mentioned reflexes an inhibitory process is part and parcel of the reflex reaction, so that the inhibition goes on side by side with excitation of other muscles opposed to those which are inhibited. This view, that the inhibition process in these reflexes is a simultaneous counterpart to the excitatory, is supported by the following evidence from the flexion-reflex. A salient feature of this reflex is flexion at the knee. For comparison of the inhibition and excitation respectively, both hind limbs are taken and so prepared that in one leg only the knee flexors can act, in the other leg only the knee-extensors. The stimuli to provoke the reflex are applied either to sym- metrical skin points or to symmetrical afferent nerves at, as far as practicable, symmetrical places in their course. For compari- son, the stimuli are made as far as possible equal on the two sides. This being arranged, certain characteristic features of the reflex have been examined on the two sides respectively.

(a) The flexion-reflex has a " receptive skin-field " which though extensive is characteristic for it. Examined by the above preparation the skin-field whence the excitation (con- traction) is elicitable and that whence the inhibition is elicitable has proved in my observations to be one and the same. Thus : stigmatic unipolar faradization of a point in the skin of a right pedal digit provokes in the homonymous limb contraction of the flexors of the knee, and similar stimulation of the correspond-

ing left digit provokes in its own limb inhibition of the extensors of the knee. Again, similar stimulation of the skin of the fore foot (in my experience that of the crossed fore foot acts more readily than that of the homonymous) induces excitation (con- traction) of the flexors of the crossed knee ; and the correspond- ing skin-region of the opposite fore limb induces inhibition (relaxation) of the extensors of the knee contralateral to it. (yS) Turning to stimuli other than electrical, it is not, as I have pointed out, every form of stimulus that, when applied within the skin-field appropriate for the direct flexion-reflex, can excite it. The kinds of skin-stimuli which excite it are those which may be termed " nocuous," ^^^ e.g'.,a prick, strong squeeze, harmful heat (the heat-beam), and chemical agents. Touches, innocuous pressures, rubbing, etc., though effective for various reflexes, e. g.y for the extensor-thrust, scratch-reflex, pinna- reflex, etc., do not in my experience excite this reflex. The stimuli which do excite it, for instance, from the planta, excite, when applied on the side where the flexor muscles alone remain intact, contraction of those muscles, and when applied corre- spondingly on the opposite side, where the extensors alone remain intact, inhibit them (relaxation).

(7) The nerve-twig, similar to that which under faradization on the ** flexors " side excites the flexors (contraction) when faradized on the "extensors" side inhibits the extensors (re- laxation). This comparison has been made not only with skin nerves, but with muscular nerves, notably with the nerves of the hamstring muscles and of the gastrocnemius. (S) The flexion-reflex, although it exhibits well the potency of summation of successive stimuli as a factor in its initia- tion, differs in my experience from various other reflexes, e. g.y extensor-thrust, scratch-reflex, pinna-reflex, in being elicit- able fairly easily by a single-induction shock. The shock may be applied either to the skin in the receptive skin- field of the reflex or to an appropriate afferent nerve either cutaneous or muscular. When this is done in the prepared limbs the single-induction shock applied on the ** flexors " side excites a brief reflex contraction of those muscles, correspond-

ingly applied on the " extensors " side it provokes a brief reflex inhibition of those muscles. (e) The flexion-reflex, unlike extensor-thrust, pinna-reflex, etc., can be well evoked in my experience by make or break of a galvanic current. This make or break reflex is shown in the " extensor " preparation by inhibition, just as it is shown in the "flexor" preparation by contraction. With suitable strength of stimulus the break of a descending current is more effective for the reflex inhibition than the make, and vice versa for an ascending current, just as with contraction. The flexion- reflex can also to a much greater extent than can the scratch- reflex be maintained by passage of the constant current In this respect it resembles the vasomotor and respiratory reflexes examined by Grutzner,'^ and by Langendorff and Oldag,^*^ and also the sensual reaction which similar stimulation excites in ourselves — a point of interest when the connection between noci'Ceptive reflexes and dolorous sensation is remembered. When the constant current is thus applied to the limb in which the extensors have been prepared, inhibition proceeds in them as does contraction in the flexors when that current is similarly applied to the limb in which the flexors have been prepared.

(JO The latent time of the flexion-reflex is short. This feature is revealed in the inhibition of the extensors just as in the contraction of the flexors. Great differences of latency in the flexion-reflex as in other reflexes can be obtained by, apart from variance in intrinsic condition of the reflex prepara- tion, variance in the external stimuli in intensity, suddenness, frequency of repetition, etc. The effect of such variations is the same in kind, and, in my experience, in extent, when tested by the reflex inhibition as when tested by the reflex contraction. Thus, with strong stimuli I have found as short a latency as 32 o- for the inhibition, which is slightly shorter than the shortest for contraction under like circumstances that I have yet met with. With weak stimuli I have occasionally met with a latency as long as 400 a for each effect.

(r/) A good criterion of comparison between the reflex in- hibition and the reflex contraction in the flexion-reflex under excitation by an intermittent stimulus is the number of stimuli summed for initiation of the reflex as exhibited on the one hand in contraction of the flexors, on the other hand in relaxation of the extensors. The number of successive single stimuli summed for the initiation is less as their individual intensity is greater.^^

When the summation is compared in the same reflex prepa- ration, in the reflex exhibited as inhibition (relaxation) in the knee-extensors of one limb and in the reflex exhibited as con- traction in the knee-flexors of the other limb, good agreement is found ; the number has been often actually the same, though the observations are made alternately, first one on one limb, then one on the other limb. Figs. 30 A and 30 B, and 31 A and 31 B are such pairs, and illustrate the kind of agreement.

(^) The course of the flexion-reflex as shown in myo- grams differs much from that of certain other reflexes of the limb, notably from the extensor-thrust and from the scratch- reflex. Its duration follows more closely that of the eliciting stimulus. If the stimulus is quite brief and not intense the myogram shows but a short continuance of the development of the effect after the external stimulus itself has ceased. The flexion-reflex by adjustment of the intensity of the stimulus can be graded as to its amplitude. This grading is seen not only as a grading of the amplitude of contraction of the flexors when the stimulus is applied to the limb with intact knee- flexors, but as a grading of the amplitude of relaxation when the stimulus is applied to the limb with intact knee-extensors.

These correspondences support the view that the reflex inhibition (relaxation) and. the reflex excitation (contraction) are part and parcel of one and the same reflex reaction ; and that although opposite in direction they are co-ordinate reciprocal factors in one united response. In the crossed extension-reflex this " reciprocal innervation " is seen conversely inhibiting the flexors while causing contrac- tion of the extensors. This reflex is well excited by stimulation of the opposite planta. The myograph lever recording the contraction of one of the hamstring muscles, isolated to sample the group, is then seen to register a quick relaxation interrupt-

Figure 30. — A and B. The " flexion-reflex " observed as reflex contraction (excitation) of the flexor muscle of the knee (Fig. 30A) and as reflex relaxation (inhibition) of the extensor muscle of the knee (Fig. 30B). The afferent nerve stimulated is a twig of the internal saphenous below the knee. The stimulation is by a series of break induction currents, the number and frequency of which is shown by the electromagnet record of the breaks and makes of the constant current feeding tlie primary spiral of the induc- torium through a rotating key. The distance of the secondary coil from the primary