LECTURE III CO-ORDINATION IN THE SIMPLE REFLEX (concluded)

Grading of intensity. A further difference between the reaction of a reflex-arc and that of a nerve-trunk lies in the greater ease with which in the latter the intensity of effect can be graded by grading the intensity of the stimulus. In the nerve-trunk this has been examined both with the action-current (Waller)¹⁶⁸ and for motor-nerves by the muscular contraction (Fick, Cybulski, and Zanietowski).¹⁴⁵ The accuracy of grading within a certain range of stimulus-intensity is so remarkable that the ratio between stimulus-intensity and response-intensity has by some observers been assigned mathematical expression. Waller finds the response in a nerve-trunk, directly stimulated, increase in much closer direct proportion to the increment of external stimulus than does the response of muscle to indirect stimulation, or the response of the optic nerve when the retina is adequately stimulated. The correspondence between intensity of external stimulus and reflex end-effect is again less close still; indeed it is often stated that reflex reactions resemble as to intensity the “all-or-nothing” principle of the cardiac beat (Wundt). Biedermann remarks of reflexes evoked by single-induction shocks in the cooled frog, that there is practically no grading of intensity: they are all maximal. Baglioni makes the same remark for other reflexes in the frog.

Yet graded intensity of reflex-effect does occur. Walton⁹¹ noted as one of the features of strychnine poisoning, that at a certain stage the grading of intensity is lost and all reflexes become maximal. Merzbacher²¹⁰ and Pari²⁹⁴ have supplied some measurements of the increment in amplitude of the reflex movements of the frog’s leg under increase of intensity of stimulation.

The flexion-reflex of the hind limb of the spinal dog increases in amplitude in correspondence with increase of intensity of stimulus—alterations of time-relations of stimulus being excluded. Increase of intensity of stimulus heightens the reflex contraction both in power and amplitude. Figure 25 shows a successive series of these reflexes, each elicited by a series of break shocks delivered at the same skin-spot by a stigmatic kathode. The increments of the reflex run fairly steadily with the up-gradient of intensity of stimulus.

In the scratch-reflex a grading of the intensity of the reflex is easily obtainable by grading the intensity of the stimulus. By a suitably weak stimulus a scratch-reflex can be elicited which exhibits but a single beat. Increase of intensity of the reaction does not show itself in increase in frequency of the rhythm of this reflex, or shows itself very slightly in that form, the refractory period being hardly curtailed at all. The increase reveals itself as greater amplitude of the individual beats of the rhythmic contraction. By simply bringing the secondary coil nearer to the primary in a dozen successive steps, it is easy to obtain a dozen grades of amplitude in a dozen successive examples of this reflex (Fig. 26). The beats in response to a strong stimulus may have six times the amplitude of those evoked by a weak. The single beat that can be obtained by a suitably feeble stimulus (Fig. 9) is not only small but slow; it resembles the last beat the reflex gives as it dies out after cessation of an ordinary stimulus. The feeble, slow character of the terminal beat of the ordinary reflex is not therefore due to fatigue, but simply to weak intensity of excitatory process at the moment.

The scratch-reflex, though it resembles the heart beat in relative immutability of rhythm under change of intensity of stimulation, differs from it in the change of intensity of its beat, which follows change in intensity of stimulus. It does not observe the “all-or-nothing” principle. It is obvious that in the heart beat the object is to put a pressure on the contents of the ventricle higher than that obtaining in the aorta, and that aim reached, any further excess of pressure is useless or harmful, for it subjects the heart and the arterial wall to an unnecessary strain. Clifford Allbutt¹⁸⁰ remarks: “It is the function of a healthy heart and arteries to promote the maximum of blood displacement with the minimal alteration of pressures.” The stress under which the heart is driven is less closely associated with intensities of stimulus than with conditions internal to itself, e. g., distension, etc. But with the scratching movement it is obvious that a strong scratching movement may remove an irritation more quickly and more effectually than weak movement.

On the crossed extension-reflex the effect of increase of intensity of stimulus shows, in my experience, somewhat differently. After a relatively slow and gradual increase of reflex-response, there appears at a certain intensity of stimulation a sudden relatively large increase of the response. This augmentation is Intensity is given in units of the Kronecker scale. Time marked below in seconds From same animal as yielded observations of Fig. 44 but on the succeeding day. chiefly in the form of “after-discharge” (Fig. 27). This reflex shows well that internal conditions play a greater rôle as compared with external in reflex conductions than in nerve-trunk conduction. Under strong stimuli the augmentation of the reaction by after-discharge becomes enormous.

The “extensor-thrust” I have failed to evoke by any stimulus easy to grade or record a measure of. But my experience of it under the particular form of mechanical stimulation it appears to require leads me to think that strength of external stimulus affects the reflex-response but little, and that this reflex does much resemble the heart in responding either not at all or fully. Its graphic record time after time in a series of stimulations repeats itself with very little difference of character.

Therefore, from the reflexes of the limb of the spinal dog, it would appear that in respect to ability to be graded in intensity in accordance with grading of intensity of stimulus, there exist great differences between the various type-reflexes. Some reflexes—e. g., the flexion-reflex and the scratch-reflex—easily exhibit grading, while others do not. The difference between reflex-conduction in various reflexes in this respect may explain the discrepancies between various observers on this point.

A factor in the grading of submaximal effects in muscle and nerve by weak stimuli may well be limitation to certain of the component fibres, whereas a maximal stimulus excites them all. It is a matter of interest how far this numerical factor explains submaximal responses from a spinal centre. If its elements are functionally separate, partial responses are open to occur in such a mechanism since it is multiple as regards its physiological components. Gotch²⁴⁴ has recently raised this question in an interesting way. He points out that in the electrical organ of Malapterurus, where the whole organ is innervated by a single nerve-fibre, the reflex-response is little variable in its intensity in comparison with the wide range of response to increasing stimulus-intensities exhibited by stimulation of the electric nerve of Torpedo,—a structure containing many nerve-fibres. Concerning the grading of motor discharges from the central nervous system he asks,—“Is it not possible that these grades are largely dependent on the number of central elements involved, and are only incidentally associated with variations in the intensity of the nervous process in any one neurone?”

That in spinal reflexes increase of the intensity of the exciting stimulus causes increase in the number of motor neurones excited is clearly shown by the wider field of musculature seen to be engaged as the reflex irradiates under intenser stimulation. This is the well-known spread which Pflüger²⁴ endeavoured to formulate rules to express. Within one and the same muscle-groups, and even within one and the same individual muscle, grading of intensity of reflex contraction by this numerical implication of more or fewer motor-cells seems not only possible but probable. It is perhaps one object of their multiplicity. The want of difference between the latent time of the incremental and initial reflexes mentioned above (Lect. I, p. 24) might be explicable thus.

With very feeble stimuli, or under spinal shock, when only feeble reflex reactions can be evoked, it is easy to see partial contractions of muscles, e. g., in the tibialis anticus, sartorius, and semimembranosus. Under like circumstances the scratch-reflex may have the form of simply a feeble rhythmic dorsi-flexion at ankle and toes, or even of the toes alone. We have referred to such phenomena before, and they harmonize well with the view of a fractional activity of the motor centre of the scratch and other reflexes.

Yet we must not lose sight of the physiological solidarity of the action of the group of elements that compose a “reflex centre” in its reflex activity. “Immediate spinal induction” (v. infra, Lect. IV) and the spatial spread of the refractory phase in scratch-reflexes evoked from separate points show (Lect. II, p. 60) that, intraspinally, the various component arcs of the type-reflex are interconnected to something like a unitary mechanism. Further, the evidence that when the scratch-reflex is being elicited from one point the refractory period obtains practically throughout its intraspinal centre indicates the same functional unity. The nerve-cells building the centre seem combined like those of the nerve-net of Medusa. The elements seem incapable of isolated excitation. Such an intra-spinal group as that involved in the scratch-reflex must extend through a considerable length of the cord. And yet though interconnected, like the web of Medusa’s nerve-net, there is evidence that in the various reflex forms which the scratching movement takes according as elicited from one point or another, one part of the centre is the more active in one form of the reflex and another in another form of the reflex. The mechanism is not therefore always equally affected throughout, and in this inequality numerical proportion of active to inactive elements may play a part. The mechanism, nevertheless, although anatomically an assemblage of units, is functionally itself a unit. And a comparable solidarity obtains in other reflex mechanisms. Even the irradiation which suggests extension to new units itself gives evidence of the welding of the unit elements of centres together into functional unit groups possessing solidarity. When in the flexion-reflex the response spreads from the knee to the hip, the spread is not gradual, but the hip flexion suddenly comes in, marking a sharp step-like rise on the record (Fig. 45, p. 153). It is not as though the irradiation gradually reached the motor elements of the hip-flexion centre cell by cell: the irradiation on involving that centre forthwith evokes discharge from it which, judging from its powerful effect, represents discharge from the centre practically as a whole. The reaction as it irradiates treats the centre as a unit.

Intensity is given in units of the Kronecker scale. Time is marked below in seconds. The record is from the same animal as yielded those of preceding Fig. 25.

The great prolongation of the reflex-discharge produced by intensifying, apart from prolonging, the external stimulus is also against the increase of discharge being explicable merely or chiefly by implication of a greater number of motor elements. In the flexion-reflex, the period of discharge may be lengthened tenfold by increasing simply the intensity of the stimulus without lengthening it. In the “crossed-extension reflex” I have seen the period of discharge lengthened more than twenty-fold. This argues that the grading of the motor discharge in these reflexes is in important measure due to graded intensities of discharge from the unit elements themselves, of which the reflex centres are compounded. The functional unity, of a reflex centre seems also evident from the fact that it is the instrument of a number of receptive organs scattered over a relatively wide field—a field which for the flexion-reflex is almost coextensive with the whole skin surface of the limb—and nevertheless an intense stimulus from any limited part of that field can elicit a reflex of full strength. This it can only attain if the whole centre of the reflex be at its disposal. Therefore, as we saw in the scratch-reflex, the whole motor centre potentially belongs to all and each of the groups of receptive organs proper to the reflex. The centre, although consisting of anatomical units which are individual, seems knitted together functionally. It is not necessarily the motor cells which conjoin—were that so one hardly sees how stimulation of the central end of a motor root could fail to excite discharge from other motor roots, which the Bell-Magendie law shows that it does actually fail to do.

Reflex conduction less resistant than nerve conduction. The differences traced thus far between reflex-arc conduction and nerve-trunk conduction have been differences brought out by variations of stimulus and other external conditions. Differences no less notable appear under changes of internal kind. Without entering on these fully, a glance at them is helpful for the understanding of reflex-arc conduction.

Conduction by nerve-trunks is but slowly affected by inter-ference with blood-supply; reflexes are nevertheless among the earliest reactions to alter or fail under asphyxial conditions, v. Baeyer²⁸⁹ found the sciatic nerve of the frog retain excitability and conductivity three to five hours in nitrogen, and on read mission of oxygen regain its powers in a few minutes. Bergmanr (cited by Biedermann) found interruption of the circulation in the frog extinguish reflexes in thirty minutes. Verworn has shown that the spinal centres of a strychnized frog, if unsupplied with oxygen, fail to react in about an hour’s time, but are promptly restored by resupply of oxygen. Baglioni²⁹³ has shown that the spinal centres of the frog, deprived of circulation and immersed in nitrogen, fail to give reflexes in about forty-five minutes, but in an atmosphere of oxygen continue to react for twenty hours.

Again, the dosage of chloroform or ether required to depress and abolish nerve-trunk conduction is much greater than is required to depress and abolish the cerebro-spinal reflexes. In Waller’s observations on extinction of action-current in nerve-trunks a 3 per cent dose of chloroform in air was required. Using in the cat indirect contraction of the gastrocnemius as an index of sciatic nerve-conduction, Miss Sowton and myself found .3 per cent chloroform in diluted blood at 36° C. required to abolish the reaction (Fig. 28). This is a much higher percentage than suffices to depress the heart’s action. Since many reflexes are abolished by doses which do not markedly depress the heart, reflex conduction is abolished by doses a fortiori smaller than those which set aside nerve-trunk conduction.

Again, a number of agents, e. g., strychnine, tetanus toxin, etc., that do not appreciably affect nerve-trunk conduction enormously alter reflex-arc conduction. All these seem to exert their influence on some part of the reflex conductor which lies in gray matter. It is interesting to ask whether they, e. g. strychnine, have an effect similar to their spinal effect when exhibited in Bethe’s preparation of the second antenna ganglion of Carcinus, whence the motor perikarya have been removed. If these agents have their locus of incidence at the synapse, it must be conceded that they act with very different intensities at different synapses.

From this rehearsal of the differences between nerve-trunk conduction and reflex-arc conduction it seems evident that certain elements of co-ordination of “the simple reflex” are to be found in the qualities of conduction of the reflex-arc. Each of the various types of simple reflex possesses to a large extent its own peculiarities of conduction. Though there are differences between conduction in various nerve-trunks, e. g., in speed of transmission of impulses, etc., these differences sink to insignificance when contrasted with the extent and variety of the conductive differences exhibited by different reflex-arcs. And in the case of each reflex-arc its idiosyncrasies of conduction form an obvious basis for the co-ordination exhibited by its reflex-act.

Functions of the perikaryon.—It may appear that our tendency is to attribute the distinctive characters of reflex-arc conduction so liberally to the synapse that the perikaryon is stripped of all functions and only equivalent to a piece of nerve-fibre. But it is to be remembered that two functions of great importance certainly belong to the perikaryon. In the first place it, even if the conductive process in it be wholly similar to that of a nerve-fibre, is at least a place where the conductor branches, often to such an extent as occurs nowhere else, so that it is a nodal point in the spatial distribution of the conductive lines. In the second place, there seems no valid reason yet to doubt the long-held view that regards the perikaryon as the nutritive centre of the neurone to which it belongs.

Certain features mentioned already as saliently distinguishing reflex-conduction from nerve-trunk conduction still remain for consideration. Among these are fatigability, facilitation, inhibitory interference, spinal induction. These will, however, be better taken under the compounding of reflexes. One feature that we have not considered may, however, with advantage be considered at once. This feature is inhibition.

Reciprocal inhibition.—In the end-effect of certain reflexes, for instance the scratch-reflex, there supervenes on a phase of excitatory state a state refractory to excitation—a refractory phase. This refractory phase is, if we seek to put it into the class of physiological phenomena to which it must obviously belong, a state of inhibition. In the scratch-reflex we have therefore a reflex in which an external stimulus evokes as its end-effect an excitatory phase, succeeded by an inhibitory phase, and this succession in this reflex, the stimuli being continued, is repeated many times. If we denote excitation as an end-effect by the sign plus (+), and inhibition as end-effect by the sign minus (−), such a reflex as the scratch-reflex can be termed a reflex of double-sign, for it develops excitatory end-effect and then inhibitory end-effect even during the duration of the exciting stimulus.

There is a further numerous class of reflexes in which the end-effect consists both in excitatory state and in inhibitory state, but the inhibitory state does not supervene on the excitatory or have the same locus of incidence as the excitatory; it occurs simultaneously with it at another interrelated locus. The ordinary flexion-reflex of the hind limb of the spinal cat and dog is a reflex of this type. The end-effect of the reflex is expressed by two groups of muscles whose contractions act in opposed direction at the same joints. This opposition is obviated in the end-effect of the reflex by the end-effect having the form of excitatory state as regards the motor-nerve to the flexor muscle, but suppression or withholding of excitatory state (central inhibition) as regards the motor neurone of the extensor. Such reflex is a reflex of double-sign, but whereas the scratch-reflex and the eyelid-reflex, etc., are reflexes with successive double-sign, the flexion-reflex and reflexes of that type, e. g., the crossed extension-reflex, are reflexes with simultaneous double-sign.

The form in which this central inhibition occurs may be best gathered from illustrative examples.

The simple reflex mechanism examined in the swimming-bell of Medusa gives little evidence of an arrangement for a form of spatial co-ordination which is very prevalent in more complex mechanisms. In many cases the body, or some part of it, can be actively moved, not merely in one direction but in two or more, opposed or partially opposed. The musculature is then usually divided into various discrete pieces called “muscles.” The contraction of one muscle, or set of muscles, produces movement in one direction; the contraction of another produces movement in another direction. Instances of this are common in the limbs, neck, tail, etc., of Vertebrates and Arthropods.

Reflex co-ordination makes separate muscles whose contractions 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 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 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,⁹⁸ Biedermann,¹⁰⁹ Piotrowski¹⁴¹) stimulation of the distal end of the cut peripheral nerve causes, under suitable conditions, 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 tympani, 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 applied 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 rootlets,¹³⁹ 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 increased, 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 afferent conductors 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 impulses 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 shown³⁰⁴ that in the crureus and vastus medialis muscles of the cat, the reflex tonus of those muscles is traceable to afferent 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 crureus.¹³⁶ 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 afferent 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, like the spinal tonus itself, dependent 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,¹³¹ Gotch,¹⁶⁷ and others) to be about 10 σ, whereas the shortest latency found by Exner⁵⁹ for reflex eyelid-closure was 45 σ and by Fr. Franck¹¹¹ for a spinal reflex about 17 σ. 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 sine 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 experimenter has, however, satisfactorily succeeded by artificial stimulation of the motor-nerve in similarly raising the direct excitability of the muscle. Moreover, Gotch¹⁶⁷ 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” contraction 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 elicitation of reflexes. Yet the extensor-thrust reflex, which is undoubtedly a true reflex, appears on measurement (p. 67) to be as brief as the knee-jerk. Its time-relations have been referred 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 palpation to at once lose their tonus and relax.³⁰⁴ 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 elicited 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 stimulus 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 accompanied 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 stimulus (tap on tendon or muscle) that otherwise excites them.

A corresponding reaction is seen also after ablation of the cerebral hemispheres and thalamencephalon. After removal of those organs, there ensues “decerebrate rigidity.”^{304, 182} 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 appropriate excitation, e. g., 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 extensor-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 symmetrical skin points or to symmetrical afferent nerves at, as far as practicable, symmetrical places in their course. For comparison, 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 (contraction) 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 corresponding 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 (contraction) of the flexors of the crossed knee; and the corresponding skin-region of the opposite fore limb induces inhibition (relaxation) of the extensors of the knee contralateral to it.

(β) 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,”²⁵² 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., 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 correspondingly on the opposite side, where the extensors alone remain intact, inhibit them (relaxation).

(γ) 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 (relaxation). 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.

(δ) The flexion-reflex, although it exhibits well the potency of summation of successive stimuli as a factor in its initiation, differs in my experience from various other reflexes, e. g., extensor-thrust, scratch-reflex, pinna-reflex, in being elicitable 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, correspondingly applied on the “extensors” side it provokes a brief reflex inhibition of those muscles.

(ε) 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 Grützner,⁷⁷ and by Langendorff and Oldag,¹⁴⁷ 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.

(ζ) 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 preparation, 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 σ 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 σ for each effect.

(η) A good criterion of comparison between the reflex inhibition 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.⁵⁷

When the summation is compared in the same reflex preparation, in the reflex exhibited as inhibition (relaxation) in the knee-extensors of one limb and in the reflex exhibited as contraction 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.

(θ) The course of the flexion-reflex as shown in myograms 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 contraction 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 interrupting the reflex contraction that until then had been in progress (Fig. 32). The speed with which the reflex inhibition occurs and is accomplished is much the same as that which reflex contraction itself exhibits. It hardly seems slower. But it is often noticeable that the relaxation thus induced in the contraction does not reduce the contraction to zero (Fig. 32). The relaxation ensues down to another grade of contraction, at which grade the inhibition often continues to hold it; at least, the muscle continues to remain at that length. In such cases the contraction is reduced suddenly from a high level of intensity to a lower level, but a remainder of contraction persists. It may be that this lower grade represents another functional act in which the muscle is simply adjuvant towards steadying the levers for other muscles which replace itself in its previous rôle of principal actor. The condition under which I have most frequently met it has been when the exposed and freed tendon of the semitendinosus (dog) has been attached to the myograph.

It is interesting that when (Fig. 33) the inhibiting stimulus is strong the relaxation of the extensor muscles is actually to a point beyond their initial length obtaining at the time the “crossed extension-reflex” began. The pre-existent “decerebrate” tonus is inhibited as well as the intercurrent reflex. The relaxation is indeed down to, as I expressed it in one of my earlier notes,³⁰⁴ the post mortem length of the muscle. The relaxation, if the crossed-reflex stimulus continues, is rapidly recovered from, and the interrupted reflex reasserts itself (Figs. 33 and 34).

Concordantly with these results examination with the myograph of the contractions of the pretibial and post-tibial muscles of the frog¹³⁶ during alternate flexor and extensor strokes of the hind limb shows in many cases, though not in all, that the contractions of the two antagonistic muscles are not synchronous, but are conversely timed. The contraction of the pretibial muscle breaks down just as that of the post-tibial ensues, and the post-tibial relaxes just as the pretibial contracts.

An early noted and in various ways typical example of this rôle of reflex “inhibition” was that discovered by E. Hering⁴³ and J. Breuer⁴⁴ (1868) in the “self-regulating” respiratory vagus action. Distension of the lung by exciting afferent fibres in the pulmonary vagus inhibits inspiration and excites expiration. I reverted to this as a fundamental instance in my first note³⁰⁴ on the subject. If we regard the heart and ring-musculature of the arteries as two antagonistic muscles, v. Cyon’s⁴¹ still earlier discovery (1866) that the afferent nerve of the heart, and aorta (A. Tschermak and Köster)²⁸⁰—from this point of view, a tendon of the heart muscle—evokes reflex inhibition of the arterial ring musculature, is another instance. The suggestiveness of these facts for the co-ordination of skeletal muscles was not recognised generally. But Meltzer, the discoverer with Kronecker⁸⁹ of the rôle of inhibition in normal deglutition, wrote in 1883,¹⁰⁰ “Of a purposeful arrangement we could expect that a nerve, the stimulation of which causes flexion, ought to contain also inhibitory fibres for the extensors. Now such an arrangement is indeed present—at least in the respiratory mechanism. Of the superior laryngeal nerve, of the second branch of the trigeminus, and of the splanchnics, we know that stimulation of their central end causes inhibition of the inspiratory and contraction of the expiratory muscles.”

Now in the case of the skeletal muscles of the mammalian limb, no efferent nerve-fibres appear to be supplied to them which under stimulation produce inhibition of their contraction. Such have been sought for by various observers, but without success. I have myself looked for them and obtained no unequivocal evidence of their existence. Moreover, Verworn²⁰⁷ has shown that during the inhibitory relaxation produced by the reflex induced from the nerve of the antagonistic muscles the excitability of the relaxed muscle and its motor-nerve to electrical stimuli remains undiminished.

Moreover, in the condition of decerebrate rigidity, when the elbow is being kept in extension by the heightened tonic action of the extensor muscles, their contraction can be inhibited not only by stimulation of the crossed hind foot, but by direct electrical stimulation of a point in the lateral column of the transected spinal cord in the hind thoracic region, as has been shown by A. Frohlich and myself.²²² The inhibition reflexly produced has therefore its seat in the spinal part of the reflexarcs. It is therefore a central inhibition.

This central inhibition appears more than equivalent to merely arresting the play of an excited afferent channel upon the motor centre. Were that all, the phenomenon should resemble the effect of suddenly stopping the stimulation of the afferent nerve causing the reflex. What happens is often not like that; the arrest is more rapid. The “after-discharge,” whatever its seat, can be at once arrested by the inhibition (Fig. 35). The “after-discharge” of a centre, with its concomitant persistence of contraction of muscles, might well be disadvantageous to the organism. That it is rapidly arrested by the inhibitory side of a succeeding reflex, is an adaptation which facilitates the successive interchange of reflexes. The inhibition can arrest some forms of clonic spasm arising during experimentation (Fig. 36).

The motor neurones of the flexor muscles of the hind limb can be excited to the clonic discharge characteristic of the scratch-reflex at a time when the flexion-reflex is inhibited from employing them. When the scratch-reflex is in progress The observation reproduced on the right was from the same experiment, but later; in it the stimulation exciting the reflex contraction was faradization of the proximal end of a twig of the internal saphenous of the contralateral leg. This stimulation lasted about two fifths of a second or less. Its cessation was quickly succeeded by faradization of the proximal end of a branch of the severed hamstring nerve as in the previous observation. The signal marks the time of this inhibiting stimulation. The after-discharge of the contraction reflex is cut short as before. Time is marked below in fifths of seconds. it is more difficult to excite a “flexion-reflex,” and vice versa. One reflex seems to be precluded from acting on a motor neurone at a time when another and different reflex is employing it.⁸⁰⁰ The preclusion of the motor neurone from one reflex while it is still left open to it to respond to other reflexes appears to be one of the services of inhibition to the organism. The motor neurone itself seems not the actual seat of the inhibition, for if so, it would be inhibited for all reflexes; unless the motor neurone is functionally divisible, and one part of it, e. g., one set of dendrites, can be inhibited at a time when another is not. The seat of the inhibition appears, therefore, with some likelihood, to lie neither in the afferent neurone proper nor in the efferent neurone proper, but in an internuncial mechanism — synapse or neurone — between them. I say “neurone proper,” meaning to exclude from that term the synapse, although in a synapse the neurone terminals are included.

The striking correspondence observed (v. s.) between the reflex inhibition and the reflex contraction, when examined in one and the same type-reflex, allows the inference that the nerve-fibres from the receptive field of the reflex each divide in the spinal cord into end-branches (e.g., collaterals), one set of which, when the nerve-fibre is active, produces excitation, while another set, when the nerve-fibre is active, produces inhibition.^{205, 304} The single afferent nerve-fibre would therefore in regard to one set of its terminal branches be specifically excitor, and in regard to another set of its central endings be specifically inhibitory. It would, in this respect, be duplex centrally (Fig. 37). There is analogy between the structural arrangement for reflex reciprocal innervation and that of Astacus claw, if it be supposed that the individual nerve-fibres of the crayfish-claw preparation dichotomise, one division of the nerve-fibre passing to the closing muscle, the other to the opening muscle; so that one division of the fibre exerts the excitor action, the other the well-known inhibitory, studied by Richet,⁹⁸ Biedermann,¹⁰⁹ Piotrowski,¹⁴¹ and others.

In denoting one set of central terminations of an afferent arc “specifically inhibitory,” it is here meant that by no mere change in intensity or mode of stimulation can they be brought to yield any other effect than inhibition. But the fact that stimulation of a single set of afferent arcs, namely a single small afferent nerve, excites frequently a reflex movement of alternating direction in which, for instance at the knee, extension succeeds primary flexion, shows that a change of internal conditions may presumably convert an intraspinal connection that under the primary conditions is inhibitory into one that under later supervening conditions becomes excitatory. The fact that under certain forms of cerebral action true antagonistic muscles can be thrown synchronously into contraction, points to the same limitation of the term “specific” in this connection. Further, there is the intraspinal action of strychnine.

There is the long recognized fact that under strychnine practically all the skeletal muscles of the body may be reflexly thrown into contraction simultaneously, and this is obviously inclusive of, and was proved for, antagonistic muscles.¹³⁶ Evidently strychnine in some way must alter or obscure reciprocal innervation. I have furnished (1892) tracings showing that the pretibial and post-tibial muscles of the frog, although in normal reflex movements so frequently exhibiting concurrent contraction and relaxation in the two groups reciprocally, under strychnine reveal in the double myogram perfectly synchronous contraction in both groups.¹³⁶

Such a result may be explicable in several ways. In order to discover what the nature of the change wrought by strychnine really is, there have to be fulfilled in the test experiments certain conditions which not every preparation of antagonistic muscles can supply. Muscles acting over two joints are to be avoided in such a test. Thus the gastrocnemius of the frog extends the ankle but flexes the knee; it antagonizes the action of the pretibial muscles which flex the ankle, but since flexion of the knee so commonly accompanies flexion of the ankle, it is synergic with the pretibial muscles in the great flexion-reflex that draws up the limb. If it acts synchronously with pretibial muscles under strychnine, we are still left in a dilemma as to whether the co-ordinate reciprocal action at the ankle is essentially destroyed, or whether a reflex attempt to flex the knee has not been simply added to it under a lowering of the intraspinal resistances. And this dilemma is the greater in that the afferent nerves and surfaces used for exciting reflexes contain admixed afferent channels, some exciting contraction in one group of the opposed muscles, and some exciting contraction in the other. Thus in the afferent nerves from the foot, both in the dog³⁰⁴ and the frog,²⁸⁸ there are commingled with fibres which excite the flexor muscles those which excite the extensor muscles — witness the extensor-thrust and flexion-reflex, both elicitable from the dog’s foot, and Baglioni’s extension-reflex of the leg and the flexion-reflex, both elicitable from the frog’s leg. That the extensor muscles of the limb should under strychnine be thrown into contraction synchronously with the flexors in these cases might be due either to the two reflexes being elicited together when spinal resistance has been lowered, or to a conversion of the inhibition part of one reflex into an excitation. And in this latter case it is still left undecided whether the extension under strychnine is due to prepotent extensor-reflex with its accompanying flexor inhibition changed into excitation, or whether it is the flexion-reflex which is changed conversely.

On similar grounds the “spontaneous” convulsions due to strychnine afford no deeper insight into the problem. These “spontaneous” convulsions are really reflex (Stannius, Cl. Bernard, H. E. Hering, and others) in the sense that they originate in the afferent arcs; and in the convulsive movements antagonistic muscles contract simultaneously. But the difficulty here again is, that the reflex source may, and probably does, operate in many afferent arcs concurrently. Some of these arcs excite extensor muscles normally, while others excite flexors. The simultaneous contraction of both flexors and extensors might thus be naturally explicable by lowered spinal resistance, both sets of reflexes being equally induced together, or the explanation might be of an alternative kind, such as suggested above. On the former view the reciprocal innervation of antagonistic muscles would merely be obscured by a simultaneous double reflex; on the latter a more profound alteration would have taken place. The occurrence and form of the convulsion fail to decide among these possibilities.

Conditions for determining the nature of the action that really occurs seem offered, however, in certain instances. Thus, in the hind limb of the cat we have two afferent nerves which never, under any normal conditions³⁰⁴ in my experience, yield as their primary reflex in the vasti-crureus muscle any action but relaxation; in other words, they, without exception, produce reflex inhibition of that muscle. To suppose that these nerves contain afferent fibres which evoke reflexly at the knee any action other than flexion would be mere hypothesis. These two nerves are the internal saphenous in its course below the knee, and the hamstring nerve, coming from the flexor muscles of the knee. Further, the vasti-crureus is a single-joint muscle, and unlike the rest of the quadriceps extensor of the thigh is not a flexor of the hip; therefore contraction in it cannot mean merely its participation in the synergy of the flexion-reflex itself, which includes flexion at the hip. A reflex preparation suited for examining the action of strychnine on reciprocal innervation can, therefore, be obtained in the hind limb by severing, in the de-cerebrate animal for instance, the following nerves: the external popliteal, the internal popliteal, the obturator and pudic in the pelvis, the superior gluteal, the external and cutaneous divisions of the anterior crural and the hamstring nerve. The last named is ligated and cut close to its entrance in the muscles, so that its central end can be stimulated. A branch of the internal saphenous nerve below the knee is also prepared for stimulation of its central end. When this is done it is found that no change in intensity or other conditions of excitation of the afferent nerve ever provokes anything but inhibition of the extensor of the knee, but a small dose of strychnine at once transmutes the inhibitory effect into an excitation effect.³⁰⁴ Reflex contraction is obtained in place of reflex relaxation. If small doses are carefully graded, it is possible to see a state in which the reflex relaxation is diminished but is not replaced by excitation. This phenomenon shows well how little competent is the view of lowered spinal resistance to really explain the action of strychnine; for at this stage the stimulated arc that normally acts on the extensor muscle by inhibition is less able to affect it than before, so that on the spinal resistance view the resistance at this stage is actually heightened.

A similar conversion of inhibitory effect into excitatory is produced more gradually but not less potently by tetanus toxin.³⁰⁴

This conversion sets in before and under smaller doses of strychnine or toxin than are required to produce the convulsive seizures characteristic of strychnine poisoning, or general tetanus.

The transformation of effect by strychnine holds good not only for the nerves above mentioned but for skin-stimuli, and also for those skin points remote from the hind limb itself, which provoke reflex inhibition of the test muscle. For instance, in the case of the knee-extensor as test muscle, the skin of the fore paws.

The conversion of inhibitory effect into excitation effect by strychnine is more easily obtained in the case of some nerves than of others. In the instances of the nerves above mentioned the conversion is least facile, i. e., requires larger doses or longer time for development, in the case of the hamstring nerve, than in the others. The inhibitory effect belonging to that nerve is readily lessened by the strychnine, but its actual replacement by excitation effect, e.g., contraction of knee-extensor, not only requires larger doses of strychnine, but is even then phasic rather than continuous. When this nerve is tested by stimulation at regular short intervals during one of these phasic periods, it can be seen that, starting from the phase in which it still evokes inhibition little, or perhaps not at all, less obviously than in the normal state, its inhibitory effect then becomes progressively less, until it is replaced by excitation effect (contraction), at first mild, later violent. This periodic phase will repeat itself many times.

The conversion of inhibition effect as thus tested on the knee-extensor might be attributable to the afferent nerves stimulated containing two kinds of afferent fibres admixed, one kind causing reflex contraction of the muscle, the other kind reflex inhibition. Strychnine might, by augmenting the action of the former or by depressing the action of the latter, change the effect of stimulation of the mixed nerve. But the latter fibres would be expected to be associated in their action with — or, as urged above, to be even the self-same fibers which evoke — contraction of the flexor muscles. Now there is at the stage of strychnization, at which the change of inhibitory into excitatory effect occurs, no trace of any paralysis or even depression of the flexor contractions. The protagonist and the antagonist muscles are thrown together into synchronous contraction as an effect of strychnine. This and other considerations appear to me to weigh against explaining the conversion of inhibition effect into excitation effect by the hypothesis of reflex antagonistic sets of fibres, oppositely poisoned centrally, commingled in these afferent nerves. Moreover, when a hamstring muscle is taken as the test muscle, a similar conversion of inhibition into excitation (contraction) by strychnine is seen under the crossed extension-reflex. This reflex, elicitable through the skin or various afferent nerves of the contralateral hind limb, normally excites the knee-extensor to contraction and inhibits the hamstrings, the knee-flexors. Under strychnine its reflex inhibition of the hamstringmuscle is converted into reflex excitation (contraction) of that muscle. The observations, as they stand at present, incline me to the inference that the action of the alkaloid is to convert in the spinal cord the process of inhibition — whatever that may essentially be — into the process of excitation — whatever that may essentially be.¹ The reflex nexus was pre-existent, but the effect across it was signalized by a different sign, namely minus prior to the strychnine or tetanus toxin, instead of plus, as afterward (See Fig. 37).

The action of the toxin in respect to inhibition resembles that of strychnine closely in several ways. Thus, in the stages of the disease in which the tetanus is still “local” and manifested in one limb, namely that (e. g., the hind limb) which received the toxin injection, the toxin early converts into excitation the reflex inhibition of the extensor muscles, normally obtainable from the internal saphenous nerve, but that obtainable from the peroneal and popliteal nerves, and from the hamstring nerve, remains unreversed, though the strength of the inhibitory effect of these nerves may be very distinctly less than normal. Later, as the condition progresses, the inhibitory effect normally belonging to the peroneal and popliteal nerves becomes actually reversed into excitation. Finally, even that of the hamstring nerve itself is reversed. This is the same sequence of effect pursued by progressive increase of dosage of strychnine.

One difference that seems apparent between the action of the tetanus toxin and the strychnine in these observations is that in the relatively slow progress of the tetanus it is easy to note the stage in which the conversion of the inhibition effect into excitation effect has occurred, while there is yet none of that obvious lowering of the threshold of reflex reaction which early marks the course of strychnine poisoning, and has been drawn attention to by many observers.

In experiments on the hind limb, I have usually introduced the toxin into the sciatic trunk well below the hamstring branch, more rarely into the hamstring nerve as well, or alone. I have found the inhibitory effect of the internal saphenous nerve (stimulated in its course below the knee) converted to excitation in forty-eight hours from the time of inoculation. In the gradual progress of the condition, I have several times found the hamstring nerve produce slight inhibition of the extensor if the initial posture taken at the knee be extension, and yet produce distinct excitation of the extensor if the initial posture taken at the knee be flexion. This recalls the results of v. Uexküll in Ophioglypha and Echinus.^291a

The conversion of inhibition into excitation by tetanus toxin is demonstrable, as is that by strychnine, with the reflexes of the fore limb as well as with those of the hind limb, and in the “decerebrate” animal as well as in the merely “spinal.”

We can understand what havoc such a change must work in the co-ordinative mechanisms.³⁰⁴ The observed difference between the facility with which strychnine and tetanus toxin convert the inhibition by the hamstring nerve into excitation, and that with which they convert the inhibition of the other limb-nerves mentioned, does not seem referable to a different action on muscular affer-ents and cutaneous afferents respectively. Stimulation of the central end of the vasto-crureus nerve evokes normally inhibition of the hamstrings of the opposite limb, but under strychnine it evokes their contraction. In that case, therefore, the strychnine converts with facility the inhibition by a muscular afferent into excitation, just as with the skin nerves mentioned.

That strychnine and tetanus can convert a central inhibition into an excitation, and that the various normal reflex spinal inhibitions show differences one from another in the ease with which they undergo conversion into excitation makes the synchronous excitation of antagonistic muscles in certain willed actions less difficult to understand. Vasodepressor reflexes under chloral (v. Cyon), chloroform (Bayliss),¹⁴⁴ etc., change into vasoconstrictor under curare, morphia, etc. Bat the reversal does not appear to occur with equal facility in all afferent nerves alike. It is stated to be impossible to obtain any vascular reflex, but a depressant one from the “depressor” nerve. This nerve, arising in the heart (v. Cyon)⁴¹ and aorta (Koster and A. Tschermak),²³⁰ may in a sense be considered the afferent nerve of the muscle antagonistic to the ring musculature of the arteries, namely, the muscle whose tonus it reflexly depresses. It is in that way comparable with the afferent nerve of the hamstring muscles in relation to the extensors of the knee. The depressor action of the hamstring nerve on the knee-extensor seems, as just said, in my experience, particularly resistant to conversion from inhibition into excitation by strychnine.

In examples of reciprocal innervation drawn from lowlier organisms and visceral organs we find the inhibition a peripheral phenomenon, that is, with its seat outside the central nervous system. On the other hand, in examples drawn from higher organisms and skeletal movements, the inhibition is a central phenomenon, e.g., intraspinal. The same considerations which traced the line of adaptation in placing the seat of the refractory phase of spinal reflexes intraspinally between the ending of receptive neurone and the commencement of motor neurone, apply here to central inhibition. The significance of the centralization of these processes of refractory phase and reciprocal inhibition seems the same as we may infer for the centrality of the central nervous system itself (vide infra, Lecture IX).