The Integrative Action of the Nervous System

Bearing these points in mind, it is obvious that as an element in locomotion its repetition is required only at intervals consider- ably longer than the duration of the thrust itself, namely, at a particular phase of each successive step taken in the progression of the animal. After the extensor-thrust, the limb has to be given over to the flexor muscles in order, without touching the ground, to swing forward in preparation for the next step by the limb. It is reasonable to suppose that part of the means by which selective adaptation has secured this result is the evolu- tion of the long refractory phase following the activity in the reflex-arc of the extensor-thrust. Zwaardemaker ^^^ has shown that the reflex movement of swallowing in the narcotized cat is followed by a refractory period,^ lasting half a second or longer. This refractory state is central, for when the reflex swallow has been elicited by the superior laryngeal nerve of one side, the after-lasting refractory period holds good also for excitation of the opposite superior laryngeal nerve.

Variation of the external stimulus has comparatively little eflect upon the length of the refractory period. But internal conditions, such as blood supply, fatigue, narcosis, etc., do influence it greatly. For reflexes which exhibit a refractory phase, a certain duration of that phase, subject to some varia- tions, is characteristic. The duration of the phase varies con- siderably in different types of these reflexes. It is clear that an essential part of many reflexes is a more or less prolonged refractory phase succeeding nervous discharge.

Refractory phase appears therefore at the one end and at the other of the animal scale as a factor of fundamental importance in the co-ordination of certain motile actions. In the lowly animal form (Medusa) it attaches locally to the neuro-muscular organ, and so also in the visceral and blood-vascular tubes of Vertebrates. But in higher forms (dog) refractory phase occurs as regards the taxis of the skeletal musculature, not in the peripheral neuro-muscular organ, but in the centres of the nervous system itself.

^ Baglioni has pointed out refractory phase in a reflex in the frog.*** Argument : Correspondence between intensity of stimulus and intensity of reflex reaction. Differences between different reflexes in this re- spect. Functional solidarity of the intraspinal group of elements composing a reflex "centre." Sensitivity of reflexes, as compared with nerve-trunks, to asphyxial and anaemic conditions, and to an- aesthetic and certain other drugs. Functional significance of the neural perikarya. Reflexes of double-sign. Reflexes of successive double-sign, and of simultaneous double-sign. Evidence of recipro- cal innervation in reflexes. Reflex inhibition of the tonus of skeletal muscles. Reflex inhibition of the knee-jerk. Time-relations and other characters of reflex inhibition as exemplified by the flexion- reflex. Other examples of inhibition as part of reflex reciprocal innervation. The seat of this reflex inhibition is intraspinal. Conver- sion of reflex inhibition into reflex excitation by strychnine and by tetanus toxin. Significance of the " central " situation of reflex in- hibition in the cases here dealt with.

Grading of intensity. A further diflference between the re- action 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) ^^ and for motor-nerves by the muscular contraction (Pick, Cybulski, and Zanietowski).^*° 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 inten- sity of external stimulus and reflex end-effect is again less

close still; indeed it is often stated that reflex reactions re- semble 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. Bag- lioni makes the same remark for other reflexes in the frog. Yet graded intensity of reflex-effect does occur. Walton ^^ 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. Merzbacher ^^^ and Pari^^ 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 in- creases in amplitude in correspondence with increase of intensity of stimulus — alterations of time-relations of stimulus being ex- cluded. 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 re- flex is easily obtainable by grading the intensity of the stimu- lus. 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 ob- serve 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 Allbutt ^^ 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.y distension, etc. But with the scratching movement it is obvious that a strong scratching movement may remove an irrita- tion more quickly and more effectually than weak movement.

On the crossed extension-reflex the effect of increase of in- tensity 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 rela- tively large increase of the response. This augmentation is Figure 25. — The flexion-reflex, showing gradient of intensity due to graded intensities of stimulus. The time of the stimulus is marked by the signal line above ; the stimulus con- sisted in each case of 12 break shocks delivered at the rate of 25 per second, applied by uni- polar method with kathode needle point in skin of a digit, the diffuse pole lying headward of the spinal transection. The interval between commencement of each reflex was two minutes.

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 r6le as com- pared 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 re- peats itself with very little diff'erence 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 re- flexes— e.g.y 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. Gotch^** 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-fibrey 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. Con- cerning 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 in- tensity of the nervous process in any one neurone?" That in spinal reflexes increase of the intensity of the excit- ing 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 Pfliiger^* 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 im- plication 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 incre- mental 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 />artial con- tractions 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, infray 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

Figure 27. — The crossed extension-reflex showing grades of intensity corresponding with grading of intensity of stimulus. The time of stimulation is shown by the signal on the line above, and in each case consisted of 12 break shocks delivered at the rate of 25 per 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 ele- ments s^em 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 an- other, 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 aff^ected through- out, and in this inequality numerical proportion of active to inactive elements may play a part. The mechanism, neverthe- less, although anatomically an assemblage of units, is function- ally itself a unit. And a comparable solidarity obtains in other reflex mechanisms. Even the irradiation which suggests exten- sion 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 practi- cally as a whole. The reaction as it irradiates treats the centre as a unit.

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 ele- ments. 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 dis- charge 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. There- fore, 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 diff'erences traced thus far between reflex-arc conduction and nerve-trunk conduction have been difl^erences brought out by variations of stimulus and other external conditions. Differ- ences 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. Baeyer ^^ found the sciatic nerve of the frog retain excitabil- ity and conductivity three to five hours in nitrogen, and on read- mission of oxygen regain its powers in a few minutes. Bergmann (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. Baglioni ^^ has shown that 1 the spinal centres of the frog, deprived of circulation and im- 1 mersed in nitrogen, fail to give reflexes in about forty-five j minutes, but in an atmosphere of oxygen continue to react j 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- j trunks a 3 per cent dose of chloroform in air was required, l 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. re- quired 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 i markedly depress the heart, reflex conduction is abolished by \ doses a fortiori smaller than those which set aside nerve-trunk fi conduction.

Again, a number of agents, e. g.y 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. \ Figure 28 (opposite). — A. Hind limb of cat. Perfused with dilute blood. Contractions of gas- ^ trocnemius muscle stimulated through its nerve. Effect of CHClj at 0.25 per cent. The \

register of flow of the blood through the blood-vessels shows a diminution at first, and then ■ a marked increase. The register of flow is the bottom line : each notch in that line in- ; dicates one emptying of the Schafer " tilter " receiving the blood at outflow from the limb. J The line next above marks the time in intervals of fifteen seconds. The third line from \ bottom signals the perfusion of blood containing chloroform 0.25 per cent; similar blood, \

but free from chloroform, being perfused before and after. The top line indicates the : pressure of delivery of the perfused blood at the entrant cannula. The chloroform reduces ^ the contractions of the muscle, stimulated through its nerve, by more than a half. 3 B. Same as above. Contractions of gastrocnemius muscle stimulated alternately, through 1 its nerve, and directly. The nerve was inexcitable before the perfusing fluid was turned on, •; and the record which begins immediately after perfusion had been started shows the gradual ]

recovery of excitability. CHCl, at 0.3 per cent abolishes the response of the muscle to 2 indirect stimulation, and reduces its direct response almost to zero. The second, fourth, ; sixth, etc., are direct responses of the muscle; the first, third, fifth, etc., are responses to \ stimulation through the nerve-trunk. In this tracing the time record is above the signal ■ record. (Sowton and Sherrington.) 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 cer- tain 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.y in speed of transmission of impulses, etc., these differences sink to insignifi- cance when contrasted with the extent and variety of the con- ductive 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 tend- ency 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 con- ductor branches, often to such an extent as occurs nowhere else, so that it is a nodal point in the spatial distribution of the con- ductive 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 distinguish- ing 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 ex- citatory 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 suc- cession in this reflex, the stimuli being continued, is repeated many times. If we denote excitation as an end-effect by the sign plus (-I-), 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 in- hibitory 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 in- hibitory 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 inter- related 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 con- tractions 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 re- flexes with successive double-sign, the flexion-reflex and reflexes of that type, e. g., the crossed extension-reflex, are reflexes with simultaneous double-sign.