Comparative Electro-Physiology: A Physico-Physiological Study

From all this it is clear that the progress of medicine may be greatly facilitated when the attention of investigators is drawn to the importance of the molecular aspects of the phenomena with which they have to deal. Thus, in examin- ing the action of drugs, a threefold question is seen to arise. It must first be determined what is the nature of the respon- normal conditions. The second matter of inquiry is, What is the critical dose, above and below which opposite effects may be expected? And, finally, as the nature of the response has been seen to be influenced by the part of the molecular curve, at which the responding tissue has arrived, when the chemical reagent is applied, it rollows that an important element in the problem lies in the determination of the tonic condition of the tissue. How important is this last factor will be seen from an experiment to be described at the end of the present chapter, where an identical course of treatment+‘in one condition of the tissue revives it from inanition, and in another hastens its death.

I have shown that when the condition of the substance is transformed from C€ to E, the response ‘also/is reversed from normal negative to abnormal positive. I shall now, therefore, proceed to show that in the course of this transition there is an intermediate stage of diphasic response. Before exhibiting this in the case of nerve, I shall give an interesting record in which the same thing is seen to take place in the mechanical response of fatigued indiarubber. Before the onset of fatigue, the normal'contractile responses were large, but at that stage—that is to say before the record

commences —they had begun to decline. In the series then recorded (fig. 397) we see how the depressed contractile responses are gradually transformed into’ abnormally expan- sive, through an intermediate diphasic. : ; Fic. 397. Fatigue in Indiarubber giving rise to Diphasic and Reversed Responses In the next series of mechanical records, obtained from nerve of frog (fig. 398), we have results exactly similar. The depressed contractile negative here passes through diphasic to abnormal positive. Thus, during the descent of the characteristic curve we obtain, as has been said before, a

Fic. 398. Fatigue inducing Diphasic Variation and Reversal of Normal a Response in Frog’s Nerve a, Diminished normal response; after tetanisation, enhanced fatigue in- duces diphasic passing'into reversed positive response, 4 ; a period of rest after this revived the normal response in c ; after long-continued tetani- sation, response is seen to be abolished in.d, by the death of nerve. repetition, but in reverse order, of all the phenomena seen during the molecular ascent; the sequence of responsive variation was from abnormal positive, through diphasic, to increasing negative. During the descent the sequence is diminishing normal response, diphasic, and abnormal positive.

The two halves of the cycle are thus strangely alike, one being, as it were, a reflection of the other. The cycle begins with sub-tonicity, due to a deficit of absorbed stimulus, and ends with the abnormality caused by excess of stimulation. The starting-point of the one may be supposed to meet the end of the other in a common fatality. The tissue comes to the same death by inanition on the one hand, through lack of stimulation, and by fatigue, on the other, through over- stimulation. But though the one half thus mimicks the other, there is, as it were, a polar difference between the two, by reason of the difference in their past histories. To revive the dying tissue, in the beginning of the cycle, stimulation is necessary ; to revive it afresh, at the termination of the cycle, a period of rest is essential.

Indications of stimulatory changes in nerve: 1, Electrical; 2, Mechanical— Transmission in both directions—Stimulatory changes in motor and sensory nerves similar—Responsive molecular changes and the correlated tones of sensation—Two kinds of nervous impulse, and their characteristics— Different manifestations of the same nervous impulse determined by nature of indicator —Electrical, motile, and sensory responses, and their mutual relations —The brain as a perceiving apparatus—Weber-Fechner’s Law—Elimination ot psychic assumption from explanation of particular relation between. stimulus and resultant sensation—Explanation of the factor of quality in sensation— Explanation of conversion from positive to negative tone of sensation after tetanisation—Various effects of progressive molecular change in nerve—FEffects of attention and inhibition—Polar variations of tonus, inducing acceleration and retardation.

IT is admitted that the molecular changes induced in the nerve by stimulus, are followed by sensations perceived in the brain. The question as to the nature of these antecedent changes induced in the nerve, and the quality of the sensation that succeeds them, falls properly, then, within the scope of a physiological inquiry ; and it is certain aspects of this which will be treated in the present chapter. I may here point out that the results which I have to describe consist of deductions drawn from direct experiment. They will in some cases lend support to the psychological hypotheses already ad- vanced ; while in others they will be found to be opposed. In such cases, therefore, it is perhaps not too much to hope, from their strictly experimental character, that they will

prove of use in deciding between rival theories; while in — others they will be found to introduce facts and considera- — Referring to the excitatory changes on which sensation depends, there has been much discussion as to whether the effects of stimulus in efferent and afferent nerves are of the same or of different natures. The difficulty in deciding this point lay in the fact that the indications of the state of excitation are different in the two cases, one exhibiting it objectively by the motile effect, and the other subjectively by sensation. It has been supposed, as we have seen, that the excitatory changes transmitted by the nerves were un- accompanied during their progress by any direct visible indications. It has been shown, however, in the course of previous chapters, that a change of form does in fact ac- company the transmission of the wave of excitation along the nerve. It was also shown that this mechanical indica- tion could be rendered extremely delicate, ranking, in degree of sensitiveness, between the galvanometer and the brain. Employing this mode of investigation, then, we found not only that the wave of excitation might be trans- mitted in either direction in any given nerve, but also that the changes induced by stimulus were similar in afferent and efferent nerves (p. 529).

Regarding the nature of this molecular change, again, it has been supposed that the nerve under excitation exhi- bited a specific variation, known as the xeura/, totally unlike those changes which take place, for instance, in muscle. We have seen, however, that this is not the case, the mechanical and electrical expressions of the molecular changes in excited nerve being of a nature essentially similar to those observed in muscle also.. Even in the matter of conduction, we have seen that non-neural tissues transmit'the state of excita- tion to a certain distance beyond the point of stimulation.

The difference in this respect is one of degree, and not of kind. We have next to deal with the question of sensation as induced by molecular changes in the nerve. It is widely admitted that the changes induced in the nerve by stimulus will cause responsive sensations. But the relation between the responsive sensation and the character of the molecular change that induces it has been regarded as unascertainable. ‘That many of our feelings depend immediately upon the condition of the nervous elements is beyond doubt... . What is the peculiar nature of the excitation upon which the different feelings depend ‘for their differences of quality ? What is the characteristic change in the excita- tion that gives rise to two kinds of tone which the feelings possess, to pleasure and to pain? Physiological psycho- logy can answer none of these questions with much con- fidence.’ !

The fundamental contrast of tone in question raises the inquiry, therefore, whether it may be possible to discover any antecedent nervous changes of opposed character. Taking an instance of response by some simple form of sensation, it is well known that while moderate stimulus produces a feeling which may be described in general as not unpleasurable, or even distinctly pleasurable, an intense stimulus of the same nature will cause a displeasurable or even painful, sensation. These fundamental differences of quality are classified as ‘positive and negative Zones’ of sensation, the term ‘ positive’ being here associated with perceptions which are not un- pleasant, or even actually pleasant, while ‘negative’ refers to the reverse. While the sensations ensuing under moderate stimulus, then, such as moderate pressure or moderate light, are of ‘positive’ tone, those brought about by more intense stimulus are apt to become converted into negative. The positive sensation grows to a maximum, according to the rise of stimulus-intensity within a certain limit. Beyond this point, sensation becomes, first, less and less positive, and then increasingly negative, as the intensity of stimulus continues to be augmented. Ora simple stimulus, suchas a light blow, which evokes a positive sensation, will, when often repeated— that is to say, when employed tetanically induce a negative or painful sensation. It is thus seen that the tone of sensation is in some way associated with the intensity or duration of

stimulus. The question, however, remains, whether or not. these opposite sensation-tones could be demonstrated to be dependent upon characteristic nervous changes of opposed characters. lf we should succeed in making such a demon: stration a physico-physiological basis of. psychical effects would have been established which would unquestionably prove to be of great value, Now we have seen, referring to previous investigations on nerves, (1) that a feeble stimulus applied to the nerve is transmitted as a pulse of expansion. This we have designated the positive wave. The propagation of this wave being more or less of the nature of a hydrostatic disturbance, we have seen that its transmission is not affected to any great extent, even when the conductivity of the tissue is diminished. (2) A more intense stimulus we have found competent to give rise to a disturbance of opposite or negative sign—that is to say, toa pulse of contraction. The velocity with which this second, or,as we have called it, the true excitatory wave, was conducted, we found to increase with the intensity of the stimulus. While with feeble stimulus the positive wave alone was transmitted, with stronger, both negative and positive were propagated, but the more intense negative was liable to mask the feeble positive. As the negative wave was dependent on the conductivity of the tissue for its propagation, we have seen that it was possible to separate the two by any means which would diminish the conductivity

lag behind the positive; or, by its complete suppression, it was even possible to exhibit the positive alone. Thus a tissue which normally gave only negative response, owing to the masking of the positive, might, by the depression of its conductivity, be made to give diphasic, or positive response alone (p. 530). So far then, as regards the detection of two nervous im- pulses of opposite sign by means of the delicate mechanical method. The same facts may also be demonstrated by the less sensitive method of electrical response, according to

which we saw that the two nervous impulses were exhibited by two opposite electro-motive variations—those of galvano- metric positivity and negativity respectively. This reaction of expansion and galvanometric positivity, however, may also occur as the expression of the increase of internal energy, in whatever way produced. Indeed, the positive form of response under moderate stimulation may be regarded as a case falling within this definition. Thus we .

see that, beginning with very moderate stimulus, we obtain in the tissue a purely positive effect; and that, as the stimulus is augmented, the true negative excitatory effect also begins to make its appearance in increasing degree, the positive component of the response being now more or less masked. The energy that afterwards remains latent in the tissue goes to enhance the tonic condition. The amount thus held latent depends on the difference between income and expenditure. As a general rule, it will be under intense stimulation that the expenditure of energy will be likely to exceed the income. Thus we have two extreme cases, first, that in which moderate stimulus brings about increase of energy ; secondly, that in which excessive stimulus brings about run-down of energy ; and between the two a large range of variation, within which either one condition or the other may predominate. It must, of course, be under- stood that anything which increases the tonic condition is for the well-being or health of the organism, and is associated with positivity. Similarly, any fall of the tonic condi- tion below par makes for exhaustion and against healthy tone.

We have next to take a rapid survey of the changes induced by stimulus in the conducting nerve itself, or any of its attached indicators. Such variations may, for purposes of convenience, be classified as motile, electrical, and sensory. In the nerve itself we have found, as has already been pointed out, by means of the Kunchangraph, that the motile change induced by feeble stimulus was one of expansion, the same change being shown electrically by galvanometric

positivity. The change induced by strong stimulus, on the other hand, was of contraction and galvanometric negativity. In the terminal motile indicator also, there are two different modes of response of opposite signs—namely, expansion and contraction. -In the highly excitable muscle, the occurrence of the former of these, brought about, as it is, by very feeble stimulus, is not easy to demonstrate. Bearing in mind, however, the fact that in nerve positive response is more easily obtained when the excitability is depressed, I succeeded in obtaining positive expansional response of the muscle, in a nerve-and-muscle preparation of frog, which had been depressed by the anzsthetic action of chloroform. At a certain stage of anzsthetisation, the response of the muscle under stimulation of the nerve was found to take place by expansion, followed by recovery. Just as in a nerve in a somewhat depressed condition, ee Fic. 399. Abnormal Response of Muscle by stimuli evoke positive Relaxation, followed by Normal Response response converted later af, Contraction

‘ 1 ; The first two responses by relaxation are into normal negative, followed by two contractile responses. so, in the muscle-pre- paration described, the abnormal positive was followed by the normal negative response. In fig. 399 I give a photo- graphic reproduction of the myographic record obtained on a smoked-glass surface. In all these different effects we obtain, by means of the mechanical response of the terminal organ, what is merely a parallel expression of changes occurring in the nerve itself. As in the nerve, so also in the muscle, there are two different kinds of responsive expression—namely, expansion and con- traction. Thus we see that the various manifestations registered by different modes of indication are only so many diverse expressions of the same fundamental molecular changes.

We turn next to the sensory mode of indication, that is to say, to the psychic effects registered in the central perceiving organ by the positive and negative waves conveyed to it along the afferent nerves. We have already seen that the stimulatory changes induced in these sensory nerves are precisely the same as those which occur in the efferent. What, then, are the effects in the central apparatus induced (1) by that positive impulse which is associated with .

expansion, and (2) by the negative impulse associated with contraction ? : mentioned, that feeble stimulus gives rise to sensations of positive or pleasurable tone, while an intense stimulus of the same kind will induce a responsive sensation which is negative or painful. We have also seen, in the course of the present work, that a feeble stimulus will give rise to a wave of expansion and galvanometric positivity, while the same stimulus, when intense, will give rise to a negative wave. We are therefore justified in regarding the positive impulse, associated with expansion and galvanometric positivity, as _pleasure-bearing, and its, opposite as pain-bearing or dolori- ferous. Numerous experiments—some being of a crucial character—will be given, in the course of the present and succeeding chapters, which will be found to lend full support to this conclusion.

This fact, that the same stimulus may induce positive sensation in the central and expansion in the motile organ, or the negative painful sensation with muscular con- traction, according only to the nature of the indicator, will furnish grounds of reconciliation to those who hold on the one hand that the motor reaction is secon- dary to the mental, and on the other, that sensation is merely an accompaniment of movements reflexly in- duced.’ ‘Many hold the motor reaction to be secondary to the mental. Of the coarser emotions it has been argued by James that the feeling does not cause,

but is caused by, the bodily expression, The bodily changes, according to him, follow directly the perception of the exciting fact, and our feeling of the same If the sensation be in fact due to definite and ascertainable physico-physiological changes in the nerve, then the various modifications of sensation must, in like manner, be traceable to corresponding modifications in the physico-physiological process. In that case, the particular relation which is known to exist as between stimulus and sensation—expressed as Weber-Fechner’s Law — must be demonstrable as directly dependent upon molecular changes induced, and not on the existence of some assumed psychic factor. This molecular theory, further, if it expresses a truth of universal applica- tion, ought to be capable of explaining not only the quantitative relation between stimulus and sensation, but also that qualitative variation of which Weber-Fechner’s Law is unable to take account. Should the Molecular Theory prove adequate to this, its truth may be regarded as demonstrated. |

We shall, however, subject this theory to further and still more crucial tests. If it be true that our sensations, opposite character, then any modification of either of these impulses by any given agent should appropriately modify the resultant sensation. We have seen, for instance, that the negative wave is complex, and contains within it the masked positive. We have also seen that by appropriate means these two waves may be made to exhibit themselves separately ; or the positive, by the total suppression of the negative, may be displayed alone. I shall therefore show that, by the employment of the same means, the subjective sensation of painful or negative tone may also be analysed into its component parts, which may thus be made to exhibit themselves in succession; and, on the other hand, that by

changes as they occur zs the emotion. Certain experiments furnish evidence— not highly satisfactory—that all pleasurable states of consciousness are accom- panied by bodily movements of extension, and all painful by movements. of flexion. These movements may be very slight. Miinsterberg concludes that the feeling of agreeableness is the mental accompaniment and outcome of reflexly-produced movements of extension, and disagreeableness of the move- ments of flexion.’--Schafer, Zext-Book of Physiology, vol. ii. (1900), p. 975-

the complete obliteration of the negative element an already painful sensation may be converted into pleasurable. Of the scheme thus laid down, the first part will be carried out in the present, and the second in the succeeding, chapters. Turning now to our sensations themselves, it may be well to consider some of the characteristics of the central perceiving | apparatus. Asa detector of nervous changes the brain is undoubtedly the most delicate of instruments, surpassing in this respect not only the galvanometer, but also the Kunchangraph. It fails, however, strictly speaking, as an accurate metrical apparatus. It is not able to discrimi- nate quantitatively, for instance, by means of sensation, through any wide range, between the finer differences of intensity in the nervous impulses it receives. In the pain- and-pleasure series, again, the distinctions which it is able to make are, to a certain extent, of a merely qualitative character, unmistakable only as between the two extremes of the series, the intervening region tending to be somewhat indefinite. The sensitiveness of the physical instruments, Kunchangraph and galvanometer, is always constant and reliable. For example, in the galvanometer, by adjusting the controlling magnet, we can obtain varying degrees of sensibility, which at any particular adjustment will remain constant. But in the perceiving apparatus, not only is the sensitiveness of different individuals widely different, but even in a single individual it undergoes great variation under different conditions.

By deliberate attention or inhibition, as by raising or lowering of the controlling magnet in the galvanometer, the sensitiveness of the perceiving field can be almost indefinitely varied. Pursuing this analogy of the galvanometer further, we find that in the brain, instead of a single coil, with its one pair of terminals, there are many coils with many pairs of terminals, receiving impulses from every part of the organism. Confining our attention, moreover, to any single circuit among these, we find again that the impulses it

conveys are varied in their character. There are, for instance, the immediate effects of stimulus, whether positive or negative, and also the persistent after-effects of stimuli previously absorbed. The central apparatus, however, is not acted on by these impulses from any single circuit alone, but from many circuits at the same time, the whole resulting in a ‘vague tremor of generalised consciousness. The individual sensation evoked by any particular stimulus bears to the rippling surface of this consciousness the relation of a larger or smaller wave.

Thus we see that there are tele conditions which will contribute to the intensity of the sensation evoked by an jndividual stimulus. There will be, first—to revert to the simile of the galvanometer-——the enhancement of the con- ductivity of the particular circuit involved; and, secondly, the suppression of all interference caused by the semi- conscious activity of other circuits. By the action of the will, producing the condition of attention or expectation, the excitability of the receptive or responsive points, and the

conductivity of particular channels, may be exalted, while they may be depressed in others by the reverse process of inhibition. The extent to which it is claimed that this power of inhibition may, with practice, be carried, would appear almost unimaginable. -I have myself known of an authenticated instance in which the pulsation of the heart was arrested and renewed at will. In India, indeed, it has been held, from very remote times, that such practices are capable of reduction to a science. It is thus believed to be possible that all nervous impulses due to external causes may one by one be inhibited, until the attention is concentrated on a given point, in complete isolation from any interference

whatever by the physical organism. Regarding the physical aspects of these processes of inhibition and concentration, There are again other elements calculated to bring about further variations in the sensitiveness of the instrument which lie more or less beyond the control of the observer, His previous habits and prepossessions all contribute, as is well known, to modify it more or less permanently. The principal reason for the constancy of the records made by the physical indicators lies in the greater or less constancy of the properties of those elements of which they are com- posed. Even here there is a fluctuation of sensitiveness, owing to changes in the properties of the material. But these changes are neither so rapid nor so considerable as in the neural apparatus, whose excitability is extremely susceptible of modification under the influence of fatigue, and of such varying factors as health and tonicity, as well as by the action of the stimulus itself. 7 : Looking now at the whole range of impulses generated in the nerves under increasing stimulus, we shall see that the positive effect is gradually augmented till it reaches a maximum. It then undergoes a decline, passing into a resultant negative. This resultant negative response con- tains, as we know, a masked positive component, which can be separated and exclusively demonstrated by appro- priate methods. With increasing stimulus the negative response undergoes an enhancement till a limit is reached. Expressed in terms of sensation, then, the effect perceived is at first of positive tone, and this, growing in intensity, is pleasurable. This positive tone, however, afterwards under- goes a diminution, and finally passes over thé zero-line ; this constitutes the commencement of a somewhat extended range, in which the resultant negative, with its masked positive, undergoes increase. Referring to the curve at the crossing of the zero-lirie, it must be said that we. have here a neutral point.