Comparative Electro-Physiology: A Physico-Physiological Study

These impressed molecular changes may not leave any visible impression behind. But let us look at the responding properties of a given substance at different points on the characteristic curve. In a sluggish A condition, that is to say, before it has even been excited, the power of response of the substance to a given stimulus will be slight or negligible. Let us suppose next that by the action of stimulus the sub- stance is raised above B. On the cessation of stimulus a slow recovery will then take place, whose completion may be indefinitely prolonged. The substance will thus approach very near the point B in the curve, without actually reaching

it. This difference between B and the point actually reached may be so small as to be undetectable by any ordinary mode of inspection. We therefore term the impression latent. But the properties of this B area, formerly acted upon, have been profoundly changed, being rendered more excitable by the impressed effect of previous stimulus. In this sensitive impression-surface will be certain areas in the A and certain others in the B condition, the former sluggish.

and the latter characterised by enhanced excitability. By the shock of an internal diffuse stimulus, a differential excita- tion may now be induced, exactly similar to that caused by primary stimulus. This zs.the revival of the memory-image. _ We may carry out a physical experiment exemplifying this process of the rise of a latent impression into vividness under the action of diffuse stimulus. We may take a sensi- tive surface, in which different areas, in consequence of pre- vious excitation, have impressed on them latent variations of excitability. Thus indifferent portions of the surface A, A,, may have their excitability represented by zero, another portion B, whose excitability has been exalted as the after- _effect of stimulatory agents previously applied, will have its normal excitability enhanced. In still a third portion, C, the excitability is artificially depressed or abolished. The responding substance was a tin wire; dilute solution of sodium carbonate, which is an exciting agent, was applied on the area B. The depressing or poisonous reagent, oxalic acid, was applied at c. After a short period of this applica- tion the wire was washed, and there was no outward indica- tion of any difference between the areas A, Bandc. Elec- trically also there was little or no permanent difference between them. One non-polarisable electrode connected with a galvanometer was kept permanently applied on the indifferent surface A,. The second exploring electrode was

the wire was excited as a whole by vibration. The galvano- meter, under this arrangement, would detect differential excitability. As long as the exploring wire moved over indifferent areas there was no effect detected in the galvano- meter. But as soon as the exploring electrode rested on the area B, the latent enhancement of excitability there showed itself by a sudden responsive up-movement of the galvano- meter. When the electrode again passed over B and reached an indifferent area, A,, response disappeared. But when it reached C, with its depressed excitability, there was another responsive movement, this time in the reversed or down direction. It is thus seen that the impress made by the

action of stimulus, though it remain latent and invisible, can be revived by the impact of a fresh excitatory impulse (fig. 406). Again, this revival of the latent image by a subsequent stimulation may be exemplified ina simpler and more striking way. We take a card and coat it with some so-called phos- phorescent material, such as luminous paint. This is kept a long time in the dark, till the whole is reduced to a uniform A condition. From a previous experiment we have deter- mined what is that duration of exposure, T, to a given

intensity of light, which will evoke a luminous or phosphor- escent response. A stencilled pattern is now placed on the prepared card, and the whole is exposed to light for the time T. On now cutting off the light and removing the stencil a luminous pattern is seen, which is the primary response. This impression slowly fades out. But the cardboard now contains a latent image, whose revival will be analogous to ceased to respond are still, in virtue of previous stimulation, in the B condition, which is more excitable than the indif- ferent A. A feeble diffuse stimulus should now, by its differential action, prove efficient to revive the latent image. We now expose the whole card to diffuse stimulation of light, of a duration shorter than T. The excitation of the indifferent background will by this means be ineffective, whereas it will be effective wherever the image proper has been impressed. We shall, therefore, obtain a revival of the positive image— that is to say, an image of the same kind as the original.

An interesting case occurs here, showing the theoretical possibility of obtaining a negative or reversed ‘memory image.” The possibility of this will be understood, from an inspection of the characteristic curve. We saw that in the region B the substance rises in excitability. But in the region of D and E, where the maximum molecular distortion has already been reached in consequence of over-stimulation, fatigue changes are induced, by which the excitability is depressed below the normal. It follows from what has already been said that an impressed image of this character will be revivable, under subsequent diffuse stimulation, but as a negative, or reversed memory-image.

I shall now describe a psycho-physiological version of this experiment. Let the observer stare at the incandescent fila- ment of an electric lamp, preferably with one eye, say the right, the left being kept closed all the time. The right eye is next closed, and is further covered by the hand. Multiple after-images will now be seen for some time, till the impression seems to have completely disappeared. No trace of the latent image is now perceivable in the field of dark vision. When this point has been reached, the hand is suddenly withdrawn from its position over the closed right eye. The light in the room now percolates through the semi-translucent eye-lid, and suddenly gives a moderate diffuse stimulus to the retina. Under these circumstances, the latent image is revived, as a negative—that is to say,as a very dark filament against a brighter background. Thus the essential condition for reviving the latent impression of stimulus would seem to be the subjecting of the unequally impressed tissue to diffuse stimulation. The revival of the image as positive or negative will then be a question of whether the stimulus have been moderate or intense.

tissues themselves, that the differential excitability induced as an after-effect of moderate stimulus (memory-impression) will give rise, on diffuse stimulation, to one kind of response, and the after-effect induced by strong stimulus to the reverse (cf. figs. 311, 312). In the former case, the moderately stimulated area, on diffuse re-stimulation exhibits induced galvanometric negativity, as compared with the indifferent contact, this being the sign of its relatively greater excitation. In the second case, the sign of response is reversed, the over-stimulated area, on re-stimulation, becoming galvano- metrically positive.

The revival of memory-images is thus seen to be due to differential response, evoked by diffuse stimulus, in an organ rendered anisotropic, by the unequal impressions which it contains of previous stimulation, A similar differential effect under diffuse stimulation has been seen in plagiotropic stems. Here the upper surface has a deep impression or memory of over-stimulating sunlight, and on diffuse stimulation this upper surface becomes galvanometrically positive, a respon- sive current flowing from below to above. It will thus be seen that there is a continuity between the impressions made on the sensitive neurile elements, and the physiological anisotropy induced by the differential action of past stimulus.

Diffuse stimulus, moreover, whether internal or external, acting on the differentially excitable tissue, gives rise to a marked indication, which may be either motile, electrical, or psychic. A stimulus is applied to the stem of JM/zmosa. This is transmitted as an excitatory impulse, and reaches the differentially excitable organ, the pulvinus. As-‘far as this organ is concerned, the transmitted stimulus may be re- garded as internal. This internal stimulus, then, gives rise to a conspicuous differential effect, shown in the fall of the leaf. In electrical fishes, similarly, the internal stimulus, delivered by the will of the animal upon the differentially excitable organ, becomes evident as an excitatory discharge In man, again, the revival of memory constitutes a psychic response, due to the play of the diffuse internal stimulus of will upon a sensitive surface rendered differentially excitable . by the presence of a latent image.

It will thus be seen that various after-effects of stimulus find expression as the phenomena of memory. The effect of primary stimulus does not disappear at once, but fades gradually, with a concomitant fading of the sensory impres- sion. From the fact that the after-effect of feeble, is less persistent than that of strong, stimulus, we understand that the sensory or memory impression also lasts longer in the latter case than in the former. Very intense stimulation, again, is apt to give multiple responses as its after-effect, and the corresponding psycho-physiological phenomenon is seen in the recurrent after-images in the retina.

When a considerable interval has elapsed after the primary stimulus, there is apparently no trace left of the latent image. But the properties of the impressed portions of the sensitive surface have undergone a more or less permanent change in consequence of stimulation. Certain channels have been rendered more conducting, and certain areas more excitable. By an internal diffuse impulse it is now possible to cause differential excitation, and thus to revivify the latent image.

Laws of response—Opposite responsive expressions of true excitation and increase of internal energy—-Separation of the positive and negative waves— Position in molecular cycle determines character of response—Abnormal sub-tonic positive and reversed fatigue positive—Effect of tetanisation— Similar effects in the inorganic—Phasic alternations—Multiple and auto- nomous response—Unmasking of antagonistic element by overshooting — Different expressions of a single fundamental molecular change —Response by change of form, by secretion or absorption, by variation of electric resistivity, or by electro-motive change—For the last, induction of anisotropy necessary—Perfect modes of stimulation : (a) Torsional vibration ; (¢) Rotary mechanical stimulation ; (c) Thermal shocks; (@) Equi-alternating electric shocks—Accurate determination of the death-point by mechanical and electrical spasms—Current of injury due to after-effect of stimulus— Explanation of characteristic electric distribution in plant and muscle cylinders—Relative positivity of dead tissue—Reversal of current of injury so-called—Unreliability of response by negative variation.

IT has been shown, in the foregoing chapters, that all the diverse phenomena of response may be summarised in the two following formule : 1, Excitatory response takes place by contraction and galvanometric negativity. 2. Increase of internal energy induces the opposite effect, of expansion and galvanometric positivity. The first of these effects is simply demonstrated by direct excitation of an excitable tissue. In order to demonstrate the second, stimulus is applied at a distance from the responding point. In consequence jof sudden local con- traction at the receptive area, a wave of increased hydrostatic tension is transmitted with great rapidity. Energy is thus conveyed hydraulically, and at the distant responsive point the transmitted effect induces expansion and galyanometric

positivity. This is followed by the more slowly transmitted wave of true excitation, which on its arrival gives rise to the normal response of contraction and galvanometric negativity. The two responsive effects can thus be exhibited separately, when one lags behind the other. When the intervening tract is short, or the conductivity great, the excitatory negativity masks the hydro-positive effect. But this hydro- selective physiological block, which depress the conduction of the true excitatory, without interfering to any appreciable extent with the passage of the hydraulic wave. In this way, the positive may be separated from the contained negative, the response being thus rendered diphasic— positive followed by negative. Or, by the complete suppression of the excitatory negative wave, a response originally negative may be converted into purely positive (figs. 45, 47, and 49).

As response is an expression of molecular derangement, it is the extent of this which determines its amplitude. The character of response is also modified by the molecular condition of the responding substance, and the different molecular conditions through which a substance may pass are indicated by the characteristic curve. From the study of such a characteristic curve we find that these molecular transformations are not specific, but of general occurrence— alike in inorganic and living tissues. When the energy of the ‘responding substance is for any reason below par, that is to’ say, when it is in the extremely sub-tonic A condition, external stimulus will be absorbed without evoking the normal excitatory expression. Response will then be abnormal, or of opposite sign to the true excitatory effect. By the absorption of impinging stimulus the substance now passes into the next stage B, where molecular transformation proceeds at a rapid rate. At this stage, the previous abnormal response is not only reversed to normal, but successive responses exhibit a staircase increase. At the next or C stage, the responses are uniform. Following this, we arrive at the maximally distorted position D, Stimulus

at this stage induces little further excitatory distortion, while the tendency to recovery is great. In this fatigue-state the amplitude of response undergoes a decline, and in. the succeeding stage E an actual reversal. : _ The various corresponding types of response—sub-tonic abnormal, staircase, uniform, fatigue-decline, and fatigue- reversal—are not exhibited by any one particular kind, but by all forms of tissues. Thus muscle may exhibit a short- lived staircase effect, and nerve, supposed to be indefatigable, not only shows decline, but even reversal of normal response, under extreme fatigue.

There are two definite conditions ander which the normal negative response is converted into abnormal positive, with an intermediate diphasic. These are (1) the condition of extreme sub-tonicity, and (2) that of fatigue brought on by over-stimulation. As regards the first, it is to be remem- bered that the normal excitability of a tissue is maintained by the supply of energy from the rest of the organism of which it forms a part. Under isolation, the latent energy or

tonic condition of the tissue is liable to fall below par, under which circumstances the response becomes abnormal positive. By the absorption of the energy of stimulus, the substance is transformed from the A to the B condition, with restoration of its normal response. The process of gradual .trans- formation may be seen in a series of records to successive stimuli, when the abnormal gradually passes into the normal, through an intermediate diphasic.. Or, an intervening tetanisation will serve to convert response from the abnormal to the normal. Abnormal or reversed response is also seen to occur under fatigue, but its genesis in the molecular curve is here in reversed order to that of the abnormal response of sub-tonicity. In the latter, during the continuous trans- formation from the A to the © phase, stimulation converted the abnormal response into normal, through diphasic. But now, during transformation induced by stimulus from C to E, the normal negative passes into abnormal positive, through intermediate diphasic. To transform the abnormal positive

into normal negative in the first case, stimulation is necessary. To do the samein the second case, rest is necessary. In the records obtained from different animal tissues, various anomalies are met with, of which there has not hitherto been any satisfactory explanation. Thus the same tissue at different times will be found to give either the normal negative, or di-phasic, or abnormal positive response. Thus it has been shown that in the two extreme cases alike, of sub-. tonicity and fatigue, the response of nerve is abnormal positive (p. 636). Numerous other examples of this fact have been met with in the course of this work, in, for example, the response of skin (p. 311), that of the glandular and digestive organs (pp. 342, 346), and that of retina (p. 423). It will thus be seen how important is the molecular condition of the tissue in determining the nature of response. This is strikingly shown in the fact that the same tetanisation which in the A condition converts the abnormal to normal, in the D will convert the normal into abnormal. Again, if tetanisation be applied at the beginning of the B stage, the subsequent re- sponses are enhanced, whereas the same tetanisation at the _end of C induces a fatigue reversal (figs. 394, 395, and 398). That the explanation of these various results is to be sought for in molecular considerations, and not in that hypo- thetical assimilation and dissimilation which really explain nothing, is fully demonstrated by the fact that precisely similar responsive variations are obtained, in the same cir- cumstances, in the case of inorganic matter, under different forms of stimulus and different methods of record. As an example, may be cited the transformation of abnormal response into normal, in tungsten, after tetanisation (fig. 391), the stimulus employed being electric radiation, and the mode of record, resistivity-variation.

Parallel effects have been shown in the case of tin, the response being recorded by the electro-motive variation, and the stimulus employed mechanical (fig. 386). The enhancement of normal response also under tetanisation, when at the B stage, has been shown in tin (fig. 388); and finally, the reversal of normal response by fatigue was shown in tungsten under electric radiation, while in the contractile response of indiarubber under thermal stimulation it took place with intermediate diphasic: (fig. 397). The characteristic curve has been shown to exhibit the history of molecular transformation under continuous stimulation. In the first part of this curve a progressive change is shown to be manifested outwardly by increasing contraction or galvanometric negativity. In the second part a reversal of this process is seen to occur. This is illustrated in records of response under continuous stimulation. Thus muscle shows increasing contraction, to be followed by fatigue-relaxation (fig. 64). The same thing is observed in Mimosa, as a fall of the leaf, followed by its re-erection (fig. 65). Electrically, this is observed as increasing galvano- metric negativity, followed by reversal to positivity. These phasic alternations may in some cases be exhibited only once, and in others repeatedly. Thus, in a certain style of Datura such phasic alternation is seen to occur twice (fig. 76); and again, in leaflets of Desmodium gyrans, at first quiescent, continuous stimulus of light gives rise to those repeated alternations of negative and positive which consti- tute multiple response (fig. 141). The distinction between the tissue which gives only one such alternation, and others which display it in repeated succession, is not, it should be borne in mind, rigid. Even skeletal muscle, under certain circumstances,.is found to give rise to rhythmic excitations. The fact that multiple response is a phenomenon of wide- spread occurrence, and not specifically characteristic of any particular kind of tissue, has been fully demonstrated in the course of the present work,

It would appear that there is a tendency of the incident stimulus, when applied continuously, to find an expression whose predominant characteristics are alternating. We may first have the exhibition of excitatory molecular distortion. But when this has reached a maximum, no further excitatory expression being possible, the incident energy becomes relatively effective in increasing the internal factor,- with attendant expansion, galvanometric positivity, and enhanced power of recovery. At the maximum point—that is to say, at the top of the tetanic curve—the two forces are balanced ; and at this point, if the stimulus be suddenly withdrawn, the particular state of unstable balance is often manifested by a brief overshooting in one or other direction. This effect’ is often noticed in the retina and in certain vegetable structures

in nerve under electric tetanisation (p. 536). That it is not primarily dependent on assimilation and dissimilation, but on the molecular factor, is seen in the fact that similar effects are also to be observed, under corresponding circumstances, in the response of inorganic substances (figs. 258 and 383). hibited under continuous stimulation may also be seen in the record of responses to successive stimuli. . The phenomenon is then regarded as an after-effect and shown by the shifting of the base-line of the record (figs. 208 and 396).

Since the effect of stimulus is to induce a molecular upset, the change in question must be attended by various concomitant physical changes. It will therefore be possible to record the excitatory effect by recording the attendant variations of any one of these. The effect of stimulus may thus be recorded by (1) the accompanying change of form, in: contraction or expansion; (2) an attendant secretion or absorption; (3) a variation of electric resistivity by dimi- nution or increase of resistance; and (4) electro-motive

changes in the responding substance as a whole, may be recorded by any one of the first three methods. But in the last, or that by the electro-motive variation, the method depends on the relative variations of the electric potential at two different points. -For if the substance be isotropic and subjected to diffuse stimulation, the electro-motive change at the two contacts being similar, there will be no resultant effect to record. For the recording of electro-motive response, then, it is necessary to obtain an effect which is differential.

The first way of doing this is to localise the stimulus at one of the two contacts. This may be done by interposing a physiological block between the two, so that the excitation of one does not reach the other. The second method is to select an experimental specimen which is anisotropic, whether naturally or artificially. Artificial anisotropy is induced by injuring one of the two contacts, and so bringing about a relative depression of excitability at that point.

The method of resistivity variation which I had pre- viously employed, in observing the response of inorganic substances, proved capable of sufficient perfectibility for the study of similar phenomena in living tissues also. The main difficulty in applying this method had hitherto lain in the disturbing electro-motive variation, consequent on a-symmetrical excitation, or the differential excitability of the structure. A detailed account of the means by which this method was rendered reliable will be found in

the excitatory variation obtained by it are in every way similar, to those made by other methods. All the different modes of taking records which have been enumerated are, it must be remembered, independent expressions of a common fundamental molecular change. Thus, on physically restrain- ing that mechanical movement in a motile organ which. is due to excitatory change, the electromotive response of galvanometric negativity continues to be given. Similarly, in a tissue in which, under the experimental arrangements, there can be no resultant electro-motive change and no con- tractile movement, the excitatory change may, nevertheless, be observed by means of the resistivity variation (p. 548).

For the obtaining of the electromotive response, the electrical mode of stimulation, unless special precautions are taken, is subject to various disturbing influences, such as current-escape and the occurrence of polarisation. For this reason it was desirable to devise sore non-electrical form of stimulation which should be capable of quantitative appli- cation ; and this I have been able to secure by no less than three distinct methods. I found that torsional to-and-fro vibration constituted an effective form of stimulus, the amplitude of which could be increased by increasing the angle of vibration. The intensity of stimulus was found to remain constant so long as the period and amplitude vibration were kept constant. The tissue, moreover, was not subject to injury by the use, within limits, of this method