Conditioned Reflexes: An Investigation of the Physiological Activity of the Cerebral Cortex

From a purely physiological point of) , the study of dif- ferentiation between a compound sips and its modification, which both contain the same elementsJbut in a different order of succession, is of considerable inten The experiments show that a compound stimulus the comp units of which remain in them- selves unaltered, and cons ly most probably affect the same cells of the cerebral cor Chaves in different: modifications as a different stimulus, orl in these cells now an excitatory process and now an inhibjt one. Plainly the experiments reveal the great importance eNe synthesizing activity of the cortical cells which are ung g excitation. These cells must form, under the conditions KP Yiven experiment, a very complicated excitatory

unit, which is functionally identical with the simple excitatory units existing in the case of more elementary conditioned reflexes. Such active cortical cells must necessarily influence one another and interact with one another, as has clearly been demonstrated in the case of compound simultaneous stimuli. The mutual interaction between the excited or inhibited cortical elements in the case of compound successive stimuli is more complicated ; the effect of an active cortical cell upon the one next excited varies according to the influence to which it was itself subjected by the cell last stimu- “lated. In this way it is seen that the order in which a given group of stimuli taking part in a stimulatory compound are arranged, and the pauses between them are the factors which determine the final result of the stimulation, and therefore most probably the form of the reaction, and we know already that different intensities of the same stimulus can be differentiated very accurately, one definite intensity being connected with excitation and another with inhibition. .

It is evident from the description given in the present lecture that we must distinguish in animals an elementary, from a higher, type of analysis and synthesis. The former, and especially the elementary type of analysis, is based principally upon the properties and activity of the peripheral receptors of the analysers, while the latter is based principally upon those of the ceriral ends of the -analysers. Conditioned reflexes afford the s bf investigating

experimentally the functions both of the ripheral and of the central parts of the analysers, and Ea have been conducted in our laboratories. The ę{aŅ}ples to:be given during the remainder of this lecture will illh@yete the scope of this field of animal experimentation. In the first example I shal&describe, it was sought to obtain by means of conditioned reflefe) experimental data regarding the resonance theory of H oltz. We conceived that by partial destruction of the or Corti the disappearance of conditioned reflexes to certain would possibly be obtained. The following

| experiment wa cted by Dr. Andréev, who is still working on | this subject. ey tones were employed, being produced by two sets of apparatus, one giving tones from 100 to 3,000 and the other | from 3, 26,000 double vibrations per second. Various con- | diti entary reflexes were established in the dog, namely, to | t imuli, visual stimuli, and different auditory stimuli (sound of a buzzer, metronome, a noise, and numerous pure tones). The cochlea was first completely destroyed on one side. When tested for the first time, six days after the operation, all the auditory conditioned reflexes were found to be present. A second operation (10th March, 1923) was now performed on the cochlea of the other side with the object of excluding only the lower part of the tonic scale. The osseous part of the cochlea was opened at the junction of its middle and upper thirds, and the exposed part of the membranous cochlea with the organ of Corti was injured with a fine needle. Already on the tenth day after the operation all the auditory stimuli, excepting tones of 600 double vibrations per second and lower, were found to be fully effective. In the course of three months following the operation, however, the effect of tones from 600 to 300 double vibrations became gradually restored. From numerous tests carried. out from this period up to two years after the operation, the upper limit of the tones that had disappeared was fixed as somewhere between 309

. and. 317 double vibrations per second. The lower limit could not be determined, since we had no pure tones below 100 double vibra- tions per second at our disposal. The following two tables are taken from the final period of the investigation : A histological examination of the cochlea has not yet been carried out, the dog still being used for experiments. It is evident, however, that the positive results of our experiments successfully replace the negative results obtained by Kalischer! with regard to this question.

Another problem which engaged our attention was whether the participation of both hemispheres was necessary for differentiation of sounds by their direction. This question was solved by the experi- ments of Dr. Bikov. The corpus callosum was severed in a dog, and after the animal had recovered from the operation the establish- ment of new conditioned alimentary reflexes was begun. Their formation presented no special difficulties, and proceeded at the same rate as in normal animals. One of the reflexes was established to the sound of a whistle, 1,500 double vibrations per second. The whistle, which was placed in a cardboard case, was supported on the wall on a level with the left ear and at a definite distance from the dog. The reflex appeared at the eighth repetition, and attained a maximum and permanent strength after 70 repetitions. The whistle was then transferred to the right side of the dog, and in this position was not reinforced by the unconditioned reflex. By repeatedly contrasting the sound from the left with that from the right, a differentiation of the direction of the sound was attempted. There was, however, not the slightest sign of any differentiation, even after 115 applications of the non-reinforced stimulus from the right, and we considered it futile to continue beyoyd\Yhis number of repetitions. It was concluded that a differenti ot the direction

of a sound required a united activity of b emispheres. The following is one of the most recent ae S: etion of Time Conditioned Stimulus Saliva in Remarks ops during $ 30 seconds 3.40 p.m. Whistle on left,gi 9 ng, LEa 3 14 f Reinforced. 4.20 ",, Whistle on t side 14 Not reinforced. SUNN ation) 4.35 ,, Whis eft side 12 Wess My yey | fe) 5 13 i Reinforced. ZO; Kane “ Weitere Mitteilung über die Ergebnisse der Dressur als physiol. U hg hungsmethode auf den Gebieten des Gehér-, Geruchs- und Faria Archiv f. Anatomie und Physiologie, Physiologische Abteilung,

Other differentiations were obtained in this dog easily and rapidly, but never one involving localization of the source of a sound. In normal dogs the differentiation of sounds by their direction presents no more difficulty than any other differentiation, and is capable of great precision. The experiments described in this and the preceding lectures leave no doubt in my mind that all the questions which have hitherto been considered as belonging to the domain of the so-called physi- ology of the organs of special sense can actually be investigated objectively by the method of conditioned reflexes. Are not Helm- holtz’s famous “ unconscious conclusions ”—in his Physiological

example the case of a drawing imitating the visual character of a relief. In actual experience, of course, the tactile and muscular stimuli proceeding from a relief represent the initial and funda- mental stimuli: the visual stimuli provided by its areas of light and shade form the signalling conditioned stimuli, which only subse- quently obtain a vital significance by being constantly reinforced by the tactile and muscular stimuli. In the further course of our lectures we shall refer to other examples which can be studied objectively in dogs, and which correspond fully with phenomena usually described only in connection with the physiology of the organs of special sense.

The irradiation and concentration of nervous processes in the cerebral cortex : (a) The irradiation and concentration of inhibition within a single analyser. Up to the present we have been concerned chiefly with what may be called the external aspect of the cortical activity. We have studied the general laws governing the establishment of the most complicated and delicate correlations between the organism and its environment. It was shown that in response to an unlimited number of stimuli there can be brought about in the cerebral hemispheres an activity which serves to signal the approach of the comparatively small number of agencies which are of vital importance to the organism either in a favourable or in an injurious sense. It is through the hemispheres that corresponding reactions are brought about, thus anticipating the actual contact or clash of the organism with those agencies. The conditioned significance of stimuli is constantly corrected or changed by the hemispheres, so that when a given stimulus no longer corresponds to the correlations existing at a given time between the organism and its environmen gep a stimulus may be rendered temporarily or permanently i tive. Finally, we have seen that in harmony with the perpe d varied fluctua- tion of nature the hemispheres may invest a role of conditioned significance on the one hand the minut ements of the environ- ment individually (“ analysis ’’), the other hand various complexes compounded of these OS (“synthesis ’’). a

The present and the tolov nectare will be devoted to the study of the internal aspect othe cortical activity, and we shall consider first the part p in it by the fundamental nervous processes of excitation ibition. The first point wi ust receive our attention is the irradiation and concentrati Srese two processes. It frequentl pens in physiological investigation that where a broad grow phenomena is to be examined, the investigation of - one of the ers of this group may be more convenient than that of oth detailed investigation of this aspect of internal

inhibition proved, in the present case, to be the most advantageous. At the same time this investigation provided a striking illustration of the numerous advantages presented by the cutaneous analyser with its extensive and easily accessible receptor surface. The experiment which revealed this new and important chapter in the physiology of the cerebral hemispheres was conducted by Dr. Krasnogorsky, to whom we owe several of the succeeding experi- ments.

Five small A opaiwtines for tactile stimulation of the skin were arranged along the hind leg of the dog. The first was fixed over the paw, and the remaining four were spaced out up the leg at distances of 3, 9, 15 and 22 cms. respectively from the first. Stimulation over | the paw was given the properties of an inhibitory stimulus, while stimulations at the four upper places were given positive conditioned properties. This effect was obtained by the usual method of experi- mental differentiation. That is to say, a positive conditioned alimentary stimulus was established first of all to a tactile stimula- tion of one of the four upper places ; on account of the initial generali- sation of the reflex, all the other places as well became spontaneously more or less effective upon stimulation. The positive conditioned effect of stimulation of the four upper places on the animal’s leg was equalized by reinforcement with food, while by the method of contrast the stimulation over the paw, which was given always without rein- forcement, lost all its positive conditioned properties a uired inhibitory ones. In the experiments given below th ditioned stimulus was applied in every case during 30 second e place on the skin which was stimulated is indicated by a er: 0 repre-

sents the inhibitory place ; 1, 2, 3, 4 represe positive places taken in order. The number of the posta is accompanied It is seen from the table (p. ea thadstimulation of each of the three places 4, 3, and 1 produced i eginning identical positive conditioned effects, measured. by ps of salivary secretion during 30 seconds. The four places a 3 and 4 were now separately tested at an interval of ex Cone minute after the last of three successive applications Oo inhibitory stimulus. The stimulation of place 1, nearest Ge inhibitory place, was at the first test absolutely ERNE nd. at the second test its effect was barely distinguishable (ey an one drop). The stimulation of place 2, next in BN m the inhibitory place, gave only half its normal

positive conditioned effect, but the stimulation of the remaining | places (3 and 4) gave a full or even an increased positive effect. | The significance of this experiment is clear. The different sensory | places on the skin must be regarded. as projecting themselves upon lll ell pd CD pol pd pd C el ell oe C pnd pi p C pad pd ern En ene we corresponding are e cortex of the hemispheres. Therefore it is reasonable t aw that the inhibitory process initiated in a

| definite point o&MiMe cortex by the tactile stimulation of the inhibi- | tory place*i iatés into the surrounding region, giving a smaller A different intensity of the inhibitory process can be produced, either by varying the number of successive applications of the inhibitory stimulus, of which the after-effects are summated, or by varying the interval between the last inhibitory stimulus and the application of the positive stimulus. In either case different figures are obtained for the salivary reflex, but their general significance remains the same. This is shown in the following experiment :

The inhibitory after-effect was tested in this experiment after a shorter time (4 minute), and after four applications of the inhibitory stimulus instead of three; under these conditions a congiderable inhibitory influence was exerted even upon the posite ace 4, which in the previous experiment when tested one ie after we gave a full reflex. If the various positive stimuli are applie Qae and the same experiment at different times after the 1 ibitory stimulus, it can clearly be brought out how the init py Fe irradiated. inhibi- tion gradually frees from its ter gh the remoter areas, and subsequently those areas nearer tg the’ cortical point in which the inhibition arose primarily.. An ple of such an experiment is given in the table shown on

est place (4) was free of inhibition ter five minutes, and place 1 after ten minutes. The more freque the differentiation is exercised in the course of days or week more rapidly are the more remote places freed from the Ww y after-effect, a fact which is sometimes exhibited in the course of a single experiment after the positive and negative stimuli‘have been repeated several times. It is worthy of note that experiments upon the irradiation of inhibition have been successfully demonstrated on numerous occa- sions without serious interference by the presence of a stranger with the experimenter in the animal’s room, and have even been carried out successfully at crowded meetings of the Petrograd Medical Society,

Interval of Secretion of time between Place of stimulation Saliva in separate stimuli | drops during We have now to inqui e the nature of the recession of inhibition from those co Qi points into which it was irradiated. Does this represent a d ion or waning of the inhibition in these places, or is it som of return or active concentration of the inhibition to i Ing-point due to some antagonistic process ? In face of the pO wth fact that strengthening of differentiation by

‘repeated. oS Gost is accompanied by a corresponding shortening of the durat nd extent of irradiation of the inhibitory after-effect, we ee more inclined to accept the second hypothesis, namely, that we deal with the reverse of irradiation, 7.e. “ concentra- tion” of the inhibition toward its initial point of origin in the cortex. A number of important facts in support of this conclusion will be adduced later. Meanwhile, it may be noted that in Dr. Krasnogorsky’s experiments the waning of the inhibition occupied several minutes. The actual spread of inhibition, however, pro- ceeded with such rapidity in these experiments that Dr. Krasnogorsky was unable to follow it.

The preliminary observations upon the antagonistic processes of irradiation and concentration seemed to us of such fundamental importance as to demand a thorough investigation by modifying and controlling the experiments in all possible ways. Our attention, therefore, was next directed to that form of internal inhibition which has been discussed under the name of experimental extinction, and these experiments were also conducted with the use of tactile cutaneous stimuli [experiments of Dr. Kogan]. As a preliminary a conditioned reflex to acid was established for a tactile stimulation of some place on the skin. While it was still in its initial, generalized phase the reflex was equalized as far as possible in strength for stimulation of any place on the skin along the whole of the surface of one side of the body before the experiments were proceeded with. A definite place was then selected to which the stimulus was applied for a minute, without reinforcement, and repeated every twe minutes until the first zero was obtained. At different inter f time, following the first zero of extinction at the give ce, tactile stimulations were tried at various other places o skin and the resulting secretory effect was compared with th sualone. These other places were found also to suffer i on temporarily to a greater or less extent. The place ted to experimental extinction is termed the place of primgr}=€xtinction,. and the places which become involved in the in nig after-effect are termed places of secondary extinction. Wearë familiar with this terminology from our discussion of the ph enon of experimental extinction in the fourth lecture, whe made quite clear that the extinc- tive inhibition does no N e itself to the actual point in the

cortex which was call€@ if*6 activity by the specific external stimulus, but irradiates over wide area. We have, in other words, a phenomenon ssh to that which has already been discussed in | connection Le erential inhibition. It "J ial in these experiments to vary the place subjected to the primary extinction. Otherwise, instead of the extinctive inhibition—from which the primarily extinguished reflex frees itself in a few minutes, or at the most 1-2 hours—there would have developed a differentiation with its very stable and lasting form of internal inhibition.

An example of an experiment such as has just been described is given in the following table : he further away on the skin the secondarily from the place which undergoes the- primary inhibition, W eaker is the irradiated inhibitory after-effect. mulation is applied to one definite place at different: If t oS time after the reflex has been extinguished to zero at another place, the greater this interval the weaker is the inhibition in the secondarily extinguished place. This is borne out by the following experiments.

It is obvious aN in this experiment we deal again with the concentration of i ition, the inhibition being gradually withdrawn initial point. Further, it becomes evident that the rate at which the inhibition is withdrawn from the places undergoing secondary inhibition varies very considerably with individual dogs, so that, for example, a process which occupies only one minute in dog No. 1 requires fifteen minutes in dog No. 2. This, of course, is a fact of considerable importance, since it gives a numerical expression to one of the most intimate sides of the highest nervous activity. That these individual differences in the three animals were not accidental is shown by the fact that they remained constant during many months in which the experiments proceeded.

In the experiments of Dr. Kogan it was possible to observe also the progress of the spreading of the inhibitory after-effect. I shall give the actual experiments in which the degree of secondary inhibi- tion corresponding to the different places of the skin was determined immediately after complete primary extinction had been obtained : Dog No. 2. \ Secretion of . Place at which . Saliva in Percentage Date conditioned stimulus was drops during o applied lst, 2nd, and | inhibition . 8rd minutes 25th Jan. Right side of chest 12,1, 4 Right hind paw 113, = 25th Jan. Right side of chest 134, Adjacent place - 100 26th Jan. Right side of chest Bee $ At a distance A 0,- 100 26th Jan. Right side of 14, 2, 24 Right hiag 13, - — 7 4th Feb. Left. si chest 12, 2,0 Qiri paw Urca 4 5th Feb. ide of chest 94, 1,0 ft scapula 33, -- 64

Ac N of these results with those of the preceding experi- "N he same dog shows clearly that immediately after the full development of inhibition for the primarily extinguished place, a complete secondary inhibition is obtained only for adjacent places, the inhibitory after-effect being absent or hardly distinguishable for places more remote. It is interesting to note that in the three dogs employed in these experiments the effect of stimulating the remoter places immediately after the primary inhibition had been produced varied considerably. In dog No. 1 not only was the reflex to stimulation of the remoter place not inhibited, but it even produced a considerably enhancéd. positive effect, whereas dog No. 3 under similar conditions revealed a considerable degree of secondary inhibition. This fact, which was frequently observed in the experiments both of Dr. Krasnogorsky and Dr. Kogan, and which will form the subject of more detailed discussion in the eleventh lecture, is well illustrated in the following experiments :

Saliva in Change in drops during strength Ist, 2nd, and of reflex 3rd minutes In addition to the fore , Dr. Kogan made a considerable number of observations illustrate in detail the length of time occupied in his three dog the phases of irradiation and concentra- tion of inhibition into tactile cutaneous analyser. These observa- tions show that i case of dog No. 1 the phase of irradiation of inhibition ocgtyed about twenty seconds, while the concentration

of inhibition occupied about. seventy-five seconds. In dog No. 2 the irradiation was complete after three minutes, while the whole inhibitory process in both its phases occupied fifteen minutes. In dog No. 3 the corresponding figures were four to five minutes for the irradiation and. twenty minutes for the two phases taken together. It is seen, therefore, that although the duration of the inhibitory after-effect differed considerably in the three dogs, the time ratio between the phases of irradiation and concentration of the inhibition remained almost constant, the phase of concentration taking four or five times as long as the phase of irradiation. It must be admitted, however, that the data relating to the experiments upon extinction cannot be regarded as. absolutely faultless, since the original magni- tude of the conditioned reflexes sometimes varied considerably in different experiments, and in some cases the causes of these variations could not be definitely determined.

An experimental investigation upon the irradiation of con- ditioned inhibition was carried out by Dr. Anrep, who also made use of the cutaneous analyser. A generalized tactile cutaneous reflex was first established, and its strength was equalized so that the stimulation of any place resulted in the same intensity of reflex response. The tactile stimulation of one definite place was now repeatedly combined with a stimulus for another analyser (the sound of a buzzer), and in this combination the stimulus remained without reinforcement by the unconditioned reflex. The lt was that the stimulus became negative or inhibitory when liéd in the com- bination, although it retained its full posit; ffect when applied singly. The places on the skin which wigs ile are indicated. by numbers: 0, between the neck oo st, in combination with the buzzer, represented the area s to the conditioned inhibi- tion. On the left side the foil places were used for positive tactile conditioned reflexes: Kon the fore limb; 2, on the fore paw ; 3, on the middle of th est; 4, on the pelvis; 5, on the thigh ; and 6, on the hi w. The experiments were conducted in the following mann a given experiment one positive place was first tested, in W to determine the normal magnitude of the conditioned epe, The inhibitory combination was now applied, and t the positive place was tested again at different