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

preceding extinction. It must be concluded, therefore, that during the repeated application of the inhibitory stimulus the inhibition again became concentrated at the point at which the inhibitory stimulus was applied. The spread of the inhibitory after-effect has thus to be regarded as proceeding not during, but entirely or mainly after, the termination of the inhibitory stimulus; while during its action the surrounding areas of the cortex are, to all evidence, subjected to positive induction.

Similar results were obtained by Dr. Podkopaev in another dog, in which positive conditioned alimentary reflexes were established to a definite tone and to a metronome beating at a rate of 120 per minute; an inhibitory reflex based upon differentiation was estab- lished to a stimulus of 60 beats of the metronome per minute. The tone, when superimposed upon the inhibitory stimulus of the metronome, gave out of nine experiments a slight trace of inhibition once, a normal effect four times, and an effect greater than normal four times.

In further experiments on the same problem two more dogs were employed. In one of these [experiments of Dr. Golovina] positive reflexes were established to a definite tone, to a sound of a whistle, and to a tactile stimulus. Three inhibitory reflexes were also established, all based on differentiation—one to a definite rate of a metronome, another to a tactile stimulus, and the third ave ashes of a lamp. When all these reflexes were well establis as peri- ments were performed in which each one of the p e stimuli in turn was applied on the background of Na the inhibi- tory stimuli. All the tests gave uniform A positive stimulus combined, in this way gave eithe ormal or else a somewhat augmented secretion, and the EAN eriod was in most

In the second dog [experiments re Pavlova] positive con- ditioned reflexes were established the sound of a whistle, to a sound of bubbling, and to a tacti ulus. An inhibitory stimulus based on differentiation was ed to a definite rate of a metro- nome. In these experim ach positive stimulus was applied several times with the i y stimulus. The results were somewhat different from those obt®ified in the first dog. Although the latent period was in most? s reduced, the positive effect of the combined stimulus was alm@) onstantly, and sometimes considerably, smaller than that XS with the positive stimulus used singly. In the

second dog, therefore, the concentration of the inhibition was not so perfect. It should be said that the last two dogs possessed functionally different types of nervous system. While in the first dog the dif- ferentiations were in general very stable and remained unaffected by the combined stimulation, in the second dog the differentiation was frequently incomplete, and was invariably still further disturbed after the experiments with superimposition.

The series of experiments described in this lecture clearly demon- strate that, on the one hand, the positive induction arising as the result of an inhibitory stimulus applied to a definite place limits the spread. of the inhibitory process, and that, on the other hand, the interaction between excitation and inhibition is determined either by the phase of establishing new relations in the cortex [experiments of Dr. Podkopaev] or by the type of nervous system in different animals [experiments by Drs. Golovina and Pavlova].

The cortex as a mosaic of functions : (a) Examples of the mosaic character of the cortex and the more obvious ways in which this character is acquired. (b) Vari- ability of the physiological properties of different points of the cortex in some instances, stability in others.—The cortex as a united complex dynamic system. Ir becomes obvious from all the previous discussion that through the medium of the cerebral cortex a great number of environmental changes establish now positive, now negative, conditioned reflexes, and determine in this manner the different effector activities of the animal organism and its everyday behaviour. All these conditioned reflexes must have definite representation in the cerebral cortex in one or another definite group of cells. One such group of cells must be connected with one definite activity of the organism, another group with another activity : one group may determine a positive activity, while another may inhibit an activity. The cerebral cortex can accordingly be represented as an exceedingly rich mosaic, or as an extremely complicated “ switchboard.” . However, iwApite of its extreme complexity as a switchboard, there are a s large spaces reserved for the development of new,connectio Moreover, points which are already involved in a definite con@tiphed activity frequently change their physiological rôle ang Qdpome connected with some other activity of the animal.

The idea of the cerebral cortex as a mo functions is in part indicated in the current anatomical Sad physiological teaching. The structural complexity of the speci) receptor organs of special sense, the rich complexity of the gular structures of the cortex,. and the complexity of their dis€r}_ution conform quite readily to the idea of the mosaic chan f the central nervous system. f fu The rather rough localizatj nction which has been achieved during the last centu experimental physiology is no less in

ever, a comple difficult matter; up to the present it has been possit ly to make the very first attempts towards an experimental study of the simplest aspects of the problem, and even these aspects demand the utmost skill and resource of the inquirer. The existence of a localization of function in the cortex is in some cases sufficiently proved by the evidence of structure alone, definite receptor elements having been shown. to stand in connection with definite cortical cells. The study of conditioned reflexes has shown, however, that a conditioned reflex appears at first in a generalized form, ż.e. that excitation irradiates from its point of initiation to embrace also cells belonging to other receptor elements beyond the boundary of the area of the cortex primarily connected with the stimulated receptor ; the problem becomes still more complicated when we take into account also the subsequent concentration of excitation upon its point of initiation.

Two different problems present themselves for consideration. In the first place the question arises how the functional demarcation of two positive cortical points each connected with a different uncon- ditioned reflex is effected, and in the second place the similar question arises as to the mechanism of the functional demarcation of neigh- bouring positive and negative cortical points belonging to the same unconditioned reflex.. The study of anatomical localization of function is obviously of no assistance in solving these problems. The investigation of the first question is being cqnducted at the present time, and therefore cannot yet be di oN our investi- gations up to the present have been confin most exclusively to the second problem, since it is the si

- We shall commence with a simple a conditioned alimentary reflex was esta KN of the skin on the right shoulder, vious case. A positive ed to a tactile stimulation egative conditioned reflex to a similar stimulation of the sin’ the right thigh. -After these reflexes had been thorouhigStasd the effect of a tactile stimulation of other places of the skin was tried. The different sites of stimulation we Q1) the front paw 17 cms. below the positive point on the er; (2) the side of the animal 12 cms. caudally from the ive place on the shoulder ; (3) the side of the animal 15 front of the negative place on the thigh ; and

(4) the hind 18 cms. below the negative place on the thigh. The G ESEA was measured. during 30 seconds of isolated stimulati each of the above places. The results are summarized in $ owing table : Conditioned tactile stimulus applied Saliva in during 30 seconds drops during 30 seconds Front paw 6 Shoulder (the positive place) 8 Point on side nearer to shoulder T Point on side nearer to thigh 3 Thigh (the negative place) 0 Hind paw 0 Similar results were obtained in two other dogs [experiments of Dr. Foursikov].

It can be seen that under the influence of two definite external stimuli, which affected the animal under opposite conditions (one reinforced by the unconditioned reflex and the other remaining without reinforcement), two perfectly definite and separate points within the cutaneous analyser were given, the one excitatory, and the other inhibitory, properties. Around each of these points there was established a corresponding region of positive or negative influence, these regions of positive and negative influence extending towards each other, although each maintaining its distinctive properties. The smallness of the positive reflex on stimulating the ek the side of the animal nearer to the thigh, and the absence itive reflex on stimulating the hind paw, indicate the ON ce of

a nucleus of inhibition the positive effect due to Q ial generaliza- tion would have spread over the whole of t alyser in such a manner that the decrement of the aa) x with increase of distance from its point of initial develop rent would have been gradual, as was shown in the tenth SA . The experiments described in gis lecture show that external stimuli evoking antagonistic meee provide the first method by which a functional mosaic r er of the cortex originates. Many other examples of thig€\fan be found in the lecture upon the analysing function of t eX. More complicated e iments were conducted upon three more dogs. In two do Sia tones [experiments of Dr. Siriatsky], and in the third actile stimulation of different areas of the skin

[experimenta’ Qr. Koupalov], were used as conditioned stimuli, sO alternate areas being respectively positive and negative. The object of the experiments was to determine the mode of development of the mosaic character, the stability and the delicacy of its pattern, the interaction of its different points, the effect of stimulation of the spaces intermediate between the positive and negative places, and the effect of development of such a functional mosaic upon the general condition of the animal. Some of the results of these experi- ments will be given now, others will be described in further lectures, although it should be mentioned that the investigations are still being pursued. In one dog all the tones C of five neighbouring octaves of an organ (64-1024 d.v.) were used as positive conditioned alimen- tary stimuli, while all the tones F (854-13654 d.v.) were used as inhibitory conditioned stimuli. In the following tables the respective C’s and F’s are designated according to Helmholtz’s scale. The following experiment illustrates the final result obtained with one dog:

In the second dog diioreng Snes from f (1702 d.v.) to f’ sharp (360 d.v.) were used in altepgateorder as positive and negative con- ditioned stimuli. e’ sha 5 d.v.) was given the properties of an excitatory stimulus, ¢’ .v.) properties of an inhibitory stimulus, ec’ (256 d.v.) excita ” a (2134 d.v.) inhibitory, g (192 d.v.) ex- citatory and f © .v.) inhibitory, these tones being enumerated in descending r. As can be seen, the intervals between the respective epôsitive and negative tones were in this dog irregular, and smal an in the first dog. The final stage of development of the

In the third dog the conditioned alimentary reflexes were tactile. The apparatuses used for the stimulation were always arranged in strictly identical positions along a line extending along the left side from the hind leg along the whole length of the body to the left leg, the apparatuses being set at a distance of 12 cms. from each other measured from the centre of one apparatus to the next. The ` stimulated places are numbered in order from No. 1, the left hind leg, to No. 9, the left fore leg. Stimulations of the places represented by odd numbers were given excitatory properties, and stimulations of the places represented by even numbers inhibitory properties. The following is a typical experiment :

Salivar Conditioned stimulation Secreti applied during 30 seconds cot & -Onds Tactile No. 7 9 Tactile No. 5 Q 104 Tactile No. 4 EALE) } Tactile No. 5 K 4 Tactile No. 7 O 6 Tactile No. 3 64 Tactile No. 6 tive) 0 Tactile No O 6 Tactile Q) 54 j (negative) 4 periments it gre D) ressively easier. The reflexes were developed not ew but-in succession. One of the most interesting points brought out by these experiments- was the spontaneous development in the first and third dogs, in the final stages, of some new reflexes, and it is important to note that the new conditioned properties in these cases developed within the region of the anta- gonistic nervous processes. In the case of the first dog the positive conditioned reflex to c” was of very long standing. In one experiment this tone c” evoked a secretion of 8 drops during 30 seconds, while on the contrary f” even on its first application failed to produce any positive effect. This inclined us to regard f” as inhibitory from the start, and the truth of such an assumption was definitely proved in an experiment on the following day, when, f” being used as the first stimulus, it not only remained without any positive effect but also left a considerable inhibitory after-effect, so that the positive reflex to the succeeding stimulus c” became very much diminished. It is obvious therefore that f” assumed its inhibitory properties spon- ` taneously, without requiring any contrasting, but to all appearance simply in virtue of its situation in the neighbourhood of the positive cortical point corresponding to c”. The same phenomenon repeated itself with c’”’, which when tested for the very first time gave a positive effect apparently in virtue of its proximity to the negative f”.

In the third dog, with tactile conditioned reflexes, the places Nos. 1 and 9 also developed their full positive effegt spontaneously without any previous reinforcement, but mo ably in virtue of being within the sphere of influence of} previously estab- lished. negative places Nos. 2 and 8. Clearly these facts should be inteypẹ®ted as due to mutual induction initiated-by the pre-existiņ® points of excitation and inhibition in regular alternation. e experiments show us why any rhythmic activity is performed fore easily and less exhaustingly than an arhythmic one. The EGE on all three dogs showed us that in the case of a rogar alternation of positive and inhibitory

stimuli all the reflexes w a regular alternati NS even within one experimental day to a more and more prepage functional localization of positive and negative cortical points S can, of course, most clearly be demonstrated in cases where Bt the beginning of the experiment the effect of the different pi was lacking in precision. The following results were obtaine a) , the dog in which tactile stimuli were employed as the KN ing excitatory and inhibitory conditioned stimuli; the

experiment was performed before the negative stimuli became well established : Conditioned stimulus during Secretion of 30 seconds Saliva during 30 seconds Tactile No. Tactile No. Tactile No. Tactile No. Tactile No. Tactile No. Tactile No. Tactile No. The following is another example of an experiment on the first dog taken at the time when the reflexes were not yet quite regular : Conditioned stimulus during Saliva in 30 seconds drops during 12.42 f P (34 ai egative) 12.58 ,, c (IAV The above he Cag indicate that the mutual induction of

the antagonistic rt Gus processes of excitation and inhibition should be wr the second contributing factor to the develop- he of a “S functions in the cerebral cortex. The same dogs were used to determine the extensity of the excitatory and inhibitory processes around the respective points of stimulation, and to determine also whether there existed any mosaic of neutral territory interwoven with the mosaic of excitation and inhibition. For this purpose, in the dogs in which a mosaic of tones — was established, other tones were used intermediate between the tones which had been given positive or negative significance, and the effect produced by these intermediate tones was observed. A positive effect, in the form of a salivary secretion, was a direct evidence of the tone having definite excitatory properties. An absence of secretory effect, on the contrary, gave no special indication whether the tone had any inhibitory conditioned properties or was merely neutral, and special experiments had to be made to test whether such tones left any inhibitory after-effect or exhibited any effect of positive induction. In the following experiment, between the positive tone 256 d.v. and the negative tone 320 d.v. three ‘tones were taken: 2662, 288 and 3032 d.v. respectively.

Salivary Conditioned stimulus applied Secretion in during 30 seconds drops during 30 seconds The above experiments show that the tones intermediate between the positive c’ and the negative e’, namely, the tone d’ and the semi- tones c’ sharp and e’ flat, assumed a different significance.’ The semitone c’ sharp produced a definite though comparatively small. positive effect, 7.e. it still belonged to the excitatory region of c’ ; on the other hand the tone d’ and the semitone e’ flat at the first glance were equal in their effect, since both gave a zero secretion. It was only by testing their inhibitory after-effect that a difference between these two tones could be revealed. The conditioned tactile stimulus when applied two minutes after the use of the semitone e’ flat diminished in its effect by 50%, t.e. it was under the influence of the inhibitory after-effect. When, however, tested under precisely the same conditions after the tone d’ the tactile stimulus gave a full positive effect. The semitone e’ flat, therefore, belonged unquestion- ably to the region of the inhibitory e’; the tone d’, however, either was entirely neutral or else carried much weaker inhibitory properties, an alternative which can be finally settled only by more delicate experiments. The whole question of the possible existence of completely neutral points in the cortex is being further inves- tigated.

It was mentioned in the first lecture and again in the beginning of the present lecture that additions can always be made jn any pattern of the functional mosaic both with respect to its e struction, one and the same point changing it significance, and becoming connected successive physiological activities of the organism. In have only one series of experiments, cond y Dr. Friedman, as follows : One and the same agent served at wen a conditioned alimentary stimulus, later it was transformed in conditioned stimulus for acid ; reversely, old conditioned @yuli to acid were transformed into alimentary ones. Two 1O used for experiments with the first set of paca nd a third dog was used for the second set. The transfo n of conditioned stimuli was effected. by the substitution of Qnepyunconditioned reflex for the other. The following is the generad sequence of events : The conditioned stimulus, on transition from.qre“inconditioned reflex to another very quickly, even within a sj experimental day, loses its secretory effect and gives a a for a comparatively long time; only after

considerable practice with the new unconditioned stimulus does it gradually reassume excitatory properties, and these now belong to a conditioned reflex based on the new unconditioned one, as shown by the very definite change in the composition of the saliva secreted by the submaxillary gland and in the character of the motor reaction. The complete replacement of the one conditioned reflex by the other required about 30 reinforcements by the new uncon- ditioned stimulus. After a considerable practice of the condi- tioned reflexes to acid the conditioned stimuli were once more transformed back again into alimentary ones ; the transformation occurred rapidly and only a few reinforcements were needed. This indicates that the original alimentary connection was still preserved in spite of the establishment of a new connection with the reflex to acid.

However, the main interest of the experiments of Dr. Friedman lay in the investigation whether a differentiation which had been established for the conditioned stimulus to one reflex would be preserved after its transformation. A detailed description of an experiment will be given in respect to one dog only, since the experi- ments with all three dogs gave identical results. The alimentary conditioned stimulus in this dog was given by the tone of 2600 d.v. ; a precise differentiation from this tone was established to the neigh- bouring tone of 2324 d.v. The positive conditiqned alimentary reflex was now transformed into a conditione Ú to acid, and when the differentiation was tested it was fong sion its very first application to be complete and. to exert t me inhibitory after- effect as before. A new and more PEO fferentiation was now established on the basis of the “aci XS ex to a note a semitone higher than the original positing Ape i.e. 2760 d.v., and it was found that when the tone K 0 d.v. was transformed back again into a conditioned alifẹħtary stimulus this new and finer differentiation also retainegyits precision. :

In the course of the ding lectures we had occasion to refer to the fact that o he same point of the cortex could, in accordance with t, iven experimental conditions, be a point of origin either of éxetation or of inhibition. These transformations of the physiglopital significance of a definite cortical point are attained wi omparative ease and are effected with considerable rapidit h in respect of positive and of negative stimuli (experi- na jth induction, p. 194), and in respect of their ultimate con-

nection with one or another unconditioned reflex (experiments just described). However, amongst our material we have a number of cases in which the definite positive or negative quality of some region of the cortex, or even a temporary correlation between the two processes, assumed an exceedingly persistent character which could be changed. only with great difficulty, or even failed to be changed. These cases were met with in the experiments of Dr. Frolov upon

conditioned, positive and negative trace reflexes. The results of these experiments were of such unique character that it is necessary to describe them in detail. In the case of one dog a trace conditioned reflex to acid was established to atone of 1740 d.v. produced by an organ pipe : the tone was continued for 15 seconds and the acid. was administered after a pause of 30 seconds. This trace reflex was repeated 994 times in the course of one year and nine months: Its latent period, counting from the beginning of the tone, was equal to very nearly 25 seconds (10 seconds reckoned from the cessation of the tone). After the termination of the investigation originally planned it was resolved to abolish the trace character of the reflex and to give it the character of a delayed reflex, evoking the positive secretory effect during the action of the tone, and not some time after its termination. For this purpose acid was administered at the 15th second after the beginning of the tone. After twenty reinforcements with this new interval it was still found that, net only did the reflex fail to appear during the 15 seconds of Gite action of the tone, but even the administration of aci e 15th second evoked a secretion only after the old late riod of 25 seconds from the beginning of the tone. The us her auditory stimuli in place of the tone did not alter the , and when the tone and the other auditory stimuli were ted. for 45 seconds

_ without the administration of acid aR. on always started at about the 25th second from the beginni d then increased rapidly, giving about 10 drops during the r Qing 20 seconds of isolated action of the conditioned stim After this failure to diminish the latent period, the stim reinforced practically simul- taneously, t.e. two seconds afjeythe beginning of the tone preceding the reinforcement. N ess, even after several score of repeti- tions the conditioned tion started only after a latent period of 20-25 seconds ao. e beginning of the tone ; this latent period could not be cha: Sheth the acid was administered at the 2nd second or KS e tone was continued singly for a much greater