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

length of time. The last experiment performed in this series is given in the following table: Length of time of isolated Latent period Time action of the conditioned of the Salivary stimulus before Secretion reinforcement with acid in seconds 1.12 p.m. 30 seconds 26 Et =. 2 >, 29 Pbk “5, 45 S 23 1.40 ,, 2 n f 32 EDAS 15 seconds followed by a pause of 30 seconds 25 A conditioned alimentary reflex to a tone f sharp of a tone variator was now developed in this dog, but the latent period of this reflex also could not be reduced below 24 seconds, and it was only when a tactile stimulation was used as a conditioned. stimulus and reinforced with acid after 2 seconds that a closer approximation to a simultaneous alimentary reflex was at last obtained. At the twenty- fourth test the reflex was measured by 12 drops during 30 seconds, with a latent period of 2 seconds.

A similar persistence of a thoroughly established cortical in- hibition was observed in the case of another dags\The trace of a tone of 1740 double vibrations produced by apypxgan pipe was used as a conditioned inhibitor to the positive cg ioned stimulus of a metronome beating at a rate of 104 pe Aiute. The trace of the tone even after one minute still exert 9 full inhibition upon the reflex to the metronome. Such A WDibition had to be developed of course gradually, starting with *ecênt traces of only a few seconds. The experiments were onaya with this conditioned inhibition for well over two years, and thefone, besides serving as a conditioned

course, led to an extr tensification of its inhibitory properties. At the terminatio=\® hese experiments the animal was used for another resear G@ywhich it was desired to develop a positive con- ditioned sete ea a sound of a microphone which happened to be practically @entical in pitch with the tone which had served as the conditio nhibitor in the first series of experiments. The positive oN? reflex refused for a long time to develop, and when the

metronome was tested shortly after the sound of the microphone had been applied a most powerful conditioned inhibition was revealed. The experiments were now modified so that the inhibitory combina- tion of the microphone with the metronome was directly reinforced by the unconditioned stimulus ; in other words, a procedure was adopted which exactly reversed that employed for the development ` of the conditioned inhibition to the original trace of the tone. The inhibitory combination now quickly acquired excitatory properties, and somewhat later the sound of the microphone applied singly acquired a positive significance of its own. However, the tone of the organ pipe which had been originally developed as the conditioned. inhibitor did not acquire a positive character; neither did it lose its inhibitory properties : these had to be destroyed. by the same

method as was used for the destruction of those of the microphone, / These cases of extreme stability of the inhibitory process must | be regarded as exceptional. It is very probable that the intensity of inhibition in these cases was favoured by some special con- ditions of the experiments, and it is possible that this exceptional persistence of the inhibitory process can be correlated with the experiments upon hypnotism and sleep which will be described further on.

Along with these cases of an extremely stable “inhibitability ” of definite points of the cerebral cortex must be placed a at of a similarly stable excitability. In an experiment by Dy well-established conditioned. alimentary reflex, tọ 256 double vibrations produced by an organ pipe Aye from twenty-two separate and distinct tones rantein pitch from 768 d.v. to 85 d.v., the tone of 256 d.v. (c’) bem + lways accompanied by food while all the others remained ,u i orced. The positive tone was contrasted in each experiment Ser! times with one or other of the negative tones. In this mannev the positive cortical point became surrounded by a series o Qhibitory points. However, this apparent encircling of the posi Qyoint by inhibitory ones did not lead to a diminution of the aes the positive tone ; on the contrary

it led to its extreme vie ion. When in subsequent experiments en the animal was experi ally subjected to a profound physiological sleep, so that, for ẹ pie, shrill whistling and banging on the door of the experime om containing the dog did not awaken it, the positive condigtehed tone awakened the animal immediately and evoked a full conditioned secretion. Experimental proof will be given in further lectures that sleep itself is nothing but a form of internal inhibition, and from this point of view the experiment just described must be regarded as a case of extreme stability of the excitatory process in a definite point of the cerebral cortex which successfully resists the surrounding inhibition. —

The foregoing discussion of the experimental evidence permits us to regard the activities of the cerebral hemispheres as a true mosaic of functions. All the numerous individual cortical points, each at any definite moment, have some very definite physiological significance, while the whole mosaic of functions is integrated into a complex dynamic system and perpetually achieves a unification of the individual activities. Every new localized influence playing upon it influences to a greater or less extent the entire system. Consider, for example, a dog which. possesses at any given moment a definite number of conditioned reflexes. The addition of new posi- tive, and especially of new negative, reflexes exercises, in the great majority of cases an immediate, though temporary, influence upon the older reflexes [experiments of Dr. Anrep]. Further, even when no new reflexes are added, and it is only a rigidly adopted sequence of their order which is changed, their magnitude undergoes distinct diminution, showing a considerable predominance of inhibition. In the following experiment by Dr. Soloveichik a dog was subjected at intervals of 10 minutes to the conditioned leary stimuli of a metronome, an electric lamp, a whistle a tactile stimulus, always repeated in this order in every expgM{rent. The following table gives the results of the final experi

stimuli : Salivary Conditidged stimulus Secretion in nie seconds drops during. 15 seconds etronome 4 lectric lamp £ Whistle aa Tactile 4 Metronome 5 Electric lamp 3 Whistle 14 Tactile 2 In an experiment on the following day the order of the stimuli was changed. The diminution in the magnitude of the conditioned reflexes observed when the order of their administration is changed sometimes appears immediately, as in the foregoing experiment, and in other cases becomes more obvious in the succeeding experiment when the I stimuli are again applied in their usual order. The diminution con- | | tinues for several days, and then the reflexes quickly return to their | normal magnitude. Such a diminution in the strength of the i reflexes as occurred towards the end of the first experiment given | above (3.59, 4.9, 4.19 p.m.) is of frequent occurrence anq will be | more fully discussed in the next lecture. . A

The development of inhibition in the cortex under the influence of conditioned stimuli. CONDITIONED stimuli, acting as they undoubtedly do through the intermediation of definite cortical cells, provide the obvious means whereby the physiological characteristics of these cortical cells can be studied. One of the most important of these properties is that under the influence of conditioned stimuli they pass, sooner or later, into inhibition. In the previous lectures upon internal inhibition it was shown that in all cases when a positive conditioned stimulus repeatedly remains unreinforced, it acquires inhibitory properties, 7.e. the corresponding cortical cells enter under its in- fluence into a state of inhibition. The present lecture will be devoted. to the study of the intimate mechanism of this phenomenon, and of the part played therein by the unconditioned reflex and by other conditions which retard or accelerate the development of this

inhibitory state. The transition of the cortical cells into an i ox. ry state is of much more general significance than could be i ed from the facts case of conditioned reflexes which in without reinforcement must be considered. only as a s nstance of a more general case, since a state of inhibiti O also when the con- ditioned reflexes are reinfo . The cortical cells under the influence of the conditiongey stimulus always tend to pass, though sometimes very slowly, a state of inhibition. The function performed by the ` oned reflex after the conditioned. reflex

ment of internal inhibition. The aoe on of inhibition in the The follo (Gy the most commonly occurring example of this phenoment We are dealing, we will suppose, with a conditioned reflex is delayed by 30 seconds, t.e. a reflex in which the conditioned stimulus acts singly for exactly 30 seconds before the addition of the unconditioned stimulus. Let us suppose that when the reflex is well established, its so-called latent period—the interval of time from the beginning of the conditioned stimulus to the onset of the secretion—is equal to five seconds. Now this latent period remains practically unaltered for a certain length of time, which varies greatly in different dogs. As time goes on the latent period lengthens out, and finally during the 30 seconds of the isolated action of the conditioned stimulus no trace of salivary secretion is produced. It is, however, only necessary to delay the administration of the unconditioned stimulus by a further 5-10 seconds for secretion again to be obtained during the prolongation of the isolated action of the conditioned stimulus. On continuing the experiment for some time as before, i.e. with a delay of 30 seconds, and then again introducing a delay increased by a further 5-10 seconds, no conditioned secretion is obtained any more. In order to obtain a conditioned secretion the administration of the unconditioned stimulus must be delayed for a still greater length of time. Finally a stage is reached when no conditioned secretion can be obtained during any length of isolated action of the conditioned stimulus. This gradual dis- appearance of the conditioned secretion in reflexes with a con- stant delay occupies very different periods of time in different dogs. -In some it takes only days or weeks, and in others it takes several years. The conditioned secretion disa s later with tactile, than with thermal, later still with yi , stimuli and latest of all with auditory stimuli, especially į latter are discontinuous. S

The following is an example of the relative drfernees between the various conditioned stimuli with respect t, apidity of transition of the cortical elements into an inhibito te under the influence of a definite delay [experiments nS Shishlo]. The first con- ditioned stimulus which was developed/in a particular dog was one belonging to the tactile analys ihe administration of food, was usually delayed 10 seconds fro Qh beginning of the tactile stimulus, but on rare occasions a 30 s’ delay was introduced. The reflex: first appeared at the 2Zt mulation, and within five weeks, after 179 stimulations, thereflex became stable at 8 drops during one minute. The development of a second alimentary conditioned. reflex to a ther taneous stimulus of 45° was now commenced, the normal pgfige of delay being as before 10 seconds. This reflex

developed quickly, and when at the twelfth stimulation a delay of . 30 seconds was introduced a secretion of 4 drops was obtained. On continuation of the usual reinforcement applied 10 seconds after the beginning of the thermal stimulus the reflex rapidly diminished in strength and at the 33rd test, when the delay was specially prolonged to one minute, only one drop of secretion was obtained. The following observation leaves no doubt that the disappearance of the conditioned reflex, notwithstanding its invariable reinforce- ment, is an expression of a progressive development of inhibition in the cortical elements. When an effective positive conditioned stimulus is applied shortly after the application of a conditioned stimulus which has, as described, just lost its positive properties, the

resulting reflex suffers a diminution. Similarly, when one among a , number of conditioned stimuli has lost its positive effect its disuse in the experiments leads to an increase in the effect of the remaining stimuli. To my mind such results can only be interpreted on the assumption that real inhibitory properties have been, acquired by those stimuli which have lost their positive effect. This phenomenon should not be confused with what was previously described as the result of internal inhibition of delay. The inhibition of delay is revealed by the so-called latent period which is observed in every conditioned reflex and which remains unchanged fog a considerable period of time. The phenomenon which is bein EN ribed here, on the other hand, is characterized by its invari progressiveness. The inhibitory state of the cortical elemen er the influence of conditioned stimuli develops more qui with longer delayed reflexes; the longer the isolated ap on of the conditioned stimulus the quicker the developm he inhibition. For example,

unchanged. in its strength fo very considerable time and thus permits of exact experimentatien ; the same reflex when delayed to 30 seconds quickly © nsuitable for experiments through the progressive developm inhibition. Such a case is taken from A dog has ioned alimentary reflex established to the sound of a me Cris and throughout the whole period of work the reflex ay: has been delayed for 10 seconds remains constant in strengthS The following experiment has been chosen at

Conditioned stimulus Salivary | Time applied during Secretion in 10 seconds drops during 10 seconds 3.0 p.m. Metronome 0 JID LS T l e E x 2 4.91.80 ad 3 4.20 _,, x 2 As soon as the isolated application of the conditioned stimulus is prolonged to 30 seconds the reflex becomes inconstant in strength, and on repetition diminishes to zero during the time of one single experiment. l Conditioned stimulus Salivary Time applied during Secretion in 30 seconds drops during 30 seconds 2.55 p.m. Metronome 6 3:20) 55 g 4 3.30 ,, if 4

The above two experiments were conducted iN terval of one day. In view of the great variations existing EN dogs it has been found very useful, and EN tial, to employ in different dogs, reflexes which are ARQ O lengths of time. It now becomes obvious roe ng-delayed reflexes . develop only with difficulty and why Quritfg the beginning of our work they could be obtained only i me of the dogs. Moreover, it becomes easy to understand. Z many of the experiments previously described the posts limentary conditioned reflexes diminish during a single e Seep, t and in some cases after only a single application—as in periment on page 232 of the previous lecture.: This ed due to the repetition of the conditioned stimulus and not to an her factor, such, for example, as a gradual satiation of the Ton during the experiment in the case of alimentary reflexes. r is obviously not the case, since on repeating any one o QH conditioned stimuli, only the effect pro-

duced by that one becomes diminished, while other conditioned stimuli may preserve their full effect up to the very end of the . experiment. When a definite positive conditioned stimulus has already shown a tendency to assume inhibitory properties, then after a short interval in the experiments, or even at the beginning of a day’s experiment, its first application produces a considerable secretion, but on repetition the stimulus quickly diminishes in its effect and becomes inhibitory in spite of its being reinforced at every application. i :

Tt is in the interest of the experimenter for most of the experiments to have at his disposal reflexes of a constant intensity. To obtain such reflexes itis necessary in many cases to fight against the pro- gressive tendency of conditioned reflexes to undergo inhibition. At first on purely empirical grounds, and subsequently more rationally, a number of ways of combating this inconvenience were evolved. For obvious reasons the more effective of these methods were such as established conditions exactly the reverse of those which led to the progressive diminution of the conditioned reflexes. Foremost among such methods was the introduction of an occasional abrupt shortening of the length of isolated action of the conditioned stimulus.

- If, for example, the reflex originally has been delayed 30 seconds, the practice is now adopted of reinforcing at the 3rd to 5th second. Of course, during this short period of time the condNioned stimulus - cannot evoke a measurable reflex, and very often Ya secretion whatever can be observed during so short a (9%j0d of delay. The short delay, however, is only introduced aya Yemporary expedient, being, so to speak, only a therapeutic meagtke applied for the purpose of regenerating the conditioned reflex Miterwards, when the usual 30 seconds’ delay is restored, it ifo that the reflex is as strong and as constant as in the Eee t is useful to make this return

from the short-delayed pee, the long-delayed one by stages, e only gradually increasing ngth of the isolated. action of the conditioned stimulus. OKlar of this method, measured by the permanence of the@@powstituted reflex, depends upon the degree of weakening of t Woi reflex, upon the time during which this weakness eu to persist, and upon the length of time during which the shordelay is practised as a therapeutic measure. A short perid practice restores the reflexes only to a small degree

and for (D) ttime. Where a profound weakening of the reflex has Pee ed to persist for a very long time, the method which has just been described, and which is, generally speaking, very effective, no longer suffices, as will be shown presently, to restore the reflex. A conditioned reflex which has become weakened in the course of long practice can be helped towards recovery by avoiding any numerous repetitions of the conditioned stimulus within a single experiment, and, if possible, confining the use of the stimulus to single applications. A similar beneficial effect results from a simple interruption, even for a few days, in the work upon the weakened conditioned reflexes.

Besides these there are several subsidiary methods, as,for example, to increase the strength of some of the conditioned stimuli or to increase their number, by the summation of positive induction, or finally by increasing the strength of the unconditioned stimuli. At present, however, interest centres mainly in the direct methods referred to above. There are cases where the extent of the diminution in the strength of conditioned reflexes is such that none of the above methods can be of any help—all positive conditioned reflexes simply disappear. The animal grows inert in the stand during the experiment, and even declines the food which is given after application of the conditioned stimulus. This can be observed even with dogs which have served, on account of the stability of the conditioned reflexes, for extremely exact experimentation during a period of may years.

What is to be done with an animal in such a a n the earlier period of our work such a dog would undoubted) ave been discarded as one which could be of no further use ur purpose. Now, on the other hand, the condition of such Q is regarded as calling for further investigation, which, as a ar of fact, can easily be carried out. It is sufficient to stop the us the old conditioned stimuli, and to develop instead Paes eae to new stimuli, for the seemingly insurmountable dine to disappear. The new conditioned. reflexes develop extr nO quickly, and this is not surprising since all the reeeo a which originally interfered with the development of c d reflexes have long since dis- appeared. The newly seve reflexes quickly attain a maximal and constant strength, e animal entirely returns to its original condition and can be,ust®f for further experimentation. In view of the extreme import of this fact I shall describe in greater detail the history of o the dogs [experiments by Dr. Podkopaev].

another different positive and negative conditioned reflexes were established. Among these were several reflexes to tactile stimulation | of different places of the skin (designated by numbers in the succeeding | tables). All the reflexes were extremely constant in their magnitude and in the length of their latent period, and the dog was used during several years for experiments on various problems. The following example illustrates the strength of the positive reflexes as tested in

| an experiment of 30th August, 1922 : | Conditioned stimulus Salivary : i= Time applied during Secretion in | Latent period [i 30 seconds ` drops during in seconds Í 30 seconds I 12.30 p.m. Tactile No. 1 14 2 | An experiment performed on the 6th August, 1923, involving Il various positive stimuli and a conditioned inhibitor gave. the | : : í Secretion in | Latent period | ae sl Sa A drops during | in oon! | 30 seconds An experiment of 12th June, a | a negative one (conditioned Oe I resulted. as follows :

lays the positive reflexes and Os: with a different inhibitor) Ml Time age ae Geaketing oi Latent period Mi ; 3 ds drops during in seconds i] 30 seconds i — ior. AE Towards the end of 1924 the stimuli very often had a zero effect and the dog no longer took immediately the food which was pre- sented. Several expedients were tried in order to get rid of this increasing inhibition. Instead of tactile stimuli auditory ones were mainly used, and instead of long delays very short ones ; intervals of as much as a month and a half were made between experiments ; an increase in the strength of the unconditioned stimuli was tried ; and the animal was kept on the floor during the experiments, instead of in the stand. Any beneficial effect produced by these methods was only fleeting: the animal became more and more languid and often altogether declined food given after the application of con- ditioned stimuli. This state of the animal persisted throughout the whole of the year 1925. At the end of 1925 the use of all the old conditioned stimuli was abandoned and new ones were introduced. This procedure led to a quick and definite change in the condition of the animal. It again became alert, and immediately took food on presentation at the end of the application of the new conditioned stimuli. The conditioned reflexes were quickly established and reached a constant and considerable strength, while the latent periods returned to normal. These results remained steady in subsequent experimentation. The following is an early experiment during this phase, performed on the 21st January, 1926. The reflexes in this experiment are delayed. by 15 seconds, and an attempt is made to reinstate among the new ES oY one of the old ones to the sound of a metronome.

Time oe diine drop ng | in seconds 9.43 a.m. Intermittent flashes of lam ang 3 9.55 __,, Bubbling sound K 6 2 The differences in the de of the conditioned reflexes in the above experiment depe Ae a certain extent on the different stages of development whiGhey have reached. The general ee cance of these experiments is obvious. The isolated K e conditioned stimulus, even though followed by the unconditioned, leads to the development of a state of inhibition in the cortical elements, and this development is the quicker the greater the length of isolated action of each single conditioned stimu- lus and the more often such a stimulus is used. It thus becomes apparent that the difference between the process of development of inhibition as studied in the early lectures with respect to different cases of internal inhibition and in those cases which have just been described is not. of fundamental importance ; although in most cases very substantial it is obviously only one of degree. In those cases in which the conditioned stimulus remains unreinforced the inhibitory process develops very quickly ; in those cases with reinforcement which have just been described the development of the inhibitory process is usually delayed—sometimes so considerably that its development may even remain unsuspected. Only in very rare cases is the rate of development of inhibition in both groups of experiments nearly or completely identical.

We now come to the problem as to the mechanism by which uncon- ditioned stimuli retard the development of the type of inhibition which we are now considering. In the second lecture we saw that conditioned refiexes do not develop when the unconditioned stimulus precedes the neutral agent which is required to be made into a con- ditioned stimulus. This is probably a result of external inhibition, the strong excitation produced by the unconditioned stimulus leading to inhibition of that cortical area which i @ realty excited as a result of the application of the neutral lus. If this be nditioned stimulus cortical areas corre- ned reflex. To test this