Electroencephalographic studies of conditional cerebral response in epileptic subjects

E L E C T R O E N C E P H A L O G R A P H I C STUDIES OF C O N D I T I O N A L C E R E B R A L RESPONSE IN E P I L E P T I C SUBJECTS 1 JANICE R. STEVF.NS, M . D .

Division of Neurology, University of Oregon Medical Schoo|, Portland 1, Oregon (Received for publication: April 8, 1959)

Current work in our laboratory concerns the identification of peripheral excitants of epileptiform discharge in patients with convulsive disorders. Specific stimuli, including music, flickered light, reading and emotional stimuli, among other " i n p u t " or centripetal factors, are frequently capable of exaggerating the tendency of epileptic patients to manifest paroxysmal EEG discharge. Whether the increased tendency for epileptiform activity to appear following certain stimuli represents a pathological " a d a p t i v e " response to certain forms of stimulation or is related lo altered EEG frequencies accompanying emotional and other responses was considered in a previous communication (Stevens 1957, 1959). In the present study, we have attempted to discover whether epileptiform EEG activity, when reliably elicited by a given stimulus (e.g., flickering light), can be conditioned to follow a previously neutral stimulus. If the epileptic paroxysm falls in the range of " a d a p t i v e " organismal behavior, we might reasonably expect that it would be subject to conditioning, differentiation, and extinction, as are certain other somatic and autonomic responses. If, however, the epileptic discharge represents an aberrant by-product of cerebral response to internal or external stimuli, conditioning of the paroxysmal activity is less likely to be anticipated. Furthermore, should the paroxysmal response be subject to conditioning, the possibility of " d e conditioning" or extinction might be contemplated. With the purpose of better defining the role of the epileptic paroxysm in the behavioral hierarchy, attempts to condition epilepti-

form EEG activity have been carried out in a number of patients with convulsive disorder. METHOD

Two groups of patients were used in these studies. In the first group (group I), 4 epileptic patients with reliable spike-wave (SW) response to frequency specific photic stimulation were subjected to repeated pairing of the S-W producing light stimulus (unconditioned stimulus, US) with a previously ineffective tone signal (conditioned stimulus, CS). The tone signal was given simultaneously with the light initially in 2 patients, but during all other presentations, the tone preceded the light by a 2 sec. interval. The light was continued until a high voltage S-W response (unconditioned response, UR) was obtained - - usually 2/~ sec. to one sec. The tone was continued throughout presentation of the light, both being turned off simultaneously following elicitation of the S-W response. Following 10 to 15 presentations of the CS-US at irregular intervals (1~ to 11/2 rain.) a different tone signal was presented for 2 sec. and was never followed by the light stimulus. This second tone was at a frequency 10 times that of the CS, but of similar volume and is considered the differential stimulus (DS). Alternate presentations of a series of CS-US sequences with a group of 4 to 6 irregularly spaced DS signals was then carried out. Following the presentation of a total of 30 to 40 CS-US sequences and 20 to 30 DS signals, the CS was sounded for 2 see. without reinforcement by the light, with the purpose of extinguishing whatever response had been elaborated to the CS. These unreinforced presentations of CS are referred to 1 Supported in part by U. S. Public Health below as CS-O stimuli. Six to 10 presentations Service Grant No. B 1140 (C2). of CS-O were followed by further CS-US 431 ]

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JANICE R. STEVENS

trials, then a second and sometimes a third CS-O series. Finally, in several subjects, investigation of trace reflexes was carried out by presenting the CS for 2 see. folh)wed by a 2 see. interval of silence before presentation of US (flickered light) at the usual provoeatiw; frequency (until elieitation of S-W). Each conditioning session was of 50 to 90 rain. duration. Three patients were subjected to at least 5 conditioning sessions; the other patient to only one session. The patients in group I I consist of 19 epileptic individuals who do not respond to photie stimulation at any frequency with S-W paroxysms but who manifest sustained frequency specific repetitive response (photie driving) to light flickered at certain frequencies. These patients were subjected to the same conditioning situation as those in group I, save that the US was flickered light at a frequency selected to produce maximum sustained photie driving, and was continued until occipital driving appeared in the E E G (2 to 8 see.). Attempts to condition the occipital driving (UR) were carried out just as described above for the S-W response in group I, as were the differentiating, extinction and trace procedures. Immediately preceding the conditioning trials, all patients were presented with tone stimuli over the audio range and flickered light at frequencies from 1 to 20 flashes per see. in order to identify responses existing previous to conditioning. Arousal or alerting responses, evidenced by desynchronization of the E E G , characteristically were present in response to presentation of new tone signals. Before tones were utilized as conditional or differential signals, the alerting E E G response was effectively abolished by frequent repetition of the signals to be utilized in the ~-onditioning studies (habituation). In most instances, 500 and 5,000 e/see, tones of moderate intensity were arbitrarily chosen as CS and DS respectively. A single patient demonstrated a persistent E E G " o n " response to the 500 e/see, tone prior to conditioning, and for this individual 300 e/see, and 3,000 c/see. tones were employed for CS and DS respectively. At no time did S-W appear to the tones prior to conditioning.

The subjects lay quietly on a emnfortahh, bed in a darkened quiet room. The lamp from the Grass Model PS1 photic stimulator w~s focused 10 to 12 inches above the bridge oi' the nose and small stethoscope type (Telexi ear phones were comfortably fitted in both external ear canals. Electrodes were placed over frontal, central, occipital, anterior a ~ l posterior ten@oral sites. A continuous bipob~r electroencephalogram was recorded on 6 eha~nels of an 8-channel Grass Model I I I D Electroencephalograph from the beginning of each session, and ineluded responses to presentations of all stimuli, prior to and during conditioning. On the other two channels, the signals (representing the auditory aml visual stimuli) were recorded. Patients remained on their usual anticonvulsant medical regime throughout the trials. t~ESULTS Group i More than 1,000 paired presentations of CS-US were presented to the 4 patients in group I. Because drowsing occurred in a number of experimental sessions, only those sessions or parts of sessions in which patients were alert are tabulated in the results. A total of 521 paired presentations of CS-US are tabulated for the 4 subjects. P r o m p t S-W in response to the US occurred in 486 of these presentations (93 per cent), (graph I). The light stimulus was continued only for a time sufficient for production of the S-W response and never to the point of clinical seizure. Two subjects reported an occasional " s h o c k " sensation infrequently during the S-W discharge. The incidence of S-W in response to US, CS, DS, CS-O and trace stimuli for the 4 patients is summarized in graph I. Paroxysmal S-W complexes occurred during the conditioned stimulus (light reinforced tone) in 15 of the 521 presentations of CS-US (2.9 per eent)~ S-W occurred during the differential tone (DS never reinforced by light;) in 47 out of 322 presentations (14 per cent). S-W occurred d u r i n g unreinforced conditioning stimulus (CS-0) in eleven out of 84 presentations (13 per cent). Finally, S&V occurred during the Trace CS signal (2 see.) and subsequent silent interval (2 see.) during 6 out of 30

E E G C O N D I T I O N I N G IN E P I L E P S Y

presentations (20 per cent). I t should be noted that this interval is twice as long as that for presentation of usual CS, DS, or CS0 stimuli. Analysis of the period into its two halves, viz., 2 sec. period of CS (tone) and 2 sec. period of silence indicates that S-W occurred d u r i n g the 2 sec. silent interval fol-

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lowing CS in 5 of the 6 positive responses. Examples of conditional, differential, extinction and trace responses are shown in figure 1. Spontaneous S-W bursts were noted on occasion from all patients and were much exaggerated by drowsiness. Experiments in which drowsing occurred or frequent S-W

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appeared between stimuli were terminated or eliminated from the reported results. One subject lost the S-W response to light after 60 paired CS-US trials (immediately after Celontin was added to his therapeutic regime with resultant cessation of clinical seizures). High voltage occipital driving then occurred in response to the US. Attempts to condition this response were unsuccessful. Our data indicate that with the methods employed, the S-W precipitated by the flickering light was not conditioned to follow the conditioning tone signal, and that the signals unreinforced by light, i.e., DS, CS-O and trace stimuli, were more frequently followed by S-W than was the conditioning stimulus. F u r thermore, one patient who demonstrated little difference in incidence of f r a n k S-W responses during CS, DS, CS-O and trace stimuli, displayed marked accentuation of paroxysmal slow activity during the DS, CS-O and trace signals (graph I I ) . I t was also noted that S-W responses occurring in the 20 sec. interval following DS and CS-O tend to be approximately twice as frequent as S-W responses following CS-US in a similar interval. In 2 patients of group I, attempt was made to increase the possibility of conditioning by introducing a " m o t i v a t i o n a l ' ' factor. Thus, patient J. E. during one training session (not included in the above report) was ' ' rewarded" for each S-W (light induced by 2 cc. of a chocolate milk shake automatically introduced in the mouth after each successful UR (S-W). This technique did not succeed in either increasing incidence of conditioned S-W or decreasing latency for appearance of UR (S-W). Patient 5. D. was "punished" for each S-W by an airblast triggered by the S-W response to the US. This failed to inhibit the S-W response to flicker and was discontinued. During the immediately subsequent four CS-US sequences unaccompanied by air blast, the CS (tone) alone precipitated S-W. Again, absent reinforcement appeared to potentiate S-W. No increase in habitual seizures occurred in any of these patients during the weeks or months d u r i n g which these studies were carried out. All but one subject achieved practical seizure control t h r o u g h d r u g management.

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l~ig. 1 J. D., a 34-year-old male with long history of warningless major seizures moderately well controlled with antieonvulsants. a. CS-US #9. CS (tone) accompanied by " o n " potential most marked from parieto-oeeipital regions. Prompt S-W (UR) to flickered light. Although patient has been subjected to more than 100 paired CS-US stimuli, no evidence of conditioning the S-W response to follow the CS is accomplished. b. Abortive S-W maximum in right frontal region to fourth presentation of unreinforeed CS (CS-O). c. Single S-W eomplex maximum in right frontal region to differential stimulus (DS). d. Small S-W during trace stimulus. The abnormal complex occurs approximately 1/5 see. after termination of CS, during the silent interval between CS and US. As with the other " i n h i b i t o r y " paroxysms the S-W is both briefer and of lower amplitude than that induced by the photie stimulus. e. Marked and prolonged polyspike complex to unreinforced CS (which immediately followed stimulus presented in (d) above).

EEG CONDITIONING IN EPILEPSY

These results tend to point in a direction opposite to that which was anticipated when we embarked upon the study. Our results suggest that the S-W response or paroxysmal slow activity was "conditioned" to follow the unreinforced stimuli to a degree greater than occurred to these tone signals prior to the IOO

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Graph I I Summary of spike-wave (S-W) and paroxysmal slow responses (A) from 4 conditioning sessions, patient J . E . There is little difference in incidence of spikewave to CS, DS, CS-O and trace. The incidence of pathological slow responses to DS, CS-O and trace signals is, however, higher than to the CS. All trace slow responses occurred in the 2 sec. silent interval interposed between tone and light.

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c o n d i t i o n i n g procedure. The e x p e r i m e n t a l conditions of d i f f e r e n t i a t i o n ( D S ) , extinction via n o n - r e i n f o r c e m e n t ( C S - O ) , a n d r e t a r d a tion (trace) comprise the t r i a d conducive to so-called " c o n d i t i o n a l i n h i b i t i o n " of P a r l o r (1927). These " i n h i b i t o r y " signals were sign i f i c a n t l y more provocative of pathological E E G a c t i v i t y in the p a t i e n t of g r o u p I t h a n the signal coupled with the S - W i n d u c i n g light. These results led us to extend o u r investigation to include a g r o u p of epileptic patients w i t h o u t S - W response to light in o r d e r to test the hypothesis t h a t stimuli g e n e r a t i n g " i n h i b i t i o n " (strictly in the P a v l o v i a n sense, i.e., i n d u c e d b y differentiation, extinction, a n d r e t a r d a t i o n ) are generally favorable to the development of e p i l e p t i f o r m characteristics in the E E G of p a t i e n t s with convulsive disorder. Group I I

Nineteen patients with convulsive disorder were selected for conditioning study because of the presence of well developed occipital driving responses to flickered light. Conditioning procedures were carried out as described

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, A.NICE R. STEVENS

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above (Method), the occipital driving representing the unconditioned response ( U R ) . The subjects range in age f r o m 11 to 49 years ; 4 had a diagnosis of centrencephalic seizures, had focal " t e m p o r a l l o b e " seizures, and 3 had p r e d o m i n a n t l y f r o n t a l or Jackson~an attacks; one had occipital E E G focus and in B.M

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Fig. 2 B. M., a 37-year-old housewife with warningless automatisms and occasional major seizures, only partially controlled by drug therapy. Sleep EEG demonstrate left anterior temporal spiking. a. First presentation of CS-US, little change to CS (minimal slowing on left) medium voltage repetitive response to flickered light (US) with latency of one sec. b. Twelfth presentation of CS-US, delayed alpha blocking to CS, medium voltage repetitive response (driving) to US, latency 0.1 sec. c. Slow and sharp potentials over left frontal and temporal region to differential tone on fourth presentation. d. Slow and sharp activity over left hemisphere more marked over frontal and temporal regions to fifth presentation of unreinforeed CS. three patients no persistent E E G focus has been determined, The results of conditioning studies in group I I are summarized in g r a p h I I I . The findings again indicate that a significant increase in p a r o x y s m a l responses occurs d u r i n g the stimulus situations designated " i n h i b i t o r y " , (e.g., differentiation and extinction) com-

forced stimuli presented to each patient. Since, however, the differential, extinction and trace procedures follow a n u m b e r of presentations o f CS-US, it was considered t h a t fatigue and subclinical drowsing d u r i n g the latter p a r t of the conditioning session might be responsible for the high incidence of pathological response to the unreinforeed signals.

EEG CONDITIONING IN EPILEPSY Accordingly, the first sequence of CS-US pairings (consisting of 10-11 consecutive randomly spaced CS-US signals) and the first sequence of DS signals (consisting of 6 consecutive randomly spaced unreinforced tones) are eliminated from the tabulation. The tabulated results include the latter two-thirds of each experimental session during which approximately equal numbers of CS-US, DS and CS-O signals are given. Analysis of the EEGs was limited to visual inspection. A significant difference in the nature of the E E G response to the CS compared with that to the unreinforced tone signals (DS and CS-O) indicates that a degree of conditioning and differentiation has evidently occurred. Thus, arousal or alerting responses (desynchronization, acceleration of EEG) occur to 24.1 per cent of CS and only after 10.6 per cent and 4.6 per cent of differential and extinction signals respectively. Furthermore, there is evidence of topographic shift of the arousal response from an initially diffuse to a primarily occipital position during the conditioning procedure.

The Condi~wned Response Prior to conditioning, patients characteristically react to presentations of the tone to be employed as CS with diffuse flattening of the EEG. Typically, this is best developed initially over the temporal regions bilaterally and occurs nearly simultaneously with presentation of the CS. As the tone is presented repeatedly without reinforcement prior to conditioning, this response drops out - - usually after 3 to 5 trials (habituation of orienting reflex). After several paired presentations of tone and light, the blocking response reappears to the tone, but characteristically is now most marked in the occipital region, i.e., the receptor area of the US. This response is often replaced or preceded by a single theta potential of brief latency, represented principally in the occipital region. In approximately one-half of the subjects the latency for the unconditioned repetitive response tends to diminish during repeated sequential presentations of CS-US (fig. 3). This tendency is interrupted by interpositioning of DS and CS-O or trace sequences (fig. 4).

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The Differential Response Initial presentation of DS following numerous CS-US sequences is associated with diffuse blocking of the background E E G activity. After several trials (never reinforced), the blocking response disappears and augmentation of voltage and relative slowing of frequencies of background activity are noted initially to follow, and subsequently to occur during the DS (fig. 2). Such changes are often associated with epileptiform activity of diffuse or focal character, depending upon the subject's underlying abnormality. Twelve to 14 c/sec, activity resembling sleep spindles emerges in some subjects if repeated DS signals are presented, augmenting the tendency for pathological bursts or focal spikes to occur. Thus, the appearance of drowsiness necessitated the termination of the experiment or discarding the results obtained.

Extinction ( CS-O ) The first presentation of the unreinforced stimulus was typically accompanied by the localized occipital blocking response characteristic of the subject's response to the usual reinforced CS. During the 10 sec. immediately following the unreinforced CS, however, exaggeration of background rhythmic waves or the occurrence of paroxysmal activity was commonly noted. Subsequent CS-O presentations enhanced the incidence of paroxysmal activity during the stimulus (fig. 5). After 4 to 6 such presentations in series, the paroxysmal response disappeared suggesting that both "excitatory" and subsequent "inhibitory" responses are extinguished.

Trace Reflexes Not all patients have been tested with this technique, which was added to our experimental sessions at the suggestion of Dr. Paul MacLean. In the 9 patients studied with this procedure it appears that the trace presentations distinctly accentuate the occurrence of paroxysmal and S-W patterns, particularly during the silent interval. Thus, the trace signal appears to precipitate the type of response associated with the unreinforced

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EEG CONDITIONING IN EPILEPSY stimuli (DS and CS-O). No consistent effect o n t h e strength of the subsequent UR (whether S-W or driving) was noted by interposing the trace interval, although the latency for the appearance of the UR was strikingly lengthened by this procedure in several patients (fig. 4). DISCUSSION Several reports in the literature indicate that conditioning of epileptiform E E G activity has been accomplished in animals and in man. There is some evidence for conditioning of cortical strychnine spikes (Shagass 1941) and of hypersynchronous discharge in animals (Naquct and Morrell 1956; Morrell and Naquet 1957). Gastaut, Regis, Dongier and Roger (1956) have reported success with classical conditioning of S-W activity in two human subjects. Recent reports by lV[orrell and Jasper (1956), Jouvet (1956), and Yoshii, Pruvot and Gastaut (1957) deal with conditioning of a repetitive EEG response to photic stimulation in animals. The limitation of our investigation to scalp recording and visual EEG analysis as well as the use of epileptic subjects could be factors in our inability to obtain definitive or consistent conditioned photic driving. The fact that all subjects were receiving anti-convulsant medication may have interfered with conditioning of the EEG response. However, Walter (1958) indicates similar inability to condition photic driving in normal human subjects, recording both from scalp and with implanted electrodes, utilizing a frequency analyser and toposcopic methods of detection. lYlorrell (1957) has noted that the conditioned repetitive response in monkeys is fleeting in occurrence during the course of elaboration of what he designates the final form of the CR, a localized occipital blocking

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response. In our subjects a frequency specific repetitive response was never persistently elicited by the CS although the suggestion of a conditioned repetitive response might occur during 2 or 3 CS presentations in a single session. We, too, then are forced to consider the appearance of the local arousal pattern to the CS evidence of a form of conditioned response. Gantt (1953) has pointed out that the conditioned response may differ considerably from the original reaction on the basis of which it was formed. He suggests that conditioning is a "filtering process rather than a duplication in toto" of the unconditioned response. Various explanations of the failure of S-W to be linked to the CS can be contemplated: (1) the occurrence of S-W per se may disrupt cerebral functions essential to learning or memory as suggested by Walter (1950), and as is implicit in Penfield's concept of a functional centrencephalic system requisite for memory recording (1954); (2) simple contiguity of the conditioned stimulus (tone) and US (flickering light) may be insufficient to establish a sustained cerebral connection (conditional reflex) possibly because the S-W serves no adaptive purpose, i.e., meets no need for "drive reduction" (Hull 1951). The second conclusion from our study is that the differential stimulus, unreinforced CS, and trace stimuli all strikingly potentiate pathological (paroxysmal slow, sharp or S-W) activity compared with the effects of the CS. This effect does not appear to be a result of fatigue or drowsing. Conditional " i n t e r n a l inhibition" as defined by Pavlov (1927) is that state induced by differential stimuli (differentiation), unreinforced conditioned stimuli (extinction), and widening of the CS-US interval .(retardation). It is strictly in relation to these three experimental conditions that the word "inhi-

Fig. 3 R. C., a 40-year-old unemployedmale with frequent adversive seizures. a. Initial presentation of CS-US is accompanied by little change in the appearance of the record during sounding of the tone, delayed repetitive response at half the frequency of the flickered light to the US.

b. Seventh presentation of paired CS-US shows relative blocking of background activity to CS, diminished latency for appearance of repetitive response to US. c. In contrast to the blocking or LCarousal" response to CS in stimulus (b) above, the differential stimulus evokes a relative enhancement of background alpha.

JANICE R. STEVENS

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Fig. 5 E. B., 3/-year-old housewife with history of focal sensorimotor attacks affecting left face and pharynx since adolescence. Well controlled on anticonvulsants. a. Tenth presentation of CS-US. Slight acceleration of frequency and reduction of amplitude during tone. Medium voltage occipital driving to light, more marked on left than right. b. Sixth presentation of differential tone. Instead of relative acceleration and amplitude decrement as to CS (see a), there is voltage augmentation and relative slowing to the differential tone (DS). e. Initial presentation of unreinforeed tone (CS-0) 40 sec. after (b). Again~ relative blocking is noted as with CS-US #10 illustrated above in (a). However, one sec. after termination of the unreinforced CS, a brief hypersynchrony and slowing occurs over both hemispheres, with maximum amplitude in the occipital regions. d. The second presentation of the unreinforced CS (CS-O2) 20 sec. following (e) is accompanied by a brief paroxysmal slow discharge during the signal, maximum in the right frontal and temporal regions (area of patient's pathological EEG focus during conventional studies).

Fig. 4 H. L., a 42-year-old woman with long history of focal sensorimotor attacks following an evident childhood cerebral vascular accident with resultant right hemiparesis. Marked asymmetry of the EEG is evident with absent alpha development over left hemisphere and small left occipital sharp waves. a. Twenty-second paired presentation of CS-US demonstrating delayed alpha blocking to tone over the right occiput, clear onset of the unconditioned repetitive response 0.2 see. after flicker is begun. b. Trace trial, no alpha blocking to CS, modest enhancement of alpha during silent interval between CS and US, and delayed unconditioned repetitive response (latency 1") to light following trace interval. c. Trace reflex. No evident change in record during CS, moderate increase in amplitude and rhythmicity in interval preceding US with frankly paroxysmal slow potential just preeeding the flickered light. Latency for UR - - 0.35 see.

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. I A N I C E R. s T E V E N S

bition" is used in this report. As shown by Jasper, Ricci and Doane (1958 a, b), "inhibition" in this Pavlovian sense cannot be supposed to predict the activity state of cortical or subcortical neurones. There is, however, some evidence to suggest that "conditional inhibition", as above defined, is associated with a tendency for augmentation of rhythmic background rhythms of the EEG, hypersynchrony of alpha, appearance of slowing, and finally emergence of spindles suggestive of drowsiness and sleep (Jasper and Shagass 1941; Motokawa and Huzimori 1949; Jouvet 1956; Gastaut et al. 1957; Rusinov-Smirnov 1957; Rowland 1957; Yoshii, Pruvut and Gastaut 1957; Anokhin 1958; Kogan 1958; Liranov 1958; Roitbak 1958). Grindell and Spirin report from Rusinov's laboratory the occurrence of delta waves in the EEG during the development of differentiation in man and the appearance of "exalted alpha waves in the occipital region which sometimes manifest signs of epileptoid impulses" (Rusinov and Rabinoviteh 1958). It is of further interest to note that during the state of "conditional inhibition" as defined above, Roitbak (1958) describes exaggeration of the primary evoked response. That procedures leading to extinction, differentiation, and retarded response may be interpreted as other than " i n h i b i t o r y " must also be considered. As Boguslavsky (1958) has pointed out in reference to conditioned defense reflexes in animals, occasional omissions of the unconditioned stimulus (in this instance an electric shock) " l e f t the animal without a cue for resumption of normal activity". Under such conditions behavior became agitated and there was prompt extinction of the conditioned response. Lack of reinforcement may leave the animal in a state of unfulfilled expectancy productive in itself of heightened excitability. Such a "conditioned expectancy" nmy represent the mental state associated with non-reinforcement in certain conditioning situations classically designated "inhibitory". That such a "conditioned expectancy" may be a stress which accounts for the increase in paroxysmal activity to unreinforeed stimuli in our epileptic group is a hypothesis requiring further investigation.

11 does appeal, that during this contrived state of absent reinforcement we discover a meehanism leading to a decreased threshold for paroxysmal EEG activity. That this state is associated with an inereased tendency to elinieal seizures has not been shown by our studies. Induction of relative slowing of eerebral frequencies by a number of methods ineluding "eonditioned inhibition" may favor appearance of spike and paroxysmal activity over cerebral areas sufficient to produee visible changes in the scalp trace. SUMMARY

Classical conditioning techniques were employed to investigate the effect of eonditioned "excitation" and "inhibition" upon the occurrence of epileptiform activity in the EEG of patients with convulsive disorders. Four patients with high voltage spike-wave response regularly elicited by photie stimulation were subjected to repeated pairing of the S-W inducing light with a neutral tone. Despite more than 500 paired presentations of the two signals, and persistence of the S-W response to the light, no evidence of conditioning the S-W to follow the tone was obtained. However, presentation of tone signals unreinforced by light (differential stimulus and extinction of CS) after numerous paired sound-light trials resulted in a highly signifieant increase in occurrence of S-W to the unreinforced stimuli. Nineteen epileptic patients with sustained photic driving responses to specific flash frequencies were subjected to a conditioning procedure in which the attempt was made to condition the occipital driving response to follow a previously neutral tone. Little evidence of conditioned driving was obrained. However, again the unreinforeed signals (differential and extinction stimuli) provoked a significant increase in incidence of sharp, paroxysmal, slow and epileptiform changes in the EEG. Retardation of the light stimulus (Trace reflex) also enhanced the propensity to pathological EEG discharge in both groups. These EEG abnormalities were similar to the focal or diffuse pathological findings noted from these patients (luring previous EEG studies.

EEG CONDITIONING I N EPILEPSY

The exaggeration of paroxysmal activity by unreinforced stimuli is considered in relation to theories of "conditioned expectation" and Pavlovian "conditional inhibition". Slowing of scalp frequencies during non-reinforcement may be a crucial factor contributing to the potentiation of abnormal EEG patterns.

443

differentiale oder AuslSschungs-Reize einen signifikanten Anstieg im Auftreten steiler paroxysmaler langsamer und epileptiformer EEG-Veriindernngen. Die Verstiirkung der paroxysmalen Aktivit~it durch nichtverstiirkte Reize wird erSrtert im Zusammenhang mit den Theorien der "bedingten Erwartung" und der Pawlow 'schen "bedingten Hemmung".

R~SUM]~ Les techniques classiques de conditionnement ont dt~ employees pour ~tudier l'effet d'excitation >>et <>conditionn~ sur l'apparition de l'aetivit~ ~pileptiforme dans I ' E E G de malades avec crises eonvulsiyes. Chez quatre malades avee pointe-onde la stimulation photique, il a dt~ impossible de conditionner cctte r~ponse £ un ton neutre en ddpit de 500 stimulations jumeldes. U n signal positif non renforc~ durant l'extinetion augmente la r~ponse pointe-onde. Chez 19 malades ~pileptiques avcc entrainement photique aueune rdponse conditionn~e n'a pu ~tre ~tablie avec an ton nentre. Toutefois, les stimuli diffdrentiels non renforcds ou d'cxtinction provoquent une augmentation significative dans le nombre de bouff~es aigu~s de changements ~pileptiformes dans I'EEG. L'augmentation de l'activit~ paroxystique par des stimuli non renforeds est raise en relation avec les thdories de <> et de <> de Pavlov. ZUSAMMENFASSUNG

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