Event-related potentials evoked by sensory stimulation in normal, mentally retarded and autistic children

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Electroencephalography and Clinical Neurophysiology, 1980, 48:140--153

© Elsevier/North-Holland Scientific Publishers, Ltd.

EVENT-RELATED POTENTIALS EVOKED BY SENSORY STIMULATION IN NORMAL, MENTALLY RETARDED AND AUTISTIC CHILDREN J. MARTINEAU, F. LAFFONT, N. BRUNEAU 1, S. ROUX and G. LELORD Laboratoire de Neurophysiologie du Conditionnement, Groupe "'Cerveau et Circulation', C.H.U. Bretouneau, 37044 Tours C$dex (France)

(Accepted for publication: May 14, 1979) In severely mentally retarded children it is often difficult to state the role played respectively by autism and by mental deficit. Clinical examination, psychologic tests and behavioural rating scales (Rimland 1971) are the tools usually employed. More recently, some data have emerged from brain evoked potential research. Chalke and Ertl (1965) noted that the latency of the visual evoked potentials (EPs) was greater in subjects with low IQ. This is also true for the auditory EP (Nodar and Graham 1968). Mongoloid subjects have been noted to have larger EP amplitudes than normal subjects (Barnet and Lodge 1967). Using conditioning techniques, Lelord et al. (1967, 1976) reported small amplitudes of conditioned EPs in mentally retarded subjects. Different investigators have attempted to study the contingent negative variation (CNV) in mentally retarded children. Low and Stoilen (1973) showed that CNV does not reflect minimal brain dysfunction, 'school failure' or specific disorders. Cohen (1973) reported CNV to be present to a greater degree in control children than in patients with learning disabilities. Karrer and Ivins (1976) found a small frontal CNV and lack of topographical differentiation in mentally retarded children. Otto et al. (1976) demonstrated that aphasic children showed greater positivity than control children during warning and recognizing intervals. 1 Attach~e de recherches, I.N.S.E.R.M.

Similar studies were performed on autistic children. Barnet (1979) recently reviewed the results concerning EPs in these patients. In most of them, EPs were smaller (Small et al. 1971; Ornitz et al. 1972; Lelord et al. 1973; Saletu et al. 1975} and were n o t elicited as frequently (Walter 1969; Lelord et al. 1973) in autistic as in normal children. Some discrepancies appear in the results concerning CNVs. Walter (1969} reported the absence of CNV in autistic children, while Small et al, (1971}, using slides as a visual stimulus, found CNVs in autistic as well as in control subjects. Lelord et al. (1973), coupling sensory stimuli, observed large CNVs in autistic children. L a f f o n t et al. (1973, 1979), coupling sound and ankle reflex, reported similar results. The purpose of the present study was to compare the characteristics of event-related potential (ERP) conditioning in mentally retarded and autistic children to find, if possible, different electrophysiological data for emotional troubles and for cognitive disturbances.

Methods A p p a r a t u s and p r o c e d u r e

The subject was isolated in a dark soundproof room and sat in a comfortable armchair. Silver-silver chloride electrodes were placed on the scalp (vertex, right frontal, temporal

ERPs IN MENTALLY RETARDED AND AUTISTIC CHILDREN and occipital areas). The c o m m o n reference was placed on the left ear lobe. The recording system allowed a bandwidth from 0.1 to 100 Hz with 3 dB attenuation. The conditioned stimulus was a brief (4 msec) sound at 1 kHz, 25 dB above the average threshold of 3 normally hearing adults, the unconditioned stimulus a 0.1 msec light flash from a lamp placed 40 cm in front of the subject's eyes and giving 1200 Lux. No instruction was given to either the normal subjects or the patients since it could not be understood by the severely retarded children. The background EEG was recorded during the whole experiment. For all subjects stimuli were only delivered when muscle artifacts were absent. EPs were averaged in groups of 20 trials with a 400-channel digital computer and recorded on an X-Y plotter. The epoch was 2 sec. Two electrodes positioned respectively 1 cm above and 1 cm below the external canthus of each eye recorded the EOG. It could be recorded in less than half the subjects because t h e y usually would not tolerate electrodes near the eyes. Generally each subject had 2 h sessions. During each session there were 10 series of 20 trials. Trials were given at random intervals, varying from 4 to 30 sec. In the first 2 series of the first session, sound was given alone to obtain habituation ('sound alone', S). In the n e x t 16 series (8 during the first session, 8 during the second), light was presented 800 msec after sound to produce conditioning ('sound and light', SL). In the last 2 series of the second session, sound was again given alone so that extinction of the conditioned responses could be studied (sound after SL, S post SL).

Subjects Two studies were performed, in which the clinical teams worked independently of the laboratory researchers. In the first study, a group of 125 children (65 boys, age ranging from 0 to 15 years) was considered. This group included 35 deeply

141

disturbed children, 35 moderately retarded children with more or less severe behavioural problems, 12 children with slight mental retardation and few emotional problems. Forty-three normal children were also considered: 27 (4--13 years) were students in public schools; the 16 youngest (0--4 years) were still at home with their parents. The clinical characteristics of each child were studied by a medical and sociological team, using questions which included response modalities (e.g., 'present', 'absent', 'intense'). Each response modality constituted a characteristic. A total of 65 clinical characteristics was delineated for each child: lack of meaningful interpersonal relationships, absent (01), present (02), severe (03); need for sameness (04, 05), withdrawal from contact (06, 07), p s y c h o m o t o r symptoms (08, 09) which, when intense, resembled catatonia (10); speech difficulties (11, 12), when intense no speech (13); anxiety (14, 15) accompanied by agitation (16); perturbed activity (17, 18), when intense incoherent (19), or with total lack of initiative (20); paradoxical agility (21, 22); sensitivity to noise (23, 24); mood difficulties {25, 26), excitement {27), depression (28), atonia (29); eating problems (30, 31); problems with bladder and bowel control (32, 33), perturbed sleep (34, 35); problems in sexual behaviour (36, 37); aggressiveness absent (38), directed toward others {39), toward self (40); schooling possible (41), impossible (42); absence of psychological or psyc h o m o t o r abnormalities (43}; difficulties beginning after birth (44), at birth (45); neurological signs (46,47); mental deficiency (48), complicated (49), isolated (50); adaptation to the examining situation (51, 52); IQ: greater than 80 (53), between 60 and 80 (54), 40 and 60 (55), 20 and 40 (56), lower than 20 (57); impossible to examine (58); homogeneous (59), non-homogeneous (60), intermediate (61); age from 0 to 2 years (62), 2--4 years (63), 4--6 years (64), 7--13 years (65). In a second study, 3 homogeneous clinical groups were defined by the clinicians. The first group was composed of 23 autis-

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tic children with ages ranging from 4.5 to 14 years (average age 9, 13 gifts). They exhibited intense autistic behaviour, withdrew from contact, related better to objects than to other humans, showed manifestations of perceptual hypersensitivity, insisted on the 'sameness' of the environment. All of them had manneristic behaviour, stereotypies, most of them exhibited periods of repetitive and destructive activity, 8 showed self-inflicted injury and 4 automutilation; most of them had problems with feeding and sleeping. In all cases neurological examination was negative and the children were well coordinated. Speech had failed to develop in 17 of them, 2 had non-communicative speech, the 4 others had poor speech with echolalia. The standard EEG was normal or less mature than the normal chronological age. In no case were there signs of epilepsy. The Termann Merril test was performed on 8 children. The resulting IQs ranged from 20 to 45; the other children could not relate and attend well enough for testing. The second group consisted of 25 mentally retarded children from 5 to 15 years (average age 10, 9 girls) with IQs between 35 and 65. Mental retardation appeared as the principal phenomenon. History of retardation was found in 15 of the families. Few pathological personal antecedents were found: 2 cases of prematurity, 2 of reanimation at birth and 2 of convulsions. Slow p s y c h o m o t o r development was noted in all (first words, first steps). The children selected had a minimum of behavioural problems except for passiveness and inhibition in 2 cases, restlessness in 3 cases, anxiety with tendency toward depression in 2 cases. Neurological examination was normal except for clumsiness and coordination difficulties in 6 cases. Five children had difficulties in reading and writing, 3 were not well lateralized. Three children had Down's syndrome (confirmed by karyotype). In others there were no important morphological abnormalities: two h y p o t r o p h y , one megacolon, one club-foot, one scaphocephaly. The EEG showed slow waves, rather abundant in 5

J. M A R T I N E A U ET AL.

subjects in whom some pathological antecedents were found. Three among those subjects exhibited spikes during hyperpnoea and interm i t t e n t light stimulation. Two-thirds of the children were capable of acquiring reading and writing. The third group was made up of 25 normal children, from 4 to 13 years (average age 8.6; 16 girls) brought to the laboratory by their parents. All of them were students in public schools. Measures

EPs to sound alone of the habituation series (S), to coupled sound and light of SL trials and to sound alone of extinction series after SL trials exhibited different wave forms, amplitudes and scalp localizations. For each series of stimuli, the responses where studied at the vertex and in the occipital area in 3 windows (Fig. 1): In the first 100 msec following stimulation, only positive or negative components arising in the 50 100 msec interval were analysed (the bandpass of our recording system precluded the study of earlier components). These will be further mentioned as the '50 100' potentials, which generally correspond to P1. $

L

I

~OuV

• 200 rns

Fig, 1. Idealized evoked potentials (EPs) and slow potentials (SPs) during coupling of sound (S) and light (L). The tracing represents the average responses to 20 stimuli. A m p l i t u d e s are measured in 3 windows: (1) first 100 msec, 80--100 El}s; (2) n e x t 300 msee, middle El}s; (3) last 400 msee, SPs, Negative deflections are upward.

ERPs IN MENTALLY RETARDED AND AUTISTIC CHILDREN In the 100--400 msec interval following stimulation, peak-to-peak amplitudes were measured between the negative c o m p o n e n t N1 (or N120) and the most prominent positive peak P2 (P200 or P300). They will be termed 'middle potentials' (Buchsbaum 1977). In the 400--800 msec interval following stimulation, event-related slow potentials (ERSPs) were analysed. They will be referred to as the 'slow potentials' (SPs). Amplitude. Each potential was measured from peak to peak for the responses f o u n d in the first and the second windows. A horizontal baseline passing equidistant to the extreme peaks recorded during the first 100 msec served as reference to measure responses in the third window. In the first two windows the potentials were generally polyphasic. In certain subjects, however, potentials in the second window were a single middle slow wave whose amplitude was measured from the baseline previously defined. The positive or negative polarity of SPs was considered in the 400--800 msec window. Usually, different SP polarities were f o u n d at the vertex and in the occipital area (localized SPs): SPs following the paired sound were mainly negative at Cz and mainly positive at the occipital electrodes. SPs were considered as 'generalized' when they showed the same polarity at the vertex and in the occipital area. Certain subjects displayed r h y t h m i c phen o m e n a in response to stimulation. During and after SL trials the phenomena usually observed were amplitude enhancem e n t of middle potentials (100--400 msec) evoked by the sound at the vertex and in the occipital region, and amplitude enhancement of the slow negative potentials (400--800 msec) similar to CNVs at the vertex. The amplitudes of responses to sound during and after SL trials were compared to those of the responses to the 2nd habituation sound series ($2). There was conditioning if the coupling augmented the amplitude of the response to $2. The amplitudes of the (conditioned)

143

responses to S during and after SL were also compared to those of the (unconditioned) responses to L during SL trials. During (extinction) series after SL, the sound alone was sometimes followed after a delay of about 7 0 0 - 8 0 0 msec by a response 'in the absence' of light. This p h e n o m e n o n is usually called 'conditioning to time' or more recently 'emitted potential'. The absolute amplitude values found for each child were compared to the mean values (m) for normal children calculated during an earlier study (Lelord et al. 1976), which were taken as reference values. The amplitude of each response was considered as equal to m if it was within m + 2o, larger if it was > m + 2o, smaller if it was < m -- 20. Percentage. the responses were counted in relation to the number of records taken in a given group. Results were presented in percentages but ×2 were computed in absolute numbers. Criteria for presence or absence of responses corresponded to whether the amplitude measures were higher or lower than 4 pV (peak to peak for EPs, peak to baseline for SPs). In study I, the responses evoked by sound alone were considered as present if they existed in S1 or $2 habituation series, absent if t h e y did n o t exist in $1 or $2. For responses to coupled sound, conditioned potentials (S of coupled SL greater than $2) were counted at the vertex or in the occipital region. They could be 'absent', 'few' if n was ~<6 o u t o f 16 records or ' m a n y ' if n was >6. For the response to light, the middle EP potentials (window 2) were 'regular' if n was > 1 2 o u t of 16 records or 'irregular' if n was ~<12. SPs were: 'absent', 'few' if n was < 6 out of 16 records, or ' m a n y ' if n was > 6 . The electrophysiological data were studied for each child using these response modality judgements (absent, present, few, many, regul a r . . . ). A total of 88 electrophysiological items were collected. Before coupling (habituation), middle EPs

144 (100--400 msec) evoked by sound at the vertex might be present (A0), absent (A1), replaced by rhythmic phenomena (A2) or by an SP (A3). The same information was sought for in the occipital area (B0, B1, B2, B3). A similar classification was made for 50--100 EPs: CO, C1, C2 and DO, D1, D2. After 400 msec SPs might be absent (E0) or present (El) at the vertex or (F0) (F1) at the occiput, rhythmic phenomena might be present (G0) or absent (G1). During coupling middle potentials evoked by light at the occiput might be regular (H0) or irregular (H1), their amplitude equal to m (I0), larger (I1) or smaller (I2). It was the same for the amplitudes at the vertex (J0, J1, J2). 50--100 Ees at the occiput might be present (K0), absent (K1), replaced by rhythmic phenomena (K2). After 400 msec rhythmic phenomena might be many (L0) or few (L1), SPs might be few (M0) or many: negative (M1), biphasic negative-positive (M2), positive (M3) at the occiput, or at the vertex (NO, N1, N2, N3). Coupling usually enhanced amplitude of the responses to sound (EP conditioning). Conditioned middle EPs might be few (O0) or many (O1) at the vertex, many (e0), few ( e l ) or absent (e2) or replaced by rhythmic phenomena (e3) at the occiput. Occipital conditioned middle EPs might be many (Q0), few (Q1) or absent (Q2). It was the same at the vertex (R0, R1, R2). Enhanced conditioned middle EPs at the occiput might be similar to the visual 100--400 EP (SO), to the auditory 100--400 EP ($1), different from both these EPs ($3), replaced by rhythmic phenomena ($2), absent (S4). Conditioned (400--800) SPs, either at the vertex or the occiput, might be absent (TO), few (T1) or many (T2). They could be localized at the vertex (U0, U1, U2), the occiput (V0, V1, V2) or generalized (W0, Wl, W2) and classified similarly. These SPs might be predominantly negative (X0) or positive (X1). Rhythmic conditioned phenomena might be many (Y0), few (Y1) or absent (Y2). After coupling (extinction) a conditioned

J. MARTINEAU ET AL. response might be still present (Z0) or absent (Zl). Comparison of conditioned responses during and after coupling and unconditioned responses showed that conditioned responses might be smaller (AA) or larger (AB) than unconditioned responses, or quite absent (nc). After coupling, conditioning 'to time' might be absent (BA), take the form of rhythmic phenomena (BB), SPs (BC), EPs (BD), mixed SPs and rhythmic phenomena (BE), mixed SPs and EPs (BG), mixed SPs, rhythmic phenomena and EPs (BH}.

Analysis of relationships A factorial analysis of relationships was done in study I for the 125 children with a UNIVAC 1108 computer. Factorial analysis of correspondences is a branch of multivariate analysis (Benzecri 1976). Letting I be the s e t of electrophysiological criteria (i) and J the collection of clinical characteristics (j), the two groups were compared in order to establish a contingency table, n i j is the number of times that we obtained the modality i of a given electrophysiological criterion concurrent with finding the modality j of a clinical characteristic. The principle of factorial analysis of correspondences is founded on considering a p-dimensional space Rj where a cloud of points N (I) represents the values of the ensemble I. The coordinates of points N (I} found in the space Rj are obtained by a probabilistic transformation of the values of the initial table. The space Rj is established in such a manner as to measure the proximity amongst the cloud of points to which can be attributed a certain mass. Radiating from its centre of gravity, the cloud has principal directions of protraction (factorial axes) which are determined as being the principal axes of inertia. It can be shown that successive factorial axes (P = I × J) are orthogonal two by two. Considering a planar representation, the pro-

ERPs IN MENTALLY RETARDED AND AUTISTIC CHILDREN jection on a plane of points of the cloud N (I) in the space Rj results in a map of electrophysiological criteria. The axes can be combined in such a way as to visualize different subjacent structures. Following the same principle, a cloud of points N (J) can also be considered in the space R1 of n dimensions; the m e t h o d is identical with respect to the extraction of factorial axes. The representations of clinical traits and electrophysiological data were made symmetrical to allow the passage from one representation to another. The t w o symmetrical representations were then superimposed on a t w o dimensional space. The relationships between electrophysiological data and clinical traits were expressed by the proximities of numbers and letters which respectively represented them.

Results

The results of the t w o studies supplemented each other.

(I) Analysis of relationships The two-dimensional space of factorial axes 1 and 2 represented 53.3% of the information. A progression for the electrophysiological factors as well as for the clinical traits could be seen along the second axis. This progression demonstrated 4 bands approximately equal and distributed from t o p to b o t t o m (Fig. 2). Area I was characterized by: many generalized conditioned SPs to S of coupled SL, conditioned SPs larger than unconditioned SPs; SPs and EPs conditioned 'to time' during extinction, many vertex visual SPs, irregular occipital visual EPs, small vertex visual EPs. Clinical traits were: withdrawal from contact, need for sameness, sensitivity to noise, catatonia, paradoxical agility, complicated mental deficiency, IQ between 20 and 40, total lack of initiative.

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Area II was characterized by the absence of conditioned response to S of SL and to S post SL: middle EPs during coupled SL were few at the vertex (O0), absent at the occiput (P2, Q2); SPs during coupled SL were absent (TO); rhythmic phenomena during coupled SL were absent (Y2); conditioned response to S post SL was absent (Z1). Conditioning 'to time' was present during extinction (BC, BB); occipital visual EPs were Small (I2). Clinical traits were: schooling impossible (42), non-homogeneous IQ (60}, anxiety with agitation (16), m o o d difficulties (26), excitement (27), neurological signs (47), lack of meaningful interpersonal relationships {02), p s y c h o m o t o r symptoms (09), speech difficulties (12). Area III could be divided into 2 subareas: superior (a) and inferior (b). In subarea (a) there were many conditioned SPs localized either at the vertex or at the occiput, few conditioned EPs during SL series, EPs conditioned 'to time' during extinction series. 50--100 EPs were evoked by S alone in the occipital region. Clinical traits were IQs between 40 and 60, depression, atonia, perturbed activity and aggressiveness directed toward others. In subarea (b) there were few conditioned EPs and few conditioned SPs during SL series, b u t conditioned EPs or SPs 'to time' after SL series. More positive than negative SPs were present. Visual EPs were regular and their amplitude was average. Clinical traits were isolated mental deficiency, absence of need for sameness, absence of aggressiveness, no perturbed sleep, etc. Area IV was characterized by many conditioned rhythmic potentials and EPs at the vertex and in the occipital region. Generalized conditioned SPs were absent: conditioned SPs were localized at the vertex. There was no conditioning to t i m e . Visual EP amplitudes were large at the vertex and average in the occipital region. Clinical traits were: absence of mental deficiency, absence of withdrawal from contact, absence of p s y c h o m o t o r symptoms, absence of speech difficulties, absence of anxiety, e t c . . . T h e points corresponding

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J. M A R T I N E A U ET AL.

4¢~,,AREAS

l II TITa-9~ AREA I

lllb BC

IV

BG : HI : AB : J2 : N2 : W2 :

conditioning "to time" (SPs + EPs) i r r e g u l a r occipital visual EP conditioned SPs larger than SPs to L smo11 vertex visual EPs many vertex visual SPs many generalized conditioned SPs

10 24 05 07 19 33 31 56 35 49 22 20

: : : : : : : : : : : :

catatonia s e n s i t i v i t y to noise need f o r sameness withdrawal frOm contact incoherent a c t i v i t y lack o f sphincter control e a t i n g problems IQ between 20 to 40 perturbed sleep complicated mental deficiency paradoxal a g i l i t y t o t a l lack o f i n i t i a t i v e

EP : evoked potentials SP : slow potentials ER : evoked responses

S : sound L : light SL : coupled Sound and l i q h t

IO 24 H1 O7

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05 AB 33

31 35

56 J2

49

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N2 20

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NO 41 U2

12 II 48 BA

Y0

AA

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10

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PO : many occipital conditioned EPs Ol : many vertex conditioned EP WO : no conditioned generalized SPs NO : few vertex visual SP U? : many vertex conditioned SPs BA : no c o n d i t i o n i n g "to time" YO : mony conditioned rythmical gs AA : cond, ER smal]er than uncond ER HI : many occipita] visual neqative S ~ I0 : mean occipital visual [Ps LO :~many rythmical occipital visual SP J1 : large vertex visual EPs GO : rhythmical auditive EPs 14 Ol 2~; 08 41 17

: : : : : : ll : 48 :

no apparent anxiety no withdrawal from contact no mood d i f f i c u l t i e s no psychomotor symptoms schooling possible no perturbed a c t i v i t y c o r r e c t speech no mental d e f i c i e n c y

AREA IV

Fig. 2. Analysis of relationships. Full r e p r e s e n t a t i o n o f areas I a n d IV. T h e r e l a t i o n s h i p s were given by t h e p r o x i m ities o f letters a n d n u m b e r s w h i c h respectively r e p r e s e n t e d e l e c t r o p h y s i o l o g i c a l c h a r a c t e r i s t i c s a n d clinical traits. A t t o p left: r e d u c e d r e p r e s e n t a t i o n o f t h e 4 p r o j e c t i o n areas along axis I.

to age g r o u p s 0 - - 2 y e a r s a n d 2--4 y e a r s were p r o j e c t e d t o t h e e x t r e m e l e f t o f area III, to subarea a and subarea b respectively.

(II) Comparison between groups In t h e s e c o n d s t u d y , significance differences in t h e n u m b e r a n d in t h e a m p l i t u d e o f

EPs a n d SPs were o b s e r v e d a m o n g t h e 3 groups. T h e 0.02 level o f c o n f i d e n c e was accepted. 50--100 EPs. O b s e r v e d d i f f e r e n c e s f o r EPs m e a s u r e d in t h e first w i n d o w , a f t e r SL series as well as a f t e r L, w e r e n o t statistically signific a n t in t h e 3 groups. I t s h o u l d be n o t e d t h a t

E R P s IN M E N T A L L Y R E T A R D E D A N D A U T I S T I C C H I L D R E N

for responses to S alone, the presence of negative peaks in the occipital area seemed greater for the t w o patient groups, and the peak-to-peak amplitude greater in autistic children than in normal children. This phenomenon disappeared during SL trials, thus eliminating the possibility of 50--100 EP con-

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ditioning in the pathological groups. Middle (100--400) EPs. As summarized in Table I, the number of conditioned auditory EPs after S of SL series was larger in normals. Very significant differences were found at the vertex and in the occipital region between the normal group and the autistic group (X2 = 58

TABLE I P e r c e n t a g e a n d a m p l i t u d e o f m i d d l e p o t e n t i a l s and slow p o t e n t i a l s . Groups

Middle p o t e n t i a l s ( 1 0 0 - - 4 0 0 ) Vertex

Occipital

S alone

S o f SL

S a f t e r SL

L

S alone

S o f SL

S a f t e r SL

L

88 1.4 80 1.7 68

82.5 2.9* 87 58** 63

84 6.6* 80 4.8 64

91 8.4* 96 19.8"* 87

33 0.6 56 1.5 43

33 30.5** 52 50** 26

29 0.4 54 3.1 32

92 4.5* 96 9.7* 90

R t N t A

16 1.2 18 0.5 14

14 1.7 17 1.3 14

13.5 1 15 1.5 12

24 0.1 24 2.6* 17

10 1.8 14.5 1.1 11

11.5 3* 17 1.2 14.5

11.5 2.7* 16.5 2.8* 11

17 6.4** 30 5.1"* 16.5

Groups

G e n e r a l i z e d slow p o t e n t i a l s ( 4 0 0 - - 8 0 0 )

Percen~s R Chi2 N Chi2 A

Amplitu~ ~

Negative

Positive

S alone

S o f SL

6 2 16 0.5 11

5 1.3 7 19 ** 18

S a f t e r SL

L

S alone

S o f SL

S a f t e r SL

L

18

6.5 0.3 7.5 1.7 10

17 2 8 0.5 9

14 13 ** 6.5 13 ** 15

21 3.5 8 0.3 11

8.7 7.4 * 4 35 ** 17

14

12.5 2.6 * 17 1.3 22

8 2.4 * 11.5 0.9 15

12.5 0.28 13 1.6 16

12.5 1.3 11 0.6 12

12 0.4 11 2.3 * 20

Percentages R Chi 2 N Chi 2 A

0 0

Amplitudes (p V) R t N t A

10 0.7 14 0.3 15

11 1.1 12 1.4 16

R = r e t a r d e d ; N = n o r m a l s ; A = autistics; S = s o u n d ; L = light; SL = c o u p l e d s o u n d a n d light; * = P ~ 0.02; ** = P ~ 0.001; t = n o n - p a i r e d t.

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J. MARTINEAU ET AL.

and 50 respectively). Smaller differences were observed in t h e v e r t e x and occipital visual EPs a f t e r light. Visual EP a m p l i t u d e s were larger in the n o r m a l g r o u p t h a n in the m e n t a l l y r e t a r d e d and autistic groups, particularly in t h e occipital region. In the n o r m a l group, t h e a m p l i t u d e o f the occipital EPs e v o k e d b y S alone (14.5 pV), was significantly e n h a n c e d (17 pV) during the coupling o f SL (t, 5.12; df, 17; P < 0.001). This p h e n o m e n o n was a b s e n t in m e n t a l l y r e t a r d e d (t, 0.09; dr, 15; P > 0.10), b u t still present in autistic, children (t, 3.07; dr, 18; P < 0.01). 400--800 SPs. As s h o w n in Table I generalized SPs, negative and positive, were particularly f r e q u e n t in autistic children during coupling SL. Positive potentials were observed in m e n t a l l y r e t a r d e d as well as in autistic chilAU TISTIC

d r e n during S o f SL series, b u t their amplit u d e s were smaller in the r e t a r d e d ones (12.5 /~V versus 16 pV). Table I also shows t h a t f o r the light-evoked positive SPs in autistic and in m e n t a l l y r e t a r d e d children, the a m p l i t u d e was larger in the autistic group. T h e data resulting f r o m the c o m p a r i s o n o f the 3 groups and the analysis o f relationships are s u m m a r i z e d in Fig. 3 which represents 3 individual profiles from 8-year-old children {one autistic, one n o r m a l l y adjusted, one moderately retarded. In the n o r m a l tracings EPs a f t e r S alone are clearly m a r k e d ; t h e i r a m p l i t u d e s are increased by c o u p l i n g SL, and r h y t h m i c p h e n o m e n a a p p e a r a f t e r sound in SL trials. T h e negative SP at the v e r t e x (CNV) is slightly amplified b y coupling SL, and this a m p l i f i c a t i o n persists a f t e r SL: SPs are localized, t h e r e is a phase

NORMAL

I

RETARDED

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1

,

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! I flash |

log ams~ Fig. 3. T h e 3 groups o f individual records s u m m a r i z e t h e principal clinical traits a n d e l e c t r o p h y s i o t o g i c a l characters of the groups. To the left: an autistic child with small conditioned EPs, large conditioned SPs; to the right: a

mentally retarded child with small conditioned EPs, positive conditioned SPs; in the middle: a normal child with regular conditioned EPs and CNV. Conditioning 'to time' is observed in autistic as well as in retarded children. Top traces: habituation; middle: conditioning; bottom : extinction. V, vertex; OC, occipital ; negativity is upward. (Reproduced by permission of D.A. Otto (Ed.), Multidisciplinary Perspectives in Event-related Brain Potential Research. U.S. Government Printing Office, 1979.)

ERPs IN MENTALLY RETARDED AND AUTISTIC CHILDREN inversion between the SP recorded at the vertex and in the occipital area: a negative vertex SP accompanies a positive occipital SP and vice versa. EPs after light are well defined and followed by rhythmicity. There are no conditioned responses 'to time'. In the autistic child's tracing, the potentials evoked by S alone are of small amplitude. They are little increased by coupling SL; however, a generalized conditioned SP of large amplitude is observed during coupling SL and persists after SL. Visual EPs are not large while the SPs which follow light are large. Conditioning 'to time' occurs on both the visual EPs and SPs. The moderately retarded child's tracing is characterized by low voltage EPs after sound, particularly in the occipital area. These occipital potentials are n o t increased during SL or after SL. Coupling produces a low voltage positive SP at the vertex. There is no phase inversion between vertex and occipital SPs. Visual EPs after light are of average amplitude at the vertex. They are followed by generalized positive SPs of average amplitude at the vertex and in the occipital area. Conditioning 'to time' is present.

Discussion Electrophysiological data help differentiate pathological from normal groups, whereas the characteristics that permit distinction of autistic children from retarded children are less evident. Small EP amplitudes have been observed in both autism (Small et al. 1973) and mental retardation (Callaway 1973; Lelord 1976), though the protocol used in these studies does n o t permit the study of EP a s y m m e t r y (Simeon and Itil 1975; Tanguay 1976). 50--100 EPs evoked in the occipital area by sound alone, present more in patients than in normals, confirm Dustman and Beck's observation (1976). Conditioning of EPs after coupling SL,

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which is expressed as an increase in the amplitude of sound EPs in the occipital area, is missing in mentally retarded, and weak in autistic, children. This result is similar to the observation made b y Shipley (1970) who gave sound and light together and recorded facilitation in normal subjects b u t n o t in retarded ones. O n the contrary, the presence of potentials evoked 'by time' both in autisticand retarded children shows a capacity for reproducing temporal sequences. This particular form of acquisition, mentioned b y Popov (1948), Rusinov (1959) and Lelord et al. (1967) in mentally retarded subjects, was more recently analysed as 'emitted potential' (Sutton and Dote 1973; Picton and Hillyard 1974) or 'congruent potential' (Buchsbaum et al. 1974) in normal subjects. This capacity may be a substitute for associative phenomena which fail to appear in these patients. Generalized conditioned SPs, positive or negative, are observed in patients. The enhancement of SPs in autistic children was n o t observed in the CNV experiments of Walter (1969) and Small et al. (1971). This difference in SPs may be due to the absence of a response task and motivation in our study, because enhanced SPs are also observed in experiments using the ankle reflex as an unconditioned stimulus (Laffont 1973). These slow conditioned waves, when they are negative, appear as a generalized negative contingent variation. Their duration is identical with the persistent negative wave (TimsitBerthier 1973). The presence of these slow waves following visual stimulation and their appearance following conditioned sound suggest a diffuse m o t o r c o m p o n e n t of perceptual and associative processes. The origin of these SPs must still be studied. It is interesting to note, however, that they can be reproduced experimentally in normally adapted subjects b y psilocybine (Laffont and Lelord 1971). Enhancement of SPs did n o t seem to be related to ocular movements because the EEG during the trials was without movement artifacts or myograms and ocular movements

150 were minimal. Eye movements were less frequent after sound (seen in 15% of the EEG tracings) than after light (in 90% of the tracings) at the end of a trial. Averaged SPs after the conditioned sound were, however, larger than averaged SPs after light. It can also be noted that the ocular potentials are generally described as large in anterior derivations and small or absent at the occiput. Our generalized conditioned SPs, however, were recorded both at the vertex and in the occipital region. Nevertheless, it appears difficult to use electrophysiological data to distinguish emotional from intellectual disturbances. First, the analysis of correspondences does not permit clear separation, from a clinical point of view, of the characteristics corresponding to autism from those of deep mental deficiency. These characteristics are mixed together in area I (withdrawal from contact and complicated mental deficiency) as well as in area II (neurological signs, schooling impossible and lack of meaningful interpersonal relationship). The electrophysiological analysis evidences the weak EP amplitudes and the absence of EP conditioning in the two areas. Widespread conditioned slow waves are present only in area I. Some signs, however, emerge from the character comparison of areas I--II versus area III of the analysis of correspondences as well as from the comparison of the two groups of children (autistic versus weakly mentally retarded ones) performed in the second study. In the retarded the conditioned SPs are rather positive. Slow small amplitude positive SPs have already been observed in mental retardates by Karrer and Ivins (1976) and by Otto (1976) in aphasic children. Such a positivity has been observed in younger children (Low and Stoilen 1973; Bruneau et al. 1977). It is present in area III of the analysis of relationships and suggests mechanisms related to a lack of maturation, because this area includes the groups from 0 to 4 years (Laffont et al. 1978; Tanguay 1978). In autistic children both studies I and II show the enhancement of either negative or positive SPs.

J. MARTINEAU ET AL. The clearest result is the small amplitude of the middle EPs and the weak conditioning of these responses obtained in sick children. Such a phenomenon is probably due to an attention trouble but perhaps it does not have the same meaning in retarded and autistic children. Some authors have explained the ~roubles of attention in the mentally retarded as due to lowered vigilance (Holden 1970; Crosby 1972) or to incomplete development of intersensory integration (Hertzig and Walter 1975). In autistic children, on the contrary, the attentional disturbances could be linked to a chronically high level of cortical arousal (Hutt and Hutt 1968; Mirsky 1969, Saletu et al. 1975), to a tendency to 'get out sensory inputs' (Ornitz 1974, 1978)2, to interfering responses (Callaway 1970}, to a reducing mechanism as observed in schizophrenia (Buchsbaum and Pfefferbaum 1971 ). The clinical features seem too complex to be related to some neurophysiological mechanisms (Buchsbaum 1977). Some biochemical data are therefore necessary (Schafer and McKean 1975; Arlot et al. 1978). Preliminary observations performed in autistic children suggest that diminution of EP amplitude may be linked to an increase of the dopamine turnover (Lelord et al. 1978).

Summary Evoked potentials (EPs) and slow potentials (SPs) were recorded during two sessions of sound (S) and light (L) conditioning (habituation: S alone; conditioning: coupling of S L; extinction: S alone after SL series). 125 children from 0 to 15 were examined: 82 exhibited signs o f autistic behaviour and/or mental retardation; 43 were normally adapted. 20rnitz suggested that kinaesthetic feedbacks (flapping or oscillating of the extremities, whirling and rocking of the bodies) led the autistic child to get out auditive and visual sensations.

ERPs IN MENTALLYRETARDED AND AUTISTICCHILDREN Two studies were performed. The first was an analysis of relationships: 65 clinical characters were noted for each child with behaviour scales and psychometric tests, 88 electrophysiological data were measured on averaged tracings. The second compared with t and ×2 square methods the electrophysiological data of 3 groups clinically defined for age and typical syndrome. Results of the two studies supplemented each other. From the clinical point of view 3 major groups appeared: (1) autism, (2) mental retardation, (3) normal adaptation. From an electrophysiological point of view 2 major groups could be defined: (1) few conditioned EPs with small amplitude, generalized conditioned SPs, small unconditioned EPs, generalized unconditioned SPs, conditioning 'to time'; (2) many conditioned EPs, many conditioned rhythmic potentials, absence of generalized SPs, many localized vertex negative SPs (CNVs), large unconditioned EPs, no conditioning to time. Some differences were observed in generalized SPs, small and positive in mentally retarded children, negative or positive in autistic children. EP and SP data clearly help to differentiate pathological groups from a normal group but are insufficient to distinguish the autistic from the mentally retarded children.

Rdsumd Potentiels lids d l'dvdnement, dvoquds par stimulation sensorielle chez des enfants normaux, retardds mentaux et autistiques

Des potentiels dvoquds (PEs) et des potentiels lents (PLs) moyennds ont dt~ enregistrds chez l'enfant au cours d'un conditionnement comportant deux sdances de couplage du son (S) et de la lumi~re (L) (habituation: S seul; conditionnement: S-L; extinction: S seul apr~s les sdries S-L). 125 enfants ~g4s de 0 ~ 15 ans ont dtd examinds. 82 d'entre eux dtaient atteints de trou-

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bles mentaux plus ou moins intrigues o~ prddominent soit des signes d'autisme, soit des signes de retard mental. Ils furent compards 43 enfants tdmoins normalement adaptds. Deux dtudes ont dtd poursuivies. La premiere comportait une analyse des correspondances entre caract~res cliniques et donndes ~lectrophysiologiques. Pour chaque enfant dtaient notds 65 caracthres cliniques prdcisds l'aide d'dchelles de comportement et de tests psychomdtriques, et 88 donndes ~lectrophysiologiques mesurdes sur les tracds des PEs et des PLs. La seconde dtude dtait une comparaison ~ l'aide des techniques du test t et du X2, des principales donn~es ~lectrophysiologiques {amplitudes et pourcentages des rdponses) recueillies dans 3 groupes d'enfants cliniquement bien d~finis. Des rdsultats comparables se ddgagent des deux dtudes. L'analyse des caract~res cliniques comme la classification des sujets tendent ~ isoler 3 groupes: (1) autisme, (2) retard mental, (3) adaptation normale. L'analyse et la classification des donndes ~lectrophysiologiques permettent de d~finir 2 groupes principaux: le premier caractdrisd par des PEs conditionnds peu nombreux et d'amplitude faible, des PLs conditionnds g~ndralisds, des PEs inconditionnds peu amples, des PLs inconditionnds gdndralisds, enfin par des potentiels conditionnds 'au temps'. Le second caractdrisd par des PEs conditionnds nombreux et par de nombreux potentiels conditionnds rythmiques, par l'absence de PLs gdndralisds contrastant avec la prdsence de nombreux PLs ndgatifs localis~s au vertex (VCNs), par des PEs inconditionnds de grande amplitude et par l'absence de potentiels conditionnds 'au temps'. Quelques diffdrences apparaissent pour les PLs g~ndralisds, d'amplitude faible et de polarit~ positive dans le retard mental, de polarit~ ndgative ou positive dans l'autisme. Ainsi les donndes ~lectrophysiologiques contribuent ~ diffdrencier les groupes pathologiques des groupes normaux mais sont insuffisantes pour distinguer l'autisme du retard mental.

152 This study was supported by ERA CNRS No. 697 'Biologic et Neuropsychiatrie', ATP INSERM No. 65789704 Contrat DGRST 78 7 2787, Subvention FRM S.O. 5-75. We wish to thank Mrs. Gauthier and Mrs. Barre for their technical work and Mrs. Besnardeau and Miss Lioret for their assistance in the development of this text.

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