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Auditory nerve and brain-stem evoked responses in normal, autistic, minimal brain dysfunction and psychomotor retarded children
380
Electroencephalography and Clinical Neurophysiology, 1978, 44:380-388 © Elsevier/North-Holland Scientific Publishers Ltd.
A U D I T O R Y N E R V E AND BRAIN-STEM EVOKED RESPONSES IN NORMAL, AUTISTIC, MINIMAL BRAIN D Y SFU N C T I O N AND PSYCHOMOTOR R E T A R D E D C H I L D R E N * H. SOHMER and M. STUDENT Department of Physiology, Hebrew University-Hadassah Medical School. Jerusalem and Department of Psychology, Tel Aviv University, Tel Aviv (Israel)
(Accepted for publication: August 18, 1977)
The causes o f m a ny forms of disturbed behavior related to aberrations in nervous system f u n c t i o n in infants and children are u n k n o w n . F o r example, t he nat ur e o f autism has been controversial bot h with respect to its definition and to its etiology ( R u t t e r 1968). Autism is considered by some workers as being due to an unspecified organic brain lesion (Bender 1946; G u b b a y et al. 1970), or by others, to environmentally induced child psychosis (Mahler 1952). The behavior seen in Minimal Brain D ys f unc t i on (MBD) is generally considered as deriving f r om some form o f organic brain disorder but such lesions have n o t been adequately described. With respect to p s y c h o m o t o r retarded children, only the more obvious brain lesions have been d e m o n s t r a t e d , while in m any cases of retardation, a brain lesion is assumed but has n o t been identified. New electrophysiological techniques may help clarify w h e t h e r brain lesions exist in these conditions and may cont r i but e to the d e t e r min atio n of their nature and location. Abnormalities in the cortical evoked responses to sound and light stimuli have already been d e m o n s t r a t e d in some of these subjects (Barnet and Lodge 1967). Averaged evoked a u d i t o r y nerve and brain-stem activity can also be recorded in response to click acoustic stimuli. Since auditory nuclei make up a relatively large volume of brain-stem tissue, recording o f the electrical responses of these * An abstract of this paper was presented at the NIMH conference on Event Related Brain Potentials in Man, Airlie, Virginia, April, 1977.
nuclei has been found to be useful in the diagnosis of brain-stem disorders due to trauma, metabolic states and t um ors (Sohmer et al. 1974a; Starr and Achor 1975; T h o r n t o n and Hawkes, 1976). The purpose of this preliminary study was to record the auditory nerve and brain-stem evoked responses in infants and children with various types of p s y c h o p a t h o l o g y in order to search for electrophysiological signs of the presumed underlying brain lesion.
Methods
(A ) S u b j e c t s (1) C o n t r o l g r o u p Eighteen normal children of ages 4--10 years constituted the control group. In 13 o f them, the recording of auditory nerve and brain-stem responses was carried o u t while t hey were awake. F o u r additional children (aged 5--10 years) were studied bot h in the awake state and during sedated sleep while being prepared for dental surgery. Records were also made in one child (age 9 years) while in com a following head injury in a road accident and again several days later when she was completely awake. (2) A u t i s t i c g r o u p T he children with autistic traits were examined by 2 clinicians, each working i n d e p e n d e n t l y of the other. Since there is a controversy as to the traits which constitute
AER IN PSYCHOPATHOLOGY IN CHILDREN autism, the criteria employed in this study were those c o m m o n to both Kanner (1943) and Creak (1963), the main features of which are failure to develop any social relationships with other individuals, absence of speech development and stereotyped behavior. This group included 13 children, aged 4--12 years. Their IQs were estimated to be above 40. Recording in these children was carried out during sleep induced either by paraldehyde, thiopentone or diazepam.
(3) Minimal Brain Dysfunction Another group of 16 children aged 3--11 years was diagnosed by 2 clinicians as having MBD, chiefly because they had one or more of the traits of hyperactivity, learning difficulties and coordination defects (Clements et al. 1968; Wright et al. 1975). Several of these children were studied during drug-induced sleep (see the Autistic group) and others were studied while awake. Records were made in one MBD child when awake and again when in sedated sleep.
(4) Psychomotor retardation An additional group of 10 children aged 2--8 years was diagnosed by 2 clinicians as suffering from p s y c h o m o t o r retardation. The criteria which they employed included low intelligence (IQ estimated to be below 70), delayed acquisition of m o t o r and speech skills and a lack of social and emotional maturity (Swaiman 1975a).
(B) Stimulation and recording Click auditory stimuli transduced by earphones applied to the subject's head were used throughout. They were presented at a rate of 10 or 20/sec and at a m a x i m u m intensity of 75 dB above the threshold of the normal adult population (i.e. 75 dB HL). In most subjects, the intensity was decreased until the electrical response threshold (lowest click intensity which still elicited an electrical response) was obtained (usually between 0--15 dB HL).
381 The electrical activity was recorded as the potential difference between an earlobe clip and a scalp vertex disc electrode. The activity was filtered (bandpass 250--5000 Hz) and amplified and the initial 10 msec following the stimulus was averaged, usually 1024 responses were averaged and photographed (Sohmer and Feinmesser 1973).
(C) Experimental procedure Recording was carried out in most of the subjects in this study during sedated sleep (paraldehyde, diazepam or suppository of thiopentone). Each child had undergone a previous otologic examination and an audiometric test. Children with obvious conductive hearing lesions (external or middle ears) were not included. Auditory nerve and brain-stem responses to the stimulation of each ear separately were recorded, first in response to 75 dB HL clicks and then, in most subjects, in response to lower click intensities. From the response average traces (photographs), the latencies of the earlobe-negative peak of each of the 5 typical response waves, Wl, W2 etc., that of the positive wave following wave 4 and the amplitudes (initial negative peak to the following positive peak) of each response wave were measured (see first trace of Fig. 5). These measurements were carried out by a student who had no knowledge of the clinical classification of the subjects. From these values a computer program (MANOVA-multivariate analysis of variance) was used to calculate the average values, standard deviations, F values and significance (one-way analysis of variance) in order to test the differences among the groups for each dependent variable (latency of each wave, time interval between wave 1 and the positive trough of wave 4, defined as 'brain-stem transmission time' and relative amplitude of each response wave). Response traces which were completely lacking a particular wave (as occasionally seen in the autistic and p s y c h o m o t o r retarded groups) were not considered in the average values but were treated separately. Since the one-way analysis
382
H. SOHMER, M. STUDENT trol group of normal children. One might think that these differences are the result of t h e f a c t t h a t m o s t o f t h e c h i l d r e n in t h e experimental groups were studied during sedated sleep while most of the control children w e r e a w a k e . H o w e v e r , n o c h a n g e w a s s e e n in t h e r e c o r d s m a d e in s e v e r a l o f t h e n o r m a l c h i l d r e n a n d in o n e o f t h e c h i l d r e n w i t h M B D when they were awake and again when they w e r e in s e d a t e d s l e e p .
shows only the general, overall differences among the groups, an additional F test was used to determine the specific differences between the groups. Results T h e r e s p o n s e t r a c e s o b t a i n e d in t h e v a r i o u s e x p e r i m e n t a l g r o u p s d i f f e r e d s i g n i f i c a n t l y in s e v e r a l w a y s f r o m t h o s e o b t a i n e d in t h e c o n -
GROUP:
:
i
~ a b
STATE :
~ LS
AWAKE
CONTROL ASLEEP i
_
I
AUTISTIC
ASLEEP
AUTISTIC O.17pV
(PROFOUND HL)
ASLEEP
AWAKE MBO ,uV
ASLEEP
S~T.
RETARDED
RETARDED
ASLEEP 05yJV
3.~v
AWAKE
Fig. 1. Auditory nerve (W~) and brain-stem responses (W2_ s ) obtained in each of the groups. The 75 dB HL click stimulus is presented at the beginning of the trace and the response waves (earlobe negativity up) are identified in the first control trace which also shows the latency of W1 and brain-stem transmission time (from peak of W~ to trough of W4 ). Other workers (Jewett and Williston 1971) use a slightly different system for wave notation (Wl = I; W2 = II;W3 = III;W4a= IV; W4b = V: W 5 = VI).
A E R IN P S Y C H O P A T H O L O G Y IN C H I L D R E N
383
CONTROL 2 3
5
4
AUTISTIC dBHL 75
o.,
55 35
o.1,vl
0.1,,u~'
15
,t 7~V I
5 1 msec Fig. 2. A u d i t o r y n e r v e and b r a i n - s t e m r e s p o n s e s to click stimuli o f several i n t e n s i t i e s in a 6-year-old n o r m a l c o n t r o l child Cleft) a n d a 5-year-old child w i t h autistic traits (right). N o t e t h e decrease in r e s p o n s e a m p l i t u d e and increase in r e s p o n s e l a t e n c y as click i n t e n s i t y is decreased. W 4 is a p p a r e n t in t h e r e c o r d s f r o m t h e c h i l d r e n even at 5 d B HL. N o t e t h a t t h e t i m e interval b e t w e e n t h e p e a k o f wave 1 a n d t h e t r o u g h o f wave 4 r e m a i n s t h e same even a t l o w s t i m u l u s intensities.
TABLE I Average values, s t a n d a r d d e v i a t i o n s , F values ( m u l t i v a r i a t e analysis o f variance, o n e way analysis) a n d P values o f t h e a b s o l u t e l a t e n c y o f e a c h r e s p o n s e wave (Wl, W~, e t c . ) a n d b r a i n - s t e m t r a n s m i s s i o n t i m e (W4--W , ).
C o n t r o l (N = 39 ears) SD A u t i s t i c (N = 14 ears) SD M B D iN = 19 ears) SD R e t a r d e d iN = 11 ears) SD F values (d.f. 3, 7 8 ) Significance P <
W~
W2
W3
W4
W5
1.341 0.104 1.380 0.098 1.424 0.150 1.518 0.259 4.860 0.004
2.416 0.146 2.513 0.159 2.633 0.273 2.586 0.212 6.098 0.001
3.379 0.189 3.443 0.179 3.661 0.224 3.545 0.259 8.147 0.001
5.159 0.285 5.200 0.433 5.547 0.343 5.286 0.500 5.171 0.003
6.679 0.306 6.860 0.239 7.211 0.385 6.945 0.589 9.014 0.001
W4--W, 4.413 0.241 4.608 0.240 4.908 0.276 4.668 0.272 16.361 0.001
H. SOHMER, M. STUDENT
384 TABLE II Intergroup significances (Dunn 1968) of the latency of the first response wave. Control Control Autistic MBD Retarded
F = 0.5809 NS F = 4.25 P < 0.05 F = 13.124 P < 0.01
Autistic
F = 0.96 NS F = 6.193 P < 0.05 (d.f. 1, 78)
R e s p o n s e s to click stimuli c o u l d n o t be o b t a i n e d in 4 o f the children with autistic traits ( t h a t is, t h e y h a d a p r o f o u n d c o c h l e a r hearing loss in a d d i t i o n to having autistic traits, see Fig. 1, 3rd trace). The remaining 9 autistic children all had a u d i t o r y nerve and brain-stem responses with n o r m a l t h r e s h o l d s b u t w h i c h differed f r o m c o n t r o l r e c o r d s in o t h e r ways. In 2 o f t h e p s y c h o m o t o r r e t a r d e d children waves 4 and 5, p r e s e n t in n o r m a l children (Fig. 1), were a b s e n t (last trace o f Fig. 1). In t h e r e m a i n i n g 8 children, all o f the response waves were p r e s e n t with n o r m a l t h r e s h o l d s b u t were a b n o r m a l in o t h e r w a y s (e.g., l o n g e r l a t e n c y o f the a u d i t o r y nerve response and l o n g e r brain-stem transmission times). Fig. 1 shows traces o b t a i n e d in children r e p r e s e n t i n g each o f the g r o u p s studied. The m o s t o b v i o u s d i f f e r e n c e is t h a t the l a t e n c y o f the c o m p o u n d cochlear action potential
MBD
Retarded
F = 3.02 NS
(W~) in the traces f r o m each o f the experim e n t a l g r o u p s is longer t h a n in the c o n t r o l g r o u p . Table ! lists the average values o f the l a t e n c y o f W1 for all children in each g r o u p and it is seen t h a t t h e c o n t r o l g r o u p has the s h o r t e s t value, f o l l o w e d by the autistic g r o u p , t h e n the MBD g r o u p , with the p s y c h o m o t o r r e t a r d e d g r o u p having the longest values. The l a t e n c y o f each o f . t h e following waves was longer in the e x p e r i m e n t a l g r o u p s t h a n in the c o n t r o l g r o u p . Table II shows the interg r o u p significances o f these values. The time interval in each trace b e t w e e n the' negative (upward-going) p e a k o f W~ and the positive t r o u g h following W4 ( f r o m the region o f the inferior colliculus) can be c o n s i d e r e d t o represent brain-stern transmission time. This value is longer in each o f the e x p e r i m e n t a l g r o u p s t h a n in t h e c o n t r o l g r o u p . Table I also lists the average values and here t o o a similar p r o g r e s s i o n is seen, a l t h o u g h the transmission
TABLE III Intergroup significances (Dunn 1968) of brain-stem transmission time.
Control Autistic MBD Retarded
Control
Autistic
F = P< F = P< F= P<
--
5.714 0.05 42.039 0.01 8.547 0.01
F = 31.637 P < 0.01 F = 0.303 NS
MBD
F = 6.193 P < 0.05
Retarded
AER IN PSYCHOPATHOLOGY IN CHILDREN time in MBD is longer than t h a t in the group of p s y c h o m o t o r retarded children. The intergroup significances of these values are shown in Table III.
Discussion These records of auditory nerve and brainstem responses to auditory stimuli in normal infants and children and in those with several forms of psychopathology have clearly demonstrated their usefulness in several ways: they constitute more objective measures of hearing, which are needed in many of these types of patients; in addition, these tests have shown that the nervous systems of the experimental groups generate statistically deviant electrophysiological responses. These effects are n o t due to sedation since there was no difference in the responses obtained in several of the control children when they were awake or when the same subjects were unconscious (coma- and drug-induced sleep, see first 2 traces in Fig. 1). Thus, the records made in the experimental group during drug-induced sleep seem to be adequately controlled. Furthermore, records were made on one MBD patient both in the awake state and again several minutes later during drug-induced sleep, and the deviant response parameters (increased latencies and transmission times) were the same in these two states (traces 5 and 6 in Fig. 1). The main response parameters studied were the presence or absence of waves, the absolute latencies of each of the waves, the time intervals between waves (especially brain-stem transmission time) and the relative amplitudes of the waves. In several of the traces recorded in some of the children in the p s y c h o m o t o r retarded group, response waves, particularly those from the region of the inferior colliculus, were absent (last trace, Fig. 1). This is very clear evidence for the presence of structural brain damage in these children. Several of the children with autistic traits also had profound hearing loss (absence of all response
385 waves); this is evidence for a neural hearing loss in these children with autistic traits. Significant differences in many of the other parameters were also found between the control group and the various experimental groups, particularly with respect to wave latency and time intervals between waves. Each of these parameters, latency, time differences and relative amplitude, is independent of the others, a time difference between waves being distinct from any previous latency increase which occurred earlier in the response chain. The latencies of these waves are highly replicable in repeated tests (Sohmer et al. 1974b) and in different groups with small standard deviations (Lieberman and Sohmer 1973; Terkildsen et al. 1973; T h o r n t o n 1975; Pratt and Sohmer 1976). (More subtle differences between the control and experimental groups may be present in the response traces but more sophisticated analysis will be required to detect them). In this study, the responses in each of the groups to 75 dB HL clicks were compared. Since the latency of each of the response waves changes in a linear and parallel fashion with changes in stimulus intensity (Thornton 1975; Pratt and Sohmer 1976), the absolute latency of each wave is intensity-dependent, while the time interval between waves is independent of the stimulus intensity. Furthermore, since a conductive lesion (due to a disturbance in the external or middle ears) is equivalent to attenuation of click intensity (Sohmer and Cohen 1976), the time interval between waves (e.g. brain-stem transmission time) is a response measure which is not influenced by the presence of any otologically undetected conductive hearing loss. Braidstem transmission time thus seems to be a particularly good measure of brain-stem function since it is independent of stimulus intensity and the presence of any conductive or cochlear hearing loss. Also, the differences between each of the 3 experimental groups and the control group with respect to this response parameter were the most significant statistically. It has also been found to be use-
386 ful in the diagnosis of neurological disease (Starr and Achor 1975). These abnormal and deviant responses thus seem to present electrophysiological evidence for the presence o f functional (or structural) brain damage, at least in the region of the brain-stem, in these infants and children with autistic traits, MBD and retardation. Since brain-stem transmission time is longer in infants (Lieberman and Sohmer 1973) and reaches adult values at 1--21/~ years (Hecox and Galambos 1974; Salamy et al. 1975), some workers would interpret these findings o f abnormal brain f unc t i on as reflecting an immatu r ity in the d e v e l o p m e n t o f certain brain mechanisms (Tanguay et al. 1976). This study can n o t at present provide clear evidence as to wh e t her the delay is due to slower axonal propagation, increased synaptic delay or dendritic disturbance. These findings o f increased latencies and transmission times and occasionally the absence of waves, are based on responses o f portions of the auditory p a t h w ay to sound stimuli, so t hat these results by themselves do n o t clarify the question as to w h e th er this functional deviation is due to a specific lesion of the auditory pathway in these patients or w he t he r there is diffuse brain damage. The findings of abnormalities in the cortical evoked response (Barnet and Lodge 1967; Ornitz et al. 1968) and in types o f behavior which are n o t related to the a u d i t o r y system (Ritvo et al. 1969; Piggot et al. 1973), seem to indicate that most o f these findings are due to diffuse lesions of the brain. F u r t h e r m o r e , the predisposing factors which have been f o u n d in retardation (Swaiman 1975b) and MBD (Wright et al. 1975) would more likely give rise to diffuse lesions. This initial study provides evidence for diffuse brain lesions in infants and children with bizarre nervous system function. There is a degree o f overlap between the different groups (control, autistic, MBD and psychom o t o r retardation) so that it is not clear w h e t h e r these groups lie along a c o n t i n u u m with respect to these responses or w he t he r
H. SOHMER, M. STUDENT t hey are distinct groups. Thus it would be worthwhile to continue these studies by making records of many electrophysiological parameters in larger, more homogenous, bet t er defined groups of patients. Such records may be able to contribute to the early diagnosis o f brain lesions in such cases and perhaps even to a differential diagnosis between several types of lesion which might be identified as the causes of different types of behavior.
Summary In several forms of abnormal behavior in infants and children, the cause is either uncertain or an unspecified organic brain lesion is assumed to be present. Evoked averaged auditory nerve and brain-stem responses to click stimuli were recorded from groups of normal, autistic, mir/imal brain d y s f u n c t i o n (MBD) and p s y c h o m o t o r retarded children in order to search for electrophysiological evidence for a brain lesion. Most o f the control children were awake and most of the experimental children were in sedated sleep but records were also made from some children while awake and again in the same children when asleep and no change was seen in the response traces. In several of the autistic children there were no electrophysiological responses (indicating a p r o f o u n d hearing loss). In several of the p s y c h o m o t o r retarded children the responses from the region of the inferior coUiculus were absent. In the ot her children in the experimental group, auditory nerve and brain-stem responses were recorded with normal response thresholds but abnormal in ot her ways: the latency of the auditory nerve response was longer than in the normal children. Also, brain-stem transmission time, measured as the time interval from the negative peak o f the auditory nerve response to the positive trough of the response from the inferior colliculus, was shortest in the control group and longest in the MBD group.
AER IN PSYCHOPATHOLOGY IN CHILDREN T h e s e results t h u s p r e s e n t e l e c t r o p h y s i o l o g ical evidence for t h e e x i s t e n c e o f an organic brain lesion in these children, at least in t h e brain-stem regions c o n c e r n e d with a u d i t o r y f u n c t i o n . T o g e t h e r with evidence f r o m o t h e r studies, t h e r e is s u p p o r t f o r t h e c o n c l u s i o n t h a t m o s t o f the a b n o r m a l b e h a v i o r seen in these p a t i e n t s is d u e to a diffuse brain lesion.
Rdsum~
R#ponses ~voqu~es du nerf auditif et du tronc c¢r~bral recueillies chez l'enfant, comparaison entre des individus normaux, des autistiques, des sujets atteints d'un dysfonctionnement c#r~bral mineur et des retard#s profonds. P o u r diverses f o r m e s de c o m p o r t e m e n t a n o r m a l chez l ' e n f a n t en bas ~ge o u plus ~ 6 , la cause est soit i n c o n n u e , soit a t t r i b u d e u n e 16sion organique cdrdbrale n o n d e t e r minde. P o u r c e t t e raison, o n a enregistr6 les rdponses 6voqudes d u n e r f auditif et d u t r o n c c6r6bral a des stimuli par clics chez des groupes d ' e n f a n t s n o r m a u x , d ' e n f a n t s autistiques, d ' e n f a n t s atteints d ' u n ldger d y s f o n c t i o n n e m e n t cdrdbral e t e n f i n chez des r e t a r d e s p s y c h o m o t e u r s , ceci en vue de r e c h e r c h e r la p r e u v e 61ectrophysiologique dventuelle d ' u n e 16sion c6rdbraie sous-jacente. Lors d e l ' e x a m e n , la p l u p a r t des e n f a n t s d u g r o u p e t ~ m o i n ( n o r m a u x ) ~taient dveillds, tandis que la p l u p a r t d e c e u x a p p a r t e n a n t au g r o u p e e x p d r i m e n t a l dtaient dans un 6tat de sommeil i n d u i t par sddation, e n c o r e que certains d e ces e n f a n t s aient p u ~tre enregistrds en dtat de veille puis de sommeil, sans a u c u n c h a n g e m e n t dans les trac6s des rdponses. Chez plusieurs e n f a n t s autistiques, a u c u n e rdponse 61ectrophysiologique ne f u t o b t e n u e s (signe d ' u n e surdit6 p r o f o n d e ) . Chez plusieurs retard6s p s y c h o m o t e u r s , les rdponses de la rdgion d u t u b e r c u l e q u a d r i j u m e a u 6taient absentes. Chez les autres e n f a n t s d u g r o u p e e x p d r i m e n t a l , des r6ponses d u n e r f a u d i t i f et d u t r o n c cdrdbral o n t 6t6 o b t e n u e s avec
387 des seuils n o r m a u x , tandis que d ' a u t r e s caractdristiques dtaient anormales; ainsi la latence des rdponses d u n e r f auditif ~tait dans c h a c u n des groupes e x p d r i m e n t a u x plus longue q u e chez les e n f a n t s n o r m a u x . De m~me, le t e m p s de c o n d u c t i o n dans le t r o n c cdrdbral, m e s u r e par l'intervale s6parant le pic negatif de la rdponse a t t r i b u d e au n e r f auditif, du c r e u x d e l ' o n d e positive p r o v e n a n t d u t u b e r cule q u a d r i j u m e a u postdrieur, etait plus c o u r t dans le g r o u p e t d m o i n et plus long chez les e n f a n t s atteints d ' u n ldger d y s f o n c t i o n n e m e n t c6r~bral. Ainsi, ces resultats f o u r n i s s e n t un a r g u m e n t 61ectrophysiologique en faveur de l'existence d ' u n e 16sion o r g a n i q u e c6rebrale chez les enfants examin6s, d u moins en ce qui c o n c e r n e les zones d u t r o n c c6r6bral i n t e r v e n a n t dans la f o n c t i o n auditive. Ces a r g u m e n t s s ' a j o u t a n t d'autres, p r o v e n a n t d ' 6 t u d e s diferentes, r e n f o r c e n t l ' h y p o t b e s e selon laquelle le comp o r t e m e n t a n o r m a l observ6 chez la p l u p a r t des ces malades s ' e x p l i q u e par une a t t e i n t e c6r6brale diffuse. The authors wish to express their sincere gratitude to Adina Shapiro for her assistance. References Barnet, A.B., and Lodge, A. Click evoked EEG responses in normal and developmentally retarded infants. Nature, 1967, 214: 252--255. Bender, L. Childhood schizophrenia: clinical study of 100 schizophrenic children. Amer. J. Orthopsychiat., 1946, 17: 40--56. Clements, S., Peters, J. and Rock, L. Minimal brain dysfunction in the school age child. Arch. gen. Psychiat., 1968, 6: 185--197. Creak, E.M. Childhood psychosis: A review of 1043 cases. Brit. J. Psychiat., 1963, 109: 84--89. Dunn, O.J. Multiple comparison test in "Experimental design procedures for the behavioral sciences". In R.E. Kirk. (Ed.), Brooks/Cole, New York, 1968. Gubbay, S.S., Lobascher, M. and Kingerlee, P. A neurological appraisal of autistic children: Results of a Western Australian survey. Develop. Med. Child Neurol., 1970, 12: 422--429. Hecox, K. and Galambos, R. Brainstem auditory evoked responses in human infants and adults. Arch. Otolaryng., 1974, 99: 30--33.
388 Jewett, D.L. and Williston, J.S. Auditory-evoked far fields averaged from the scalp of humans. Brain, 1971, 94: 681--696. Kanner, L. Autistic disturbances of effective contact. Nerv. Child., 1943, 2: 217--250. Leiberman, A. and Sohmer, H. Standard values of amplitude and latency of cochlear audiometry (electro-cochleography) responses in different age groups. Arch. klin. exp. Ohr.-, Nas.-, u. Kehlk.Heilk., 1973, 203: 267--273. Mahler, M.S. On child psychosis and schizophrenia: autistic and symbiotic infantile psychoses. Psychoan. Stud. Child., 1952, 7: 286--305. Ornitz, E., Ritvo, E.R., Panman, L.M., Lee, Y.M., Carr, E.R. and Walter, R.D. The auditory evoked responses in normal and autistic children during sleep. Electroenceph. clin. Neurophysio!., 1968, 25: 221--230. Piggot, L., Ax, A.F., Bamford, J.L. and Fetzner, J.M. Respiration sinus arrhythmia in psychotic children. Psychophysioiogy, 1973, 10: 401--414. Pratt, H. and Sohmer, H. Intensity and rate functions of cochlear and brainstem evoked responses to click stimuli in man. Arch. oto-rhino-laryng., 1976, 212: 85--92. Ritvo, E.R., Ornitz, E.M., Eviatar, A., Markham, C.H., Brown, M.B. and Mason, A. Decreased postrotatory nystagmus in early infantile autism. Neurology, 1969, 19: 653--658. Rutter, M. Concepts of autism: a review of research. J. Child Psychol. Psychiat., 1968, 9: 1--25. Salamy, A., McKean, C.M. and Buda, F.B. Maturationa] changes in auditory transmission as reflected in human brainstem potentials. Brain Res., 1975, 96: 361--366. Sohmer, H. and Feinmesser, M. Routine use of electrocochleography (cochlear audiometry) on human subjects. Audiology, 1973, 13: 167--173. Sohmer, H. and Cohen, D. Responses of the auditory
H. SOHMER, M. STUDENT pathway in several types of hearing loss. In Ruben, Elberling and Salomon (Eds.), Electrocochleography. University Park Press, Baltimore, 1976. Sohmer, H., Feinmesser, M. and Szabo, G. Sources of electrocochleographic responses as studied in patients with brain damage. Electroenceph. clin. Neurophysiol., 1974a, 37: 663--669. Sohmer, H., Pratt, H. and Feinmesser, M. Electrocochleography or evoked cortical responses: which is preferable in diagnosis of hearing loss? Rev. Laryngol. 1974b, 95: 515--522. Starr, A. and Achor, J. Auditory brainstem responses in neurological disease. Arch. Neurol. (Chic.) 1975, 32: 761--768. Swaiman, K.F. Intellectual and motor deterioration. In K.F. Swaiman and F.S. Wright (Eds.), The Practice of Pediatric Neurology. C.V. Mosby, St. Louis, 1975a. Swaiman, K.F. Mental retardation. In K.F. Swaiman and F.S. Wright (Eds.), The Practice of Pediatric Neurology. C.V. Mosby, St. Louis, 1975b. Tanguay, E.P., Ornitz, E.M., Forsythe, A.B. and Ritvo, E.R. Rapid eye movement (REM) activity in normal and autistic children during REM sleep. J. Autism Child Schizo., 1976, 6: 275--288. Terkildsen, K., Osterhammel, P. and Huis in't Veld, F. Electrocochleography with a far field technique. Scand. Audiol., 1973, 2: 141--148. Thornton, A.R.D. Statistical properties of surfacerecorded electrocochleographic responses. Scand. Audiol., 1975, 4: 91--102. Thornton, A.R.D. and Hawkes, C. Neurological application of surface-recorded electrocochleography. J. Neurol. Neurosurg. Psychiat. 1976, 39: 586--592. Wright, F.S., Schain, R.J., Weinberg, W.A. and Rapin, I. Learning disabilities and associated conditions. In K.F. Swaiman and F.S. Wright (Eds.), The Practice of Pediatric Neurology. C.V. Mosby, St. Louis, 1975.
Electroencephalography and Clinical Neurophysiology, 1978, 44:380-388 © Elsevier/North-Holland Scientific Publishers Ltd.
A U D I T O R Y N E R V E AND BRAIN-STEM EVOKED RESPONSES IN NORMAL, AUTISTIC, MINIMAL BRAIN D Y SFU N C T I O N AND PSYCHOMOTOR R E T A R D E D C H I L D R E N * H. SOHMER and M. STUDENT Department of Physiology, Hebrew University-Hadassah Medical School. Jerusalem and Department of Psychology, Tel Aviv University, Tel Aviv (Israel)
(Accepted for publication: August 18, 1977)
The causes o f m a ny forms of disturbed behavior related to aberrations in nervous system f u n c t i o n in infants and children are u n k n o w n . F o r example, t he nat ur e o f autism has been controversial bot h with respect to its definition and to its etiology ( R u t t e r 1968). Autism is considered by some workers as being due to an unspecified organic brain lesion (Bender 1946; G u b b a y et al. 1970), or by others, to environmentally induced child psychosis (Mahler 1952). The behavior seen in Minimal Brain D ys f unc t i on (MBD) is generally considered as deriving f r om some form o f organic brain disorder but such lesions have n o t been adequately described. With respect to p s y c h o m o t o r retarded children, only the more obvious brain lesions have been d e m o n s t r a t e d , while in m any cases of retardation, a brain lesion is assumed but has n o t been identified. New electrophysiological techniques may help clarify w h e t h e r brain lesions exist in these conditions and may cont r i but e to the d e t e r min atio n of their nature and location. Abnormalities in the cortical evoked responses to sound and light stimuli have already been d e m o n s t r a t e d in some of these subjects (Barnet and Lodge 1967). Averaged evoked a u d i t o r y nerve and brain-stem activity can also be recorded in response to click acoustic stimuli. Since auditory nuclei make up a relatively large volume of brain-stem tissue, recording o f the electrical responses of these * An abstract of this paper was presented at the NIMH conference on Event Related Brain Potentials in Man, Airlie, Virginia, April, 1977.
nuclei has been found to be useful in the diagnosis of brain-stem disorders due to trauma, metabolic states and t um ors (Sohmer et al. 1974a; Starr and Achor 1975; T h o r n t o n and Hawkes, 1976). The purpose of this preliminary study was to record the auditory nerve and brain-stem evoked responses in infants and children with various types of p s y c h o p a t h o l o g y in order to search for electrophysiological signs of the presumed underlying brain lesion.
Methods
(A ) S u b j e c t s (1) C o n t r o l g r o u p Eighteen normal children of ages 4--10 years constituted the control group. In 13 o f them, the recording of auditory nerve and brain-stem responses was carried o u t while t hey were awake. F o u r additional children (aged 5--10 years) were studied bot h in the awake state and during sedated sleep while being prepared for dental surgery. Records were also made in one child (age 9 years) while in com a following head injury in a road accident and again several days later when she was completely awake. (2) A u t i s t i c g r o u p T he children with autistic traits were examined by 2 clinicians, each working i n d e p e n d e n t l y of the other. Since there is a controversy as to the traits which constitute
AER IN PSYCHOPATHOLOGY IN CHILDREN autism, the criteria employed in this study were those c o m m o n to both Kanner (1943) and Creak (1963), the main features of which are failure to develop any social relationships with other individuals, absence of speech development and stereotyped behavior. This group included 13 children, aged 4--12 years. Their IQs were estimated to be above 40. Recording in these children was carried out during sleep induced either by paraldehyde, thiopentone or diazepam.
(3) Minimal Brain Dysfunction Another group of 16 children aged 3--11 years was diagnosed by 2 clinicians as having MBD, chiefly because they had one or more of the traits of hyperactivity, learning difficulties and coordination defects (Clements et al. 1968; Wright et al. 1975). Several of these children were studied during drug-induced sleep (see the Autistic group) and others were studied while awake. Records were made in one MBD child when awake and again when in sedated sleep.
(4) Psychomotor retardation An additional group of 10 children aged 2--8 years was diagnosed by 2 clinicians as suffering from p s y c h o m o t o r retardation. The criteria which they employed included low intelligence (IQ estimated to be below 70), delayed acquisition of m o t o r and speech skills and a lack of social and emotional maturity (Swaiman 1975a).
(B) Stimulation and recording Click auditory stimuli transduced by earphones applied to the subject's head were used throughout. They were presented at a rate of 10 or 20/sec and at a m a x i m u m intensity of 75 dB above the threshold of the normal adult population (i.e. 75 dB HL). In most subjects, the intensity was decreased until the electrical response threshold (lowest click intensity which still elicited an electrical response) was obtained (usually between 0--15 dB HL).
381 The electrical activity was recorded as the potential difference between an earlobe clip and a scalp vertex disc electrode. The activity was filtered (bandpass 250--5000 Hz) and amplified and the initial 10 msec following the stimulus was averaged, usually 1024 responses were averaged and photographed (Sohmer and Feinmesser 1973).
(C) Experimental procedure Recording was carried out in most of the subjects in this study during sedated sleep (paraldehyde, diazepam or suppository of thiopentone). Each child had undergone a previous otologic examination and an audiometric test. Children with obvious conductive hearing lesions (external or middle ears) were not included. Auditory nerve and brain-stem responses to the stimulation of each ear separately were recorded, first in response to 75 dB HL clicks and then, in most subjects, in response to lower click intensities. From the response average traces (photographs), the latencies of the earlobe-negative peak of each of the 5 typical response waves, Wl, W2 etc., that of the positive wave following wave 4 and the amplitudes (initial negative peak to the following positive peak) of each response wave were measured (see first trace of Fig. 5). These measurements were carried out by a student who had no knowledge of the clinical classification of the subjects. From these values a computer program (MANOVA-multivariate analysis of variance) was used to calculate the average values, standard deviations, F values and significance (one-way analysis of variance) in order to test the differences among the groups for each dependent variable (latency of each wave, time interval between wave 1 and the positive trough of wave 4, defined as 'brain-stem transmission time' and relative amplitude of each response wave). Response traces which were completely lacking a particular wave (as occasionally seen in the autistic and p s y c h o m o t o r retarded groups) were not considered in the average values but were treated separately. Since the one-way analysis
382
H. SOHMER, M. STUDENT trol group of normal children. One might think that these differences are the result of t h e f a c t t h a t m o s t o f t h e c h i l d r e n in t h e experimental groups were studied during sedated sleep while most of the control children w e r e a w a k e . H o w e v e r , n o c h a n g e w a s s e e n in t h e r e c o r d s m a d e in s e v e r a l o f t h e n o r m a l c h i l d r e n a n d in o n e o f t h e c h i l d r e n w i t h M B D when they were awake and again when they w e r e in s e d a t e d s l e e p .
shows only the general, overall differences among the groups, an additional F test was used to determine the specific differences between the groups. Results T h e r e s p o n s e t r a c e s o b t a i n e d in t h e v a r i o u s e x p e r i m e n t a l g r o u p s d i f f e r e d s i g n i f i c a n t l y in s e v e r a l w a y s f r o m t h o s e o b t a i n e d in t h e c o n -
GROUP:
:
i
~ a b
STATE :
~ LS
AWAKE
CONTROL ASLEEP i
_
I
AUTISTIC
ASLEEP
AUTISTIC O.17pV
(PROFOUND HL)
ASLEEP
AWAKE MBO ,uV
ASLEEP
S~T.
RETARDED
RETARDED
ASLEEP 05yJV
3.~v
AWAKE
Fig. 1. Auditory nerve (W~) and brain-stem responses (W2_ s ) obtained in each of the groups. The 75 dB HL click stimulus is presented at the beginning of the trace and the response waves (earlobe negativity up) are identified in the first control trace which also shows the latency of W1 and brain-stem transmission time (from peak of W~ to trough of W4 ). Other workers (Jewett and Williston 1971) use a slightly different system for wave notation (Wl = I; W2 = II;W3 = III;W4a= IV; W4b = V: W 5 = VI).
A E R IN P S Y C H O P A T H O L O G Y IN C H I L D R E N
383
CONTROL 2 3
5
4
AUTISTIC dBHL 75
o.,
55 35
o.1,vl
0.1,,u~'
15
,t 7~V I
5 1 msec Fig. 2. A u d i t o r y n e r v e and b r a i n - s t e m r e s p o n s e s to click stimuli o f several i n t e n s i t i e s in a 6-year-old n o r m a l c o n t r o l child Cleft) a n d a 5-year-old child w i t h autistic traits (right). N o t e t h e decrease in r e s p o n s e a m p l i t u d e and increase in r e s p o n s e l a t e n c y as click i n t e n s i t y is decreased. W 4 is a p p a r e n t in t h e r e c o r d s f r o m t h e c h i l d r e n even at 5 d B HL. N o t e t h a t t h e t i m e interval b e t w e e n t h e p e a k o f wave 1 a n d t h e t r o u g h o f wave 4 r e m a i n s t h e same even a t l o w s t i m u l u s intensities.
TABLE I Average values, s t a n d a r d d e v i a t i o n s , F values ( m u l t i v a r i a t e analysis o f variance, o n e way analysis) a n d P values o f t h e a b s o l u t e l a t e n c y o f e a c h r e s p o n s e wave (Wl, W~, e t c . ) a n d b r a i n - s t e m t r a n s m i s s i o n t i m e (W4--W , ).
C o n t r o l (N = 39 ears) SD A u t i s t i c (N = 14 ears) SD M B D iN = 19 ears) SD R e t a r d e d iN = 11 ears) SD F values (d.f. 3, 7 8 ) Significance P <
W~
W2
W3
W4
W5
1.341 0.104 1.380 0.098 1.424 0.150 1.518 0.259 4.860 0.004
2.416 0.146 2.513 0.159 2.633 0.273 2.586 0.212 6.098 0.001
3.379 0.189 3.443 0.179 3.661 0.224 3.545 0.259 8.147 0.001
5.159 0.285 5.200 0.433 5.547 0.343 5.286 0.500 5.171 0.003
6.679 0.306 6.860 0.239 7.211 0.385 6.945 0.589 9.014 0.001
W4--W, 4.413 0.241 4.608 0.240 4.908 0.276 4.668 0.272 16.361 0.001
H. SOHMER, M. STUDENT
384 TABLE II Intergroup significances (Dunn 1968) of the latency of the first response wave. Control Control Autistic MBD Retarded
F = 0.5809 NS F = 4.25 P < 0.05 F = 13.124 P < 0.01
Autistic
F = 0.96 NS F = 6.193 P < 0.05 (d.f. 1, 78)
R e s p o n s e s to click stimuli c o u l d n o t be o b t a i n e d in 4 o f the children with autistic traits ( t h a t is, t h e y h a d a p r o f o u n d c o c h l e a r hearing loss in a d d i t i o n to having autistic traits, see Fig. 1, 3rd trace). The remaining 9 autistic children all had a u d i t o r y nerve and brain-stem responses with n o r m a l t h r e s h o l d s b u t w h i c h differed f r o m c o n t r o l r e c o r d s in o t h e r ways. In 2 o f t h e p s y c h o m o t o r r e t a r d e d children waves 4 and 5, p r e s e n t in n o r m a l children (Fig. 1), were a b s e n t (last trace o f Fig. 1). In t h e r e m a i n i n g 8 children, all o f the response waves were p r e s e n t with n o r m a l t h r e s h o l d s b u t were a b n o r m a l in o t h e r w a y s (e.g., l o n g e r l a t e n c y o f the a u d i t o r y nerve response and l o n g e r brain-stem transmission times). Fig. 1 shows traces o b t a i n e d in children r e p r e s e n t i n g each o f the g r o u p s studied. The m o s t o b v i o u s d i f f e r e n c e is t h a t the l a t e n c y o f the c o m p o u n d cochlear action potential
MBD
Retarded
F = 3.02 NS
(W~) in the traces f r o m each o f the experim e n t a l g r o u p s is longer t h a n in the c o n t r o l g r o u p . Table ! lists the average values o f the l a t e n c y o f W1 for all children in each g r o u p and it is seen t h a t t h e c o n t r o l g r o u p has the s h o r t e s t value, f o l l o w e d by the autistic g r o u p , t h e n the MBD g r o u p , with the p s y c h o m o t o r r e t a r d e d g r o u p having the longest values. The l a t e n c y o f each o f . t h e following waves was longer in the e x p e r i m e n t a l g r o u p s t h a n in the c o n t r o l g r o u p . Table II shows the interg r o u p significances o f these values. The time interval in each trace b e t w e e n the' negative (upward-going) p e a k o f W~ and the positive t r o u g h following W4 ( f r o m the region o f the inferior colliculus) can be c o n s i d e r e d t o represent brain-stern transmission time. This value is longer in each o f the e x p e r i m e n t a l g r o u p s t h a n in t h e c o n t r o l g r o u p . Table I also lists the average values and here t o o a similar p r o g r e s s i o n is seen, a l t h o u g h the transmission
TABLE III Intergroup significances (Dunn 1968) of brain-stem transmission time.
Control Autistic MBD Retarded
Control
Autistic
F = P< F = P< F= P<
--
5.714 0.05 42.039 0.01 8.547 0.01
F = 31.637 P < 0.01 F = 0.303 NS
MBD
F = 6.193 P < 0.05
Retarded
AER IN PSYCHOPATHOLOGY IN CHILDREN time in MBD is longer than t h a t in the group of p s y c h o m o t o r retarded children. The intergroup significances of these values are shown in Table III.
Discussion These records of auditory nerve and brainstem responses to auditory stimuli in normal infants and children and in those with several forms of psychopathology have clearly demonstrated their usefulness in several ways: they constitute more objective measures of hearing, which are needed in many of these types of patients; in addition, these tests have shown that the nervous systems of the experimental groups generate statistically deviant electrophysiological responses. These effects are n o t due to sedation since there was no difference in the responses obtained in several of the control children when they were awake or when the same subjects were unconscious (coma- and drug-induced sleep, see first 2 traces in Fig. 1). Thus, the records made in the experimental group during drug-induced sleep seem to be adequately controlled. Furthermore, records were made on one MBD patient both in the awake state and again several minutes later during drug-induced sleep, and the deviant response parameters (increased latencies and transmission times) were the same in these two states (traces 5 and 6 in Fig. 1). The main response parameters studied were the presence or absence of waves, the absolute latencies of each of the waves, the time intervals between waves (especially brain-stem transmission time) and the relative amplitudes of the waves. In several of the traces recorded in some of the children in the p s y c h o m o t o r retarded group, response waves, particularly those from the region of the inferior colliculus, were absent (last trace, Fig. 1). This is very clear evidence for the presence of structural brain damage in these children. Several of the children with autistic traits also had profound hearing loss (absence of all response
385 waves); this is evidence for a neural hearing loss in these children with autistic traits. Significant differences in many of the other parameters were also found between the control group and the various experimental groups, particularly with respect to wave latency and time intervals between waves. Each of these parameters, latency, time differences and relative amplitude, is independent of the others, a time difference between waves being distinct from any previous latency increase which occurred earlier in the response chain. The latencies of these waves are highly replicable in repeated tests (Sohmer et al. 1974b) and in different groups with small standard deviations (Lieberman and Sohmer 1973; Terkildsen et al. 1973; T h o r n t o n 1975; Pratt and Sohmer 1976). (More subtle differences between the control and experimental groups may be present in the response traces but more sophisticated analysis will be required to detect them). In this study, the responses in each of the groups to 75 dB HL clicks were compared. Since the latency of each of the response waves changes in a linear and parallel fashion with changes in stimulus intensity (Thornton 1975; Pratt and Sohmer 1976), the absolute latency of each wave is intensity-dependent, while the time interval between waves is independent of the stimulus intensity. Furthermore, since a conductive lesion (due to a disturbance in the external or middle ears) is equivalent to attenuation of click intensity (Sohmer and Cohen 1976), the time interval between waves (e.g. brain-stem transmission time) is a response measure which is not influenced by the presence of any otologically undetected conductive hearing loss. Braidstem transmission time thus seems to be a particularly good measure of brain-stem function since it is independent of stimulus intensity and the presence of any conductive or cochlear hearing loss. Also, the differences between each of the 3 experimental groups and the control group with respect to this response parameter were the most significant statistically. It has also been found to be use-
386 ful in the diagnosis of neurological disease (Starr and Achor 1975). These abnormal and deviant responses thus seem to present electrophysiological evidence for the presence o f functional (or structural) brain damage, at least in the region of the brain-stem, in these infants and children with autistic traits, MBD and retardation. Since brain-stem transmission time is longer in infants (Lieberman and Sohmer 1973) and reaches adult values at 1--21/~ years (Hecox and Galambos 1974; Salamy et al. 1975), some workers would interpret these findings o f abnormal brain f unc t i on as reflecting an immatu r ity in the d e v e l o p m e n t o f certain brain mechanisms (Tanguay et al. 1976). This study can n o t at present provide clear evidence as to wh e t her the delay is due to slower axonal propagation, increased synaptic delay or dendritic disturbance. These findings o f increased latencies and transmission times and occasionally the absence of waves, are based on responses o f portions of the auditory p a t h w ay to sound stimuli, so t hat these results by themselves do n o t clarify the question as to w h e th er this functional deviation is due to a specific lesion of the auditory pathway in these patients or w he t he r there is diffuse brain damage. The findings of abnormalities in the cortical evoked response (Barnet and Lodge 1967; Ornitz et al. 1968) and in types o f behavior which are n o t related to the a u d i t o r y system (Ritvo et al. 1969; Piggot et al. 1973), seem to indicate that most o f these findings are due to diffuse lesions of the brain. F u r t h e r m o r e , the predisposing factors which have been f o u n d in retardation (Swaiman 1975b) and MBD (Wright et al. 1975) would more likely give rise to diffuse lesions. This initial study provides evidence for diffuse brain lesions in infants and children with bizarre nervous system function. There is a degree o f overlap between the different groups (control, autistic, MBD and psychom o t o r retardation) so that it is not clear w h e t h e r these groups lie along a c o n t i n u u m with respect to these responses or w he t he r
H. SOHMER, M. STUDENT t hey are distinct groups. Thus it would be worthwhile to continue these studies by making records of many electrophysiological parameters in larger, more homogenous, bet t er defined groups of patients. Such records may be able to contribute to the early diagnosis o f brain lesions in such cases and perhaps even to a differential diagnosis between several types of lesion which might be identified as the causes of different types of behavior.
Summary In several forms of abnormal behavior in infants and children, the cause is either uncertain or an unspecified organic brain lesion is assumed to be present. Evoked averaged auditory nerve and brain-stem responses to click stimuli were recorded from groups of normal, autistic, mir/imal brain d y s f u n c t i o n (MBD) and p s y c h o m o t o r retarded children in order to search for electrophysiological evidence for a brain lesion. Most o f the control children were awake and most of the experimental children were in sedated sleep but records were also made from some children while awake and again in the same children when asleep and no change was seen in the response traces. In several of the autistic children there were no electrophysiological responses (indicating a p r o f o u n d hearing loss). In several of the p s y c h o m o t o r retarded children the responses from the region of the inferior coUiculus were absent. In the ot her children in the experimental group, auditory nerve and brain-stem responses were recorded with normal response thresholds but abnormal in ot her ways: the latency of the auditory nerve response was longer than in the normal children. Also, brain-stem transmission time, measured as the time interval from the negative peak o f the auditory nerve response to the positive trough of the response from the inferior colliculus, was shortest in the control group and longest in the MBD group.
AER IN PSYCHOPATHOLOGY IN CHILDREN T h e s e results t h u s p r e s e n t e l e c t r o p h y s i o l o g ical evidence for t h e e x i s t e n c e o f an organic brain lesion in these children, at least in t h e brain-stem regions c o n c e r n e d with a u d i t o r y f u n c t i o n . T o g e t h e r with evidence f r o m o t h e r studies, t h e r e is s u p p o r t f o r t h e c o n c l u s i o n t h a t m o s t o f the a b n o r m a l b e h a v i o r seen in these p a t i e n t s is d u e to a diffuse brain lesion.
Rdsum~
R#ponses ~voqu~es du nerf auditif et du tronc c¢r~bral recueillies chez l'enfant, comparaison entre des individus normaux, des autistiques, des sujets atteints d'un dysfonctionnement c#r~bral mineur et des retard#s profonds. P o u r diverses f o r m e s de c o m p o r t e m e n t a n o r m a l chez l ' e n f a n t en bas ~ge o u plus ~ 6 , la cause est soit i n c o n n u e , soit a t t r i b u d e u n e 16sion organique cdrdbrale n o n d e t e r minde. P o u r c e t t e raison, o n a enregistr6 les rdponses 6voqudes d u n e r f auditif et d u t r o n c c6r6bral a des stimuli par clics chez des groupes d ' e n f a n t s n o r m a u x , d ' e n f a n t s autistiques, d ' e n f a n t s atteints d ' u n ldger d y s f o n c t i o n n e m e n t cdrdbral e t e n f i n chez des r e t a r d e s p s y c h o m o t e u r s , ceci en vue de r e c h e r c h e r la p r e u v e 61ectrophysiologique dventuelle d ' u n e 16sion c6rdbraie sous-jacente. Lors d e l ' e x a m e n , la p l u p a r t des e n f a n t s d u g r o u p e t ~ m o i n ( n o r m a u x ) ~taient dveillds, tandis que la p l u p a r t d e c e u x a p p a r t e n a n t au g r o u p e e x p d r i m e n t a l dtaient dans un 6tat de sommeil i n d u i t par sddation, e n c o r e que certains d e ces e n f a n t s aient p u ~tre enregistrds en dtat de veille puis de sommeil, sans a u c u n c h a n g e m e n t dans les trac6s des rdponses. Chez plusieurs e n f a n t s autistiques, a u c u n e rdponse 61ectrophysiologique ne f u t o b t e n u e s (signe d ' u n e surdit6 p r o f o n d e ) . Chez plusieurs retard6s p s y c h o m o t e u r s , les rdponses de la rdgion d u t u b e r c u l e q u a d r i j u m e a u 6taient absentes. Chez les autres e n f a n t s d u g r o u p e e x p d r i m e n t a l , des r6ponses d u n e r f a u d i t i f et d u t r o n c cdrdbral o n t 6t6 o b t e n u e s avec
387 des seuils n o r m a u x , tandis que d ' a u t r e s caractdristiques dtaient anormales; ainsi la latence des rdponses d u n e r f auditif ~tait dans c h a c u n des groupes e x p d r i m e n t a u x plus longue q u e chez les e n f a n t s n o r m a u x . De m~me, le t e m p s de c o n d u c t i o n dans le t r o n c cdrdbral, m e s u r e par l'intervale s6parant le pic negatif de la rdponse a t t r i b u d e au n e r f auditif, du c r e u x d e l ' o n d e positive p r o v e n a n t d u t u b e r cule q u a d r i j u m e a u postdrieur, etait plus c o u r t dans le g r o u p e t d m o i n et plus long chez les e n f a n t s atteints d ' u n ldger d y s f o n c t i o n n e m e n t c6r~bral. Ainsi, ces resultats f o u r n i s s e n t un a r g u m e n t 61ectrophysiologique en faveur de l'existence d ' u n e 16sion o r g a n i q u e c6rebrale chez les enfants examin6s, d u moins en ce qui c o n c e r n e les zones d u t r o n c c6r6bral i n t e r v e n a n t dans la f o n c t i o n auditive. Ces a r g u m e n t s s ' a j o u t a n t d'autres, p r o v e n a n t d ' 6 t u d e s diferentes, r e n f o r c e n t l ' h y p o t b e s e selon laquelle le comp o r t e m e n t a n o r m a l observ6 chez la p l u p a r t des ces malades s ' e x p l i q u e par une a t t e i n t e c6r6brale diffuse. The authors wish to express their sincere gratitude to Adina Shapiro for her assistance. References Barnet, A.B., and Lodge, A. Click evoked EEG responses in normal and developmentally retarded infants. Nature, 1967, 214: 252--255. Bender, L. Childhood schizophrenia: clinical study of 100 schizophrenic children. Amer. J. Orthopsychiat., 1946, 17: 40--56. Clements, S., Peters, J. and Rock, L. Minimal brain dysfunction in the school age child. Arch. gen. Psychiat., 1968, 6: 185--197. Creak, E.M. Childhood psychosis: A review of 1043 cases. Brit. J. Psychiat., 1963, 109: 84--89. Dunn, O.J. Multiple comparison test in "Experimental design procedures for the behavioral sciences". In R.E. Kirk. (Ed.), Brooks/Cole, New York, 1968. Gubbay, S.S., Lobascher, M. and Kingerlee, P. A neurological appraisal of autistic children: Results of a Western Australian survey. Develop. Med. Child Neurol., 1970, 12: 422--429. Hecox, K. and Galambos, R. Brainstem auditory evoked responses in human infants and adults. Arch. Otolaryng., 1974, 99: 30--33.
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