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Since the first description of infantile autism by Kanner, many physiopathological hypotheses have been suggested to explain this syndrome. In order to confirm these hypotheses, a lot of biological technics have been used among which the cerebral electroencephalography plays a leading part. The authors describe the main electroencephalographical technics used in autistic children. For each sort of examination, the physiopathological contribution has been studied. Then, these electrophysiological data have been confronted with neuroanatomical hypotheses (temporal, frontal, mesencephalic functional troubles) or neurobiochemical hypotheses (dysfunctioning of the corresponding dopaminergic systems).

Slow cerebral waves are recorded from 10 adults during an experiment consisting of the application of isolated or coupled sensorial stimulations, the weak sound occuring 880 msec prior to the strong light when coupled. Prior to coupling, the stimulations evoke on the vertex generally negative slow waves which would indicate an orientation reaction. After coupling, the responses to sound become constantly negative and are considered as waves described as "negative contingent variations". To the contrary, responses to light are inverted and become constantly positive. Such a phenomenon equally observed during experiments consisting of sound coupled to a reflex movement recalls the resolution of the negative contingent variation, the decision wave and the motor potentiel that accompanies the execution of voluntary movement, however here, it is produced during conditioning which does not require active motor participation by the subject. These results demonstrate that the simple coupling of two stimulations following the protocol developed by Pavlov provokes in man a complex collection of responses containing a motor component analogous to that which one observes in more elaborate experiments destined to prove the anticipation of the decision.

Auditory evoked responses (AER) were obtained from Cz and Fz in 30 adults (14 male, 16 female) from 20-80 years old. Sound bursts (1000 Hz-200 msec) of four different intensities were used. Peak to trough amplitudes of P1N1 and N1P2 and latencies of P1, N1 and P2 peaks were measured with increasing stimulus intensity and slopes of amplitude - intensity and latency - intensity curves were analysed for assessment of an age effect. The main result is that the increase in P1N1 amplitude with increasing stimulus intensity is more pronounced in older persons. Previous studies have established a negative correlation between the augmenting-reducing responses and HVA levels in the CSF (with lower amounts of HVA in the CSF of "augmenters"). Decreased dopamine metabolism in old subjects could account for our results, so further studies should focus on patients with pathological dopamine deficiencies.

Several biological theories were proposed to explain symptoms of childhood autism in terms of monoamine metabolic dysfunction. Clinical, electrophysiological and biochemical markers which support the dopaminergic hypothesis will be given in this paper. A factorial analysis, performed on the 'behavior summarized evaluation' (BSE, scoring behavioral data), exhibits a first component corresponding to the autistic DSM III criteria, and also shows that the disturbances of attention and perception belonged to this component. So, as well as communication, selective attention, perception and gestures, usually considered as regulated by the dopaminergic system are deeply modified and appeared as primary symptoms in autistic syndromes. Many electrophysiological data recorded in autistic children suggest both faulty modulation of sensory input and deficiency in dealing with sensory cross-modal association which have been related to a dysfunctioning of the dopaminergic system. Elevated homovanillic acid levels, the main dopamine metabolite, have been attributed to a reduced re-uptake of dopamine related to a 'longer occupation' of the receptors which is in agreement with the electrophysiological 'sensory overload'. The relationships found between these markers are discussed. Such an approach would contribute to a better understanding of the underlying mechanism of autism.

Urinary catecholamines (DA, NE, E) and their main metabolites (HVA, DOPAC, MHPG) were analyzed both as free and conjugates in eight children diagnosed as autistic according to DSM-III criteria and eight normal children. Significant differences appeared for the urinary excretion of both DA and NE and their respective metabolites: Autistic children showed low DA, high HVA, high NE, low MHPG urinary levels. These results are consistent with previous findings on altered catecholamine metabolism in autistic children. They suggest that autistic behaviors might be related to an abnormal functional imbalance among monoamines either at a molecular level or at a system level. Furthermore, they emphasize the special interest of urinary assays in pediatric research.

Auditory evoked potentials (AEPs) were recorded from 2 sites (Cz and Fz) on 17 subjects while awake. Five sound intensities were used (40-50-60-70-80 dB). Regression slopes relating AEP amplitude (N1-P2 component) to stimulus intensity were used to describe augmentation or reduction (A/R) of amplitude with increasing intensity. The individual differences thereby obtained have been related with the individual responsiveness to methylphenidate (MPD) measured by the modifications of polygraphic sleep parameters after absorption of this substance. The sleep parameters were recorded under 3 conditions: N1, night of habituation; N2, reference night (placebo); N3, night after 20 mg of methylphenidate (MPD); nights 2 and 3 consisted of a double blind cross-over. For the placebo condition, the lower the A/R slope while awake (and particularly the Fz slope), the higher the sleep efficiency, with scarcity of nocturnal awakening and precocity of the morning awakening. Individual differences concerning MPD responsiveness measured with sleep parameter modifications are significantly correlated with the frontal A/R slopes: the wakefulness effect of MPD increases as the frontal A/R slope weakens while a paradoxal drowsiness effect is observed at the other extreme (frontal augmenters). Moreover, sleep modifications due to the first night effect show similarities with those due to MPD and are correlated in the same way with frontal A/R slopes.

Childhood autism is not usually considered as a neurological disease although frequent antecedents of ante, peri and postnatal injuries are found in its antecedents. Several symptoms of autism particularly in the early development, resemble the signs observed in frontal, temporal, striatal and brainstem dysfunctioning. These cerebral structures are connected with the central dopaminergic system which may be disturbed in autistic children. Such hypotheses suggest the necessary elaboration of an infant and child "behavioral neurology".

Transcranial Doppler ultrasonographic recordings of the middle cerebral arteries were performed on eight children with autistic behavior compared to eight controls. Blood flow measurements were assessed at rest and during auditory and visual stimulations. The main result was obtained during the auditory stimulations and concerned the left artery blood flow which is lower in autistics than in controls in these conditions (p less than .02). This result confirms the possibility of a left hemisphere dysfunctioning in autistics and may be related to clinical features as language disabilities and paradoxical reactivity to auditory stimuli.

Infantile autism is a behaviorally defined syndrome. Many investigators suggest that it is probably related to a brain dysfunctioning in which catecholamine metabolism is involved. The aim of the following paper is to study the validity of different clinical and biological markers of this syndrome: 1. clinical scores using a behavioral rating scale, 2. amplitude and variability of conditioned auditory evoked potentials, 3. urinary levels of homovanillic acid. The response of these markers in autistic children treated with vitamin B6 and magnesium have been assessed. The relationships found between clinical and biological data are discussed. It can be expected that such an approach would contribute to a better understanding of the underlying mechanism of autism.

Modifications in serotonin and dopamine metabolism were evaluated in 13 children with autistic behavior and related to their responsiveness to fenfluramine treatment. A double-blind medication-placebo crossover design was used. Each patient received 1.5 mg/kg fenfluramine daily for 3 months followed and preceded by placebo for 1 month. Clinical improvement was observed in 6 children (responders). It included reduction of behavioral symptoms such as motor activity, anxiety, mood disturbances, and distractibility. Modifications of serotonin (5-HT), dopamine (DA), and DA metabolites [homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC)] were assessed at urinary levels. Responders and nonresponders showed a significant decrease of urinary 5-HT levels on fenfluramine. The main differences between the two groups of subjects were found with HVA, the major metabolite of DA. Fenfluramine significantly increased HVA levels in responders whereas no significant modification was found in nonresponders. Moreover the initial level of HVA (lower in responders) significantly differentiated the two groups. These results suggest that the clinical response to fenfluramine could be related to the dopaminergic action of this drug and that urinary DA metabolite levels could be considered as indicators of the responsiveness to fenfluramine treatment in children with autistic behavior.

Evoked potentials to auditory stimulations varying in intensity were studied in 13 children with autistic behavior treated with fenfluramine. Modifications of both amplitude and single-trial potential variability were considered according to the clinical and biochemical responsiveness to this drug. Six children (responders) were clinically improved by the treatment. Electrophysiological data were affected according to the clinical and biochemical responsiveness to fenfluramine: the auditory evoked potential amplitude increased, and the single-trial potential variability decreased at each intensity level only in responders whose dopaminergic metabolism was significantly modified by fenfluramine treatment. No modification was found in nonresponders. Both biochemical and electrophysiological results argued for an amphetamine-like action of fenfluramine in those autistic children whose attention deficits are associated with motor disturbances including hyperactivity.

The aim of this study was to study the relationships between conditioned AEPs and homovanillic acid (HVA) levels in autistic children (A, 9 boys, average age 6.3) compared to normal children (9 boys, average age 6.5) and to mentally retarded children (MR, 9 boys, average age 6.1) without any autistic behavior. AEPs were recorded at Cz and Oz during two sessions. The auditory stimulus (S) was first presented alone (habituation); the visual stimulus (L) was then presented 800 msec after S (conditioning). S was again presented alone (extinction). Urinary HVA dosage was performed on samples of urine taken after a 48-h tyrosine-free diet. Conditioning induced enhancement of AEPs. Latencies and amplitudes were smaller in autistic children. AEP presence was smaller in patients than in normal children and smaller in MR than in A children. Urinary HVA level was higher in patients and higher in the MR group than in the A group. A negative correlation between HVA level and Cz AEP presence was observed. Results showing higher Cz AEP variability and higher HVA level in MR than in autistic children tend to lead us to consider that both syndromes are related to common neurological dysfunctionings rather than indicating autistic syndrome behavioral specificity.

Relationships between augmenting-reducing (Aug/Red) in auditory modality and dopaminergic metabolism were investigated in young adults with respect to sex. The slope values of evoked potential amplitude changes with increasing intensities were used to evaluate Aug/Red both at Cz and Fz for each of the five components: P1, N1, P2, P1N1, N1P2. The greatest slopes (Aug) were found in females. Individual differences in dopaminergic metabolism were estimated by assaying free and conjugated forms of homovanillic acid (HVA) in urines. HVA excretion rates were significantly more variable in males than in females. Relationships between Aug/Red and HVA levels were only found in males. The lower the Aug/Red slopes recorded at Fz site for the N1 component (weak augmenter or reducer responses), the higher the urinary HVA level and particularly the conjugated forms of HVA. These results are of interest for further applications in psychopathology.

Anomalies in dopamine metabolism were investigated by assaying total homovanillic acid, and its free and conjugated fractions, in the urine of 34 autistic, 34 normal and 34 mentally retarded children. An increase in total homovanillic acid in autistic and retarded children is apparently due to an increase of free homovanillic acid in the autistic group and to an increase of conjugated homovanillic acid in the retarded group. Further research needs to be carried out into the central origin of homovanillic acid and to establish its relevance to autistic children.

Relationships between augmenting/reducing (aug/red) in auditory modality and dopaminergic metabolism were investigated in young normal adults. Auditory evoked potentials (AEP) to tones (750 Hz, 200 msec) varying from 50 to 80 sB SPL were recorded at Cz and Fz sites. Individual differences in dopaminergic metabolism were estimated by assaying homovanillic acid levels in urines (u-HVA). The slopes values of P1, N1 and P2 amplitude changes with increasing stimulus intensities were used to evaluate the relationships between aug/red and u-HVA levels. The results of this study showed significant negative correlations between the aug/red of the N1 component recorded at Fz site and the u-HVA concentrations: the higher the aug/red slopes (augmenting tendency), the lower the u-HVA levels. In fact, the main result was that this finding was in accordance with previous ones relating aug/red to HVA when assayed in cerebrospinal fluid (CSF). Our data also showed that in further studies on auditory aug/red, the interest should be focused on the N1 component at Fz site.