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Biomedical subjects

N Bruneau

Publications and source records attributed to N Bruneau.

At least 19 recordsLinked to original sources

Blood flow response to auditory stimulations in normal, mentally retarded, and autistic children: a preliminary transcranial Doppler ultrasonographic study of the middle cerebral arteries.

Using the noninvasive transcranial ultrasonic Doppler method, flow dynamics of the middle cerebral arteries were investigated in relation to auditory stimulations in 12 children with autistic behavior compared with 12 normal controls and 10 mentally retarded children. In normal children, auditory stimulation evoked lateralized modifications: blood flow increased and resistance index decreased on the left side; such modifications were not recorded on the right side. This pattern should indicate vasodilatation mechanisms induced by changes in the metabolism of the brain areas supplied by the left middle cerebral arteries (MCA). Although less asymmetrical, this pattern was also found in the mentally retarded children. Autistic children significantly differed from these two groups. They displayed a symmetric pattern of responses with a blood flow decrease and resistance-index increase on both sides; this could suggest abnormal metabolic mechanisms induced by auditory stimulation in autistic children and could be related to the previous hypothesis of impairment in the development of cerebral lateralization in autism. These preliminary results show that transcranial Doppler ultrasonography may be a valuable and practicable tool for the noninvasive study of evoked blood flow responses in psychopathology.

Arousal

[Demonstration of cerebral lateralisation disorder in autistic children: study of auditory reactivity by transcranial pulsed Doppler].

Transcranial Doppler Ultrasonographic recordings of the middle cerebral arteries were performed on children with autistic behavior (AUT), compared to retarded children without autistic behavior (NON-AUT) and normal children (NOR). Blood flow measurements (resistance index) were performed at rest and during auditory stimulations. Compared to NOR and NON-AUT, significant differences of the resistance index were found in AUT on the left side, thus suggesting differences in metabolic mechanisms evoked by auditory stimulations. This result confirms the hypothesis of abnormal development of cerebral lateralization in autism.

Autistic Disorder

Auditory evoked responses (AER) and augmenting-reducing phenomenon in patients with progressive supranuclear palsy (PSP).

Variations in amplitude and latency of P1, N1 and P2 waves of AER induced by increasing the stimulus intensity (augmenting-reducing) were measured in PSP patients and compared to those observed in normal subjects. The studied population included 17 patients (10 male, 7 female, mean age 66 +/- 8 yr) with a typical PSP symptomatology and 17 normal subjects (10 male, 7 female, mean age 66 +/- 9 yr). All subjects from both the groups showed a normal auditory threshold (less than 30 db SPL or a moderately increased threshold never exceeding 10 db SPL). Nine patients had normal BAER; 4 patients showed an abnormal III wave; 3 patients showed an abnormal V wave. One patient had a poorly individualized BAER. Latencies and amplitudes of P1, N1 and P2 waves derived from Cz and Fz (linked ear reference) were studied with 50, 60, 70 and 80 db intensities and for each patient slopes of amplitude-stimulus intensity and latency-stimulus intensity curves were studied. Although patients showed decreased AER amplitudes, the augmenting-reducing phenomenon was not different from controls regarding either latency or amplitude changes with increasing stimulus intensity. Previous studies had established a negative correlation between the augmenting-reducing responses and HVA levels in the cerebrospinal fluid (CSF). Similarity of augmenting-reducing mechanisms in PSP and normal subjects favors the hypothesis of unimpaired mesocortical and mesolimbic dopaminergic pathways in PSP. This hypothesis is also supported by postmortem studies using biochemical markers.

Aged

Urinary dopamine metabolites as indicators of the responsiveness to fenfluramine treatment in children with autistic behavior.

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.

3,4-Dihydroxyphenylacetic Acid

Effect of age on auditory evoked responses (AER) and augmenting-reducing.

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.

Acoustic Stimulation

Auditory evoked potential modifications according to clinical and biochemical 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.

3,4-Dihydroxyphenylacetic Acid

[Measurement of cerebral blood flow by transcranial Doppler ultrasonography in children presenting with autistic behavior. Preliminary results].

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.

Acoustic Stimulation

Urinary free and conjugated catecholamines and metabolites in autistic children.

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.

3,4-Dihydroxyphenylacetic Acid

Urinary homovanillic acid levels of autistic children.

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.

Autistic Disorder

[Significance of clinical and biological markers in autistic syndromes in children].

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.

Autistic Disorder

[High-amplitude auditory evoked potentials as a function of the intensity of stimulation. Relation to dopaminergic metabolism].

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.

Acoustic Stimulation

Frontal auditory-evoked potential augmenting-reducing and urinary homovanillic acid.

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.

Adult

Frontal auditory evoked potentials and augmenting-reducing.

Auditory evoked potentials (AEPs) to tones (750 Hz--200 msec) ranging from 50 to 80 dB SPL were studied at Cz and Fz leads in 29 normal adults (15 males) ranging in age from 20 to 22. Peak-to-trough amplitudes were measured for the P1-N1 and the N1-P2 wave forms as well as baseline (500 msec prestimulus)-to-peak amplitudes for each component, i.e., P1, N1 and P2. Amplitudes were examined as a function of intensity and electrode location. Cz-Fz amplitude differences increased with increasing stimulus intensity, the differentiating peak being the N1 component. An overall reducing phenomenon was found at Fz in the 70-80 dB range whereas an augmenting effect was observed at Cz for these intensities. The augmenting/reducing groups defined by analysis of individual amplitude-intensity patterns were different whether we considered Fz or Cz results: Fz reducers were more numerous than Cz reducers. These results on prominent reducing at the frontal level were examined in relation to the data concerning the modulatory function of the frontal cortex on auditory EPs. Implications were drawn for the role of the frontal cortex in cortical augmenting-reducing.

Adult

[Relation between auditory evoked potentials (presence, amplitude) during sound and light conditioning and levels of dopamine derivatives in infantile autism].

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.

Attention Deficit Disorder with Hyperactivity

[Frontal evoked potentials and sensitivity to methylphenidate. Individual differences].

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.

Adult