[ERPs (N200, P300 and CNV) in alcoholics: relapse risk assessment]. / Les potentiels évoqués cognitifs chez les patients alcooliques: évaluation du risque de rechute.

The cognitive event-related potentials were studied in a group of 55 alcoholic patients, paired in age and sex with a group of 18 control subjects, using a protocol oddball (visual and auditory) and a protocol VCN Go/Nogo. The N200 obtained using an auditory oddball paradigm had lower amplitude in alcoholics than in controls. A significant amplitude decrease of visual P300 was also observed in alcoholic male subjects. There was however no difference in auditory P300 between alcoholics and control subjects. Using a Go/Nogo paradigm, a significant difference on the final part of the VCN appears between alcoholic and pilot subjects. In addition, the longitudinal follow-up of the same alcoholic patients showed an electrophysiological profile that allowed dividing them into two different groups. On the initial recording (17 days after weaning), the auditory oddball P300 amplitude was significantly higher at Cz and Pz among patients who relapsed during the 3 months follow-up. The same effect appeared on the CNV protocol, where the amplitude of P300 was higher in patients who subsequently relapsed than for those who remained abstinent. Cognitive ERPs may be clinically useful to improve the prediction of risk of relapse among alcoholic patients.

[Interest of neurophysiological exploration in clinical psychiatry]. / Intérêt de l'exploration neurophysiologique en psychiatrie clinique.

Cerebral functional exploration using Event related potentials (ERPs) is greatly relevant in clinical psychiatry. Although ERP usefulness as a diagnostic tool is limited due to the complexity of psychiatric diagnosis, which raises theoretical, methodological and ethical problems that cannot be resolved by neurobiological methods, ERP offers relevant information in 3 different topics: the choice of psychotropes in pharmacotherapy; the description and understanding of cognitive processes; the psychotherapeutic relation. 1) Converging arguments from experimental studies support the hypothesis that the amplitude of P300 and CNV as well as the loudness dependence of the auditory N1/P2 response (LDAEP) are regulated by central catecholaminergic and serotoninergic neurotransmission. These systems also are the target of several psychotropes, and therefore the neurophysiological assessment may bring reliable indicators to predict favourable response to psychotropes and drug intolerance. 2) Moreover the assessment of Reaction Times and P300 and VCN parameters, jointly recorded in a single investigation, brings information about the self-organization and self-regulation of cerebral functioning, and might help the clinicians to understand the functional meaning of attentional disorders in Psychiatry. 3) Finally, the discussion of the neurophysiological results with the patient, in comparing objective and subjective data, might help him to better understand his/her difficulties and to modify his/her subjective experience of the disease.

[Study of the stress response: role of anxiety, cortisol and DHEAs]. / Etude de la réponse de stress: rôle de l'anxiété, du cortisol et du DHEAs.

AIM OF THE STUDY: Several studies have exhibited the psychological processes that are implied in the stress response and have shown, according to Selye's research, the participation of the hypothalamic-pituitary-adrenal axis and the major role of cortisol. The possible action of another adrenal steroïd, dehydroepiandrosterone (DHEA), is increasingly documented. The beneficial effect of the latter and his antistress role would be related to an antagonistic action to that of cortisol. The aim of our study was, first to assess biological and psychological aspects of the stress response, then to define the relationships that exist between these two processes. POPULATION AND METHODOLOGY: 40 subjects (21 women) aged 42 +/- 12 years, who consulted within a clinic of stress (CITES Prevert, Liege, Belgium) were studied. They all felt stressed but, according to DSM IV, were without mental disorders and drug free when examined. Subjects were asked to accomplish simple cognitive tasks: 1 - to distinguish two different auditory stimulations. The first one was a high-pitched sound of 1 470 Hz, which was presented unfrequently (20%). The second one, a low frequency tone of 800 Hz, was presented more frequently (80%). The interval between both stimuli was 1 s. The subject had to press a button when the rare stimulus was recognized. 2 - to extinguish a light after a warning tone of 64 dB, 50 ms and 1 000 Hz. The light, which followed one second later the tone, consisted of a series of flashes of 18 c/s that the subject had to stop by pressing a button. The purpose of this second procedure was that the subject was warned and had to prepare and anticipate the most rapid response. After that, subjects were submitted to self-evaluation psychological tests. The impact of psychosocial factors was assessed by Amiel-Lebigre life events questionnaire. Personality features and emotional response (state anxiety, related to experimental situation) were assessed by Spielberger inventory (STAI: State and Trait Anxiety Inventory). Psychological tests are practised immediately after experimental situation. Cortisol and DHEAs (dehydroepiandrosterone sulfate) were measured in blood samples taken before (t1) and after (t2) the experimental test. Cortisol was measured by radio-immunology and expressed as ng/ml of plasma. DHEAs was measured by radio-immunoassay and expressed as g/liter of plasma. RESULTS AND DISCUSSION: The majority of subjects displayed high scores of trait anxiety (37 subjects had a score>42) and life events impact (35 subjects had a score>200). These data confirmed that the subjects were fragile and were obviously stressed. In response to the cognitive tasks, that constituted for each subject a new event with which it was necessary to cope, 25 subjects exhibited high level of state anxiety (score>42) and an increase of cortisol plasmatic concentrations occurred solely in 11 persons. Ten among them were in the group of subjects which displayed a score of state anxiety>42 (p=0,0223, Chi square). Base on these data three types of stress response were identified: 1 - the experimental situation was experienced without anxiety ( psychological silence ) and without any increase in cortisol level ( biological silence ). There was no stress and these subjects were, despite their vulnerability, close to a normal health state . 2 - high emotional reaction (high level of state anxiety) was observed. This response reveals a psychological vulnerability that can be considered as the expression of a consecutive psychological distress induced by a threatening experimental situation. There were no biological manifestations ( biological silence ). 3 - high state anxiety and increased plasma cortisol levels were observed. The corresponding subjects were obviously more vulnerable. CONCLUSION: These results allow us to propose that the emergence of state anxiety is the first stress response and the primary protest . Up to a certain level, a plateau level, anxiety remains stable. Then, nature of the stress response changes and takes a biological aspect. Increased of cortisol plasma levels, the secondary protest , is observed and gives evidence of an intensified and sustained stress response. Such a gradual phenomenon is particularly reported in elevated psychological distress which is associated with loss of control. It is important to note that identical scores of state anxiety (Mann Whitney test) were observed in anxious subjects with or without rise of plasma cortisol levels. DHEAs was also implied in the stress response. The enhancement of plasma levels of DHEAs were dependent on cortisol, as shown by the close correlation between both hormones (r=0,433, p=0,0033, Spearman test). The hypothesis of an antagonism between these two hormones is based on the fact that DHEAs opposes the action of cortisol and exerts a true anticortisol effect. This antagonism might be related to a competition in their synthesis and release by the adrenal gland. In the present case, high level of anxiety (state and trait) was associated with an increase of cortisol, while low level (of anxiety) was related to an exclusive rise of DHEAs. Intermediate anxious score was observed in subjects who showed increases of both cortisol and DHEAs (p=0,0225, Kruskall Wallis test). Furthermore, a close relationship (negative correlation: Spearman test), was observed between increases in DHEAS and scores of state anxiety (r=- 0,382, p=0,06) and trait anxiety (r=- 0,0097, p=0,527). This means that the worriness and the underlying anxious ruminations and negative anticipations, which characterize trait anxiety, were less important in subjects who increased plasma DHEAs levels. In addition, emotional tension and uneasiness, which accompanies state anxiety, were also less marked. There are no studies reporting a relation between DHEA(s) and state or trait anxiety. Nevertheless, many authors have proposed a beneficial action of DHEA on the feeling of well-being. This beneficial role could be related to a double action of DHEA: a direct effect provided by its transformation into sexual hormones, an indirect one mediated by its competition with cortisol, of which the synthesis and consequently the activity decrease.

[Opioid addiction: P300 assessment in treatment by methadone substitution]. / Toxicomanie aux opiacés: étude au moyen de la P300 du sevrage et du traitement de substitution par la méthadone.

The aim of this study was to assess cognitive functions in two clinical conditions, namely during heroin detoxification and during substitution treatment by methadone. Two groups of chronic heroin user inpatients, meeting DSM-III-R criteria for concurrent opiate dependence, were tested using an auditory oddball paradigm of P300. The first group (four women and six men) were drug-free and the second (five women, ten men) received methadone treatment. Patients were also compared to a control group of non-dependent healthy subjects (five women, nine men). The patients were recorded 6-10 days after the beginning of either detoxification or methadone treatment. There were significant P300 alterations in the two patient groups, with amplitude decrease and latency increase, at a time when self-reported signs of withdrawal were absent or minimal. Paradoxically, the reaction time was accelerated in the two groups of patients, who also showed increased discrimination errors. These abnormalities were found with a lesser degree in the methadone-treated group than in detoxification patients.

[Interindividual variability of contingent negative variation]. / Etude de la variabilité interindividuelle de la variation contingente négative (VCN).

The use of CNV in clinical practice requires the choice of a standardised protocol, the constitution of reference normative data and the consideration of intra- and interindividual variability. For this purpose, we recorded CNV in 86 control subjects (44 men and 42 women, 18 to 62 years old (mean age = 34 +/- 13 years) during a reaction time paradigm with a warning signal and a 1-second S1-S2 interval. Moreover, the role of inter-stimulation interval was analysed in a group of 12 subjects through the comparison of recordings made with 1- and 3-second intervals. The CNV amplitude, its morphology and topographic distribution as well as its resolution mode and evolution through the recording were studied. The subjects' performances and their interactions with electroencephalographic data were also included in the analyses. Our results underscore the contribution of age and gender and psychological factors to CNV variability. CNV amplitude (both M1 and M2) increased and changed topographic distribution toward more central sites in older. Men had faster reaction times than women and lower post-S1 P300. Moreover, the life events-related stress and the subject's current anxiety level were accompanied by a decreased CNV amplitude.

The basic pattern of activation in motor and sensory temporal tasks: positron emission tomography data.

Positron emission tomography (PET) data were obtained from subjects performing a synchronization task (target duration 2700 ms). A conjunction analysis was run to identify areas prominently activated both in this task and in a temporal generalization task (target duration 700 ms) used previously. The common pattern of activation included the right prefrontal, inferior parietal and anterior cingulate cortex, the left putamen and the left cerebellar hemisphere. These areas are assumed to play a major role in time processing, in relation to attention and memory mechanisms.

[Stress, anxiety and and event related potentials]. / Stress, anxiété et potentiels liés aux événements.

Our aim was to study the relationships between stress and anxiety with both psychological and neurophysiological (Events Related Potentials: CNV and P300) methods. The study was divided into 2 parts. In the first part, the research was carried out among 32 out-patients suffering from anxiety disorders (generalized anxiety disorders) according to DSM IV. All of them were drug free and displayed scores higher than 45 on the Spielberger Anxiety State and Trait Scale. They were compared to 40 controls paired in age and sex. The 2 groups displayed a score higher than 200 on the Amiel-Lebigre Life Events scale. In the second part, the control subjects were divided into 2 sub-groups The first one displayed scores higher than 45 (anxious controls) on the Spielberger Anxiety-State Scale while the second one displayed scores lower than 45 (non anxious controls). Two ERPs were recorded, the P300 by using the classical "Oddball" experimental paradigm in auditive modality and the Contingent Negative Variation (CNV) by using a reaction time task with warning stimulus. The results showed not only clear differences between the subjects who suffered from anxiety and the controls but also showed opposite results between anxious out-patients (anxiety disorders) and anxious controls. The non anxious controls were intermediate. While the outpatients showed a decreased P300, the group of anxious control showed an increase of this potential. The first one displayed a CNV/M1 (contingent negativity variation/early part) increase and a longest reaction time, while the second one exhibit an early CNV decrease and normally reaction time. It appears that the stress response expressed itself differently according to the psychological state and the stress situation. The behavioral and neurophysiological data will be discussed in the framework of cognitive, behavioral and psychophysiological theories.

Intensity dependence of auditory evoked potentials is pronounced in migraine: an indication of cortical potentiation and low serotonergic neurotransmission?

Migraine is associated with stimulus hypersensitivity, increased evoked cortical responses, and abnormal 5-HT levels in peripheral blood. We studied cortical auditory evoked potentials (AEPs) between attacks in 35 patients suffering from migraine without aura (MO, n = 25) or with aura (MA, n = 10) and in 25 healthy volunteers. Binaural tones were delivered at 40, 50, 60, and 70 dB sensation level (SL) in a pseudorandomized order. The intensity dependence of the auditory N1-P2 component was significantly greater in MO (p = 0.003) and MA (p = 0.02) patients than in healthy controls, resulting in a much steeper amplitude/stimulus intensity function slope. When three sequential blocks of 40 averaged responses were analyzed at the 40- and 70-dB SL intensities, N1-P2 amplitude decreased in second and third blocks at both intensities in controls, but increased in migraineurs, a difference that was significant in both blocks for the 70-dB SL stimulus. The strong interictal dependence of AEPs on stimulus intensity may thus be due to potentiation (instead of habituation) of the response during repetition of the high-intensity stimulation. In concordance with previous studies of visual evoked potentials, these results confirm that migraine is characterized between attacks by an abnormality of cortical information processing, which might be a consequence of low 5-HT transmission and favor cortical energy demands.

Brain activation induced by estimation of duration: a PET study.

Duration information about a visual stimulus requires processing as do other visual features such as size or intensity. Using positron emission tomography, iterative H215O infusions, and statistical parametric mapping, we investigated the neural correlates of time processing. Nine normal subjects underwent six serial rCBF. Three tasks were studied: (a) A temporal generalization task (D task) in which the subjects had to judge (by pressing one of two keys) whether the duration of the illumination of a green LED was equal to or different from that of a previously presented standard; (b) An intensity generalization task (I task) in which the judgment concerned the intensity of the LED; and (c) A control task (C task) in which the subjects had to press one of the two keys at random in response to LED illumination. A significant increase in rCBF during the D task, compared to that during the C task, was observed in right prefontal cortex, right inferior parietal lobule, anterior cingulate cortex, vermis, and a region corresponding to the left fusiform gyrus. A significant increase in rCBF during the I task, compared to that during the C task, was observed in right prefontal cortex, right inferior parietal lobule, right extrastriate cortex, anterior cingulate cortex, left inferior parietal lobule, vermis, and two symmetrical regions corresponding to the fusiform gyri. No significant activation was observed in the D task when compared to that in the I task. We propose that these cortical maps are best explained by the recruitment of visual attention and memory structures, which play a major role in prospective time judgements as indicated by behavioral studies. The data also suggest that the temporal dimension of a visual stimulus is processed in the same areas as other visual attributes.

Catecholaminergic function and P300 amplitude in major depressive disorder (P300 and catecholamines).

The neurobiology of P300 is still a subject of controversy. P300 amplitude appears to be modulated by multiple neurotransmitter systems, especially dopaminergic, noradrenergic as well as cholinergic and GABAergic. In this study, we investigated the relationship between P300 amplitude and catecholaminergic neurotransmission as assessed by the growth hormone (GH) response to clonidine and apomorphine challenges in 20 major depressive patients. Results showed a correlation of P300 amplitude with the apomorphine test (r = 0.54; P = 0.01), but not with the clonidine test (r = 0.22; NS). This study supports a role for dopamine in the neurobiological modulation of P300 amplitude.

Cognitive functions in migraine without aura between attacks: a psychophysiological approach using the "oddball" paradigm.

"Oddball" paradigm studies of auditory P300 have yielded conflicting results in migraine. We therefore undertook an additional study of auditory event-related potentials (ERPs) using an improved method of EEG processing, strict criteria for patients selection, and comparison with behavioral data. Twenty-one healthy subjects were compared to 20 patients suffering from migraine without aura between attacks. Migraine patients differed significantly from control subjects on several parameters: shorter latency of N1 (Cz) evoked by standard stimuli, longer latencies of both P3a and P3b (Pz) evoked by target stimuli, longer interval between N1 and P3b (Cz), smaller P3b (Cz) amplitude, longer reaction time (RT), higher number of errors (false alarm and/or omissions) and higher mean score on Plutchik-Van Praag's (PVP) inventory for depression. Errors were significantly correlated with RT and PVP scores. From a behavioral perspective, these results may suggest that patients suffering from migraine without aura between attacks display a higher level of arousal and more superficial attention, but require more time for automatic and/or voluntary processes. According to the inverted U-shaped relationship between performance and arousal, these patients may have difficulties in adjusting their attention level to perform a task in a optimal way.

[Interindividual variability of exogenous and endogenous auditory evoked potentials in a condition of voluntary attention]. / Etude de la variabilité interindividuelle des potentiels évoqués auditifs exogènes et endogènes en condition d'attention volontaire.

The use of P300 in psychopathology raises the important problem of the constitution of reference normative data and of the high variability of auditive ERP's in controls. To handle better this problem, we recorded 86 control subjects, using an auditory oddball paradigm with motor response. We analyzed the successive components of the ERP's evoked by target and standard stimuli (N1, P2, N2, P3a, P3b and slow wave negativity). Our results underlined the role of age, sex and psychological factors on the ERP's interindividual variability: P3 amplitude decreased and its latency increased with age, while its topography was more frontal in the older than in the younger subjects. The P300 occurrence after standard stimuli and P3 amplitude after target stimuli were different according to sex. Moreover, P300 amplitude, latency and topography were related to the subject's anxiety level. Finally, our results also propose new description modes of ERP's relying on P3a and P3b relative peak amplitude (P300 with prominent P3a or P3b), topographical predominance (frontal or parietal P300) and duration of the late positive complex (brief or long-lasting P300). These data will improve the clinical use of P300.

[McLean's theory. Which brain model for which psychiatric practice?]. / La théorie de McLean. Quel modèle de cerveau pour quelle pratique psychiatrique?

The aim of this paper is to present the evolutionary considerations of McLean about the "Triune Brain". This author described by this term a hierarchy of three-brains-in-one, consisted by three evolutionary formations, radically different in structure and in chemistry. They are characterized as reptilian, paleomammalian, and neomammalian. Each of them plays an important role in the regulation of behavior, but there heterogeneity can induce schizophreniform ideas and feelings. Mc Lean speculations about Psychiatry emphasize genetic and biological factors in the genesis of mental disorders and lead to neglect the role of socio-cultural and familial factors.

Neurohypophyseal peptides and psychiatric diseases.

The study of neurohypophyseal function in various neuropsychiatric diseases is interesting because: (1) The main neurohypophyseal peptides vasopressin (AVP) and oxytocin (OT) share by themselves modulatory influence on behavior. (2) Hypothalamo-posterior pituitary axis is directly influenced by modifications of central neurotransmitter metabolism involved in behavior control.

Contingent negative variation: methods and potential interest in headache.

Contingent negative variation (CNV) is an event-related slow cerebral potential which has been found abnormal in migraine. Its methodology is described. Contrary to other neurophysiological techniques, CNV needs special equipment and expertise. On average, CNV amplitude is increased and its habituation is lacking in migraine without aura between attacks, but not in migraine with aura. The sensitivity of CNV as a diagnostic tool is low, but its specificity is high. CNV amplitude normalizes after treatment with beta-blockers. The CNV abnormalities in migraine might be due to hyperreactivity of central catecholaminergic pathways.

[The value of cognitive psychophysiological studies in a comprehensive approach to schizophrenia (treatment of information and attention capacities in acute-stage schizophrenia)]. / Intérêts de l'exploration en psychophysiologie cognitive dans l'approche compréhensive des schizophrénies (traitement de l'information et capacités attentionnelles dans la schizophrénie en phase aiguë).

According to information processing theory, attention deficits appear to be a nuclear disorder in schizophrenia which the study has been renewed with the development of neurophysiology technique. The originality of our research was to study in a same subject Event-Related-Potentials in three different conditions: passive and active auditory oddball paradigm for Mismatch Negativity (MMN) and P 300, and a simple reaction time task with warming stimulus for the Contingent Negative Variation (CNV). The study was carried out among 20 schizophrenic subjects (paranoid subtype with acute exacerbation, DSM-III-R) and 20 healthy volunteers. Patients differed from controls as the following: a lower amplitude of N1-P2 components of the auditive evoked potentials, a lower amplitude of MMN (absent in 20% of the psychotic subjects), a lower amplitude and a longer latency of P300, and a lower amplitude of CNV. These results suggest a fundamental dysfunction of information processing which involves the early stages of automatic and voluntary attentional cognitive processes in schizophrenia.

Apomorphine stimulation of vasopressin- and oxytocin-neurophysins. Evidence for increased oxytocinergic and decreased vasopressinergic function in schizophrenics.

Apomorphine challenge tests (0.5 mg SC) were performed in 14 normal male volunteers and in 9 male schizophrenic inpatients, drug-free for at least 2 wk. In the normal volunteers, apomorphine induced an increase of serum growth hormone (GH) (maximum at 40 min), of vasopressin-neurophysin (hNpI) (maximum at 20 min), and oxytocin-neurophysin (hNpII) (maximum at 20 min). The release of neurophysins was independent of digestive side effects. In the schizophrenics, the GH level and release pattern were similar to those in the controls. The basal level of hNpI was reduced (t0: 0.42 +/- 0.1 ng/ml in the schizophrenics and 0.66 +/- 0.05 ng/ml in the controls, p < 0.02). In contrast, the basal level of hNpII was increased (3.34 +/- 0.04 ng/ml in the schizophrenics to 0.92 +/- 0.21 ng/ml in the controls, p = 0.001). The response to apomorphine was blunted, with no significant release of hNpI or of hNpII. Although the hNpII data are consistent with an increased dopaminergic tone, the psychopathological meaning of the increased basal oxytocinergic and decreased vasopressinergic functions remains to be defined.