M. Timsit-Berthier

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 Nl-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 amplitudeistimulus 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.

Contingent Negative Variation in Migraine

SYNOPSIS

Contingent Negative Variation and Efficacy of Beta-Blocking Agents in Migraine:

Thirty-three patients with common migraine underwent contingent negative variation (CNV) recordings before receiving prophylactic beta-blocker treatment with either metoprolol (27 patients) or propranolol (6 patients) at mean daily dosages of 110 mg and 122 mg, respectively. After 3 months the therapeutic efficacy of the beta-blocker was assessed in each patient by means of a global severity score and compared with the initial CNV recordings. The mean clinical improvement was 62%. A significant positive correlation was found between CNV amplitude before prophylaxis and the clinical response to beta-blockers: patients with higher CNV tended to respond better to therapy. Eight of 10 patients with a CNV amplitude higher than -25 V had a more than 50% reduction of the severity score—that is, a good or excellent response to the beta-blocking agent—whereas only 2 of 9 patients with an amplitude lower than -20 V had a good response.

Slow potential changes in psychiatry: I. Contingent negative variation.

Abstract Contingent negative variation (CNV) amplitude, morphology, and duration have been studied in 370 subjects, distributed in 3 groups: controls (100 subjects), neurotics (135 subjects) and psychotics (135 subjects). Neurotics, especially those with hysterical characteristics, have a tendency to present small amplitude and Type A “field dependency” CNVs ( P > 0.05). Small amplitude or prolonged CNVs (Type III and Type IV curves with a “plateau” or “dome” aspect) occur significantly more often among psychotics than either normal or neurotic subjects ( P >0.001). It appears that psychotic patients seem able to respond only on the principle of “all or nothing” to the CNV paradigm.

Slow potential changes in psychiatry. II. Motor potential

Abstract The study of the motor potential was carried out on a population of 252 subjects, divided into three groups: controls (72 subjects), neurotics (86 subjects) and psychotics (94 subjects). Mainly among psychotics, and to a lesser degree among neurotics, a very different type of motor potential appears, not at all like that described in the literature concerning normal subjects (Type P motor potential). It is interesting because no inversion of polarity occurs during the muscular contraction. The negative readiness potential may present variable amplitude and duration, but in all cases it persists after the end of the motor activity and ends with a more gradual slope than is seen in the normal motor potential.

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.

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.

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.

Action of Lysine-Vasopressin on Human Electroencephalographic Activity

This study is an investigation of the central effects of vasopressin in man, as this hormone proved able to modify learning processes in animals and was applied successfully to post-traumatic, amnesic patients. Electrophysiological techniques were used to assess the effects of lysine-vasopressin (LVP) given by nasal spray (7 and 14 IU) on night sleep pattern (12 subjects), auditory evoked potentials (AEP; 26 subjects), and contingent negative variation (CNV; 26 subjects). Night sleep EEG was not modified to a great extent: in particular REM sleep did not undergo any change after LVP. Nor were AEPs modified, either in the 6-hour period following drug administration or 1 week after; CNV, however, reacted in a significant manner 6 h after drug intake, and the modifications were still present after 1 week. LVP did not affect CNV amplitude itself but its evolution through time, as CNV habituation was prevented. Such effects are discussed with regard to the neurochemical mechanisms of vasopressin action and CNV genesis.

Neuroendocrine evaluation of catecholaminergic neurotransmission in mania

Several lines of evidence suggest catecholamine overactivity (noradrenergic and/or dopaminergic) in mania. We studied the growth hormone (GH) response to clonidine (an alpha-adrenergic agonist) and apomorphine (a dopaminergic agonist) in seven inpatients meeting Research Diagnostic Criteria for mania. They had been completely drug free for at least 3 months before the neuroendocrine procedures and were age- and sex-matched to seven major depressive and seven minor depressive inpatients, drug free for at least 2 weeks. GH was assayed every 20 min for 40 min before and 120 min after either clonidine (0.15 mg i.v.) or apomorphine (0.5 mg s.c.), with an interval of at least 2 days between the tests. The three groups differed significantly in the GH peak response: after clonidine (mean +/- SD), 3.2 +/- 2.4 ng/ml in manics, 3.2 +/- 2.4 ng/ml in major depressives, and 13.2 +/- 8.7 ng/ml in minor depressives; after apomorphine, 10.5 +/- 7.4, 3.2 +/- 1.9, and 26.9 +/- 15.8, respectively. While there were significant differences between manics and minor depressives and between major and minor depressives after both clonidine and apomorphine, manics did not significantly differ from major depressives on either test. These results do not provide neuroendocrine support to the catecholaminergic hypothesis of manic disorders.