Emmanuel Balzamo

Sleep disorders in Parkinson's disease: The contribution of the MPTP non-human primate model

To replicate the sleep-wake disorders of Parkinsons disease (PD) and to understand the temporal relationship between these sleep disturbances and the occurrence of parkinsonism, we performed long-term continuous electroencephalographic monitoring of vigilance states in unrestrained rhesus monkeys using an implanted miniaturized telemetry device and tested the effect of MPTP intoxication on their sleep-wake organization. MPTP injection yielded a dramatic disruption of sleep-wake architecture with reduced sleep efficacy that persisted years after MPTP administration. Primary deregulation of REM sleep and increased daytime sleepiness occurring before the emergence of motor symptoms were a striking feature of the MPTP effect. This was concomitant with a breakdown of dopaminergic homeostasis, as evidenced by decreased dopamine turnover measured after a single MPTP injection. In the long term, partial re-emergence of REM sleep paralleled the partial adaptation to parkinsonism, the latter being known to result from compensatory mechanisms within the dopaminergic system. Altogether, these findings highlight the suitability of the MPTP model of PD as a tool to model the sleep/wake disturbances of the human disease. Ultimately, this may help in deciphering the specific role of dopamine depletion in the occurrence of these disorders.

Fatigue-induced changes in diaphragmatic afferents and cortical activity in the cat

The rationale for the present study was to test the hypothesis that changes in phrenic sensory activity during diaphragmatic fatigue may modify the transmission of phrenic afferent action potentials to the cortex and also the spontaneous EEG activity. This was performed in anesthetized cats. Diaphragmatic fatigue was produced by intermittent direct muscle stimulation for a 30 min period. Diaphragmatic metaboreceptors (tonically active afferents) and mechanoreceptors (phasic phrenic activity) were identified by their activation by intraarterial lactic acid injection or their discharge in phase with diaphragmatic contraction, respectively. Cortical phrenic evoked potentials (CPEPs) and spontaneous EEG activity were recorded from the left sensorimotor area. Diaphragmatic failure was shown from the 10th minute of stimulation. Then, the activity of tonic phrenic afferents increased markedly whereas, in parallel, the phasic discharge of mechanoreceptors decreased progressively. This was associated with progressive lengthening in onset and peak latencies of CPEPs. The main EEG changes (visual and fast Fourier transform analysis) were characterized by a transient increased energy in the delta frequency band during the first minutes of the fatigue run, followed by decreased energy in the theta frequency band after 11-25 min of stimulation. Denervation of the diaphragm suppressed the EEG changes during the fatigue run. The present observations suggest that the cortical integration of sensory information from the diaphragm may be altered during fatigue.

Quantitative EEG changes under various conditions of hyperventilation in the sensorimotor cortex of the anaesthetized cat

The effects on the EEG rhythms recorded from the sensorimotor cortex (post-sigmoid gyrus) of anaesthetized cats were studied under 4 conditions of artificial mechanical hyperventilation (HV) before and after cervical bilateral vagotomy. In animals with intact vagus nerves, using visual examination, EEG changes were only observed within the 2nd min during HV produced by increased stroke volume (delta V) with associated hypocapnia. Quantitative EEG (qEEG) showed that, for the same increase in minute ventilation and the same degree of hypocapnia, delta V induced a greater and earlier relative decrease (2nd min) in the power density of delta, theta and alpha bands, than increased pump frequency (delta F). The delta F tests produced a fall only in the theta band and within the 3rd min. With constant paCO2, transient modifications occurred only with delta V and were limited to the first 30 sec. In bivagotomized cats, moderate EEG responses to delta V plus associated hypocapnia persisted partly in the alpha band. Finally, no changes appeared with delta V or delta F when the vagus nerves were cut and paCO2 was maintained constant. The present data suggest strongly that, in anaesthetized cats, peripheral vagal afferents from the respiratory system play a major role in the EEG changes caused by artificial hyperventilation.

Papio anubis: Un primate parmi les primates. Etats de vigilance et activites ponto-geniculo-corticales (PGC)

Abstract EEG, sleep-waking organization and phasic sleep activities (PGC) were studied in 6 adult female Papio anubis with chronically implanted electrodes and partially constrained. Papio anubis shows a well characterized sleep (besides an individuality peculiar to each baboon): short sleep latency (18 ± 14 min), very brief REM latency (5 ± 5 min), stable stage 1 (86 ± 11 min), REM duration with little variation (70 ± 15 min) and abundant deep sleep (stage 4 = 79 ± 44 min). Geniculate spikes, in general biphasic, occur in great number in this species: 34,778 ± 7355 per night (44.6% of them in REM). The frequency of spike discharges perminute minute in REM reaches a mean of 218 ± 10. In true slow sleep (SS 1), 4–5 spikes per group prevail; in slow sleep followed by a REM episode (SS 2), 6–10 spikes per group are the most numerous. REM is characterized by groups of 6–10 or more spikes. Several specific features are seen: (1) alternation and/or asymmetry of the bursts from the 2 lateral geniculate (LG) nuclei during SS 2 and REM, tendency towards symmetry in SS 1; (2) inversion of spike polarity in the lowest LG layers; (3) variation in spike form from one instant to another and from one LG to the other; (4) presence of spikes in the optic tract. At the cortical level, PGC phasic activities resemble the ‘saw tooth waves’ described in man. The PGC activities of various primates, and particularly of Papio anubis , seem, by their complexity, to reflect a more elaborated evolution of this particular phenomenon of sleep and differ from those of cat. The monkey lends itself, hence, as a better model for any extrapolation to man. Finally these results raise the question of species within a single genus.

Facilitation de l'etat de veille d'un traitement semi-chronique par la Sulbutiamine (Arcalion) chez Macaca mulatta

Summary Cortical electroencephalographic (EEG) activities and nycthemeral states of vigilance organization were studied in 6 adult rhesus monkeys during subchronic administration (10 days) of Sulbutiamine, a synthesized derivative of thiamine (300 mg/kg/day). Sulbutiamine induced the following modifications: o (1) In the EEG activities: increase in occurrence of fast rhythms (over 28 c/sec) during waking and also during slow sleep (SS) in which their amplitude doubled. SS spindles increased in number and amplitude. (2) In vigilance organization: waking was enhanced all along the 24 h recording and SS was reorganized (particularly at night), mostly light sleep: large decrease in stage 2 duration, increase in stage 1. REM sleep duration remained stable. These changes, occurring at around day 5 of the treatment, were more pronounced on day 10 and disappeared 2–5 days after withdrawal. This study demonstrated the clear action of Sulbutiamine upon the mechanisms regulating waking and light sleep.

Activité particulière et aléatoire chez Macaca: Le rythme delta vertex

Despite the fact that waking and sleeping EEG activities are well known in cercopithecinae, a striking random activity was noted in 3 macaque species: M. mulatta, M. fascicularis, M. nemestrina. It occurred in bursts of monophasic slow waves (250-400 msec) at 3/sec (2.5-4/sec, according to the moment and the individual at 50-480 microV amplitude, with a waxing and waning aspect. The duration was 2-24 sec. It predominated along the midline, in the precentral and supplementary motor areas; hence its name, the delta vertex rhythm. It occurred either isolated or several times within the same REM or waking episode. In some monkeys it was more or less frequent on different recording nights; however, in other monkeys it could be totally absent. Its mean total duration, for a 12 h recording, was 0.45% for M. mulatta and 0.065% for M. fascicularis. No significant correlations were found between its occurrence and the age, sex, the moment of occurrence of eye movements and sawtooth waves.