[Sleep changes induced by chronic administration of S. 1694 (Survector) (author's transl)]. / Etude chez le singe rhésus des modifications du sommeil induites par le S. 1694 en administration prolongée.

Five adult Macaca mulatta were studied during chronic administration (24 days) of S. 1694 (10 mg/kg, i.m.). This substance induced a significant increase of the first awakening (delaying sleep onset) and an enhancement of the duration of REM and stage 4 sleep. After withdrawal, the waking effect desappeared, but the increase in stage 4 sleep was maintained for one week and REM enhancement kept rising for 15 days. This observation of long-term action underlined the validity of drug experiments in chronic treatment: S. 1694 might set a new type of monoaminergic systems regulation.

Changes in afferent and efferent phrenic activities with electrically induced diaphragmatic fatigue.

In anesthetized artificially ventilated cats, diaphragmatic fatigue was produced by direct muscle stimulation with trains of pulses for 30 min. Failure of contraction was assessed from decrease in the maximal relaxation rate of transdiaphragmatic pressure twitches. Motor activities (electromyogram and motor phrenic neurogram) were processed by fast-Fourier transform analysis, which provided the power spectrum density function (PSDF). The discharge frequency of diaphragmatic afferents was also measured. In control conditions (before fatigue), intra-arterial bolus injection of lactic acid enhanced tonically active diaphragmatic afferents, whereas it reduced the firing rate of afferent fibers activated in phase with diaphragmatic contraction or relaxation. The same sensory response pattern was observed with the development of diaphragmatic fatigue. Leftward shift in PSDFs of motor phrenic neurogram also occurred, but it preceded the failure of diaphragmatic contraction as well as the changes in the electromyogram's PSDF and afferent paths, which were closely associated with lengthening of both inspiratory and total breath durations. After section of the phrenic nerves, the motor phrenic response disappeared during the fatigue trial. This demonstrates the existence of complex reflex-induced changes in the ventilatory control during diaphragmatic fatigue. They seem to involve the participation of several types of phrenic afferents.

[Evolution of visual evoked responses during various states of vigilance in Papio papio (author's transl)]. / Evolution des réponses évoquées le long de la voie visuelle au cours du sommeil nocturne chez Papio papio

Averaged evoked responses (AER) to light flashes were recorded in baboons (Papio papio) during wakefulness, slow-wave sleep and rapid eye movement (REM) periods, at the visual cortex, retrocalcarine sulcus, optic tract (OT), lateral geniculate (LG) and pulvinar. Waking AERs were composed: in the OT, of a negative, low amplitude wave at 13.3 msec (I), a high amplitude wave at 34.8 msec (II), a negative wave at 72 msec (III) and a late component at 151 msec; in the LG, a small positive wave (II) with a peak latency of 40 msec, a high amplitude negative wave (III) with a latency of 70 msec and a late component; in the pulvinar of two low amplitude short latency waves (I and II), respectively negative and positive at 25 msec and 40 msec, then a high amplitude negative wave (III) at 75 msec and a late component; in the retrocalcarine sulcus 3 positive waves (I, II and III) were recorded at 25, 45 and 100 msec and a late component; in the visual cortex, 3 low amplitude negative waves (II, III and IV at 40, 50 and 54 msec, then a positive wave at 80 msec and some late components. In slow-wave sleep, AERs did not change in the OT, but in the LG and pulvinar, they showed an increase in the amplitude of wave II from stage 1 to stage 3. At the cortical level, early waves (II for the retrocalcarine sulcus, II and IV for the visual cortex) presented a marked increase in amplitude during stages 2 and 3, but only a slight increase for stage 1. Peak latency increase of each wave in cortical and subcortical AERs was seen during slow-wave sleep. REM AERs resembled, in amplitude and peak latency, those recorded in the LG and pulvinar during wakefulness; in the visual cortex and retrocalcarine sulcus, they were similar to those obtained during wakefulness and stage 1. In conclusion, a different evoked response was found between visual cortex and deep structures (except for the OT): firstly, during slow-wave sleep (the AERs showed a difference for stage 1 between the visual cortex or the retrocalcarine sulcus and the LG or the pulvinar), secondly, in REM (on the cortex, REM AERs looked like wakefulness and stage 1 responses); on the contrary, in the LG and pulvinar, REM AERs were similar only to those recorded during waking. Finally, it can be said that for Papio papio the differentiation and structural responses between the various stages of sleep (particularly light sleep and REM) were greater in the cortex than in the thalamic structures.

Short-latency components of evoked potentials to median nerve stimulation recorded by intracerebral electrodes in the human pre- and postcentral areas.

OBJECTIVE: To study whether sensory afferents of the hand projected directly to the primary motor cortex (M1) as they have been well electrophysiologically described in monkeys but not in humans. METHODS: We recorded intracerebrally in the central areas (pre- and/or postcentral gyrus) somatosensory evoked potentials (SEPs) to median nerve stimulation in 5 (4 women, 1 man; age 14-37 years) epileptic patients during presurgical evaluation. RESULTS: The primary somatosensory cortex (S1) showed negative-positive components peaking at about 20 and 30 ms, respectively. By contrast, M1 disclosed SEPs of two types of waveforms depending on the portion of the precentral gyrus explored by the different contacts of the electrode. Here, we demonstrated, for the first time, in the medial portion of M1, shaped like an omega in the axial plane, corresponding to the motor hand area, the occurrence of a primary negative component as in S1, but of higher amplitude and peaking at about 4 ms later. In other respects, the lateral portion of M1 disclosed positive-negative components peaking at about 21 and 31 ms, respectively. CONCLUSIONS: These electrophysiological findings, based on accurate spatial and temporal resolution of intracerebral recordings, suggested that somatosensory inputs from the hand projected directly to M1 in its medial portion.

Resistive loading reduces ventilatory response to strychnine in anesthetized rabbits.

Breathing through an inspiratory resistance induces a hypoventilation in mammals despite an increased diaphragmatic activity. We showed in previous works that an increase in GABA and endogenous opioid release in the central respiratory network could explain in part the inadequate increase in the inspiratory drive during inspiratory loading. In the present experiment, we speculated about an additional role of glycine, another inhibitory neurotransmitter. The ventilatory effects of the glycine antagonist strychnine were evaluated in two groups of anesthetized rabbits, breathing either through an inspiratory resistive load (IRL) or not (control group). In the control group, strychnine raised (+7%, P < 0.05) the minute ventilation, V, and the rate of increase in integrated diaphragmatic discharge (Edi peak/T peak: +29%, P < 0.01). In the IRL group, strychnine did not change V and produced a lesser increase in Edi peak/T peak (+9%, P < 0.05). In both groups, strychnine induced a tonic diaphragmatic discharge. These data show that there is a weak inhibition of inspiration by glycine during resistive loading, but the effect is modest compared with that observed during unloaded ventilation. Thus, it seems that IRL breathing reduces the efficacy and/or the release of this neurotransmitter in the central nervous system, in this experimental situation.

Cardiorespiratory response to bicuculline during resistive loaded breathing in anesthetized rabbits.

We hypothesized that hypoventilation induced by resistive loaded breathing may result in part from an increase in gamma-aminobutyric acid (GABA) concentration in the central nervous system. Accordingly, ventilatory depression should be minimized by GABA receptor blockade. The effects of subseizure doses of the GABAA receptor antagonist bicuculline on the cardiorespiratory variables and cortical activities were evaluated in two groups of urethane anesthetized rabbits, breathing either through an inspiratory resistive load (IRL) or not. Bicuculline induced cardiorespiratory changes which consisted mainly of an augmented respiratory rate, through shortening of expiratory duration, and of bradycardia. Bicuculline effects did not significantly differ between both groups and were accompanied by high amplitude delta rhythmic cortical activities. These data show that GABAA receptors may exert a tonic depressive effect on the respiratory circuit and suggest that endogenous GABA release is not augmented by an acute increase in the work of breathing.

Increasing background inspiratory resistance changes somatosensory sensations in healthy man.

The central purpose of the study was to investigate if increasing background inspiratory resistance, a circumstance which activated afferents from the lungs and respiratory muscles, modified somatosensory and/or auditory sensations in healthy individuals. Estimation of mechanical stimulations applied on the middle finger (somatosensory sensation) and unilateral sound-pressure stimulations (auditory sensation) was based on the computation of Stevens' power function psi = k.phi n, where psi is the estimate and phi is either the somatosensory stimuli or sound-pressures. This was studied during eupnoeic unloaded ventilation then during a 10-min period of loaded breathing followed by a 10-min recovery period. Loaded breathing significantly lowered the estimate of somatosensory stimuli (decreased n coefficient). This effect persisted during the two first minutes of recovery period. By contrast, loaded breathing did not modify the perception of auditory stimulus. As somesthetic and respiratory afferents, but not auditory afferents, project on the same area in the sensory cortex we suggest the existence of central interactions which could explain observations of the difficulties to execute accurate tasks in patients suffering from obstructive lung disease independently from the alterations in their arterial blood gases.

Influence of respiratory afferents upon the proprioceptive reflex of skeletal muscles in healthy humans.

Relationships between respiratory afferents and the motor drive to skeletal muscles are well documented in animals, but human data are scarce. Tonic vibratory response (TVR) elicited by mechanical tendon vibrations were explored in an arm (extensor digitorum, ED) and a leg (vastus lateralis, VL) muscle, in healthy subjects. Tendon vibrations were delivered during unloaded breathing and after 10 breathing cycles while the subject breathed through an inspiratory or expiratory resistive load in order to activate respiratory afferents. Inspiratory loaded breathing significantly enhanced TVR in ED and VL muscles whereas the effects of expiratory loading depended on the vibrated muscle (increased TVR in ED; decreased TVR in VL). These results suggest that inspiratory muscle afferents activated during inspiratory loading facilitate the gamma motor drive to arm and leg muscles whereas the activation of pulmonary vagal afferents during expiratory loading can exert a facilitating or suppressive influence on the gamma motor drive, depending on the limb muscle group.

Activation of respiratory afferents by resistive loaded breathing modifies somatosensory evoked potentials to median nerve stimulation in humans.

The cortical projections of respiratory afferents (vagus and respiratory muscle nerves) are well documented in humans. It is also shown that their activation during loaded breathing modifies the perception of tactile sensation as well as the motor drive to skeletal muscles. The effects of expiratory or inspiratory loaded breathing on somatosensory evoked potentials (SEPs) elicited by median nerve stimulation were studied in eight healthy subjects. No significant changes occurred in latencies of N20, N30 and P40 throughout the expiratory loading period, except for a significant lengthening in P1 latency compared with unloaded breathing. However, inspiratory loading induced a significant increase in peak latency of N20, N30 and P40 components. We suggest that projections of inspiratory afferents from the diaphragm and the intercostal muscles, activated by inspiratory loading, could be responsible for the lengthened latency of median nerve SEP components. Thus, respiratory afferents very likely interact with pathways of the somatosensory system.

Resistive loaded breathing changes the motor drive to arm and leg muscles in man.

Breathing through inspiratory or expiratory resistive loads activates respiratory afferents. In healthy individuals, we explored the recruitment of motor units in arm (adductor pollicis, AP and biceps branchialis, BB) and leg (vastus lateralis, VL) muscle groups during voluntary contractions sustained at 80% of maximal force. Quantitative EMG analysis consisted of measurement of energies in high (EH) and low (EL) frequency bands. EH and EL changes were measured at constant time, i.e. 10 and 20 s after the onset of plateau contraction. The resistive load was added to the inspiratory or the expiratory circuit for 10-min periods. Its value was high but not enough to induce changes in blood gases and blood pressure. Compared to muscle contractions performed during non-loaded breathing periods, inspiratory loading did not affect BB and VL contractions, whereas it induced significant changes in AP contraction, characterized by enhanced variations in EL value measured at 10 s. Expiratory loading affected solely the VP contraction. Then, EH decreased at 10 and 20 s while it increased always when VP contractions were executed during non-loaded breathing. Expiratory loading elevated the functional residual capacity (FRC), but the load-induced changes in VL contraction persisted when subjects adjusted their FRC to the control level. These data suggest that respiratory afferents influence the skeleto-motor drive. Thus, viscero-somatic reflex may be present in patients with severe obstructive pulmonary disease.

Photically induced epilepsy in Papio papio as a model for drug studies.

Neurophysiological studies employing drugs have been undertaken in the natural syndrome of photically induced epilepsy in the Senegalese baboon Papio papio. GABA-mediated inhibition, both pre- and posysynaptic, plays an important role in the epileptic manifestations seen in this syndrome synapses can significantly modify photically induced epileptic responses, partly as a result of changes in afferent activity. The level of activity in dopaminergic systems can also modify the epileptic signs. Among anticonvulsant drugs, barbiturates and benzodiazepines are very effective against this type of epilepsy, whereas many other drugs are weakly active or toxic. A modification of the natural model (using allylglycine as a priming agent) is convenient for correlating acute anticonvulsant activity and neurological toxicity with plasma concentrations of anticonvulsant agents.

[Night sleep study in acute and chronic psychosis (author's transl)]. / Sommeil de nuit des psychoses aiguës et chroniques.

A group of 22 psychotics (19 schizophrenics) was recorded in acute and/or chronic phase by series of 3 consecutive nights. Our main purposes were to study correlations between subgroups and sleep patterns and to follow the clinical evolution of these patients in looking at the quantitative and/or qualitative modifications of the various sleep states. Schizoaffective psychotics showed a lack of the "first night effect". The patients recorded in acute and in remission phases differ from unmedicated normal subjects: the former had less deep sleep and more "intermediate phases": the later presented an increase, sometimes very high, of REM total duration. Finally, within each subgroup, the analysis of individuals pointed out, for some of them, an evolution opposite to the general tendency.

[Night sleep study in chronic psychotics under long term flupenthixol treatment (author's transl)]. / Sommeil de nuit de psychotiques en traitement au long cours sous flupentixol.

Ten chronic psychotics under long term Flupentixol treatment were recorded by series of 3 consecutive nights (8 h.). Only minor sleep organization disturbances were found: decrease of total sleep time (stages 1, 3, 4) and lengthening of sleep onset latency. Total REM duration remained close related to control one. However, intermediary phases were frequent and over 20 min. by night. The "first night effect" was to the second but only slow sleep was implicated.

[Epidural hematoma in a child with hemophilia: diagnostic difficulties]. / Hématome épidural chez l'enfant hémophile: difficultés diagnostiques.

UNLABELLED: Spinal epidural hematoma is an uncommon complication in hemophilia. CASE REPORTS: The cases of an extensive epidural hematoma in two boys with severe hemophilia are reported. CONCLUSION: Acute onset of severe neck pain or backache leads to the diagnosis of epidural hematoma in children with hemophilia, even in the absence of neurologic symptoms. Early diagnosis is important and relies on magnetic resonance imaging. Replacement therapy is mandatory and must be prescribed before neuroradiologic imaging. Generally, children have a good neurologic outcome.

Alterations of body temperature, feeding, drinking, and sleep-wake circadian rhythms in Rhesus monkey during a 19 day Spacelab flight simulation.

Previous experiments performed with mammals during spaceflight suggest that microgravity may affect the circadian timekeeping system. However, this system could also be influenced by other factors related to the spaceflight environment, such as the animal compartment. The Rhesus project is a joint program of C.N.E.S. and N.A.S.A in which investigators in various disciplines of physiology will take advantage of flights of the Spacelab to study problems that interest them, using the Rhesus monkey as animal model. The technical characteristics of the Rhesus Research Facility in the Spacelab have been described elsewhere. In order to clarify the influence of the spaceflight environment, other than microgravity itself, on the circadian timekeeping system, we evaluated the characteristics of the circadian rhythms of body temperature, food and water intake, and sleep-wake cycles in Rhesus monkeys during the first 19-day flight simulation of this project.

Sleep-wake cycles in rhesus monkeys during Spacelab flight simulations.

Neurophysiological data has been obtained in orbital flight from various non-human Primates. Aboard Russian satellites during both Bion and Biocosmos missions, impairments in duration and organization of the states of vigilance were observed in rhesus monkeys during flight: increase in nocturnal awakening, decrease of Rapid Eye Movements-sleep (REM-sleep). It was assumed that weightlessness played a role in these changes. The former "Rhesus Project", a joint program between CNES and NASA, was devoted to physiological studies using the rhesus monkey as a human model aboard Spacelab, during 14 to 16 day orbital flights. In the first stage of this project, we investigated the effect of experimental conditions as well as specific restraint and confinement on the circadian sleep-wake rhythm in a group of rhesus monkeys. Prior to flight, our aim was to determine quantitatively and qualitatively sleep-wake cycles. These control data would thus be compared with inflight data in order to assess the influence of weightlessness.

[States of wakefulness and ponto-geniculo-cortical activities (PGC) in Papio anubis (author's transl)]. / Papio anubis: un primate parmi les primates. Etats de vigilance et activités ponto-géniculo-corticales (PGC).

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 per 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.