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Abstract Fluctuations of consciousness and their rhythmicities have been rarely studied in patients with a disorder of consciousness after acute brain injuries. 24-h assessment of brain (EEG), behaviour (eye-opening), and circadian (clock-controlled hormones secretion from urine) functions was performed in acute brain-injured patients. The distribution, long-term predictability, and rhythmicity (circadian/ultradian) of various EEG features were compared with the initial clinical status, the functional outcome, and the circadian rhythmicities of behaviour and clock-controlled hormones. Here we show that more physiological and favourable patterns of fluctuations are associated with a higher 24 h predictability and sharp up-and-down shape of EEG switches, reminiscent of the Flip-Flop model of sleep. Multimodal rhythmic analysis shows that patients with simultaneous circadian rhythmicity for brain, behaviour, and hormones had a favourable outcome. Finally, both re-emerging EEG fluctuations and homogeneous 24-h cycles for EEG, eye-opening, and hormones appeared as surrogates for preserved functionality in brainstem and basal forebrain, which are key prognostic factors for later improvement. While the recovery of consciousness has previously been related to a high short-term complexity, we suggest in this exploratory study the importance of the high predictability of the 24 h long-term generation of brain rhythms and highlight the importance of circadian body-brain rhythms in awakening.

The interpretation of the Maintenance Wakefulness Test (MWT) relies on sleep onset detection. However, microsleeps (MSs), i.e., brief periods of sleep intrusion during wakefulness, may occur before sleep onset. We assessed the prevalence of MSs during the MWT and their contribution to the diagnosis of residual sleepiness in patients treated for obstructive sleep apnea (OSA) or hypersomnia. The MWT of 98 patients (89 OSA, 82.6% male) were analyzed for MS scoring. Polysomnography parameters and clinical data were collected. The diagnostic value for detecting sleepiness (Epworth Sleepiness Scale > 10) of sleep onset latency (SOL) and of the first MS latency (MSL) was assessed by the area under the receiver operating characteristic (ROC) curve (AUC, 95% CI). At least one MS was observed in 62.2% of patients. MSL was positively correlated with SOL (r = 0.72, p < 0.0001) but not with subjective scales, clinical variables, or polysomnography parameters. The use of SOL or MSL did not influence the diagnostic performance of the MWT for subjective sleepiness assessment (AUC = 0.66 95% CI (0.56, 0.77) versus 0.63 95% CI (0.51, 0.74)). MSs are frequent during MWTs performed in patients treated for sleep disorders, even in the absence of subjective sleepiness, and may represent physiological markers of the wake-to-sleep transition.

Abstract Long-range cortico-cortical functional connectivity has long been theorized to be necessary for conscious states. In the present work, we estimate long-range cortical connectivity in a series of intracranial and scalp EEG recordings experiments. In the two first experiments intracranial-EEG (iEEG) was recorded during four distinct states within the same individuals: conscious wakefulness (CW), rapid-eye-movement sleep (REM), stable periods of slow-wave sleep (SWS) and deep propofol anaesthesia (PA). We estimated functional connectivity using the following two methods: weighted Symbolic-Mutual-Information (wSMI) and phase-locked value (PLV). Our results showed that long-range functional connectivity in the delta-theta frequency band specifically discriminated CW and REM from SWS and PA. In the third experiment, we generalized this original finding on a large cohort of brain-injured patients. FC in the delta-theta band was significantly higher in patients being in a minimally conscious state (MCS) than in those being in a vegetative state (or unresponsive wakefulness syndrome). Taken together the present results suggest that FC of cortical activity in this slow frequency band is a new and robust signature of conscious states.

Objective: Vestibular afferents converge with nociceptive ones within the posterior insula, and can therefore modulate nociception. Consistent with this hypothesis, caloric vestibular stimulation (CVS) has been shown to reduce experimental and clinical pain. Since CVS can induce undesirable effects in a proportion of patients, here we explored an alternative means to activate non-invasively the vestibular pathways using innocuous bi-mastoid galvanic stimulation (GVS), and assessed its effects on experimental pain. Methods: Sixteen healthy volunteers participated in this study. Experimental pain was induced by noxious laser-heat stimuli to the left hand while recording pain ratings and related brain potentials (LEPs). We evaluated changes of these indices during left- or right-anodal GVS (cathode on contralateral mastoid), and contrasted them with those during sham GVS, optokinetic vestibular stimulation (OKS) using virtual reality, and attentional distraction to ascertain the vestibular-specific analgesic effects of GVS. Results: GVS elicited brief sensations of head/trunk deviation, inoffensive to all participants. Both active GVS conditions showed analgesic effects, greater for the right anodal stimulation. OKS was helpful to attain significant LEP reductions during the left-anodal stimulation. Neither sham-GVS nor the distraction task were able to modulate significantly pain ratings or LEPs. Conclusions: GVS appeared as a well-tolerated and powerful procedure for the relief of experimental pain, probably through physiological interaction within insular nociceptive networks. Either isolated or in combination with other types of vestibular activation (e.g., optokinetic stimuli), GVS deserves being tested in clinical settings.

In research and clinical contexts, parents’ report and sleep diary filled in by parents are often used to characterize sleep-wake rhythms in children. The current study aimed to investigate children self-perception of their sleep, by comparing sleep diaries filled in by themselves, actigraphic sleep recordings, and parental subjective estimation. Eighty children aged 8–9 years wore actigraph wristwatches and completed sleep diaries for 7 days, while their parents completed a sleep-schedule questionnaire about their child’ sleep. The level of agreement and correlation between sleep parameters derived from these three methods were measured. Sleep parameters were considered for the whole week and school days and weekends separately and a comparison between children with high and low sleep efficiency was carried out. Compared to actigraphy, children overestimated their sleep duration by 92 min and demonstrated significant difficulty to assess the amount of time they spent awake during the night. The estimations were better in children with high sleep efficiency compared to those with low sleep efficiency. Parents estimated that their children went to bed 36 min earlier and obtained 36.5 min more sleep than objective estimations with actigraphy. Children and parents’ accuracy to estimate sleep parameters was different during school days and weekends, supporting the importance of analyzing separately school days and weekends when measuring sleep in children. Actigraphy and sleep diaries showed good agreement for bedtime and wake-up time, but not for SOL and WASO. A satisfactory agreement for TST was observed during school days only, but not during weekends. Even if parents provided more accurate sleep estimation than children, parents’ report, and actigraphic data were weakly correlated and levels of agreement were insufficient. These results suggested that sleep diary completed by children provides interesting measures of self-perception, while actigraphy may provide additional information about nocturnal wake times. Sleep diary associated with actigraphy could be an interesting tool to evaluate parameters that could contribute to adjust subjective perception to objective sleep values.

During non-REM sleep, the thalamus produces spindles and the cortex produces downstates, but the interaction between these two areas in these sleep phenomena is not understood. Here, authors describe the dynamic loop between the thalamus and cortex that organizes the production of spindles and downstates in the human brain.

Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy, direct onsets of rapid eye movement (REM) sleep from wakefulness (DREMs) and deficiency of orexins, neuropeptides that promote wakefulness largely via activation of histamine (HA) pathways. The hypothesis that the orexin defect can be circumvented by enhancing HA release was explored in narcoleptic mice and patients using tiprolisant, an inverse H3-receptor agonist. In narcoleptic orexin−/− mice, tiprolisant enhanced HA and noradrenaline neuronal activity, promoted wakefulness and decreased abnormal DREMs, all effects being amplified by co-administration of modafinil, a currently-prescribed wake-promoting drug. In a pilot single-blind trial on 22 patients receiving a placebo followed by tiprolisant, both for 1 week, the Epworth Sleepiness Scale (ESS) score was reduced from a baseline value of 17.6 by 1.0 with the placebo (p>0.05) and 5.9 with tiprolisant (p

Sleep spindles and K-complexes (KCs) define stage 2 NREM sleep (N2) in humans. We recently showed that KCs are isolated downstates characterized by widespread cortical silence. We demonstrate here that KCs can be quasi-synchronous across scalp EEG and across much of the cortex using electrocorticography (ECOG) and localized transcortical recordings (bipolar SEEG). We examine the mechanism of synchronous KC production by creating the first conductance based thalamocortical network model of N2 sleep to generate both spontaneous spindles and KCs. Spontaneous KCs are only observed when the model includes diffuse projections from restricted prefrontal areas to the thalamic reticular nucleus (RE), consistent with recent anatomical findings in rhesus monkeys. Modeled KCs begin with a spontaneous focal depolarization of the prefrontal neurons, followed by depolarization of the RE. Surprisingly, the RE depolarization leads to decreased firing due to disrupted spindling, which in turn is due to depolarization-induced inactivation of the low-threshold Ca2+ current (IT). Further, although the RE inhibits thalamocortical (TC) neurons, decreased RE firing causes decreased TC cell firing, again because of disrupted spindling. The resulting abrupt removal of excitatory input to cortical pyramidal neurons then leads to the downstate. Empirically, KCs may also be evoked by sensory stimuli while maintaining sleep. We reproduce this phenomenon in the model by depolarization of either the RE or the widely-projecting prefrontal neurons. Again, disruption of thalamic spindling plays a key role. Higher levels of RE stimulation also cause downstates, but by directly inhibiting the TC neurons. SEEG recordings from the thalamus and cortex in a single patient demonstrated the model prediction that thalamic spindling significantly decreases before KC onset. In conclusion, we show empirically that KCs can be widespread quasi-synchronous cortical downstates, and demonstrate with the first model of stage 2 NREM sleep a possible mechanism whereby this widespread synchrony may arise.

Autonomic dysfunction is recognized to contribute to cardiovascular consequences in obstructive sleep apnea/hypopnea syndrome (OSAHS) patients who present predominant cardiovascular sympathetic activity that persists during wakefulness. Here, we examined 1) the factors that influence sympathetic cardiac modulation in response to apneas/hypopneas; and 2) the influence of autonomic activity during apneas/hypopneas on CA. Sixteen OSAHS patients underwent in-hospital polysomnography. RR interval (RR) and RR spectral analysis using wavelet transform were used to study parasympathetic (high frequency power: HF(WV)) and sympathetic (low frequency power: LF(WV) and LF(WV)/HF(WV) ratio) activity before and after apnea/hypopnea termination. Autonomic cardiac modulations were compared according to sleep stage, apnea/hypopnea type and duration, arterial oxygen saturation, and presence of CA. At apnea/hypopnea termination, RR decreased (p

Although several cognitive processes, including speech processing, have been studied during sleep, working memory (WM) has never been explored up to now. Our study assessed the capacity of WM by testing speech perception when the level of background noise and the sentential semantic length (SSL) (amount of semantic information required to perceive the incongruence of a sentence) were modulated. Speech perception was explored with the N400 component of the event-related potentials recorded to sentence final words (50% semantically congruent with the sentence, 50% semantically incongruent). During sleep stage 2 and paradoxical sleep: (1) without noise, a larger N400 was observed for (short and long SSL) sentences ending with a semantically incongruent word compared to a congruent word (i.e. an N400 effect); (2) with moderate noise, the N400 effect (observed at wake with short and long SSL sentences) was attenuated for long SSL sentences. Our results suggest that WM for linguistic information is partially preserved during sleep with a smaller capacity compared to wake.