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Resume Introduction Afin d’assurer une dispensation de qualite avec les conseils adaptes, il est important que les pharmaciens disposent de toutes les informations sur la pathologie concernee. Cette etude a pour objectif d’evaluer les connaissances du pharmacien d’officine sur la narcolepsie et l’hypersomnie idiopathique et de mettre en place via la messagerie securisee, l’envoi de fiches d’informations pour les pharmaciens d’officines et les patients. Methodes Un questionnaire portant sur l’evaluation des connaissances des pharmaciens d’officines sur ces pathologies et leurs traitements, a ete envoye a 5117 pharmaciens d’officines. Par ailleurs, des fiches d’informations sur la prise en charge de la narcolepsie et de l’hypersomnie idiopathique ont ete envoyees par messagerie securisee aux pharmaciens d’officines (n = 103) de patients suivis dans les centres lyonnais de reference pediatrique et de competence adulte pour la narcolepsie et l’hypersomnie idiopathique. Resultats Cent vingt-trois pharmaciens ont repondu au questionnaire d’evaluation des connaissances. La note moyenne d’autoevaluation des connaissances des pharmaciens etait de 0,96/3. Au total, 99,2 % des repondants ont declare avoir besoin de plus d’information sur ces pathologies. Un retour tres positif a ete recu de la part des pharmaciens d’officines ayant beneficie d’un envoi d’information par messagerie securisee MonSisra. Discussion Cette etude a montre qu’il existe un besoin d’information des pharmaciens d’officines pour la prise en charge des patients atteints de narcolepsie ou d’hypersomnie idiopathique. Le transfert d’informations par messagerie securisee pourrait favoriser le lien ville/hopital dans ce contexte et permettre d’optimiser la prise en charge des patients atteints de maladies rares tout au long de leur parcours.

STUDY OBJECTIVES: First, to determine whether the 3-item Observation and Interview-based Diurnal Sleepiness Inventory (ODSI) measures the degree of excessive daytime sleepiness in patients with suspected narcolepsy or idiopathic hypersomnia (IH). Second, to assess the correlation between the ODSI and the Epworth Sleepiness Scale (ESS) as well as objective polysomnographic measurements. Third, to test the accuracy of the ODSI to detect narcolepsy or IH (narcolepsy/IH) compared with the ESS. METHODS: A total of 181 patients complaining of excessive daytime sleepiness filled in the ESS and the ODSI and underwent measurements including actigraphy, full-night polysomnography, Multiple Sleep Latency Test, and 24-hour bedrest sleep recording. RESULTS: Narcolepsy or IH was diagnosed in 76 patients. The ODSI found excessive daytime sleepiness in 92.3% of all patients and in 98.7% of those diagnosed with narcolepsy/IH. In the whole population, the ODSI was significantly positively correlated with the ESS (R = .547; 95% confidence interval: .436, .642; P < .001) and weakly with 24-hour total sleep time on bedrest recording (R = .208; 95% confidence interval: .056, .350; P = .047) but not with the Multiple Sleep Latency Test. The ODSI offered a higher negative (92.9%) and positive (44.9%) predictive value to detect narcolepsy/IH than did the ESS (66.7% and 43.3%, respectively). In the IH group, the ODSI’s third-item score (daily sleepiness duration) was significantly higher in patients with than without increased 24-hour total sleep time (P = .023). CONCLUSIONS: The ODSI is a brief, simple first-line questionnaire that explores both intensity and duration of daytime sleepiness and offers a high sensitivity to detect narcolepsy and IH. CITATION: Peter-Derex L, Subtil F, Lemaitre G, et al. Observation and Interview-based Diurnal Sleepiness Inventory for measurement of sleepiness in patients referred for narcolepsy or idiopathic hypersomnia. J Clin Sleep Med. 2020;16(9):1507–1515.

The alpha rhythm is the longest-studied brain oscillation and has been theorized to play a key role in cognition. Still, its physiology is poorly understood. In this study, we used microelectrodes and macroelectrodes in surgical epilepsy patients to measure the intracortical and thalamic generators of the alpha rhythm during quiet wakefulness. We first found that alpha in both visual and somatosensory cortex propagates from higher-order to lower-order areas. In posterior cortex, alpha propagates from higher-order anterosuperior areas toward the occipital pole, whereas alpha in somatosensory cortex propagates from associative regions toward primary cortex. Several analyses suggest that this cortical alpha leads pulvinar alpha, complicating prevailing theories of a thalamic pacemaker. Finally, alpha is dominated by currents and firing in supragranular cortical layers. Together, these results suggest that the alpha rhythm likely reflects short-range supragranular feedback, which propagates from higher- to lower-order cortex and cortex to thalamus. These physiological insights suggest how alpha could mediate feedback throughout the thalamocortical system.

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.

Nociceptive stimuli disrupt sleep, but may, or may not, entail an arousal. While arousal reactions go along with the activation of a widespread cortical network, the factors enabling such activation remain unknown. Here we used intracranial EEG in humans to test the relation between the cortical activity immediately preceding a noxious stimulus and the capacity of such a stimulus to trigger arousal. Intracranial EEG signals were analyzed during all-night sleep in 14 epileptic patients (4 women), who received laser stimuli slightly above their individual pain threshold. During 5 s preceding each stimulus, the functional correlation (spectral phase-coherence) between the main spinothalamic sensory area (posterior insula) and 12 other brain regions, grouped in four networks, as well as their spectral contents, were contrasted according to the presence of a stimulus-induced arousal, and then fed into a logistic regression model to assess their predictive value. Enhanced prestimulus phase-coherence between the sensory posterior insula and neocortical and limbic areas increased significantly the probability of arousal to nociceptive stimuli, in both slow-wave (N2) and rapid eye movements/paradoxical sleep. Furthermore, during N2 sleep, arousal was facilitated by stimulus delivery in periods of attenuated slow-wave activity. Together, these data indicate that sleep micro-states with enhanced interareal communication facilitate information transfer from sensory to higher-order cortical areas, and hence physiological arousal. SIGNIFICANCE STATEMENT Sleep is commonly subdivided into stages based on specific electrophysiological characteristics; however, within each single sleep stage, the functional state of the brain is continuously changing. Here we show that the probability for a phasic noxious stimulus to entail an arousal is modulated by the prestimulus interareal phase-coherence between sensory and higher-level cortical areas. Fluctuations in interareal communication immediately before the noxious stimulus may determine the responsiveness to incoming input by facilitating or preventing the transfer of noxious information from sensory to multiple higher-level cortical networks.

STUDY OBJECTIVES: To assess the performance of the single-channel automatic sleep staging (AS) software ASEEGA in adult patients diagnosed with various sleep disorders. METHODS: Sleep recordings were included of 95 patients (38 women, 40.5 ± 13.7 years) diagnosed with insomnia (n = 23), idiopathic hypersomnia (n = 24), narcolepsy (n = 24), and obstructive sleep apnea (n = 24). Visual staging (VS) was performed by two experts (VS1 and VS2) according to the American Academy of Sleep Medicine rules. AS was based on the analysis of a single electroencephalogram channel (Cz-Pz), without any information from electro-oculography nor electromyography. The epoch-by-epoch agreement (concordance and Conger’s coefficient [κ]) was compared pairwise (VS1-VS2, AS-VS1, AS-VS2) and between AS and consensual VS. Sleep parameters were also compared. RESULTS: The pairwise agreements were: between AS and VS1, 78.6% (κ = 0.70); AS and VS2, 75.0% (0.65); and VS1 and VS2, 79.5% (0.72). Agreement between AS and consensual VS was 85.6% (0.80), with the following distribution: insomnia 85.5% (0.80), narcolepsy 83.8% (0.78), idiopathic hypersomnia 86.1% (0.68), and obstructive sleep disorder 87.2% (0.82). A significant low-amplitude scorer effect was observed for most sleep parameters, not always driven by the same scorer. Hypnograms obtained with AS and VS exhibited very close sleep organization, except for 80% of rapid eye movement sleep onset in the group diagnosed with narcolepsy missed by AS. CONCLUSIONS: Agreement between AS and VS in sleep disorders is comparable to that reported in healthy individuals and to interexpert agreement in patients. ASEEGA could therefore be considered as a complementary sleep stage scoring tool in clinical practice, after improvement of rapid eye movement sleep onset detection. CITATION: Peter-Derex L, Berthomier C, Taillard J, et al. Automatic analysis of single-channel sleep EEG in a large spectrum of sleep disorders. J Clin Sleep Med. 2021;17(3):393–402.

Cognitive behavioural therapy for insomnia is the recommended treatment for chronic insomnia. However, up to a quarter of patients dropout from cognitive behavioural therapy for insomnia programmes. Acceptance, mindfulness and values-based actions may constitute complementary therapeutic tools to cognitive behavioural therapy for insomnia. The current study sought to evaluate the efficacy of a remotely delivered programme combining the main components of cognitive behavioural therapy for insomnia (sleep restriction and stimulus control) with the third-wave cognitive behavioural therapy acceptance and commitment therapy in adults with chronic insomnia and hypnotic dependence on insomnia symptoms and quality of life. Thirty-two participants were enrolled in a pilot randomized controlled trial: half of them were assigned to a 3-month waiting list before receiving the four "acceptance and commitment therapy-enhanced cognitive behavioural therapy for insomnia" treatment sessions using videoconference. The primary outcome was sleep quality as measured by the Insomnia Severity Index and the Pittsburgh Sleep Quality Index. All participants also filled out questionnaires about quality of life, use of hypnotics, depression and anxiety, acceptance, mindfulness, thought suppression, as well as a sleep diary at baseline, post-treatment and 6-month follow-up. A large effect size was found for Insomnia Severity Index and Pittsburgh Sleep Quality Index, but also daytime improvements, with increased quality of life and acceptance at post-treatment endpoint in acceptance and commitment therapy-enhanced cognitive behavioural therapy for insomnia participants. Improvement in Insomnia Severity Index and Pittsburgh Sleep Quality Index was maintained at the 6-month follow-up. Wait-list participants increased their use of hypnotics, whereas acceptance and commitment therapy-enhanced cognitive behavioural therapy for insomnia participants evidenced reduced use of them. This pilot study suggests that web-based cognitive behavioural therapy for insomnia incorporating acceptance and commitment therapy processes may be an efficient option to treat chronic insomnia and hypnotic dependence.

Resume L’enregistrement des reponses cerebrales a une douleur experimentale, chez des patients epileptiques avec des electrodes implantees dans differentes zones de la matrice douleur, plaide pour des reponses precoces preconscientes : les reponses insulaires posterieures et amygdaliennes avant 200 ms precedent les reponses conscientes de la matrice douleur. On peut aussi enregistrer des reponses insulaires posterieures a la projection d’images infraliminaires exprimant la douleur alors que le sujet ne percoit pas consciemment l’image. La reponse douloureuse subjective peut etre manipulee par le contexte temporel ou empathique de l’experience, sans que le sujet soit conscient de cette variation de contexte. Dans le conditionnement a une douleur repetee, beaucoup de comportements automatiques dependent de phenomenes preconscients sous controle de l’amygdale. Ainsi la douleur experimentale aide a comprendre les mecanismes preconscients des comportements emotionnels en particulier ceux dependant de l’amygdale dont on sait le role dans le stress post traumatique.

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.

Intracranial EEG (iEEG) studies have suggested that the conscious perception of pain builds up from successive contributions of brain networks in less than 1 s. However, the functional organization of cortico-subcortical connections at the multisecond time scale, and its accordance with iEEG models, remains unknown. Here, we used graph theory with modular analysis of fMRI data from 60 healthy participants experiencing noxious heat stimuli, of whom 36 also received audio stimulation. Brain connectivity during pain was organized in four modules matching those identified through iEEG, namely: 1) sensorimotor (SM), 2) medial fronto-cingulo-parietal (default mode-like), 3) posterior parietal-latero-frontal (central executive-like), and 4) amygdalo-hippocampal (limbic). Intrinsic overlaps existed between the pain and audio conditions in high-order areas, but also pain-specific higher small-worldness and connectivity within the sensorimotor module. Neocortical modules were interrelated via “connector hubs” in dorsolateral frontal, posterior parietal, and anterior insular cortices, the antero-insular connector being most predominant during pain. These findings provide a mechanistic picture of the brain networks architecture and support fractal-like similarities between the micro-and macrotemporal dynamics associated with pain. The anterior insula appears to play an essential role in information integration, possibly by determining priorities for the processing of information and subsequent entrance into other points of the brain connectome.

Summary Objective Differential diagnosis between sleep-related epileptic seizures and NREM parasomnia remains challenging. Pathophysiological markers to differentiate both conditions are needed. Activation of autonomic system is present in arousal reactions and epileptic seizures. Our study investigated whether cardiac reactivity differed between arousal disorders and sleep-related seizures. Methods Nocturnal recordings of 50 patients (10 in each group: frontal lobe epilepsy [FLE], temporal lobe epilepsy [TLE], nocturnal terror [NT], confusional arousal [CA], normal arousals [NA]) were retrospectively selected. Timing of the first motor sign and description of behaviours were assessed. Beat-to-beat RR intervals (RRI) as well as heart rate variability were analysed over a period of 60 heartbeats before and after first motor manifestation. The slope and area under the curve (AUC) of RRI were calculated. Results A significant decrease in RRI was observed at the onset of all events. Statistical analysis revealed: lower RRI in TLE than in other groups; higher slope of RRI in FLE than in NA and TLE, and higher AUC in NT and FLE than in TLE, and in NT than in NA. Sleep stage, episode duration, vocalization characteristics, lateralized or abnormal posture, exploratory behaviour differed between epileptic and parasomnia groups. Discussion Analysis of cardiac reactivity seems to be a useful objective tool, together with clinical features, for diagnosing abnormal behaviour during sleep. Cardiac reactivity in TLE could reflect epileptic discharge propagation to brain areas involved in autonomic control, while FLE and NT might involve a strong non-specific activation of the sympathetic system.

Intra-epidermal electrical stimulation (IEES) has been shown to activate selectively Aδ fibers subserving spinothalamic-mediated sensations. Owing to electrically induced highly synchronous afferent volleys, IEES induces Aδ-mediated evoked potentials at nonpainful intensities, contrasting with thermo-nociceptive laser pulses which entail painful pricking sensations. Here, we recorded intracortical responses from sensory and limbic-cognitive regions of human subjects in response to IEE and laser stimuli, in order to test the hypothesis that IEES could dissociate the sensory from nonsensory networks of nociceptive processing. Intracortical evoked potentials were obtained in 11 epileptic patients with stereotactically implanted electrodes in sensory regions receiving spinothalamic afferents (posterior insula), limbic regions receiving spino-parabrachial input (amygdalar nucleus), and high-order affective-cognitive regions (anteromedial frontal cortex, including perigenual anterior cingulate and rostromedial prefrontal areas). Responses in the sensory posterior insula were of similar amplitude and latency to IEE and laser stimuli (after accounting for heat-transduction time of laser), and consistent in both cases with spinothalamic activation. However, responses to IEES in the amygdala and the anteromedial frontal regions were inconsistent and significantly smaller compared to those evoked to the laser stimulation. Thus, IEES can effectively activate the spinothalamic-sensory system with little recruitment of affective-motivational networks, including those triggered by spino-parabrachio-amygdalar projections. The fact that identical sensory responses were associated to either painful or nonpainful percepts underscores that subjective pain perception is not solely dependent on the sensory recruitment, but rather on the combined activation of sensory, limbic and cognitive areas with precise spatiotemporal relations.

BACKGROUND Source modeling of EEG traditionally relies on interplay between physiological hypotheses and mathematical estimates. We propose to optimize the process by using evidence gathered from brain imaging and intracortical recordings. METHODS We recorded laser-evoked potentials in 18 healthy participants, using high-density EEG. Brain sources were modeled during the first second poststimulus, constraining their initial position to regions where nociceptive-related activity has been ascertained by intracranial EEG. These comprised the two posterior operculo-insular regions, primary sensorimotor, posterior parietal, anterior cingulate/supplementary motor (ACC/SMA), bilateral frontal/anterior insular, and posterior cingulate (PCC) cortices. RESULTS The model yielded an average goodness of fit of 91% for individual and 95.8% for grand-average data. When compared with intracranial recordings from 27 human subjects, no significant difference in peak latencies was observed between modeled and intracranial data for 5 of the 6 assessable regions. Morphological match was excellent for operculo-insular, frontal, ACC/SMA and PCC regions (cross-correlation > 0.7) and fair for sensori-motor and posterior parietal cortex (c-c ∼ 0.5). CONCLUSIONS Multiple overlapping activities evoked by nociceptive input can be disentangled from high-density scalp EEG guided by intracranial data. Modeled sources accurately described the timing and morphology of most activities recorded with intracranial electrodes, including those coinciding with the emergence of stimulus awareness. Hum Brain Mapp 38:6083-6095, 2017. © 2017 Wiley Periodicals, Inc.

Key points Sleep spindles have recently been shown to occur not only across multiple neocortical regions but also locally in restricted cortical areas. Here we show that local spindles are indeed present in the human posterior thalamus. Thalamic local spindles had lower spectral power than non-local ones. While non-local thalamic spindles had equal local and non-local cortical counterparts, local thalamic spindles had significantly more local cortical counterparts (i.e. occurring in a single cortical site). The preferential association of local thalamic and cortical spindles supports the notion of thalamocortical loops functioning in a modular way. Abstract Sleep spindles are believed to subserve many sleep-related functions, from memory consolidation to cortical development. Recent data using intracerebral recordings in humans have shown that they occur across multiple neocortical regions but may also be spatially restricted to specific brain areas (local spindles). The aim of this study was to characterize spindles at the level of the human posterior thalamus, with the hypothesis that, besides the global thalamic spindling activity usually observed, local spindles could also be present in the thalamus. Using intracranial, time-frequency EEG recordings in 17 epileptic patients, we assessed the distribution of thalamic spindles during natural sleep stages N2 and N3 in six thalamic nuclei. Local spindles (i.e. spindles present in a single pair of recording contacts) were observed in all the thalamic regions explored, and compared with non-local spindles in terms of intrinsic properties and cortical counterparts. Thalamic local and non-local spindles did not differ in density, frequency or duration, but local spindles had lower spectral power than non-local ones. Each thalamic spindle had a cortical counterpart. While non-local thalamic spindles had equal cortical local and non-local counterparts, local thalamic spindles had significantly more local cortical counterparts (i.e. occurring in a single cortical site). The preferential association of local thalamic and cortical spindles supports the notion of thalamocortical loops functioning in a modular way.

While long-range cortico-cortical functional connectivity has been reported by several studies as a necessary condition of conscious state, precise empirical evidence is still scarce. In the present work we provide such a direct and conclusive evidence in a set of three experiments. In the two first experiments intracranial-EEG was recorded during four distinct states in the same individuals: conscious wakefulness (CW), rapid-eye-movement sleep (REM), stable periods of slow-wave sleep (SWS) and deep propofol anaesthesia (PA). We discovered that long-range FC, computed by the weighted Symbolic-Mutual-Information (wSMI) in the 2-5Hz frequency band was a specific marker of conscious states that could discriminate CW and REM from SWS and PA. In the third experiment, we generalized this original finding on a large cohort of brain-injured patients by revealing that wSMI in the 2-5 Hz range was also able to accurately discriminate patients in the vegetative state (or unresponsive wakefulness syndrome) from patients in the minimally conscious state. Taken together the present results suggest that 2-5Hz FC is a new and robust signature of conscious states.

Objectif Les mecanismes physiologiques du bâillement sont complexes et impliquent entre autres les voies dopaminergiques. Ainsi, les bâillements spontanes sont rares dans la maladie de Parkinson idiopathique. Nous rapportons pour la premiere fois un bâillement observe dans le cadre d’un trouble du comportement sommeil paradoxal (TCSP). Methodes Un patient de 70 ans est adresse pour agitation nocturne depuis treize ans avec apparition plus recente de comportements moteurs violents au cours du sommeil. Il presente une hyposmie depuis de nombreuses annees, sans syndrome extra-pyramidal (score UPDRS moteur 0/56) ni signes dysautonomiques. Il est traite par Sertraline pour un syndrome depressif. Resultats L’enregistrement polysomnographique trouve une forme severe de syndrome d’apnees obstructives du sommeil (SAOS, IAH 40/h) associee a une perte de l’atonie musculaire en SP. L’analyse de la video montre de nombreux episodes d’agitation nocturne en SP (coups de poings, sursauts, somniloquie) evocateurs de TCSP. A deux reprises on observe des bâillements typiques au cours de ce stade en dehors des micro-eveils. Conclusion Le bâillement joue un role dans le maintien de la vigilance et sa survenue lors du sommeil est par definition pathologique. Les antidepresseurs serotoninergiques peuvent favoriser la reprise de tonus en SP et la survenue de bâillement mais a la veille. Des bâillements excessifs ont ete rapportes dans le contexte de lesions ischemiques pontiques. Chez notre patient, la survenue de bâillements dans le cadre de TCSP pourrait ainsi temoigner d’une atteinte de la region du locus subcoeruleus.

Objectif L’interpretation des tests de maintien de l’eveil (TME) repose sur la detection d’un endormissement. Nous avons evalue la prevalence des micro-sommeils (MS) au cours des TME et leur apport au diagnostic de la somnolence residuelle chez des patients souffrant de syndrome d’apnees du sommeil (SAOS) ou d’hypersomnie, traites. Methodes Les TME de 98 patients (89 SAOS, 82.6 % d’hommes, 45,3 (± 10,8) ans) ont ete relus a la recherche de MS (3 a 15 s). Les parametres de la polysomnographie (PSG) realisee la veille des TME et les donnees cliniques incluant le score d’Epworth (ESS) ont ete recueillis. La valeur diagnostique pour detecter la somnolence (ESS > 10) de la latence d’endormissement (LE) et de la latence du 1er MS (LMS) a ete evaluee par l’aire sous la courbe ROC (IC 95 %). Resultats Au moins un MS a ete observe chez 62,2 % des patients. La LMS etait positivement correlee a la LE (r = 0,68, p Conclusion Les MS sont observes dans deux tiers des TME et constituent des marqueurs d’endormissement. En situation de conduite, leur association a une baisse de performance a deja ete montree mais leur impact reel lorsqu’ils sont detectes au cours des TME reste a evaluer.

Conscious perception of painful stimuli needs the contribution of an extensive cortico-subcortical network, and is completed in less than one second. While initial activities in operculo-insular and mid-cingulate cortices have been extensively assessed, the activation timing of most areas supporting conscious pain has barely been studied. Here we used intracranial EEG to investigate the dynamics of 16 brain regions (insular, parietal, prefrontal, cingulate, hippocampal and limbic) during the first second following nociceptive-specific laser pulses. Three waves of activation could be defined according to their temporal relation with conscious perception, ascertained by voluntary motor responses. Pre-conscious activities were recorded in the posterior insula, operculum, mid-cingulate and amygdala. Antero-insular, prefrontal and posterior parietal activities started later and developed during time-frames consistent with conscious voluntary reactions. Responses from hippocampus, perigenual and perisplenial cingulate developed latest and persisted well after conscious perception occurred. Nociceptive inputs reach simultaneously sensory and limbic networks, probably through parallel spino-thalamic and spino-parabrachial pathways, and the initial limbic activation precedes conscious perception of pain. Access of sensory information to consciousness develops concomitant to fronto-parietal activity, while late-occurring responses in the hippocampal region, perigenual and posterior cingulate cortices likely underlie processes linked to memory encoding, self-awareness and pain modulation. Hum Brain Mapp 37:4301-4315, 2016. © 2016 Wiley Periodicals, Inc.

Objectif La therapie par rescenarisation d’images mentales (IRT, Imagery Rescripting Therapy) est recommandee pour le traitement des cauchemars. L’objectif de cette etude est de la valider en France, de confirmer sa faisabilite par visioconsultation pour des cas de cauchemars chroniques idiopathiques ou comorbides a un trouble traumatique. Methodes Cette etude prospective a inclus 48 adultes residant dans 28 departements differents qui ont suivi l’IRT standardise a distance. Des mesures standardisees ont ete realisees avant, 3 mois et 6 mois apres le traitement. Resultats Les ameliorations cliniques surviennent a 3 mois et sont maintenues a 6 mois : reduction de la frequence et de l’intensite des cauchemars, amelioration de la qualite du sommeil, et reduction des autres symptomes du trouble traumatique pour les patients qui en souffraient. Les tailles d’effets sont elevees et comparables a ceux des protocoles IRT en face a face. La dynamique des changements oniriques sera presentee. Une partie des resultats a ete publies dans Psychotherapy & Psychosomatics. Conclusion L’IRT est realisable a distance aussi bien pour les cauchemars idiopathiques que pour ceux symptomatiques d’un etat de stress post-traumatique.

Objectif L’analyse automatique du sommeil (AA) ASEEGA a ete developpee et validee sur la voie CzPz. L’objectif etait d’evaluer la robustesse de l’analyse automatique (AA) sur une voie frontale dans une population adulte presentant differentes pathologies du sommeil. Methodes Les polysomnographies (PSG) de 95 patients (38 femmes, 40 ± 13 ans) ont ete analysees : insomnie (n = 23), hypersomnie (n = 24), narcolepsie (n = 24), syndrome d’apnees obstructives du sommeil (SAOS) (n = 24). L’interpretation visuelle des PSG a ete realisee par 2 experts independants (AV1 et AV2, AASM). AA a analyse les voies EEG CzPz puis Fp2 sans information sur l’EOG ni l’EMG. L’impact du changement de voie sur l’accord epoque par epoque (concordance et coefficient kappa) entre les AV et AA a ete calcule. Resultats L’accord entre AA et le consensus des AV passe de 86 % (k = 0,80) a 82 % (0,74) avec comme repartition : insomnie de 86 % (0,80) a 83 % (0,76), hypersomnie de 86 % (0,80) a 82 % (0,72), narcolepsie de 84 % (0,78) a 79 % (0,70) et SAS de 87 (0,82) a 84 % (0,77). Conclusion La concordance entre AA et AV baisse quand AA est utilisee en frontale, mais elle reste superieure a 80 % sur l’ensemble du corpus. La concordance diminue differemment en fonction des pathologies. Elle est la plus basse dans la narcolepsie et reste la plus elevee pour le SAOS. Cette etude demontre la robustesse globale de l’analyse automatique en frontal et delimite son perimetre d’utilisation. Des usages innovants tels que l’ajout d’une voie EEG en polygraphie ventilatoire (« polygraphie amelioree ») pour ameliorer l’IAH sont possible.

While the world reputation of Michel Jouvet in sleep research is based on his huge work on sleep and paradoxical sleep, especially in cats, a far less-known part of his activity was dedicated to investigate and take care of patients with neurological diseases. Indeed, he was also a physician, specialized in neurophysiology and working at the neurological hospital of Lyon. He was most interested first in patients with disorders of consciousness and secondly in those with sleep/wake disorders, and especially in modafinil for the treatment of patients with narcolepsy and idiopathic hypersomnia.

Since their discovery, slow oscillations have been observed to group spindles during non-REM sleep. Previous studies assert that the slow oscillation downstate (DS) is preceded by slow spindles (10-12Hz), and followed by fast spindles (12-16Hz). Here, using both direct transcortical recordings in patients with intractable epilepsy (n=10, 8 female), as well as scalp EEG recordings from a healthy cohort (n=3, 1 female), we find in multiple cortical areas that both slow and fast spindles follow the DS. Although discrete oscillations do precede DSs, they are theta bursts (TB) centered at 5-8Hz. TBs were more pronounced for DSs in NREM stage N2 compared with N3. TB with similar properties occur in the thalamus, but unlike spindles they have no clear temporal relationship with cortical TB. These differences in corticothalamic dynamics, as well as differences between spindles and theta in coupling high frequency content, are consistent with NREM theta having separate generative mechanisms from spindles. The final inhibitory cycle of the TB coincides with the DS peak, suggesting that in N2, TB may help trigger the DS. Since the transition to N1 is marked by the appearance of theta, and the transition to N2 by the appearance of DS and thus spindles, a role of TB in triggering DS could help explain the sequence of electrophysiological events characterizing sleep. Finally, the coordinated appearance of spindles and DSs are implicated in memory consolidation processes, and the current findings redefine their temporal coupling with theta during NREM sleep.Significance StatementSleep is characterized by large slow waves which modulate brain activity. Prominent among these are ‘downstates,’ periods of a few tenths of a second when most cells stop firing, and ‘spindles,’ oscillations at about twelve times a second lasting for about a second. In this study, we provide the first detailed description of another kind of sleep wave: ‘theta bursts,’ a brief oscillation at about six cycles per second. We show, recording during natural sleep directly from the human cortex and thalamus, as well as on the human scalp, that theta bursts precede, and spindles follow downstates. Theta bursts may help trigger downstates in some circumstances, and organize cortical and thalamic activity so that memories can be consolidated during sleep.

Key points Sleep spindle are usually considered to play a major role in inhibiting sensory inputs. Using nociceptive stimuli in humans, we tested the effect of spindles on behavioural, autonomic and cortical responses in two experiments using surface and intracerebral electroencephalographic recordings. We found that sleep spindles do not prevent arousal reactions to nociceptive stimuli and that autonomic reactivity to nociceptive inputs is not modulated by spindle activity. Moreover, neither the surface sensory, nor the insular evoked responses were modulated by the spindle, as detected at the surface or within the thalamus. The present study comprises the first investigation of the effect of spindles on nociceptive information processing and the results obtained challenge the classical inhibitory effect of spindles. Abstract Responsiveness to environmental stimuli declines during sleep, and sleep spindles are often considered to play a major role in inhibiting sensory inputs. In the present study, we tested the effect of spindles on behavioural, autonomic and cortical responses to pain, in two experiments assessing surface and intracerebral responses to thermo-nociceptive laser stimuli during the all-night N2 sleep stage. The percentage of arousals remained unchanged as a result of the presence of spindles. Neither cortical nociceptive responses, nor autonomic cardiovascular reactivity were depressed when elicited within a spindle. These results could be replicated in human intracerebral recordings, where sleep spindle activity in the posterior thalamus failed to depress the thalamocortical nociceptive transmission, as measured by sensory responses within the posterior insula. Hence, the assumed inhibitory effect of spindles on sensory inputs may not apply to the nociceptive system, possibly as a result of the specificity of spinothalamic pathways and the crucial role of nociceptive information for homeostasis. Intriguingly, a late scalp response commonly considered to reflect high-order stimulus processing (the ‘P3’ potential) was significantly enhanced during spindling, suggesting a possible spindle-driven facilitation, rather than attenuation, of cortical nociception.

International audience; While nociceptive cortical activation is now well characterized in humans, understanding of the nociceptive thalamus remains largely fragmentary. We used laser stimuli and intracerebral electrodes in 17 human subjects to record nociceptive-specific field responses in 4 human thalamic nuclei and a number of cortical areas. Three nuclei known to receive spinothalamic (STT) projections in primates (ventro-postero-lateral [VPL], anterior pulvinar [PuA], and central lateral [CL]) exhibited responses with similar latency, indicating their parallel activation by nociceptive afferents. Phase coherence analysis, however, revealed major differences in their functional connectivity: while VPL and PuA drove a limited set of cortical targets, CL activities were synchronized with a large network including temporal, parietal, and frontal areas. Our data suggest that STT afferents reach simultaneously a set of lateral and medial thalamic regions unconstrained by traditional nuclear borders. The broad pattern of associated cortical networks suggests that a single nociceptive volley is able to trigger the sensory, cognitive, and emotional activities that underlie the complex pain experience. The medial pulvinar, an associative nucleus devoid of STT input, exhibited delayed responses suggesting its dependence on descending cortico-thalamic projections. Its widespread cortical connectivity suggests a role in synchronizing parietal, temporal, and frontal activities, hence contributing to the access of noxious input to conscious awareness.

The aversive experience we call "pain" results from the coordinated activation of multiple brain areas, commonly described as a "pain matrix". This is not a fixed arrangement of structures but rather a fluid system composed of several interacting networks: A 'nociceptive matrix' includes regions receiving input from ascending nociceptive systems, and ensures the bodily characteristics of physical pain. A further set of structures receiving secondary input supports the 'salience' attributes of noxious stimuli, triggers top-down cognitive controls, and -most importantly- ensures the passage from pre-conscious nociception to conscious pain. Expectations and beliefs can still modulate the conscious experience via activity in supramodal regions with widespread cortical projections such as the ventral tegmental area. Intracortical EEG responses in humans show that nociceptive cortical processing is initiated in parallel in sensory, motor and limbic areas; it progresses rapidly to the recruitment of anterior insular and fronto-parietal networks, and finally to the activation of perigenual, posterior cingulate and hippocampal structures. Functional connectivity between sensory and high-level networks increases during the first second post-stimulus, which may be determinant for access to consciousness. A model is described, progressing from unconscious sensori-motor and limbic processing of spinothalamic and spino-parabrachial input, to an immediate sense of awareness supported by coordinated activity in sensorimotor and fronto-parieto-insular networks, and leading to full declarative consciousness through integration with autobiographical memories and self-awareness, involving posterior cingulate and medial temporal areas. This complete sequence is only present during full vigilance states. We contend, however, that even in unconscious subjects, repeated limbic and vegetative activation by painful stimuli via spino-amygdalar pathways can generate implicit memory traces and stimulus-response abnormal sequences, possibly contributing to long-standing anxiety or hyperalgesic syndromes in patients surviving coma.

Every night, the human brain produces thousands of downstates and spindles during non-REM sleep. Previous studies indicate that spindles originate thalamically and downstates cortically, loosely grouping spindle occurrence. However, the mechanisms whereby the thalamus and cortex interact in generating these sleep phenomena remain poorly understood. Using bipolar depth recordings, we report here a sequence wherein: (1) convergent cortical downstates lead thalamic downstates; (2) thalamic downstates hyperpolarize thalamic cells, thus triggering spindles; and (3) thalamic spindles are focally projected back to cortex, arriving during the down-to-upstate transition when the cortex replays memories. Thalamic intrinsic currents, therefore, may not be continuously available during non-REM sleep, permitting the cortex to control thalamic spindling by inducing downstates. This archetypical cortico-thalamo-cortical sequence could provide the global physiological context for memory consolidation during non-REM sleep., 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.

International audience; Despite sleep-induced drastic decrease of self-awareness, human sleep allows some cognitive processing of external stimuli. Here we report the fortuitous observation in a patient who, while being recorded with intra-cerebral electrodes, was able, during paradoxical sleep, to reproduce a motor behaviour previously performed at wake to consciously indicate her perception of nociceptive stimulation. Noxious stimuli induced behavioural responses only if they reached the cortex during periods when mid-frontal networks (pre-SMA, pre-motor cortex) were pre-activated. Sensory responses in the opercular cortex and insula were identical whether the noxious stimulus was to evoke or not a motor behaviour; conversely, the responses in mid-anterior cingulate were specifically enhanced for stimuli yielding motor responses. Neuronal networks implicated in the voluntary preparation of movements may be reactivated during paradoxical sleep, but only if behavioural-relevant stimuli reach the cortex during specific periods of "motor awareness". These local activation appeared without any global sleep stage change. This observation opens the way to further studies on the currently unknown capacity of the sleeping brain to interact meaningfully with its environment.

Objectif L’analyse visuelle (AV) du sommeil est chronophage et experience-dependante, ce qui justifie la recherche d’alternatives fiables. L’analyse automatique (AA) monovoie Aseega a ete validee chez des sujets sains (Berthomier, 2007). L’objectif de notre etude etait d’evaluer Aseega dans une population de patients adultes presentant differentes pathologies du sommeil. Methodes Les polysomnographies (PSG) de 95 patients (38 femmes, 40,4 ± 13 ans) ont ete inclues : insomnie (n = 23), hypersomnie (n = 24), narcolepsie (n = 24), syndrome d’apnees obstructives (n = 24). L’interpretation visuelle des PSG a ete realisee par un expert selon les regles de l’AASM. L’AA, basee sur l’analyse d’une unique voie EEG sans information sur l’EOG ni l’EMG, a ete faite sur la derivation CzPz. L’accord epoque par epoque (concordance et coefficient kappa de Cohen) entre AV et AA a ete calcule. Resultats L’accord global entre AA et AV etait de 78,6 % (kappa = 0,70), avec la repartition suivante : hypersomnie 79,8 % (0,71), insomnie 78,8 % (0,71), narcolepsie 76,9 (0,69) et SAS 78,4 (0,70). La comparaison qualitative des hypnogrammes indique une organisation globale du sommeil tres proche entre les deux analyses mais une sous-detection par l’AA des endormissements en sommeil paradoxal dans le groupe narcolepsie. Conclusion La concordance entre AA et AV chez nos patients est comparable a celle rapportee entre AA et AV chez des sujets controles et entre AV et AV chez des patients. L’utilisation clinique de cet outil est envisageable si la detection des endormissements en sommeil paradoxal est affinee et le scorage des evenements implemente.

Objectif La variabilite et le cout de l’analyse visuelle (AV) du sommeil justifient la recherche d’alternatives. L’objectif de l’etude etait d’evaluer l’analyse automatique (AA) Aseega dans une population adulte presentant differentes pathologies du sommeil. Methodes Les polysomnographies (PSG) de 95 patients (38 femmes, 40 ± 13 ans) ont ete analysees : insomnie (n = 23), hypersomnie (n = 24), narcolepsie (n = 24), syndrome d’apnees obstructives (n = 24). L’interpretation visuelle des PSG a ete realisee par 2 experts independants (AV1 et AV2) selon les regles de l’AASM. L’AA score uniquement la voie EEG CzPz sans information sur l’EOG ni l’EMG. L’accord epoque par epoque (concordance et coefficient kappa) entre les AV et AA a ete calcule. Resultats Les accords etaient AA-AV1 = 78,6 % (kappa = ,70), AA-AV2 = 75 % (,65), AV1-AV2 = 79,5 % (,72). L’accord entre AA et le consensus des AV etait 85,6 % (,69) avec comme repartition : hypersomnie 87,0 % (,68), insomnie 86,1 % (,68), narcolepsie 84,6 (,67) et SAS 87,7 (,67). Sur les 20,5 % de desaccord entre AV, AA etait en accord avec une AV dans 85,5 % des cas. La comparaison qualitative des hypnogrammes indiquait une organisation globale du sommeil tres proche entre les analyses mais une sous-detection par l’AA des endormissements en sommeil paradoxal dans le groupe narcolepsie. Conclusion La concordance entre AA et AV est comparable a celle rapportee entre AA et AV chez des sujets controles et entre AV et AV chez des patients. L’utilisation clinique de cet outil est envisageable si la detection des endormissements en sommeil paradoxal est affinee et le scorage des evenements implemente.

Objectif L’objectif de Narcowork etait d’etudier l’impact de la narcolepsie sur le parcours scolaire et professionnel des patients. Methodes Soixante-neuf patients (51 NT1 et 18 NT2 ; 42,5 ± 18,2 ans) ont ete inclus entre octobre 2017 et juillet 2018 au Centre de Medecine du Sommeil adulte de Lyon. Ils ont rempli des questionnaires sur leur parcours scolaire et professionnel, leur maladie (NSS), et des echelles de qualite de vie (EQ-5D), de depression (BDI) et de somnolence (ESS). Ces donnees ont ete comparees a celles de temoins apparies sur l’âge et le sexe. Resultats Les scores de depression etaient plus eleves (OR depression severe = 4,4(1,6–12,6), p = 0,02) et la qualite de vie moins bonne (67,3 ± 18,4 vs 80,6 ± 13,2, p = 0,0007) chez les patients que chez les temoins. Aucune difference sur le redoublement ou le dernier diplome obtenu n’etait observee mais les patients avaient plus souvent vecu une reorientation scolaire (28,6 % vs 9,9 %, p = 0,01) et jugeaient leur scolarite plus difficile (45,5 % vs 16,9 %, p = 0,0007). Il n’y avait pas de difference pour la categorie et le statut professionnels mais les patients etaient significativement moins satisfaits au travail. Un meilleur parcours professionnel etait associe a une somnolence moindre (p = 0,007), une NT2 (vs NT1, p = 0,02) et une meilleure qualite de vie (p = 0,004). Conclusion Le parcours scolaire et professionnel des patients narcoleptiques semble objectivement peu differer de celui des temoins mais le vecu est plus difficile. Cette etude pilote sera suivie par l’etude multicentrique NarcoScol-narcoVitae.

Objectif Le questionnaire ODSI (Observation and interview based Diurnal Sleepiness Inventory) a ete propose comme outil d’evaluation de la somnolence chez les sujets âges. Il evalue la somnolence diurne en situation passive, active et quantifie sa duree. Notre objectif etait d’evaluer l’apport diagnostique de l’ODSI chez des patients adresses pour suspicion d’hypersomnie neurologique (HN). Methodes Cent neuf patients ont ete inclus entre juillet 2017 et juin 2018. Ils ont beneficie d’une actimetrie, d’une polysomnographie, de TILE, d’un Holter 24 h et remplis des questionnaires (ESS, Pichot, BDI, ODSI). Ils ont ete classes en 5 groupes selon la cause de la somnolence : hypersomnie neurologique (HN) (n = 52), hypersomnie psychiatrique (n = 12), SAOS (n = 21), privation de sommeil (n = 18), diagnostic incertain (n = 6). Les correlations (Spearman) entre les resultats des tests ont ete etudiees. Resultats Le score ODSI : – est positivement correle a l’ESS dans la population complete (ρ = 0,55 et p – n’est pas correle au resultat des TILE (tendance ns pour les HN) ; – a une bonne sensibilite (94 %) et valeur predictive negative (73 %) mais une faible valeur predictive positive (50 %) pour le diagnostic des HN. Conclusion L’ODSI est un questionnaire simple bien correle a l’ESS dans une population non geriatrique de sujets somnolents. L’absence de correlation entre tests subjectifs et objectifs souligne les multiples dimensions de la somnolence et l’importance d’une approche diagnostique globale.

Objectives Intra-epidermal electrical stimulation (IES) is considered to stimulate selectively and directly A δ fibres, by-passing the heat-mediated receptor process of laser stimulation. However, there has been only extra-cranial data to argue such fiber selectivity. Here, we recorded intracranial responses to IE and laser stimulations, to assess whether the two types of stimulation can demonstrate identical responses in precisely-localized brain regions. Methods We analysed intracranial evoked potentials to IE and laser (Nd:YAP) stimulations in 11 epileptic patients with stereotactically-implanted electrodes in the spinothalamic-receiving posterior insula (12 contacts) and affective-cognitive regions (amygdala, 8 contacts; anteromedial frontal region, 13 contacts). Results While both IE and laser stimuli were perceived as ‘pricking’ sensations, those elicited by IES were of lesser intensity and intrusiveness. In the posterior insula, IES-evoked and laser-evoked potentials were similar in waveform and amplitude. Peak-latencies were significantly shorter for IES than for laser, the mean latency difference being of 15.8 ms. In both the amygdala and anteromedial frontal regions, amplitudes were significantly attenuated for IES, as compared to laser. Discussion The latency difference in the posterior insula was concordant with the heat-transduction time of laser, suggesting the ability of IES to activate selectively the spinothalamic system. The depressed activations in the amygdala and anteromedial frontal regions, while preserved in the posterior sensory insula, were compatible with modest attentional-affective drive for IES. Conclusions IES can effectively activate the A δ -mediated sensory-encoding system (posterior insula) at non-nociceptive levels of stimulus intensity. Significance IES can minimize aversive reactions of patients while ensuring spinothalamic-specific sensory assessment.