Regional variability in intracerebral properties of NREM to REM sleep transitions in humans.

Transitions between wake and sleep states show a progressive pattern underpinned by local sleep regulation. In contrast, little evidence is available on non-rapid eye movement (NREM) to rapid eye movement (REM) sleep boundaries, considered as mainly reflecting subcortical regulation. Using polysomnography (PSG) combined with stereoelectroencephalography (SEEG) in humans undergoing epilepsy presurgical evaluation, we explored the dynamics of NREM-to-REM transitions. PSG was used to visually score transitions and identify REM sleep features. SEEG-based local transitions were determined automatically with a machine learning algorithm using features validated for automatic intra-cranial sleep scoring (10.5281/zenodo.7410501). We analyzed 2988 channel-transitions from 29 patients. The average transition time from all intracerebral channels to the first visually marked REM sleep epoch was 8 s ± 1 min 58 s, with a great heterogeneity between brain areas. Transitions were observed first in the lateral occipital cortex, preceding scalp transition by 1 min 57 s ± 2 min 14 s (d = -0.83), and close to the first sawtooth wave marker. Regions with late transitions were the inferior frontal and orbital gyri (1 min 1 s ± 2 min 1 s, d = 0.43, and 1 min 1 s ± 2 min 5 s, d = 0.43, after scalp transition). Intracranial transitions were earlier than scalp transitions as the night advanced (last sleep cycle, d = -0.81). We show a reproducible gradual pattern of REM sleep initiation, suggesting the involvement of cortical mechanisms of regulation. This provides clues for understanding oneiric experiences occurring at the NREM/REM boundary.

Intracerebral Dynamics of Sleep Arousals: A Combined Scalp-Intracranial EEG Study.

As an intrinsic component of sleep architecture, sleep arousals represent an intermediate state between sleep and wakefulness and are important for sleep-wake regulation. They are defined in an all-or-none manner, whereas they actually present a wide range of scalp-electroencephalography (EEG) activity patterns. It is poorly understood how these arousals differ in their mechanisms. Stereo-EEG (SEEG) provides the unique opportunity to record intracranial activities in superficial and deep structures in humans. Using combined polysomnography and SEEG, we quantitatively categorized arousals during nonrapid eye movement sleep into slow wave (SW) and non-SW arousals based on whether they co-occurred with a scalp-EEG SW event. We then investigated their intracranial correlates in up to 26 brain regions from 26 patients (12 females). Across both arousal types, intracranial theta, alpha, sigma, and beta activities increased in up to 25 regions (p < 0.05; d = 0.06-0.63), while gamma and high-frequency (HF) activities decreased in up to 18 regions across the five brain lobes (p < 0.05; d = 0.06-0.44). Intracranial delta power widely increased across five lobes during SW arousals (p < 0.05 in 22 regions; d = 0.10-0.39), while it widely decreased during non-SW arousals (p < 0.05 in 19 regions; d = 0.10-0.30). Despite these main patterns, unique activities were observed locally in some regions such as the hippocampus and middle cingulate cortex, indicating spatial heterogeneity of arousal responses. Our results suggest that non-SW arousals correspond to a higher level of brain activation than SW arousals. The decrease in HF activities could potentially explain the absence of awareness and recollection during arousals.

Psychobehavioural profile in narcolepsy type 1 with and without REM sleep behaviour disorder.

REM sleep behaviour disorder (RBD) is common in narcolepsy type 1 (NT1). Abnormalities in the reward system have been observed in NT1, possibly related to impaired orexin projections towards the mesolimbic reward system, but also in RBD when associated with Parkinson's disease. Our study aimed to explore the psychobehavioural profile of NT1 patients with and without RBD compared with healthy controls (HC). Forty patients with NT1 were compared with 20 sex- and age-matched HC. All patients with NT1 underwent a video-polysomnography including a measure of REM sleep without atonia (RSWA). The following neuropsychobehavioural variables were assessed: apathy, impulsivity, depression, cognition, subjective and objective attention, sensation-seeking, and behavioural addictions. The patient population included 22 patients with NT1-RBD and 18 patients with NT1-noRBD. Compared with the healthy controls, patients with NT1 had higher scores of apathy, impulsivity, and depression; a lower score on global cognition, and poorer self-perceived attention. No differences were found between patients with NT1 with and without RBD in all neuropsychological variables, except for impaired objective attention in patients with NT1-RBD. In patients with NT1, a positive correlation was observed between RSWA and both apathy and impulsivity subscale. Moreover, in patients with NT1-RBD, RSWA was positively correlated with depression. Patients with NT1 showed higher depression, apathy, and impulsivity compared with controls. These measures correlate with the severity of RSWA, suggesting a transdiagnostic association between RBD and abnormalities of the reward system at least for patients with NT1.

Revisiting the maintenance of wakefulness test: from intra-/inter-scorer agreement to normative values in patients treated for obstructive sleep apnea.

The Maintenance of Wakefulness Test is widely used to objectively assess sleepiness and make safety-related decisions, but its interpretation is subjective and normative values remain debated. Our work aimed to determine normative thresholds in non-subjectively sleepy patients with well-treated obstructive sleep apnea, and to assess intra- and inter-scorer variability. We included maintenance of wakefulness tests of 141 consecutive patients with treated obstructive sleep apnea (90% men, mean (SD) age 47.5 (9.2) years, mean (SD) pre-treatment apnea-hypopnea index of 43.8 (20.3) events/h). Sleep onset latencies were independently scored by two experts. Discordant scorings were reviewed to reach a consensus and half of the cohort was double-scored by each scorer. Intra- and inter-scorer variability was assessed using Cohen's kappa for 40, 33, and 19 min mean sleep latency thresholds. Consensual mean sleep latencies were compared between four groups according to subjective sleepiness (Epworth Sleepiness Scale score < versus ≥11) and residual apnea-hypopnea index (< versus ≥15 events/h). In well-treated non-sleepy patients (n = 76), the consensual mean (SD) sleep latency was 38.4 (4.2) min (lower normal limit [mean - 2SD] = 30 min), and 80% of them did not fall asleep. Intra-scorer agreement on mean sleep latency was high but inter-scorer was only fair (Cohen's kappa 0.54 for 33-min threshold, 0.27 for 19-min threshold), resulting in changes in latency category in 4%-12% of patients. A higher sleepiness score but not the residual apnea-hypopnea index was significantly associated with a lower mean sleep latency. Our findings suggest a higher than usually accepted normative threshold (30 min) in this context and emphasise the need for more reproducible scoring approaches.

Sleep and epilepsy: A snapshot of knowledge and future research lines.

Sleep and epilepsy have a reciprocal relationship, and have been recognized as bedfellows since antiquity. However, research on this topic has made a big step forward only in recent years. In this narrative review we summarize the most stimulating discoveries and insights reached by the "European school." In particular, different aspects concerning the sleep-epilepsy interactions are analysed: (a) the effects of sleep on epilepsy; (b) the effects of epilepsy on sleep structure; (c) the relationship between epilepsy, sleep and epileptogenesis; (d) the impact of epileptic activity during sleep on cognition; (e) the relationship between epilepsy and the circadian rhythm; (f) the history and features of sleep hypermotor epilepsy and its differential diagnosis; (g) the relationship between epilepsy and sleep disorders.

Rapid Eye Movement Sleep Sawtooth Waves Are Associated with Widespread Cortical Activations.

Sawtooth waves (STW) are bursts of frontocentral slow oscillations recorded in the scalp electroencephalogram (EEG) during rapid eye movement (REM) sleep. Little is known about their cortical generators and functional significance. Stereo-EEG performed for presurgical epilepsy evaluation offers the unique possibility to study neurophysiology in situ in the human brain. We investigated intracranial correlates of scalp-detected STW in 26 patients (14 women) undergoing combined stereo-EEG/polysomnography. We visually marked STW segments in scalp EEG and selected stereo-EEG channels exhibiting normal activity for intracranial analyses. Channels were grouped in 30 brain regions. The spectral power in each channel and frequency band was computed during STW and non-STW control segments. Ripples (80-250 Hz) were automatically detected during STW and control segments. The spectral power in the different frequency bands and the ripple rates were then compared between STW and control segments in each brain region. An increase in 2-4 Hz power during STW segments was found in all brain regions, except the occipital lobe, with large effect sizes in the parietotemporal junction, the lateral and orbital frontal cortex, the anterior insula, and mesiotemporal structures. A widespread increase in high-frequency activity, including ripples, was observed concomitantly, involving the sensorimotor cortex, associative areas, and limbic structures. This distribution showed a high spatiotemporal heterogeneity. Our results suggest that STW are associated with widely distributed, but locally regulated REM sleep slow oscillations. By driving fast activities, STW may orchestrate synchronized reactivations of multifocal activities, allowing tagging of complex representations necessary for REM sleep-dependent memory consolidation.SIGNIFICANCE STATEMENT Sawtooth waves (STW) present as scalp electroencephalographic (EEG) bursts of slow waves contrasting with the low-voltage fast desynchronized activity of REM sleep. Little is known about their cortical origin and function. Using combined stereo-EEG/polysomnography possible only in the human brain during presurgical epilepsy evaluation, we explored the intracranial correlates of STW. We found that a large set of regions in the parietal, frontal, and insular cortices shows increases in 2-4 Hz power during scalp EEG STW, that STW are associated with a strong and widespread increase in high frequencies, and that these slow and fast activities exhibit a high spatiotemporal heterogeneity. These electrophysiological properties suggest that STW may be involved in cognitive processes during REM sleep.

Dynamics of hippocampus and orbitofrontal cortex activity during arousing reactions from sleep: An intracranial electroencephalographic study.

Sleep is punctuated by transient elevations of vigilance level called arousals or awakenings depending on their durations. Understanding the dynamics of brain activity modifications during these transitional phases could help to better understand the changes in cognitive functions according to vigilance states. In this study, we investigated the activity of memory-related areas (hippocampus and orbitofrontal cortex) during short (3 s to 2 min) arousing reactions detected from thalamic activity, using intracranial recordings in four drug-resistant epilepsy patients. The average power of the signal between 0.5 and 128 Hz was compared across four time windows: 10 s of preceding sleep, the first part and the end of the arousal/awakening, and 10 s of wakefulness. We observed that (a) in most frequency bands, the spectral power during hippocampal arousal/awakenings is intermediate between wakefulness and sleep whereas frontal cortex shows an early increase in low and fast activities during non-rapid-eye-movement (NREM) sleep arousals/awakenings; (b) this pattern depends on the preceding sleep stage with fewer modifications for REM than for non-REM sleep arousal/awakenings, potentially reflecting the EEG similarities between REM sleep and wakefulness; (c) a greater activation at the arousing reaction onset in the prefrontal cortex predicts longer arousals/awakenings. Our findings suggest that hippocampus and prefrontal arousals/awakenings are progressive phenomena modulated by sleep stage, and, in the neocortex, by the intensity of the early activation. This pattern of activity could underlie the link between sleep stage, arousal/awakening duration and restoration of memory abilities including dream recall.

Sleep Disruption in Epilepsy: Ictal and Interictal Epileptic Activity Matter.

OBJECTIVE: Disturbed sleep is common in epilepsy. The direct influence of nocturnal epileptic activity on sleep fragmentation remains poorly understood. Stereo-electroencephalography paired with polysomnography is the ideal tool to study this relationship. We investigated whether sleep-related epileptic activity is associated with sleep disruption. METHODS: We visually marked sleep stages, arousals, seizures, and epileptic bursts in 36 patients with focal drug-resistant epilepsy who underwent combined stereo-electroencephalography/polysomnography during presurgical evaluation. Epileptic spikes were detected automatically. Spike and burst indices (n/sec/channel) were computed across four 3-second time windows (baseline sleep, pre-arousal, arousal, and post-arousal). Sleep stage and anatomic localization were tested as modulating factors. We assessed the intra-arousal dynamics of spikes and their relationship with the slow wave component of non-rapid eye-movement sleep (NR) arousals. RESULTS: The vast majority of sleep-related seizures (82.4%; 76.5% asymptomatic) were followed by awakenings or arousals. The epileptic burst index increased significantly before arousals as compared to baseline and postarousal, irrespective of sleep stage or brain area. A similar pre-arousal increase was observed for the spike index in NR stage 2 and rapid eye-movement sleep. In addition, the spike index increased during the arousal itself in neocortical channels, and was strongly correlated with the slow wave component of NR arousals (r = 0.99, p < 0.0001). INTERPRETATION: Sleep fragmentation in focal drug-resistant epilepsy is associated with ictal and interictal epileptic activity. The increase in interictal epileptic activity before arousals suggests its participation in sleep disruption. An additional increase in the spike rate during arousals may result from a sleep-wake boundary instability, suggesting a bidirectional relationship. ANN NEUROL 2020;88:907-920.

Telehealth-delivered CBT-I programme enhanced by acceptance and commitment therapy for insomnia and hypnotic dependence: A pilot randomized controlled trial.

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.

The human K-complex: Insights from combined scalp-intracranial EEG recordings.

Sleep spindles and K-complexes (KCs) are a hallmark of N2 sleep. While the functional significance of spindles is comparatively well investigated, there is still ongoing debate about the role of the KC: it is unclear whether it is a cortical response to an arousing stimulus (either external or internal) or whether it has sleep-promoting properties. Invasive intracranial EEG recordings from individuals with drug-resistant epilepsy offer a unique opportunity to study in-situ human brain physiology. To better understand the function of the KC, we aimed to (i) investigate the intracranial correlates of spontaneous scalp KCs, and (ii) compare the intracranial activity of scalp KCs associated or not with arousals. Whole-night recordings from adults with drug-resistant focal epilepsy who underwent combined intracranial-scalp EEG for pre-surgical evaluation at the Montreal Neurological Institute between 2010 and 2018 were selected. KCs were visually marked in the scalp and categorized according to the presence of microarousals: (i) Pre-microarousal KCs; (ii) KCs during an ongoing microarousal; and (iii) KCs without microarousal. Power in different spectral bands was computed to compare physiological intracranial EEG activity at the time of scalp KCs relative to the background, as well as to compare microarousal subcategories. A total of 1198 scalp KCs selected from 40 subjects were analyzed, resulting in 32,504 intracranial KC segments across 992 channels. Forty-seven percent of KCs were without microarousal, 30% were pre-microarousal, and 23% occurred during microarousals. All scalp KCs were accompanied by widespread cortical increases in delta band power (0.3-4 â€‹Hz) relative to the background: the highest percentages were observed in the parietal (60-65%) and frontal cortices (52-58%). Compared to KCs without microarousal, pre-microarousal KCs were accompanied by increases (66%) in beta band power (16-30 â€‹Hz) in the motor cortex, which was present before the peak of the KC. In addition, spatial distribution of spectral power changes following each KC without microarousal revealed that certain brain regions were associated with increases in delta power (25-62%) or decreases in alpha/beta power (11-24%), suggesting a sleep-promoting pattern, whereas others were accompanied by increases of higher frequencies (12-27%), suggesting an arousal-related pattern. This study shows that KCs can be generated across widespread cortical areas. Interestingly, the motor cortex shows awake-like EEG activity before the onset of KCs followed by microarousals. Our findings also highlight region-specific sleep- or arousal-promoting responses following KCs, suggesting a dual role for the human KC.

Rapid eye movement sleep behaviour disorder symptomatic of a brain stem cavernoma.

A 75-year-old man complained of excessive daytime sleepiness (EDS), difficulty falling asleep and nocturnal agitation during sleep. Restless legs syndrome (RLS) was diagnosed and treated. Because of persistent EDS, snoring and nycturia, a nocturnal polysomnography (PSG) was performed. PSG showed high sleep fragmentation related to a moderate to severe obstructive sleep apnea syndrome. Continuous positive airway pressure treatment (CPAP) was proposed. Because of the persistence of abnormal nocturnal behaviours, characterized by screaming, punching and falling out of bed, a video-PSG with CPAP treatment was performed. The recording showed typical chin electromyography (EMG) activity increase associated with violent movements during rapid eye movement (REM) sleep, suggesting REM sleep behaviour disorders (RBD). Clinical neurological examination found no parkinsonian syndrome, no dysautonomic sign and no neurological focal sign. Dopamine transporter imaging [123I-FP-CIT single photon emission computed tomography (SPECT)] did not find any presynaptic dopaminergic pathways degeneration. Brain magnetic resonance imaging showed a vascular lesion suggestive of cavernoma located in the pons. The present case illustrates the complexity of sleep disturbance diagnosis with a possible entanglement of aetiologies responsible for nocturnal agitation, and confirms that an isolated pons cavernoma should be considered among the rare causes of RBD.

Sleep Disturbances and Osteoarthritis.

Sleep disturbances are particularly troublesome in patients with painful rheumatic disease. This article reviews the literature specifically published on sleep disturbances in osteoarthritis, a prevalent pathology and leading cause of disability. Several aspects of the relationship between sleep and osteoarthritis are discussed, including epidemiology, pathophysiological hypotheses, and treatment outcomes. Sleep is of central importance in the well-being of patients and should systematically be assessed in patients with osteoarthritis. When needed, a specific treatment of sleep disorders should be associated with an optimal management of pain to achieve synergistic improvements in quality of life. More large-scale studies are needed to identify predictive factors of sleep impairment in osteoarthritis.

Heterogeneity of arousals in human sleep: A stereo-electroencephalographic study.

Wakefulness, non-rapid eye movement (NREM), and rapid eye movement (REM) sleep are characterized by specific brain activities. However, recent experimental findings as well as various clinical conditions (parasomnia, sleep inertia) have revealed the presence of transitional states. Brief intrusions of wakefulness into sleep, namely, arousals, appear as relevant phenomena to characterize how brain commutes from sleep to wakefulness. Using intra-cerebral recordings in 8 drug-resistant epileptic patients, we analyzed electroencephalographic (EEG) activity during spontaneous or nociceptive-induced arousals in NREM and REM sleep. Wavelet spectral analyses were performed to compare EEG signals during arousals, sleep, and wakefulness, simultaneously in the thalamus, and primary, associative, or high-order cortical areas. We observed that 1) thalamic activity during arousals is stereotyped and its spectral composition corresponds to a state in-between wakefulness and sleep; 2) patterns of cortical activity during arousals are heterogeneous, their manifold spectral composition being related to several factors such as sleep stages, cortical areas, arousal modality ("spontaneous" vs nociceptive-induced), and homeostasis; 3) spectral compositions of EEG signals during arousal and wakefulness differ from each other. Thus, stereotyped arousals at the thalamic level seem to be associated with different patterns of cortical arousals due to various regulation factors. These results suggest that the human cortex does not shift from sleep to wake in an abrupt binary way. Arousals may be considered more as different states of the brain than as "short awakenings." This phenomenon may reflect the mechanisms involved in the negotiation between two main contradictory functional necessities, preserving the continuity of sleep, and maintaining the possibility to react.

From physiological awakening to pathological sleep inertia: Neurophysiological and behavioural characteristics of the sleep-to-wake transition.

Sleep inertia refers to the transient physiological state of hypoarousal upon awakening, associated with various degrees of impaired neurobehavioral performance, confusion, a desire to return to sleep and often a negative emotional state. Scalp and intracranial electro-encephalography as well as functional imaging studies have provided evidence that the sleep inertia phenomenon is underpinned by an heterogenous cerebral state mixing local sleep and local wake patterns of activity, at the neuronal and network levels. Sleep inertia is modulated by homeostasis and circadian processes, sleep stage upon awakening, and individual factors; this translates into a huge variability in its intensity even under physiological conditions. In sleep disorders, especially in hypersomnolence disorders such as idiopathic hypersomnia, sleep inertia may be a daily, serious and long-lasting symptom leading to severe impairment. To date, few tools have been developed to assess sleep inertia in clinical practice. They include mainly questionnaires and behavioral tests such as the psychomotor vigilance task. Only one neurophysiological protocol has been evaluated in hypersomnia, the forced awakening test which is based on an event-related potentials paradigm upon awakening. This contrasts with the major functional consequences of sleep inertia and its potentially dangerous consequences in subjects required to perform safety-critical tasks soon after awakening. There is a great need to identify reproducible biomarkers correlated with sleep inertia-associated cognitive and behavioral impairment. These biomarkers will aim at better understanding and measuring sleep inertia in physiological and pathological conditions, as well as objectively evaluating wake-promoting treatments or non-pharmacological countermeasures to reduce this phenomenon.

Sleepiness should be reinvestigated through the lens of clinical neurophysiology: A mixed expertal and big-data Natural Language Processing approach.

Historically, the field of sleep medicine has revolved around electrophysiological tools. However, the use of these tools as a neurophysiological method of investigation seems to be underrepresented today, from both international recommendations and sleep centers, in contrast to behavioral and psychometric tools. The aim of this article is to combine a data-driven approach and neurophysiological and sleep medicine expertise to confirm or refute the hypothesis that neurophysiology has declined in favor of behavioral or self-reported dimensions in sleep medicine for the investigation of sleepiness, despite the use of electrophysiological tools. Using Natural Language Processing methods, we analyzed the abstracts of the 18,370 articles indexed by PubMed containing the terms 'sleepiness' or 'sleepy' in the title, abstract, or keywords. For this purpose, we examined these abstracts using two methods: a lexical network, enabling the identification of concepts (neurophysiological or clinical) related to sleepiness in these articles and their interconnections; furthermore, we analyzed the temporal evolution of these concepts to extract historical trends. These results confirm the hypothesis that neurophysiology has declined in favor of behavioral or self-reported dimensions in sleep medicine for the investigation of sleepiness. In order to bring sleepiness measurements closer to brain functioning and to reintroduce neurophysiology into sleep medicine, we discuss two strategies: the first is reanalyzing electrophysiological signals collected during the standard sleep electrophysiological test; the second takes advantage of the current trend towards dimensional models of sleepiness to situate clinical neurophysiology at the heart of the redefinition of sleepiness.

Objective evaluation of excessive daytime sleepiness.

Excessive daytime sleepiness (EDS) is multifactorial. It combines, among other things, an excessive propensity to fall asleep ("physiological sleepiness") and a continuous non-imperative sleepiness (or drowsiness/hypo-arousal) leading to difficulties remaining awake and maintaining sustained attention and vigilance over the long term ("manifest sleepiness"). There is no stand-alone biological measure of EDS. EDS measures can either capture the severity of physiological sleepiness, which corresponds to the propensity to fall asleep, or the severity of manifest sleepiness, which corresponds to behavioral consequences of sleepiness and reduced vigilance. Neuropsychological tests (The psychomotor vigilance task (PVT), Oxford Sleep Resistance Test (OSLeR), Sustained Attention to Response Task (SART)) explore manifest sleepiness through several sustained attention tests but the lack of normative values and standardized protocols make the results difficult to interpret and use in clinical practice. Neurophysiological tests explore the two main aspects of EDS, i.e. the propensity to fall asleep (Multiple sleep latency test, MSLT) and the capacity to remain awake (Maintenance of wakefulness test, MWT). The MSLT and the MWT are widely used in clinical practice. The MSLT is recognized as the "gold standard" test for measuring the severity of the propensity to fall asleep and it is a diagnostic criterion for narcolepsy. The MWT measures the ability to stay awake. The MWT is not a diagnostic test as it is recommended only to evaluate the evolution of EDS and efficacy of EDS treatment. Even if some efforts to standardize the protocols for administration of these tests have been ongoing, MSLT and MWT have numerous limitations: age effect, floor or ceiling effects, binding protocol, no normal or cutoff value (or determined in small samples), and no or low test-retest values in some pathologies. Moreover, the recommended electrophysiological set-up and the determination of sleep onset using the 30­sec epochs scoring rule show some limitations. New, more precise neurophysiological techniques should aim to detect very brief periods of physiological sleepiness and, in the future, the brain local phenomenon of sleepiness likely to underpin drowsiness, which could be called "physiological drowsiness".

Timing matters for accurate identification of the epileptogenic zone.

OBJECTIVE: Interictal biomarkers of the epileptogenic zone (EZ) and their use in machine learning models open promising avenues for improvement of epilepsy surgery evaluation. Currently, most studies restrict their analysis to short segments of intracranial EEG (iEEG). METHODS: We used 2381 hours of iEEG data from 25 patients to systematically select 5-minute segments across various interictal conditions. Then, we tested machine learning models for EZ localization using iEEG features calculated within these individual segments or across them and evaluated the performance by the area under the precision-recall curve (PRAUC). RESULTS: On average, models achieved a score of 0.421 (the result of the chance classifier was 0.062). However, the PRAUC varied significantly across the segments (0.323-0.493). Overall, NREM sleep achieved the highest scores, with the best results of 0.493 in N2. When using data from all segments, the model performed significantly better than single segments, except NREM sleep segments. CONCLUSIONS: The model based on a short segment of iEEG recording can achieve similar results as a model based on prolonged recordings. The analyzed segment should, however, be carefully and systematically selected, preferably from NREM sleep. SIGNIFICANCE: Random selection of short iEEG segments may give rise to inaccurate localization of the EZ.

Effectiveness of an intervention program on physical activity in children with narcolepsy type 1.

OBJECTIVES: Physical activity (PA) is recommended as part of the management of narcolepsy type 1 (NT1). This study aimed at 1) characterizing PA in children and adolescents treated for NT1 using objective and subjective measurements, 2) evaluating how PA is associated with NT1 symptoms and comorbidities, and 3) evaluating the effects of an Adapted Physical Activity (APA) program on PA and clinical characteristics. PATIENTS/METHODS: Patients with NT1 from the National Reference Center of Narcolepsy (Lyon, France) were consecutively included in an APA intervention protocol. Narcolepsy symptoms and comorbidities were collected using standardized questionnaires and sustained attention was evaluated using the Bron-Lyon Attention Stability Test before and after the four-week APA intervention. PA was measured objectively using actigraphy throughout the study. RESULTS: Twenty-seven NT1 patients were included (median age 14.7 years [8.3-18.4], cataplexy 88.9%, obesity 37.0%). At baseline, 52.4% of the patients had satisfactory PA levels according to international recommendations. Patients with leisure-time PA (LTPA) showed higher quality of life than patients without. 45% of the patients increased PA during the intervention compared to baseline. These responsive patients had more depressive feelings and tended to have lower objective PA than non-responsive patients at baseline. No significant correlation was found between PA levels before and during the intervention and other clinical data. CONCLUSIONS: Most children with NT1 showed satisfying PA levels despite their daytime sleepiness. LTPA engagement was associated with higher quality of life. An APA intervention could be effective in children with narcolepsy, especially for those with depressive feelings.

Impaired post-sleep apnea autonomic arousals in patients with drug-resistant epilepsy.

OBJECTIVE: Sudden and unexpected deaths in epilepsy (SUDEP) pathophysiology may involve an interaction between respiratory dysfunction and sleep/wake state regulation. We investigated whether patients with epilepsy exhibit impaired sleep apnea-related arousals. METHODS: Patients with drug-resistant (N = 20) or drug-sensitive (N = 20) epilepsy and obstructive sleep apnea, as well as patients with sleep apnea but without epilepsy (controls, N = 20) were included. We explored (1) the respiratory arousal threshold based on nadir oxygen saturation, apnea-hypopnea index, and fraction of hypopnea among respiratory events; (2) the cardiac autonomic response to apnea/hypopnea quantified as percentages of changes from the baseline in RR intervals (RRI), high (HF) and low (LF) frequency powers, and LF/HF. RESULTS: The respiratory arousal threshold did not differ between groups. At arousal onset, RRI decreased (-9.42%) and LF power (179%) and LF/HF ratio (190%) increased. This was followed by an increase in HF power (118%), p < 0.05. The RRI decrease was lower in drug-resistant (-7.40%) than in drug-sensitive patients (-9.94%) and controls (-10.91%), p < 0.05. LF and HF power increases were higher in drug-resistant (188%/126%) than in drug-sensitive patients (172%/126%) and controls (177%/115%), p < 0.05. CONCLUSIONS: Cardiac reactivity following sleep apnea is impaired in drug-resistant epilepsy. SIGNIFICANCE: This autonomic dysfunction might contribute to SUDEP pathophysiology.