Fractal Similarity of Pain Brain Networks.

The conscious perception of pain is the result of dynamic interactions of neural activities from local brain regions to distributed brain networks. Mapping out the networks of functional connections between brain regions that form and disperse when an experimental participant received nociceptive stimulations allow to characterize the pattern of network connections related to the pain experience.Although the pattern of intra- and inter-areal connections across the brain are incredibly complex, they appear also largely scale free, with "fractal" connectivity properties reproducing at short and long-time scales. Our results combining intracranial recordings and functional imaging in humans during pain indicate striking similarities in the activity and topological representation of networks at different orders of temporality, with reproduction of patterns of activation from the millisecond to the multisecond range. The connectivity analyzed using graph theory on fMRI data was organized in four sets of brain regions matching those identified through iEEG (i.e., sensorimotor, default mode, central executive, and amygdalo-hippocampal).Here, we discuss similarities in brain network organization at different scales or "orders," in participants as they feel pain. Description of this fractal-like organization may provide clues about how our brain regions work together to create the perception of pain and how pain becomes chronic when its organization is altered.

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.

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.

Functional connectivity between medial pulvinar and cortical networks as a predictor of arousal to noxious stimuli during sleep.

The interruption of sleep by a nociceptive stimulus is favoured by an increase in the pre-stimulus functional connectivity between sensory and higher level cortical areas. In addition, stimuli inducing arousal also trigger a widespread electroencephalographic (EEG) response reflecting the coordinated activation of a large cortical network. Because functional connectivity between distant cortical areas is thought to be underpinned by trans-thalamic connections involving associative thalamic nuclei, we investigated the possible involvement of one principal associative thalamic nucleus, the medial pulvinar (PuM), in the sleeper's responsiveness to nociceptive stimuli. Intra-cortical and intra-thalamic signals were analysed in 440 intracranial electroencephalographic (iEEG) segments during nocturnal sleep in eight epileptic patients receiving laser nociceptive stimuli. The spectral coherence between the PuM and 10 cortical regions grouped in networks was computed during 5 s before and 1 s after the nociceptive stimulus and contrasted according to the presence or absence of an arousal EEG response. Pre- and post-stimulus phase coherence between the PuM and all cortical networks was significantly increased in instances of arousal, both during N2 and paradoxical (rapid eye movement [REM]) sleep. Thalamo-cortical enhancement in coherence involved both sensory and higher level cortical networks and predominated in the pre-stimulus period. The association between pre-stimulus widespread increase in thalamo-cortical coherence and subsequent arousal suggests that the probability of sleep interruption by a noxious stimulus increases when it occurs during phases of enhanced trans-thalamic transfer of information between cortical areas.

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.

Aspects clinico-neurophysiologiques des troubles du sommeil dans une population d'adultes jeunes entre 18-35 ans / Clinical-neurophysiological aspects of sleep disorders in a population of young adults aged 18-35 years

Contexte et objectifs : L'accès aux tests neurophysiologiques pour le diagnostic des Troubles du Sommeil (TS) est très limité dans les pays d'Afrique subsaharienne. La présente étude avait pour objectif de déterminer les caractéristiques épidémiologiques, cliniques et neurophysiologiques des (TS) dans un groupe de jeunes adultes. Méthodes : Il s'est agi d'une étude descriptive d'une série de cas, réalisée au centre de Médecine du sommeil et des maladies respiratoires de l'hôpital de la Croix-Rousse de Lyon du 1er janvier au 31 mars 2019. Les patients hospitalisés pendant cette période pour l'exploration d'un (TS) ont été sélectionnés. Etaient éligibles ceux dont l'âge était compris entre 18 et 35 ans, des deux sexes, ayant renseigné un questionnaire et ayant bénéficié au minimum d'une polysomnographie (PSG). Résultats : Quatre-vingt-onze patients étaient examinés. Les femmes étaient les plus affectées (59,3 %). Leur âge moyen était de 26,6 ± 5 ans. La PSG a incriminé le Syndrome d'Apnée Hypopnée Obstructive du sommeil (SAHOS) comme étiologie principale (66 %). Pour les patients sans SAHOS, 38,7 % avaient une PSG normale et la PSG avec d'autres tests de sommeil ont objectivé, pour le reste (61,3 %), d'autres types de (TS). La dépression (50,7 %) et la fatigue chronique (84,6 %) étaient très fréquentes. L'indice d'efficacité du sommeil était faible pour 70 % des patients avec SAHOS. Il y avait un déséquilibre de la durée des stades du sommeil, augmentée pour le sommeil lent léger et diminuée pour le sommeil lent profond dans la population avec SAHOS, tandis que la durée du sommeil paradoxal chez ceux sans SAHOS était augmentée. Conclusion Le SAHOS est fréquent dans cette formation hospitalière, avec des répercussions significatives à type de dépression et de fatigue chronique. Il est important que des mesures rendant accessible l'usage des tests d'exploration du sommeil particulièrement en Afrique au sud du Sahara, soient mises en place pour diagnostiquer ces troubles

Context and objective. Access to neurophysiological tests for diagnostic of sleep disorders (SD) is very limited in Sub-Saharan Africa countries. The objective was to determine the epidemiological, clinical and neurophysiological characteristics of SD in a young adult group. Methods. This was a descriptive serial cases study carried out at the Sleep Medicine and Respiratory Diseases Center of the CroixRousse hospital of Lyon between January 1st and March 31th, 2019. Patients hospitalized during this period with tests for SD were selected. Eligible were those aged between 18 and 35 years, both sexes, who completed a questionnaire and who received at least a polysomnography (PSG). Results. Ninety-one patients were involved. Women remained the most affected (59.3%). Mean age was 26.6±5 years. PSG incriminated obstructive sleep apnea (OSA) syndrome as the primary etiology (66%). For patients without OSA, 38.7% had normal PSG. For the remaining 61.3% of patients, other types of SD were found using PSG with various sleep tests. Depression (50.7%) was an important comorbidity, and chronic fatigue (84.6%) was the most frequent complaint. Sleep efficiency index was low for 70% of sleep apnea patients. There was an imbalance in the duration of sleep stages, with an increase in light slow-wave sleep in the OSA population and a decrease in their deep slow-wave sleep, while REM sleep duration in patients without OSA was increased. Conclusion: OSA was the primary etiology in our study, with significant repercussions like depression and chronic fatigue. Public health measures such as increasing access to the use of sleep exploration tests, especially in subSaharan Africa, should be put in place for the diagnosis of these sleep disorders and their consequences

Twenty-four-hour rhythmicities in disorders of consciousness are associated with a favourable outcome.

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.

Cognitive Behavioral Therapy and Acceptance and Commitment Therapy for the Discontinuation of Long-Term Benzodiazepine Use in Insomnia and Anxiety Disorders.

Benzodiazepines have proven to be highly effective for treating insomnia and anxiety. Although considered safe when taken for a short period of time, a major risk-benefit dilemma arises in the context of long-term use, relating to addiction, withdrawal symptoms, and potential side effects. For these reasons, benzodiazepines are not recommended for treating chronic sleep disorders, anxiety disorders, nor for people over the age of 65, and withdrawal among long-term users is a public health issue. Indeed, only 5% of patients manage to discontinue using these drugs on their own. Even with the help of a general practitioner, this rate does not exceed 25 to 30% of patients, of which approximately 7% manage to remain drug-free in the long term. Cognitive Behavioral Therapies (CBT) offer a crucial solution to this problem, having been shown to increase abstinence success to 70-80%. This article examines traditional and novel CBT techniques in this regard, such as Acceptance and Commitment Therapy, which address both the underlying condition (insomnia/anxiety) and the substance-related disorder. The theoretical framework and evidence supporting the use of these approaches are reviewed. Finally, current research gaps are discussed, and key research perspectives are proposed.

Microsleep versus Sleep Onset Latency during Maintenance Wakefulness Tests: Which One Is the Best Marker of Sleepiness?

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.

Intracortical Functional Connectivity Predicts Arousal to Noxious Stimuli during Sleep in Humans.

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.

Automatic analysis of single-channel sleep EEG in a large spectrum of sleep disorders.

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.

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.

Brain-scale cortico-cortical functional connectivity in the delta-theta band is a robust signature of conscious states: an intracranial and scalp EEG study.

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 and Subjective Assessments of Sleep in Children: Comparison of Actigraphy, Sleep Diary Completed by Children and Parents' Estimation.

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.

Observation and Interview-based Diurnal Sleepiness Inventory for measurement of sleepiness in patients referred for narcolepsy or idiopathic hypersomnia.

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.

Local sleep spindles in the human thalamus.

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.

The Modular Organization of Pain Brain Networks: An fMRI Graph Analysis Informed by Intracranial EEG.

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.

Cortical modulation of nociception by galvanic vestibular stimulation: A potential clinical tool?

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.

The generation and propagation of the human alpha rhythm.

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.