Reconsidering sleep perception in insomnia: from misperception to mismeasurement.

So-called 'sleep misperception' refers to a phenomenon in which individuals have the impression of sleeping little or not at all despite normal objective measures of sleep. It is unknown whether this subjective-objective mismatch truly reflects an abnormal perception of sleep, or whether it results from the inability of standard sleep recording techniques to capture 'wake-like' brain activity patterns that could account for feeling awake during sleep. Here, we systematically reviewed studies reporting sleep macro- and microstructural, metabolic, and mental correlates of sleep (mis)perception. Our findings suggest that most individuals tend to accurately estimate their sleep duration measured with polysomnography (PSG). In good sleepers, feeling awake during sleep is the rule at sleep onset, remains frequent in the first non-rapid eye movement sleep cycle and almost never occurs in rapid eye movement (REM) sleep. In contrast, there are patients with insomnia who consistently underestimate their sleep duration, regardless of how long they sleep. Unlike good sleepers, they continue to feel awake after the first sleep cycle and importantly, during REM sleep. Their mental activity during sleep is also more thought-like. Initial studies based on standard PSG parameters largely failed to show consistent differences in sleep macrostructure between these patients and controls. However, recent studies assessing sleep with more refined techniques have revealed that these patients show metabolic and microstructural electroencephalography changes that likely reflect a shift towards greater cortical activation during sleep and correlate with feeling awake. We discuss the significance of these correlates and conclude with open questions and possible ways to address them.

Dusk2Dawn: an EEGLAB plugin for automatic cleaning of whole-night sleep electroencephalogram using Artifact Subspace Reconstruction.

Whole-night sleep electroencephalogram (EEG) is plagued by several types of large-amplitude artifacts. Common approaches to remove them are fraught with issues: channel interpolation, rejection of noisy intervals, and independent component analysis are time-consuming, rely on subjective user decisions, and result in signal loss. Artifact Subspace Reconstruction (ASR) is an increasingly popular approach to rapidly and automatically clean wake EEG data. Indeed, ASR adaptively removes large-amplitude artifacts regardless of their scalp topography or consistency throughout the recording. This makes ASR, at least in theory, a highly-promising tool to clean whole-night EEG. However, ASR crucially relies on calibration against a subset of relatively clean "baseline" data. This is problematic when the baseline changes substantially over time, as in whole-night EEG data. Here we tackled this issue and, for the first time, validated ASR for cleaning sleep EEG. We demonstrate that ASR applied out-of-the-box, with the parameters recommended for wake EEG, results in the dramatic removal of slow waves. We also provide an appropriate procedure to use ASR for automatic and rapid cleaning of whole-night sleep EEG data or any long EEG recording. Our procedure is freely available in Dusk2Dawn, an open-source plugin for EEGLAB.

Objective polysomnography-based sleep features and major depressive disorder subtypes in the general population.

Insomnia and its opposite hypersomnia are part of the diagnostic criteria for major depressive disorder (MDD). However, no study has investigated whether the postulated sleep alterations in clinical subtypes of MDD are reflected in polysomnography (PSG)-derived objective sleep measures. The objective of this study was to establish associations between the melancholic, atypical and unspecified subtypes of MDD and objective PSG-based sleep features. This cross-sectional analysis included 1820 community-dwelling individuals who underwent PSG and a semi-structured psychiatric interview to elicit diagnostic criteria for MDD and its subtypes. Adjusted robust linear regression was used to assess associations between MDD subtypes and PSG-derived objective sleep measures. Current melancholic MDD was significantly associated with decreased absolute delta power and sleep efficiency and with increased wake after sleep onset. Remitted unspecified MDD was significantly associated with increased rapid eye movements density. No other significant associations were identified. Our findings reflect that some PSG-based sleep features differed in MDD subtypes compared with no MDD. The largest number of significant differences were observed for current melancholic MDD, whereas only rapid eye movements density could represent a risk factor for MDD as it was the only sleep measure that was also associated with MDD in remitted participants.

Pulse Wave Amplitude Drops Index: A Biomarker of Cardiovascular Risk in Obstructive Sleep Apnea.

Rationale: It is currently unclear which patients with obstructive sleep apnea (OSA) are at increased cardiovascular risk. Objective: To investigate the value of pulse wave amplitude drops (PWADs), reflecting sympathetic activations and vasoreactivity, as a biomarker of cardiovascular risk in OSA. Methods: PWADs were derived from pulse oximetry-based photoplethysmography signals in three prospective cohorts: HypnoLaus (N = 1,941), the Pays-de-la-Loire Sleep Cohort (PLSC; N = 6,367), and "Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome. Effect of intervention with CPAP" (ISAACC) (N = 692). The PWAD index was the number of PWADs (>30%) per hour during sleep. All participants were divided into subgroups according to the presence or absence of OSA (defined as ⩾15 or more events per hour or <15/h, respectively, on the apnea-hypopnea index) and the median PWAD index. Primary outcome was the incidence of composite cardiovascular events. Measurements and Main Results: Using Cox models adjusted for cardiovascular risk factors (hazard ratio; HR [95% confidence interval]), patients with a low PWAD index and OSA had a higher incidence of cardiovascular events compared with the high-PWAD and OSA group and those without OSA in the HypnoLaus cohort (HR, 2.16 [1.07-4.34], P = 0.031; and 2.35 [1.12-4.93], P = 0.024) and in the PLSC (1.36 [1.13-1.63], P = 0.001; and 1.44 [1.06-1.94], P = 0.019), respectively. In the ISAACC cohort, the low-PWAD and OSA untreated group had a higher cardiovascular event recurrence rate than that of the no-OSA group (2.03 [1.08-3.81], P = 0.028). In the PLSC and HypnoLaus cohorts, every increase of 10 events per hour in the continuous PWAD index was negatively associated with incident cardiovascular events exclusively in patients with OSA (HR, 0.85 [0.73-0.99], P = 0.031; and HR, 0.91 [0.86-0.96], P < 0.001, respectively). This association was not significant in the no-OSA group and the ISAACC cohort. Conclusions: In patients with OSA, a low PWAD index reflecting poor autonomic and vascular reactivity was independently associated with a higher cardiovascular risk.

Effect of oxybutynin and reboxetine on obstructive sleep apnea: a randomized, placebo-controlled, double-blind, crossover trial.

STUDY OBJECTIVES: Although recent investigations combining noradrenergic and antimuscarinic drugs have shown promising short-term results to treat obstructive sleep apnea (OSA), the mid-term effect and optimal dosage remain uncertain. The present study aimed to evaluate the effect of 1 week of 5 mg oxybutynin and 6 mg reboxetine (oxy-reb) on OSA versus placebo. METHODS: We performed a randomized, placebo-controlled, double-blind, crossover trial comparing the effect of 1 week of oxy-reb versus 1 week of placebo on OSA severity. At-home polysomnography was performed at baseline and after each week of intervention. RESULTS: Fifteen participants (male 66.7%) aged 59 [44-62] years (median [interquartile range]) with a mean body mass index of 33.1 ± 6.6 kg/m2 were included. No significant difference in apnea-hypopnea index (AHI) was observed between conditions (estimated marginal means [95% confidence interval] at baseline: 39.7 [28.5-55.3]; oxy-reb: 34.5 [22.7-52.3]; placebo: 37.9 [27.1-52.9]; p = 0.652), but oxy-reb improved average oxygen desaturation (p = 0.016) and hypoxic burden (p = 0.011) and lowered sleep efficiency (p = 0.019) and rapid eye movement sleep (p = 0.002). Moreover, participants reported reduced sleep quality during the week of oxy-reb compared to the week of placebo (4.7 [3.5; 5.9] vs. 6.5 [5.5; 7.5] on a 0-10 visual analogic scale, respectively; p = 0.001). No significant differences in sleepiness, vigilance, and fatigue were observed. No serious adverse events occurred. CONCLUSIONS: Administration of oxybutynin 5 mg and reboxetine 6 mg did not improve OSA severity assessed by AHI, but did alter sleep architecture and sleep quality. Reduced average oxygen desaturation and hypoxic burden were also observed. CLINICAL TRIAL: ClinicalTrials.gov, https://clinicaltrials.gov, NCT04394143.

Sleep spindles in people with schizophrenia, schizoaffective disorders or bipolar disorders: a pilot study in a general population-based cohort.

BACKGROUND: Sleep spindles have been involved in sleep stabilization and sleep-related memory mechanisms and their deficit emerged as possible biomarker in schizophrenia. However, whether this sleep phenotype is also present in other disorders that share psychotic symptoms remains unclear. To address this gap, we assessed sleep spindles in participants of a prospective population-based cohort who underwent psychiatric assessment (CoLaus|PsyCoLaus) and polysomnographic recording (HypnoLaus). METHODS: Sleep was recorded using ambulatory polysomnography in participants (N = 1037) to the PsyCoLaus study. Sleep spindle parameters were measured in people with a lifelong diagnosis of schizophrenia (SZ), schizoaffective depressive (SAD), schizoaffective manic (SAM), bipolar disorder type I (BP-I) and type II (BP-II). The associations between lifetime diagnostic status (independent variables, SZ, SAD, SAM, BPD-I, BPD-II, controls) and spindle parameters (dependent variables) including density, duration, frequency and maximum amplitude, for all (slow and fast), slow- and fast-spindle were assessed using linear mixed models. Pairwise comparisons of the different spindle parameters between the SZ group and each of the other psychiatric groups was performed using a contrast testing framework from our multiple linear mixed models. RESULTS: Our results showed a deficit in the density and duration of sleep spindles in people with SZ. They also indicated that participants with a diagnosis of SAD, SAM, BP-I and BP-II exhibited different sleep spindle phenotypes. Interestingly, spindle densities and frequencies were different in people with a history of manic symptoms (SAM, BP-I, and BP-II) from those without (SZ, SAD). CONCLUSIONS: Although carried out on a very small number of participants due to the low prevalence of these disorders in general population, this pilot study brought new elements that argued in favor of a deficit of sleep spindles density and duration in people with schizophrenia. In addition, while we could expect a gradual change in intensity of the same sleep spindle parameters through psychotic diagnoses, our results seem to indicate a more complex situation in which the frequency of sleep spindles might be more impacted by diagnoses including a history of mania or hypomania. Further studies with a larger number of participants are required to confirm these effects.

Association Between Sleep Microstructure and Incident Hypertension in a Population-Based Sample: The HypnoLaus Study.

Background Poor sleep quality is associated with increased incident hypertension. However, few studies have investigated the impact of objective sleep structure parameters on hypertension. This study investigated the association between sleep macrostructural and microstructural parameters and incident hypertension in a middle- to older-aged sample. Methods and Results Participants from the HypnoLaus population-based cohort without hypertension at baseline were included. Participants had at-home polysomnography at baseline, allowing assessment of sleep macrostructure (nonrapid eye movement sleep stages 1, 2, and 3; rapid eye movement sleep stages; and total sleep time) and microstructure including power spectral density of electroencephalogram in nonrapid eye movement sleep and spindles characteristics (density, duration, frequency, amplitude) in nonrapid eye movement sleep stage 2. Associations between sleep macrostructure and microstructure parameters at baseline and incident clinical hypertension over a mean follow-up of 5.2 years were assessed with multiple-adjusted logistic regression. A total of 1172 participants (42% men; age 55±10 years) were included. Of these, 198 (17%) developed hypertension. After adjustment for confounders, no sleep macrostructure features were associated with incident hypertension. However, low absolute delta and sigma power were significantly associated with incident hypertension where participants in the lowest quartile of delta and sigma had a 1.69-fold (95% CI, 1.00-2.89) and 1.72-fold (95% CI, 1.05-2.82) increased risk of incident hypertension, respectively, versus those in the highest quartile. Lower spindle density (odds ratio, 0.87; 95% CI, 0.76-0.99) and amplitude (odds ratio, 0.98; 95% CI, 0.95-1.00) were also associated with higher incident hypertension. Conclusions Sleep microstructure is associated with incident hypertension. Slow-wave activity and sleep spindles, 2 hallmarks of objective sleep continuity and quality, were inversely and consistently associated with incident hypertension. This supports the protective role of sleep continuity in the development of hypertension.

Abnormal timing of slow wave synchronization processes in non-rapid eye movement sleep parasomnias.

STUDY OBJECTIVES: Sleepwalking, confusional arousals, and sleep terrors are parasomnias occurring out of non-rapid eye movement (NREM) sleep. Several previous studies have described EEG changes associated with NREM parasomnia episodes, but it remains unclear whether these changes are specific to parasomnia episodes or whether they are part of the normal awakening process. Here we directly compared regional brain activity, measured with high-density (hd-) EEG, between parasomnia episodes and normal awakenings (without behavioral manifestations of parasomnia). METHODS: Twenty adult patients with non-rapid eye movement parasomnias underwent a baseline hd-EEG recording (256 electrodes) followed by a recovery sleep recording after 25 h of total sleep deprivation, during which auditory stimuli were administered to provoke parasomnia episodes. RESULTS: Both normal awakenings (n = 25) and parasomnia episodes (n = 96) were preceded by large, steep, and "K-complex-like" slow waves in frontal and central brain regions, and by a concomitant increase in high-frequency EEG (beta) activity. Compared to normal awakenings, parasomnia episodes occurred on a less activated EEG background and displayed higher slow wave activity (SWA) and lower beta activity in frontal and central brain regions after movement onset. CONCLUSIONS: Our results suggest that non-rapid eye movement awakenings, irrespective of behavioral manifestations of parasomnia episodes, involve an arousal-related slow wave synchronization process that predominantly recruits frontal and central brain areas. In parasomnia episodes, this synchronization process comes into play abnormally during periods of high SWA and is associated with higher SWA after movement onset. Thus, an abnormal timing of arousal-related slow wave synchronization processes could underlie the occurrence of NREM parasomnias.

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.

Conscious experiences and high-density EEG patterns predicting subjective sleep depth.

What accounts for feeling deeply asleep? Standard sleep recordings only incompletely reflect subjective aspects of sleep and some individuals with so-called sleep misperception frequently feel awake although sleep recordings indicate clear-cut sleep. To identify the determinants of sleep perception, we performed 787 awakenings in 20 good sleepers and 10 individuals with sleep misperception and interviewed them about their subjective sleep depth while they underwent high-density EEG sleep recordings. Surprisingly, in good sleepers, sleep was subjectively lightest in the first 2 h of non-rapid eye movement (NREM) sleep, generally considered the deepest sleep, and deepest in rapid eye movement (REM) sleep. Compared to good sleepers, sleep misperceptors felt more frequently awake during sleep and reported lighter REM sleep. At the EEG level, spatially widespread high-frequency power was inversely related to subjective sleep depth in NREM sleep in both groups and in REM sleep in misperceptors. Subjective sleep depth positively correlated with dream-like qualities of reports of mental activity. These findings challenge the widely held notion that slow wave sleep best accounts for feeling deeply asleep. Instead, they indicate that subjective sleep depth is inversely related to a neurophysiological process that predominates in early NREM sleep, becomes quiescent in REM sleep, and is reflected in high-frequency EEG activity. In sleep misperceptors, this process is more frequently active, more spatially widespread, and abnormally persists into REM sleep. These findings help identify the neuromodulatory systems involved in subjective sleep depth and are relevant for studies aiming to improve subjective sleep quality.

Role of corpus callosum in sleep spindle synchronization and coupling with slow waves.

Sleep spindles of non-REM sleep are transient, waxing-and-waning 10-16 Hz EEG oscillations, whose cortical synchronization depends on the engagement of thalamo-cortical loops. However, previous studies in animal models lacking the corpus callosum due to agenesis or total callosotomy and in humans with agenesis of the corpus callosum suggested that cortico-cortical connections may also have a relevant role in cortical (inter-hemispheric) spindle synchronization. Yet, most of these works did not provide direct quantitative analyses to support their observations. By studying a rare sample of callosotomized, split-brain patients, we recently demonstrated that the total resection of the corpus callosum is associated with a significant reduction in the inter-hemispheric propagation of non-REM slow waves. Interestingly, sleep spindles are often temporally and spatially grouped around slow waves (0.5-4 Hz), and this coordination is thought to have an important role in sleep-dependent learning and memory consolidation. Given these premises, here we set out to investigate whether total callosotomy may affect the generation and spreading of sleep spindles, as well as their coupling with sleep slow waves. To this aim, we analysed overnight high-density EEG recordings (256 electrodes) collected in five patients who underwent total callosotomy due to drug-resistant epilepsy (age 40-53, two females), three non-callosotomized neurological patients (age 44-66, two females), and in a sample of 24 healthy adult control subjects (age 20-47, 13 females). Individual sleep spindles were automatically detected using a validated algorithm and their properties and topographic distributions were computed. All analyses were performed with and without a regression-based adjustment accounting for inter-subject age differences. The comparison between callosotomized patients and healthy subjects did not reveal systematic variations in spindle density, amplitude or frequency. However, callosotomized patients were characterized by a reduced spindle duration, which could represent the result of a faster desynchronization of spindle activity across cortical areas of the two hemispheres. In contrast with our previous findings regarding sleep slow waves, we failed to detect in callosotomized patients any clear, systematic change in the inter-hemispheric synchronization of sleep spindles. In line with this, callosotomized patients were characterized by a reduced extension of the spatial association between temporally coupled spindles and slow waves. Our findings are consistent with a dependence of spindles on thalamo-cortical rather than cortico-cortical connections in humans, but also revealed that, despite their temporal association, slow waves and spindles are independently regulated in terms of topographic expression.

Impact of smoking on sleep macro- and microstructure.

OBJECTIVES: Existing data suggest that smoking may be associated with sleep disturbances. This study aimed to determine the association between smoking and both subjective and objective sleep quality. METHODS: Cross-sectional analysis of sleep characteristics in 3233 participants from the population-based CoLaus-HypnoLaus cohort (52.2% women, mean age 56.6 ± 10.2 years) who completed questionnaires on sleep quality, of whom 1489 (46%) had a full polysomnography. Smoking data were self-reported; participants were classified by smoking status as current, former or never smokers. Primary outcomes were subjective sleep quality assessed by sleep questionnaires, and objective sleep quality based on polysomnography (sleep macrostructure), including power spectral analysis of the electroencephalogram on C4 electrode (sleep microstructure), quantifying the relative amount of delta power (1-4 Hz), a marker of sleep depth, and arousal-associated alpha power (8-12 Hz). RESULTS: Current smokers had a shift toward faster sleep electroencephalogram activity with lower delta power in non-REM sleep compared with former and never smokers (-2.8 ± 0.4% and -2.4 ± 0.4%, respectively; both p < 0.001) and higher alpha power (+0.8 ± 0.2%; p < 0.001) compared with never smokers. There was a dose-dependent negative association between electroencephalogram delta power and smoking intensity (r2 = -1.2 [-1.9, -0.5]; p = 0.001). Additionally, mean nocturnal oxygen saturation was lower in current smokers. CONCLUSIONS: Current smokers had decreased objective sleep quality, with a dose-dependent association between smoking intensity and decrease in electroencephalogram delta power during non-REM sleep, in addition to an increase in alpha power. Considering the importance of sleep quality for wellbeing and health, these results provide further data to support smoking cessation.

Cortical and subcortical hemodynamic changes during sleep slow waves in human light sleep.

EEG slow waves, the hallmarks of NREM sleep are thought to be crucial for the regulation of several important processes, including learning, sensory disconnection and the removal of brain metabolic wastes. Animal research indicates that slow waves may involve complex interactions within and between cortical and subcortical structures. Conventional EEG in humans, however, has a low spatial resolution and is unable to accurately describe changes in the activity of subcortical and deep cortical structures. To overcome these limitations, here we took advantage of simultaneous EEG-fMRI recordings to map cortical and subcortical hemodynamic (BOLD) fluctuations time-locked to slow waves of light sleep. Recordings were performed in twenty healthy adults during an afternoon nap. Slow waves were associated with BOLD-signal increases in the posterior brainstem and in portions of thalamus and cerebellum characterized by preferential functional connectivity with limbic and somatomotor areas, respectively. At the cortical level, significant BOLD-signal decreases were instead found in several areas, including insula and somatomotor cortex. Specifically, a slow signal increase preceded slow-wave onset and was followed by a delayed, stronger signal decrease. Similar hemodynamic changes were found to occur at different delays across most cortical brain areas, mirroring the propagation of electrophysiological slow waves, from centro-frontal to inferior temporo-occipital cortices. Finally, we found that the amplitude of electrophysiological slow waves was positively related to the magnitude and inversely related to the delay of cortical and subcortical BOLD-signal changes. These regional patterns of brain activity are consistent with theoretical accounts of the functions of sleep slow waves.

Risk factors of excessive daytime sleepiness in a prospective population-based cohort.

Although excessive daytime sleepiness is commonly evaluated in clinical and research settings using the Epworth Sleepiness Scale, few studies have assessed the factors associated with its incidence in the general population. We prospectively investigated the predictors of incident and persistent excessive daytime sleepiness in 2,751 subjects (46.1% men, mean age 56.0 ± 9.8 years) from the CoLaus-PsyCoLaus population-based cohort (Lausanne, Switzerland) over 5 years. Participants completed the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index, and underwent a full clinical evaluation at baseline and 5 years afterwards. Ambulatory polysomnography was performed at baseline in a sub-sample of 1,404 subjects. Among the 2,438 subjects without excessive daytime sleepiness (Epworth Sleepiness Scale ≤ 10) at baseline, the 5-year incidence of excessive daytime sleepiness was 5.1% (n = 124). Multivariate logistic regression revealed that male sex, depressive symptoms, reported poor sleep quality and moderate to severe obstructive sleep apnea were independent predictors of incident excessive daytime sleepiness, while older age, moderate coffee consumption, periodic leg movement during sleep and hypertension were independent protective factors. Stratified analysis according to sex and age showed some distinctive associations. Among the 313 patients with excessive daytime sleepiness at baseline, 137 (43.8%) had persistent excessive daytime sleepiness 5 years later. Our findings provide new insights into the predictors of incident excessive daytime sleepiness, but interventional studies are needed to understand the impact of treating these risk factors on the incidence of excessive daytime sleepiness.

Cross-participant prediction of vigilance stages through the combined use of wPLI and wSMI EEG functional connectivity metrics.

Functional connectivity (FC) metrics describe brain inter-regional interactions and may complement information provided by common power-based analyses. Here, we investigated whether the FC-metrics weighted Phase Lag Index (wPLI) and weighted Symbolic Mutual Information (wSMI) may unveil functional differences across four stages of vigilance-wakefulness (W), NREM-N2, NREM-N3, and REM sleep-with respect to each other and to power-based features. Moreover, we explored their possible contribution in identifying differences between stages characterized by distinct levels of consciousness (REM+W vs. N2+N3) or sensory disconnection (REM vs. W). Overnight sleep and resting-state wakefulness recordings from 24 healthy participants (27 ± 6 years, 13F) were analyzed to extract power and FC-based features in six classical frequency bands. Cross-validated linear discriminant analyses (LDA) were applied to investigate the ability of extracted features to discriminate (1) the four vigilance stages, (2) W+REM vs. N2+N3, and (3) W vs. REM. For the four-way vigilance stages classification, combining features based on power and both connectivity metrics significantly increased accuracy relative to considering only power, wPLI, or wSMI features. Delta-power and connectivity (0.5-4 Hz) represented the most relevant features for all the tested classifications, in line with a possible involvement of slow waves in consciousness and sensory disconnection. Sigma-FC, but not sigma-power (12-16 Hz), was found to strongly contribute to the differentiation between states characterized by higher (W+REM) and lower (N2+N3) probabilities of conscious experiences. Finally, alpha-FC resulted as the most relevant FC-feature for distinguishing among wakefulness and REM sleep and may thus reflect the level of disconnection from the external environment.

Apical drive-A cellular mechanism of dreaming?

Dreams are internally generated experiences that occur independently of current sensory input. Here we argue, based on cortical anatomy and function, that dream experiences are tightly related to the workings of a specific part of cortical pyramidal neurons, the apical integration zone (AIZ). The AIZ receives and processes contextual information from diverse sources and could constitute a major switch point for transitioning from externally to internally generated experiences such as dreams. We propose that during dreams the output of certain pyramidal neurons is mainly driven by input into the AIZ. We call this mode of functioning "apical drive". Our hypothesis is based on the evidence that the cholinergic and adrenergic arousal systems, which show different dynamics between waking, slow wave sleep, and rapid eye movement sleep, have specific effects on the AIZ. We suggest that apical drive may also contribute to waking experiences, such as mental imagery. Future studies, investigating the different modes of apical function and their regulation during sleep and wakefulness are likely to be richly rewarded.

Dreams and nightmares in healthy adults and in patients with sleep and neurological disorders.

Dreams are experiences that occur during sleep, while we are disconnected from the environment. Thanks to recent progress in neuroimaging techniques, it is now becoming possible to relate dream features to specific patterns of brain activity. Some conditions occurring in patients with neurological disorders, such as lucid dreams and parasomnias, not only have diagnostic value, but also offer a window into the dream process. They show that dreaming is reflected in physiological signals, behaviours, and brain activity patterns, and that the body can enact dream content. Yet, the dream body can also be distinct from the real body; in their dreams, patients with congenital paraplegia can walk, those with sleep apnoea rarely suffocate, and phantom limb pain can disappear. These conditions provide valuable models for future studies investigating the mechanisms that underlie oneiric experiences.

Sleep: The Sensory Disconnection of Dreams.

It has been known for some time that the brain can react selectively to meaningful sensory stimuli during sleep. A recent study shows that this ability may be selectively suppressed during rapid eye movements of sleep.

Integrity of Corpus Callosum Is Essential for theCross-Hemispheric Propagation of Sleep Slow Waves:A High-Density EEG Study in Split-Brain Patients.

The slow waves of non-rapid eye movement (NREM) sleep reflect experience-dependent plasticity and play a direct role in the restorative functions of sleep. Importantly, slow waves behave as traveling waves, and their propagation is assumed to occur through cortico-cortical white matter connections. In this light, the corpus callosum (CC) may represent the main responsible for cross-hemispheric slow-wave propagation. To verify this hypothesis, we performed overnight high-density (hd)-EEG recordings in five patients who underwent total callosotomy due to drug-resistant epilepsy (CPs; two females), in three noncallosotomized neurologic patients (NPs; two females), and in a sample of 24 healthy adult subjects (HSs; 13 females). In all CPs slow waves displayed a significantly reduced probability of cross-hemispheric propagation and a stronger inter-hemispheric asymmetry. In both CPs and HSs, the incidence of large slow waves within individual NREM epochs tended to differ across hemispheres, with a relative overall predominance of the right over the left hemisphere. The absolute magnitude of this asymmetry was greater in CPs relative to HSs. However, the CC resection had no significant effects on the distribution of slow-wave origin probability across hemispheres. The present results indicate that CC integrity is essential for the cross-hemispheric traveling of slow waves in human sleep, which is in line with the assumption of a direct relationship between white matter integrity and slow-wave propagation. Our findings also revealed a residual cross-hemispheric slow-wave propagation that may rely on alternative pathways, including cortico-subcortico-cortical loops. Finally, these data indicate that the lack of the CC does not lead to differences in slow-wave generation across brain hemispheres.SIGNIFICANCE STATEMENT The slow waves of NREM sleep behave as traveling waves, and their propagation has been suggested to reflect the integrity of white matter cortico-cortical connections. To directly assess this hypothesis, here we investigated the role of the corpus callosum in the cortical spreading of NREM slow waves through the study of a rare population of totally callosotomized patients. Our results demonstrate a causal role of the corpus callosum in the cross-hemispheric traveling of sleep slow waves. Additionally, we found that callosotomy does not affect the relative tendency of each hemisphere at generating slow waves. Incidentally, we also found that slow waves tend to originate more often in the right than in the left hemisphere in both callosotomized and healthy adult individuals.