The Hierarchy of Coupled Sleep Oscillations Reverses with Aging in Humans.

A well orchestrated coupling hierarchy of slow waves and spindles during slow-wave sleep supports memory consolidation. In old age, the duration of slow-wave sleep and the number of coupling events decrease. The coupling hierarchy deteriorates, predicting memory loss and brain atrophy. Here, we investigate the dynamics of this physiological change in slow wave-spindle coupling in a frontocentral electroencephalography position in a large sample (N = 340; 237 females, 103 males) spanning most of the human life span (age range, 15-83 years). We find that, instead of changing abruptly, spindles gradually shift from being driven by slow waves to driving slow waves with age, reversing the coupling hierarchy typically seen in younger brains. Reversal was stronger the lower the slow-wave frequency, and starts around midlife (age range, ∼40-48 years), with an established reversed hierarchy between 56 and 83 years of age. Notably, coupling strength remains unaffected by age. In older adults, deteriorating slow wave-spindle coupling, measured using the phase slope index (PSI) and the number of coupling events, is associated with blood plasma glial fibrillary acidic protein levels, a marker for astrocyte activation. Data-driven models suggest that decreased sleep time and higher age lead to fewer coupling events, paralleled by increased astrocyte activation. Counterintuitively, astrocyte activation is associated with a backshift of the coupling hierarchy (PSI) toward a "younger" status along with increased coupling occurrence and strength, potentially suggesting compensatory processes. As the changes in coupling hierarchy occur gradually starting at midlife, we suggest there exists a sizable window of opportunity for early interventions to counteract undesirable trajectories associated with neurodegeneration.SIGNIFICANCE STATEMENT Evidence accumulates that sleep disturbances and cognitive decline are bidirectionally and causally linked, forming a vicious cycle. Improving sleep quality could break this cycle. One marker for sleep quality is a clear hierarchical structure of sleep oscillations. Previous studies showed that sleep oscillations decouple in old age. Here, we show that, rather, the hierarchical structure gradually shifts across the human life span and reverses in old age, while coupling strength remains unchanged. This shift is associated with markers for astrocyte activation in old age. The shifting hierarchy resembles brain maturation, plateau, and wear processes. This study furthers our comprehension of this important neurophysiological process and its dynamic evolution across the human life span.

Genetic contribution to sleep homeostasis in early adolescence.

The sleep homeostatic process in adults is moderately stable over time and unique to an individual. Work in transgenic mice has suggested a role of genes in sleep homeostasis. The current study quantified the genetic contribution to sleep homeostasis in adolescence. We use slow wave energy (SWE) as a metric for sleep pressure dissipation during sleep. This measure reflects both sleep intensity and duration. High-density (58 derivations) sleep electroencephalogram (EEG) was recorded in 14 monozygotic and 12 dizygotic adolescent twin pairs (mean age = 13.2 years; standard deviation [SD] = 1.1; 20 females). SWE at the end of sleep was quantified as the cumulative delta power (1-4.6 Hz) over the night. We also examined the time constant of the decay and the level of slow wave activity (SWA) at the beginning of the sleep episode. Structural equation modelling was used to quantify the amount of variance in SWE and the dissipation of sleep pressure due to genes. We found that most (mean = 76% across EEG derivations) of the variance in SWE was due to genes. In contrast, genes had a small (mean = 33%) influence on the rate of dissipation of sleep pressure, and this measure was largely (mean = 67%) driven by environmental factors unique to each twin. Our results show that the amount of dissipated sleep pressure is largely under genetic control; however, the rate of sleep pressure dissipation is largely due to unique environmental factors. Our findings are in line with research in animals and suggest that the heritability of the rate of sleep pressure dissipation is limited.

Maternal immune activation exerts long-term effects on activity and sleep in male offspring mice.

Exposure to infectious or non-infectious immune activation during early development is a serious risk factor for long-term behavioural dysfunctions. Mouse models of maternal immune activation (MIA) have increasingly been used to address neuronal and behavioural dysfunctions in response to prenatal infections. One commonly employed MIA model involves administering poly(I:C) (polyriboinosinic-polyribocytdilic acid), a synthetic analogue of double-stranded RNA, during gestation, which robustly induces an acute viral-like inflammatory response. Using electroencephalography (EEG) and infrared (IR) activity recordings, we explored alterations in sleep/wake, circadian and locomotor activity patterns on the adult male offspring of poly(I:C)-treated mothers. Our findings demonstrate that these offspring displayed reduced home cage activity during the (subjective) night under both light/dark or constant darkness conditions. In line with this finding, these mice exhibited an increase in non-rapid eye movement (NREM) sleep duration as well as an increase in sleep spindles density. Following sleep deprivation, poly(I:C)-exposed offspring extended NREM sleep duration and prolonged NREM sleep bouts during the dark phase as compared with non-exposed mice. Additionally, these mice exhibited a significant alteration in NREM sleep EEG spectral power under heightened sleep pressure. Together, our study highlights the lasting effects of infection and/or immune activation during pregnancy on circadian activity and sleep/wake patterns in the offspring.

Sleep regularity in healthy adolescents: Associations with sleep duration, sleep quality, and mental health.

Current evidence points to the importance of sleep for adolescent physical and mental health. To date, most studies have examined the association between sleep duration/quality and health in adolescence. An emerging line of research suggests that regularity in the timing of sleep may also play an important role in well-being. To address this aspect of sleep, the present study investigated daily variability of sleep, quantified using the sleep regularity index (SRI), in 46 adolescents (M = 12.78 ± 1.07 years) and its association with depressive symptoms/mental health. Sleep was measured during a 6 month period (M = 133.11 ± 36.42 nights) using actigraphs to quantify SRI values calculated for school days, weekends and holidays. Depressive symptoms and general psychopathology were assessed at the beginning (baseline) and end (follow-up) of the actigraphy measurements. Sleep was most regular during school days and associated with a longer total sleep time, shorter sleep onset latency, and higher sleep efficiency. Moreover, a higher SRI on school days was associated with fewer depressive symptoms at follow-up, whereas higher SRI on weekends was associated with less overall psychopathology at follow-up. Furthermore, the change in overall psychopathology, but not depressive symptoms across the two assessments was correlated with sleep regularity index. Our results suggest that regular timing of sleep is associated with sleep that is of longer duration and higher quality and may be protective of adolescent mental health. Therefore, adolescents should be encouraged not only to get enough sleep, but also to retain regular sleeping patterns to promote well-being and mental health.

Feasibility, efficacy, and functional relevance of automated auditory closed-loop suppression of slow-wave sleep in humans.

Slow-wave sleep (SWS) is a fundamental physiological process, and its modulation is of interest for basic science and clinical applications. However, automatised protocols for the suppression of SWS are lacking. We describe the development of a novel protocol for the automated detection (based on the whole head topography of frontal slow waves) and suppression of SWS (through closed-loop modulated randomised pulsed noise), and assessed the feasibility, efficacy and functional relevance compared to sham stimulation in 15 healthy young adults in a repeated-measure sleep laboratory study. Auditory compared to sham stimulation resulted in a highly significant reduction of SWS by 30% without affecting total sleep time. The reduction of SWS was associated with an increase in lighter non-rapid eye movement sleep and a shift of slow-wave activity towards the end of the night, indicative of a homeostatic response and functional relevance. Still, cumulative slow-wave activity across the night was significantly reduced by 23%. Undisturbed sleep led to an evening to morning reduction of wake electroencephalographic theta activity, thought to reflect synaptic downscaling during SWS, while suppression of SWS inhibited this dissipation. We provide evidence for the feasibility, efficacy, and functional relevance of a novel fully automated protocol for SWS suppression based on auditory closed-loop stimulation. Future work is needed to further test for functional relevance and potential clinical applications.

Local slow-wave activity over the right prefrontal cortex reveals individual risk preferences.

In everyday life, we have to make decisions under varying degrees of risk. Even though previous research has shown that the manipulation of sleep affects risky decision-making, it remains unknown whether individual, temporally stable neural sleep characteristics relate to individual differences in risk preferences. Here, we collected sleep data under normal conditions in fifty-four healthy adults using a portable high-density EEG at participants' home. Whole-brain corrected for multiple testing, we found that lower slow-wave activity (SWA, an indicator of sleep depth) in a cluster of electrodes over the right prefrontal cortex (PFC) is associated with higher individual risk propensity. Importantly, the association between local sleep depth and risk preferences remained significant when controlling for total sleep time and for time spent in deep sleep, i.e., sleep stages N2 and N3. Moreover, the association between risk preferences and SWA over the right PFC was very similar in all sleep cycles. Because the right PFC plays a central role in cognitive control functions, we speculate that local sleep depth in this area, as reflected by SWA, might serve as a dispositional indicator of self-regulatory ability, which in turn reflects risk preferences.

Sleep and physical activity: results from a long-term actigraphy study in adolescents.

PURPOSE: Research to date suggests that physical activity is associated with improved sleep, but studies have predominantly relied on self-report measures and have not accounted for school day/free day variability. To address these gaps in the literature, the aim of the present study was to (a) quantify physical activity in adolescents using long-term daily actigraphy measurement and (b) to examine the association between actigraphically assessed steps and sleep behavior in a sample of healthy adolescents. To be able to capture intra- and inter-individual differences in the daily physical activity of adolescents, we examined within as well as between subjects effects and its association with sleep. METHODS: Fifty adolescents between 10 and 14 years of age were included in the present study. In total 5989 days of actigraphy measurement (average of 119 ± 40 days per participant; range = 39-195 days) were analyzed. We use multilevel modeling to disentangle the within and between subject effects of physical activity on sleep. In this way, we examine within an individual, the association between steps during the day and subsequent sleep on a day-to-day basis. On the other hand, our between subjects' analysis allows us to ascertain whether individuals with more overall physical activity have better sleep. RESULTS: Within a subject more steps on school and free days were associated with later bed times on school and free days as well as later rise times on school days only. On the other hand, comparing between subjects' effects, more steps were associated with lower sleep efficiency on free and school days. No other significant associations were found for the other sleep variables. CONCLUSION: Our results obtained through objective and long-term measurement of both sleep and number of steps suggest weak or non-significant associations between these measures for most sleep variables. We emphasize the importance of the methodology and the separation of within subject from between subject features when examining the relationship between physical activity and sleep.

Naps not as effective as a night of sleep at dissipating sleep pressure.

The two-process model of sleep posits that two processes interact to regulate sleep and wake: a homeostatic (Process S) and a circadian process (Process C). Process S compensates for sleep loss by increasing sleep duration and intensity. Process C gates the timing of sleep/wake favouring sleep during the circadian night in humans. In this study, we examined whether taking six naps throughout a 24-hr period would result in the same amount of dissipation of homeostatic pressure at the end of the day as a night of sleep, when time in bed is equivalent. Data from 46 participants (10-23 years; mean = 14.5 [±â€…2.9]; 25 females) were analysed. Slow-wave energy, normalized to account for individual differences in slow-wave activity, was used as a measure of sleep homeostasis. In the nap condition, slow-wave energy of six naps distributed equally during a 24-hr period was calculated. In the baseline condition, slow-wave energy was measured after 9-hr time in bed. A paired t-test was used to compare nap and baseline conditions. A linear regression was used to examine whether slow-wave energy varied as a function of age. Slow-wave energy was greater during baseline than the nap condition (p < .001). No association between age and slow-wave energy was found for baseline or nap conditions. Our findings indicate that multiple naps throughout the day are not as effective at dissipating sleep pressure as a night of sleep. This is likely due to the influence of the circadian system, which staves off sleep during certain times of the day.

Sleep neurophysiology in childhood onset schizophrenia.

Altered sleep neurophysiology has consistently been reported in adult patients with schizophrenia. Converging evidence suggests that childhood onset schizophrenia (COS), a rare but severe form of schizophrenia, is continuous with adult onset schizophrenia. The aim of the current study was to characterize sleep neurophysiology in COS. An overnight sleep electroencephalogram (EEG) was recorded in 17 children and adolescents with COS (16 years ± 6.6) and 17 age and gender-matched controls. Non-rapid eye movement (NREM) and rapid eye movement (REM) sleep EEG power and coherence for the frequency bands delta (1.6-4.8 Hz), theta (5-8.4 Hz), alpha (8.6-11 Hz), beta 1 (16.4-20.2 Hz) and beta 2 (20.4-24.2 Hz) were compared between COS patients and controls. COS patients exhibited significant and widespread deficits in beta power during NREM and REM sleep. With regard to coherence, we found increases in COS patients across brain regions, frequency bands and sleep states. This study demonstrates the utility of the sleep EEG for studying vulnerable populations and its potential to aid diagnosis.

Environmental Factors Shape Sleep EEG Connectivity During Early Adolescence.

Quantifying the degree to which genetic and environmental factors shape brain network connectivity is critical to furthering our understanding of the developing human brain. Sleep, a state of sensory disengagement, provides a unique opportunity to study brain network activity noninvasively by means of sleep electroencephalography (EEG) coherence. We conducted a high-density sleep EEG study in monozygotic (MZ; n = 38; mean age = 12.46; 20 females) and dizygotic (DZ; n = 24; mean age = 12.50; 12 females) twins to assess the heritability of sleep EEG coherence in early adolescence-a period of significant brain rewiring. Structural equation modeling was used to estimate three latent factors: genes, environmental factors shared between twins and environmental factors unique to each twin. We found a strong contribution of unique environmental factors (66% of the variance) and moderate genetic influence (19% of the variance) on sleep EEG coherence across frequencies and sleep states. An exception to this was sleep spindle activity, an index of the thalamocortical network, which showed on average a genetic contribution of 48% across connections. Furthermore, we observed high intraindividual stability of coherence across two consecutive nights suggesting that despite only a modest genetic contribution, sleep EEG coherence is like a trait. Our findings in adolescent humans are in line with earlier findings in animals that show the primordial cerebral map and its connections are plastic and it is through interaction with the environment that the pattern of brain network connectivity is shaped. Therefore, even in twins living together, small differences in the environment may cascade into meaningful differences in brain connectivity.

Nature and Nurture: Brain Region-Specific Inheritance of Sleep Neurophysiology in Adolescence.

Sleep-specific oscillations of spindles and slow waves are generated through thalamocortical and corticocortical loops, respectively, and provide a unique opportunity to measure the integrity of these neuronal systems. Understanding the relative contribution of genetic factors to sleep oscillations is important for determining whether they constitute useful endophenotypes that mark vulnerability to psychiatric illness. Using high-density sleep EEG recordings in human adolescent twin pairs (n = 60; 28 females), we find that over posterior regions 80-90% of the variance in slow oscillations, slow wave, and spindle activity is due to genes. Surprisingly, slow (10-12 Hz) and fast (12-16 Hz) anterior spindle amplitude and σ power are largely driven by environmental factors shared among the twins. To our knowledge this is the first example of a neural phenotype that exhibits a strong influence of nature in one brain region, and nurture in another. Overall, our findings highlight the utility of the sleep EEG as a reliable and easy to measure endophenotype during adolescence. This measure may be used to measure disease risk in development before the onset of a psychiatric disorder; the location within the brain of deficits in sleep neurophysiology may suggest whether the ultimate cause is genetic or environmental.SIGNIFICANCE STATEMENT Two cardinal oscillations of sleep, slow waves and sleep spindles, play an important role in the core functions of sleep including memory consolidation, synaptic plasticity, and the recuperative function of sleep. In this study, we use a behavioral genetics approach to examine the heritability of sleep neurophysiology using high-density EEG in a sample of early adolescent twins. Our findings reveal a strong influence of both environmental and genetic factors in shaping these oscillations, dependent on brain region. Thus, during a developmental period when brain structure and function is in flux, we find that the sleep EEG is among the most heritable of human traits over circumscribed brain regions.

Association between depressive symptoms and sleep neurophysiology in early adolescence.

BACKGROUND: Depression is highly prevalent among adolescents, and depressive symptoms rise rapidly during early adolescence. Depression is often accompanied by subjective sleep complaints and alterations in sleep neurophysiology. In this study, we examine whether depressive symptoms, measured on a continuum, are associated with subjective and objective (sleep architecture and neurophysiology) measures of sleep in early adolescence. METHODS: High-density sleep EEG, actigraphy, and self-reported sleep were measured in 52 early adolescents (12.31 years; SD: 1.121; 25 female). Depressive symptoms were measured on a continuum using the Center for Epidemiological Studies Depression Scale (CES-D). The association between depressive symptoms and 2 weeks of actigraphy, self-reported sleep, sleep architecture, and sleep neurophysiology (slow wave activity and sigma power) was determined via multiple linear regression with factors age, sex, and pubertal status. RESULTS: Despite no association between polysomnography measures of sleep quality and depressive symptoms, individuals with more depressive symptoms manifested worse actigraphically measured sleep. Less sleep spindle activity, as reflected in nonrapid eye movement sleep sigma power, was associated with more depressive symptoms over a large cluster encompassing temporal, parietal, and occipital regions. Furthermore, worse subjectively reported sleep quality was also associated with less sigma power over these same areas. Puberty, age, and sex did not impact this association. CONCLUSIONS: Sleep spindles have been hypothesized to protect sleep against environmental disturbances. Thus, diminished spindle power may be a subtle sign of disrupted sleep and its association with depressive symptoms in early adolescence may signal vulnerability for depression.

Mapping Slow Waves by EEG Topography and Source Localization: Effects of Sleep Deprivation.

Slow waves are a salient feature of the electroencephalogram (EEG) during non-rapid eye movement (non-REM) sleep. The aim of this study was to assess the topography of EEG power and the activation of brain structures during slow wave sleep under normal conditions and after sleep deprivation. Sleep EEG recordings during baseline and recovery sleep after 40 h of sustained wakefulness were analyzed (eight healthy young men, 27 channel EEG). Power maps were computed for the first non-REM sleep episode (where sleep pressure is highest) in baseline and recovery sleep, at frequencies between 0.5 and 2 Hz. Power maps had a frontal predominance at all frequencies between 0.5 and 2 Hz. An additional occipital focus of activity was observed below 1 Hz. Power maps ≤ 1 Hz were not affected by sleep deprivation, whereas an increase in power was observed in the maps ≥ 1.25 Hz. Based on the response to sleep deprivation, low-delta (0.5-1 Hz) and mid-delta activity (1.25-2 Hz) were dissociated. Electrical sources within the cortex of low- and mid-delta activity were estimated using eLORETA. Source localization revealed a predominantly frontal distribution of activity for low-delta and mid-delta activity. Sleep deprivation resulted in an increase in source strength only for mid-delta activity, mainly in parietal and frontal regions. Low-delta activity dominated in occipital and temporal regions and mid-delta activity in limbic and frontal regions independent of the level of sleep pressure. Both, power maps and electrical sources exhibited trait-like aspects.

An update on adolescent sleep: New evidence informing the perfect storm model.

The maturation of sleep regulatory systems during adolescence in combination with psychosocial and societal pressures culminate in a "Perfect Storm" of short and ill-timed sleep and the associated consequences for many youngsters. This model, first described by Carskadon in 2011, guides our current thinking of adolescent sleep behavior. Since the original description, the field has moved forward with remarkable pace, and this review aims to summarize recent progress and describe how this new work informs our understanding of sleep regulation and sleep behavior during this developmental time frame.

Interindividual differences in the dynamics of the homeostatic process are trait-like and distinct for sleep versus wakefulness.

The sleep homeostatic Process S reflects the build-up of sleep pressure during waking and its dissipation during sleep. Process S is modelled as a saturating exponential function during waking and a decreasing exponential function during sleep. Slow wave activity is a physiological marker for non-rapid eye movement (non-REM) sleep intensity and serves as an index of Process S. There is considerable interindividual variability in the sleep homeostatic responses to sleep and sleep deprivation. The aim of this study was to investigate whether interindividual differences in Process S are trait-like. Polysomnographic recordings of 8 nights (12-h sleep opportunities, 22:00-10:00 hours) interspersed with three 36-h periods of sustained wakefulness were performed in 11 healthy young adults. Empirical mean slow wave activity per non-REM sleep episode at episode mid-points were used for parameter estimation. Parameters of Process S were estimated using different combinations of consecutive sleep recordings, resulting in two to three sets of parameters per subject. Intraclass correlation coefficients were calculated to assess whether the parameters were stable across the study protocol and they showed trait-like variability among individuals. We found that the group-average time constants of the build-up and dissipation of Process S were 19.2 and 2.7 h, respectively. Intraclass correlation coefficients ranged from 0.48 to 0.56, which reflects moderate trait variability. The time constants of the build-up and dissipation varied independently among subjects, indicating two distinct traits. We conclude that interindividual differences in the parameters of the dynamics of the sleep homeostatic Process S are trait-like.

Web-Based Assessment of Mental Well-Being in Early Adolescence: A Reliability Study.

BACKGROUND: The ever-increasing use of the Internet among adolescents represents an emerging opportunity for researchers to gain access to larger samples, which can be queried over several years longitudinally. Among adolescents, young adolescents (ages 11 to 13 years) are of particular interest to clinicians as this is a transitional stage, during which depressive and anxiety symptoms often emerge. However, it remains unclear whether these youngest adolescents can accurately answer questions about their mental well-being using a Web-based platform. OBJECTIVE: The aim of the study was to examine the accuracy of responses obtained from Web-based questionnaires by comparing Web-based with paper-and-pencil versions of depression and anxiety questionnaires. METHODS: The primary outcome was the score on the depression and anxiety questionnaires under two conditions: (1) paper-and-pencil and (2) Web-based versions. Twenty-eight adolescents (aged 11-13 years, mean age 12.78 years and SD 0.78; 18 females, 64%) were randomly assigned to complete either the paper-and-pencil or the Web-based questionnaire first. Intraclass correlation coefficients (ICCs) were calculated to measure intrarater reliability. Intraclass correlation coefficients were calculated separately for depression (Children's Depression Inventory, CDI) and anxiety (Spence Children's Anxiety Scale, SCAS) questionnaires. RESULTS: On average, it took participants 17 minutes (SD 6) to answer 116 questions online. Intraclass correlation coefficient analysis revealed high intrarater reliability when comparing Web-based with paper-and-pencil responses for both CDI (ICC=.88; P<.001) and the SCAS (ICC=.95; P<.001). According to published criteria, both of these values are in the "almost perfect" category indicating the highest degree of reliability. CONCLUSIONS: The results of the study show an excellent reliability of Web-based assessment in 11- to 13-year-old children as compared with the standard paper-pencil assessment. Furthermore, we found that Web-based assessments with young adolescents are highly feasible, with all enrolled participants completing the Web-based form. As early adolescence is a time of remarkable social and behavioral changes, these findings open up new avenues for researchers from diverse fields who are interested in studying large samples of young adolescents over time.

The spectrum of the non-rapid eye movement sleep electroencephalogram following total sleep deprivation is trait-like.

The sleep electroencephalogram (EEG) spectrum is unique to an individual and stable across multiple baseline recordings. The aim of this study was to examine whether the sleep EEG spectrum exhibits the same stable characteristics after acute total sleep deprivation. Polysomnography (PSG) was recorded in 20 healthy adults across consecutive sleep periods. Three nights of baseline sleep [12 h time in bed (TIB)] following 12 h of wakefulness were interleaved with three nights of recovery sleep (12 h TIB) following 36 h of sustained wakefulness. Spectral analysis of the non-rapid eye movement (NREM) sleep EEG (C3LM derivation) was used to calculate power in 0.25 Hz frequency bins between 0.75 and 16.0 Hz. Intraclass correlation coefficients (ICCs) were calculated to assess stable individual differences for baseline and recovery night spectra separately and combined. ICCs were high across all frequencies for baseline and recovery and for baseline and recovery combined. These results show that the spectrum of the NREM sleep EEG is substantially different among individuals, highly stable within individuals and robust to an experimental challenge (i.e. sleep deprivation) known to have considerable impact on the NREM sleep EEG. These findings indicate that the NREM sleep EEG represents a trait.

The human circadian metabolome.

The circadian clock orchestrates many aspects of human physiology, and disruption of this clock has been implicated in various pathologies, ranging from cancer to metabolic syndrome and diabetes. Although there is evidence that metabolism and the circadian clockwork are intimately linked on a transcriptional level, whether these effects are directly under clock control or are mediated by the rest-activity cycle and the timing of food intake is unclear. To answer this question, we conducted an unbiased screen in human subjects of the metabolome of blood plasma and saliva at different times of day. To minimize indirect effects, subjects were kept in a 40-h constant routine of enforced posture, constant dim light, hourly isocaloric meals, and sleep deprivation. Under these conditions, we found that ~15% of all identified metabolites in plasma and saliva were under circadian control, most notably fatty acids in plasma and amino acids in saliva. Our data suggest that there is a strong direct effect of the endogenous circadian clock on multiple human metabolic pathways that is independent of sleep or feeding. In addition, they identify multiple potential small-molecule biomarkers of human circadian phase and sleep pressure.

Sleep respiratory disturbances and arousals at moderate altitude have overlapping electroencephalogram spectral signatures.

An ascent to altitude has been shown to result in more central apneas and a shift towards lighter sleep in healthy individuals. This study employs spectral analysis to investigate the impact of respiratory disturbances (central/obstructive apnea and hypopnea or periodic breathing) at moderate altitude on the sleep electroencephalogram (EEG) and to compare EEG changes resulting from respiratory disturbances and arousals. Data were collected from 51 healthy male subjects who spent 1 night at moderate altitude (2590 m). Power density spectra of Stage 2 sleep were calculated in a subset (20) of these participants with sufficient artefact-free data for (a) epochs with respiratory events without an accompanying arousal, (b) epochs containing an arousal and (c) epochs of undisturbed Stage 2 sleep containing neither arousal nor respiratory events. Both arousals and respiratory disturbances resulted in reduced power in the delta, theta and spindle frequency range and increased beta power compared to undisturbed sleep. The similarity of the EEG changes resulting from altitude-induced respiratory disturbances and arousals indicates that central apneas are associated with micro-arousals, not apparent by visual inspection of the EEG. Our findings may have implications for sleep in patients and mountain tourists with central apneas and suggest that respiratory disturbances not accompanied by an arousal may, none the less, impact sleep quality and impair recuperative processes associated with sleep more than previously believed.

A Thalamocortical Perspective on Sleep Spindle Alterations in Neurodevelopmental Disorders.

Purpose of Review: Neurodevelopmental disorders are a group of conditions that affect the development and function of the nervous system, typically arising early in life. These disorders can have various genetic, environmental, and/or neural underpinnings, which can impact the thalamocortical system. Sleep spindles, brief bursts of oscillatory activity that occur during NREM sleep, provide a unique in vivo measure of the thalamocortical system. In this manuscript, we review the development of the thalamocortical system and sleep spindles in rodent models and humans. We then utilize this as a foundation to discuss alterations in sleep spindle activity in four of the most pervasive neurodevelopmental disorders-intellectual disability, attention deficit hyperactivity disorder, autism, and schizophrenia. Recent Findings: Recent work in humans has shown alterations in sleep spindles across several neurodevelopmental disorders. Simultaneously, rodent models have elucidated the mechanisms which may underlie these deficits in spindle activity. This review merges recent findings from these two separate lines of research to draw conclusions about the pathogenesis of neurodevelopmental disorders. Summary: We speculate that deficits in the thalamocortical system associated with neurodevelopmental disorders are exquisitely reflected in sleep spindle activity. We propose that sleep spindles may represent a promising biomarker for drug discovery, risk stratification, and treatment monitoring.