Sleep SWA Research Articles

0218 Changes in sleep architecture and topography of sleep EEG slow wave activity following acute wake extension in early adolescence

Abstract Introduction A progression of peak sleep EEG slow wave activity (SWA; EEG power 0.5-4Hz) from posterior to anterior expression reflects brain development. Further, increased EEG SWA after extended wakefulness is a marker of sleep pressure. However, it is unclear whether recovery sleep SWA in later youth is expressed in a similar scalp topography as typical sleep. Using experimental wake-extension, we investigated homeostatic changes in sleep architecture and SWA topography in early adolescence. Methods Twenty-two young adolescents (M±SD: 12.03±1.14y, 12F) participated in two consecutive laboratory stays after at least a week of at-home actigraphy-monitored stabilization (9.5h in bed). A baseline night (BSL; 9.5h 21:00-06:30) was followed by wake-extension (WE) to 02:30 and a 4h recovery sleep opportunity (RS; 02:30-06:30), each monitored by polysomnography including a 25-channel EEG array. The current analyses examined R&K sleep architecture at BSL and RS. SWA in RS was compared to the first 4h of BSL in two ways: (1) absolute NREM power (µV2); (2) an index (TI) of the topographical distribution of midline SWA (FPz-AFz-Fz-FCz-Cz-CPz-Pz-POz-Oz) providing a score of 1 to 9 indicating frontal to occipital peak distribution. Results WE significantly altered RS sleep architecture, including an increase in slow-wave sleep (%TST) versus BSL (M±SD BSL: 26.76±5.69%, RS: 51.65±7.83%, t(21)=-17.09, p<.001, d=-3.65). SWA was also significantly greater in RS (channel-averaged SWA BSL: 11883.50±5142.17 µV2, RS: 18955.82±7451.20 µV2, t(21)=-8.67, p<.001) with 22/25 individual electrodes meeting Bonferroni-corrected significance (ps<.001). Finally, we observed a small frontal shift (t(21)=2.39, p=.027, d=.51) of maximal SWA in RS (TI: 4.46±2.58; i.e., FCz/Cz) compared to BSL (5.32±2.78, i.e., Cz/CPz). Conclusion These data indicate robust sleep homeostasis in young adolescents after wake extension, expressed as increased SWA across the scalp. The findings also add to existing literature by indicating that SWA topography may also be sensitive to homeostatic challenge. Specifically, a baseline centroparietal locus of maximal SWA typical to this age became more frontocentral in recovery sleep. This anterior shift may reflect a homeostatic need over developmentally sensitive prefrontal cortex. Next steps will assess how individual responses may reflect a child’s neurodevelopment (e.g., inattention symptoms) or manifested behavior after wake extension and recovery sleep. Support (if any) K01MH109854, P20GM139743, R01HD103655

Functional networks of working memory abilities in children with complex congenital heart disease: a sleep EEG study

ABSTRACT Working memory is frequently impaired in children with complex congenital heart disease (CHD), but little is known about the functional neuronal correlates. Sleep slow wave activity (SWA; 1–4.5 Hz EEG power) has previously been shown to reliably map neurofunctional networks of cognitive abilities in children with and without neurodevelopmental impairments. This study investigated whether functional networks of working memory abilities are altered in children with complex CHD using EEG recordings during sleep. Twenty-one children with complex CHD (aged 10.9 [SD: 0.3] years) and 17 typically-developing peers (10.5 [0.7] years) completed different working memory tasks and an overnight high-density sleep EEG recording (128 electrodes). The combined working memory score tended to be lower in children with complex CHD (CHD group: −0.44 [1.12], typically-developing group: 0.55 [1.24], d = 0.59, p = .06). The working memory score and sleep SWA of the first hour of deep sleep were correlated over similar brain regions in both groups: Strong positive associations were found over prefrontal and fronto-parietal brain regions – known to be part of the working memory network – and strong negative associations were found over central brain regions. Within these working memory networks, the associations between working memory abilities and sleep SWA (r between −.36 and .58, all p < .03) were not different between the two groups (no interactions, all p > .05). The current findings suggest that sleep SWA reliably maps working memory networks in children with complex CHD and that these functional networks are generally preserved in these patients.

The experience-dependent increase in deep sleep activity is reduced in children with attention-deficit/hyperactivity disorder

Objective/BackgroundLearning of a visuomotor adaptation task during wakefulness leads to a local increase in slow–wave activity (SWA, EEG power between 1 and 4.5 Hz) during subsequent deep sleep. Here, we examined this relationship between learning and SWA in children with attention-deficit/hyperactivity disorder (ADHD). Patients/MethodsParticipants were 15 children with ADHD (9.7–14.8 y, one female) and 15 age-matched healthy controls (9.6–15.7 y, three female). After the completion of a visuomotor adaptation task in the evening, participants underwent an all-night high-density (HD, 128 electrodes) sleep-EEG measurement. ResultsHealthy control children showed the expected right-parietal increase in sleep SWA after visuomotor learning. Despite no difference in visuomotor learning, the local up-regulation during sleep was significantly reduced in ADHD patients compared to healthy controls. ConclusionsOur results indicate that the local, experience-dependent regulation of SWA is different in ADHD patients. Because the customarily observed heightened regulation in children was related to sensitive period maturation, ADHD patients may lack certain sensitive periods or show a developmental delay.

Chronic high-caloric diet modifies sleep homeostasis in mice.

Obesity prevalence and sleep habit changes are commonplace nowadays, due to modern lifestyle. A bidirectional relationship likely exists between sleep quality and metabolic disruptions, which could impact quality of life. In our study, we investigated the effects of a chronic high-caloric diet on sleep architecture and sleep regulation in mice. We studied the effect of 3months high-caloric diet (HCD, 45% fat) on sleep and the sleep electroencephalogram (EEG) in C57BL/6J mice during 24-hr baseline (BL) recordings, and after 6-hr sleep deprivation (SD). We examined the effect of HCD on sleep homeostasis, by performing parameter estimation analysis and simulations of the sleep homeostatic Process S, a measure of sleep pressure, which is reflected in the non-rapid-eye-movement (NREM) sleep slow-wave-activity (SWA, EEG power density between 0.5 and 4.0Hz). Compared to controls (n=11, 30.7±0.8g), mice fed with HCD (n=9, 47.6±0.8g) showed an increased likelihood of consecutive NREM-REM sleep cycles, increased REM sleep and decreased NREM sleep EEG SWA. After SD, these effects were more pronounced. The simulation resulted in a close fit between the time course of SWA and Process S in both groups. HCD fed mice had a slower time constant (Ti =15.98hr) for the increase in homeostatic sleep pressure compared with controls (5.95hr) indicating a reduced effect of waking on the increase in sleep pressure. Our results suggest that chronic HCD consumption impacts sleep regulation.

Chronic social stress leads to altered sleep homeostasis in mice

Disturbed sleep and altered sleep homeostasis are core features of many psychiatric disorders such as depression. Chronic uncontrollable stress is considered an important factor in the development of depression, but little is known on how chronic stress affects sleep regulation and sleep homeostasis. We therefore examined the effects of chronic social stress (CSS) on sleep regulation in mice. Adult male C57BL/6 mice were implanted for electrocortical recordings (ECoG) and underwent either a 10-day CSS protocol or control handling (CON). Subsequently, ECoG was assessed across a 24-h post-stress baseline, followed by a 4-h sleep deprivation, and then a 20-h recovery period. After sleep deprivation, CSS mice showed a blunted increase in sleep pressure compared to CON mice, as measured using slow wave activity (SWA, electroencephalographic power between 1–4Hz) during non-rapid eye movement (NREM) sleep. Vigilance states did not differ between CSS and CON mice during post-stress baseline, sleep deprivation or recovery, with the exception of CSS mice exhibiting increased REM sleep during recovery sleep. Behavior during sleep deprivation was not affected by CSS. Our data provide evidence that CSS alters the homeostatic regulation of sleep SWA in mice. In contrast to acute social stress, which results in a faster SWA build-up, CSS decelerates the homeostatic build up. These findings are discussed in relation to the causal contribution of stress-induced sleep disturbance to depression.

Widespread reduction in sleep spindle activity in socially anxious children and adolescents

Social anxiety disorder (SAD) is one of the most prevalent psychiatric diseases typically emerging during childhood and adolescence. Biological vulnerabilities such as a protracted maturation of prefrontal cortex functioning together with heightened reactivity of the limbic system leading to increased emotional reactivity are discussed as factors contributing to the emergence and maintenance of SAD. Sleep slow wave activity (SWA, 0.75–4.5 Hz) and sleep spindle activity (9–16 Hz) reflect processes of brain maturation and emotion regulation. We used high-density electroencephalography to characterize sleep SWA and spindle activity and their relationship to emotional reactivity in children and adolescents suffering from SAD and healthy controls (HC). Subjectively rated arousal was assessed using an emotional picture-word association task. SWA did not differ between socially anxious and healthy participants. We found a widespread reduction in fast spindle activity (13–16 Hz) in SAD patients compared to HC. SAD patients rated negative stimuli to be more arousing and these arousal ratings were negatively correlated with fast spindle activity. These results suggest electrophysiological alterations that are evident at an early stage of psychopathology and that are closely linked to one core symptom of anxiety disorders such as increased emotional reactivity. The role of disturbed GABAergic neurotransmission is discussed as an underlying factor.

Sleep EEG maps the functional neuroanatomy of executive processes in adolescents born very preterm

Executive function deficits are among the most frequent sequela of very preterm birth but the underlying neuronal mechanisms are not fully understood. We used high-density electroencephalography (EEG) recordings during sleep to assess alterations in the functional neuroanatomy of executive processes in adolescents born very preterm. The topographical distribution of sleep slow wave activity (SWA; 1–4.5 Hz EEG power) has previously been used to map cognitive abilities and is known to reflect the intensity of the prior use of the respective neuronal networks. We assessed 38 adolescents born before 32 weeks of gestation [age at assessment: 12.9 (SD: 1.7), range: 10.6–16.7 years] and 43 term-born peers [13.1 (2.0), 10.0–16.9]. Executive function abilities were quantified with a composite score derived from a comprehensive task battery. All-night high-density EEG (128 electrodes) was recorded and SWA of the first hour of sleep was calculated. Abilities were significantly poorer in the very preterm compared to the term-group, particularly, if the tasks demands were high (p < .01). The score was positively correlated with sleep SWA in a cluster of 15 electrodes over frontal and negatively in a cluster of 14 electrodes over central brain regions after controlling for age at assessment and correcting for multiple comparisons. Within the frontal cluster, sleep SWA was higher in very preterm compared to term-born participants when controlling for executive function performance and age at assessment (p = .02). No difference in SWA between very preterm and term-born participants was found for the central cluster (p = .29). Our results demonstrate a local increase of sleep SWA over brain regions associated with executive processes in adolescents born very preterm compared to similarly performing term-born peers. Thus, sleep SWA seems to map the higher effort needed for executive function tasks in adolescents born very preterm.

Sleep slow-wave activity reveals developmental changes in experience-dependent plasticity.

Experience-dependent plasticity, the ability of the brain to constantly adapt to an ever-changing environment, has been suggested to be highest during childhood and to decline thereafter. However, empirical evidence for this is rather scarce. Slow-wave activity (SWA; EEG activity of 1-4.5 Hz) during deep sleep can be used as a marker of experience-dependent plasticity. For example, performing a visuomotor adaptation task in adults increased SWA during subsequent sleep over a locally restricted region of the right parietal cortex, which is known to be involved in visuomotor adaptation. Here, we investigated whether local experience-dependent changes in SWA vary as a function of brain maturation. Three age groups (children, adolescents, and adults) participated in a high-density EEG study with two conditions (baseline and adaptation) of a visuomotor learning task. Compared with the baseline condition, sleep SWA was increased after visuomotor adaptation in a cluster of eight electrodes over the right parietal cortex. The local boost in SWA was highest in children. Baseline SWA in the parietal cluster and right parietal gray matter volume, which both indicate region-specific maturation, were significantly correlated with the local increase in SWA. Our findings indicate that processes of brain maturation favor experience-dependent plasticity and determine how sensitive a specific brain region is for learning experiences. Moreover, our data confirm that SWA is a highly sensitive tool to map maturational differences in experience-dependent plasticity.

Light modulation of human sleep depends on a polymorphism in the clock gene Period3

Non-image-forming (NIF) responses to light powerfully modulate human physiology. However, it remains scarcely understood how NIF responses to light modulate human sleep and its EEG hallmarks, and if there are differences across individuals. Here we investigated NIF responses to light on sleep in individuals genotyped for the PERIOD3 (PER3) variable-number tandem-repeat (VNTR) polymorphism. Eighteen healthy young men (20–28 years; mean±SEM: 25.9±1.2) homozygous for the PER3 polymorphism were matched by age, body-mass index, and ethnicity. The study protocol comprised a balanced cross-over design during the winter, during which participants were exposed to either light of 40lx at 6500K (blue-enriched) or light at 2500K (non-blue enriched), during 2h in the evening. Compared to light at 2500K, light at 6500K induced a significant increase in all-night NREM sleep slow-wave activity (SWA: 1.0–4.5Hz) in the occipital cortex for PER35/5 individuals, but not for PER34/4 volunteers. Dynamics of SWA across sleep cycles revealed increased occipital NREM sleep SWA for virtuallyall sleep episode only for PER35/5 individuals. Furthermore, they experienced light at 6500K as significantly brighter. Intriguingly, this subjective perception of brightness significantly predicted their increased occipital SWA throughout the sleep episode. Our data indicate that humans homozygous for the PER35/5 allele are more sensitive to NIF light effects, as indexed by specific changes in sleep EEG activity. Ultimately, individual differences in NIF light responses on sleep may depend on a clock gene polymorphism involved in sleep–wake regulation.

Chronic Sleep Restriction Disrupts Sleep Homeostasis and Behavioral Sensitivity to Alcohol by Reducing the Extracellular Accumulation of Adenosine

Sleep impairments are comorbid with a variety of neurological and psychiatric disorders including depression, epilepsy, and alcohol abuse. Despite the prevalence of these disorders, the cellular mechanisms underlying the interaction between sleep disruption and behavior remain poorly understood. In this study, the impact of chronic sleep loss on sleep homeostasis was examined in C57BL/6J mice following 3 d of sleep restriction. The electroencephalographic power of slow-wave activity (SWA; 0.5-4 Hz) in nonrapid eye movement (NREM) sleep and adenosine tone were measured during and after sleep restriction, and following subsequent acute sleep deprivation. During the first day of sleep restriction, SWA and adenosine tone increased, indicating a homeostatic response to sleep loss. On subsequent days, SWA declined, and this was accompanied by a corresponding reduction in adenosine tone caused by a loss of one source of extracellular adenosine. Furthermore, the response to acute sleep deprivation (6 h) was significantly attenuated in sleep-restricted mice. These effects were long-lasting with reduced SWA and adenosine tone persisting for at least 2 weeks. To investigate the behavioral consequences of chronic sleep restriction, sensitivity to the motor-impairing effects of alcohol was also examined. Sleep-restricted mice were significantly less sensitive to alcohol when tested 24 h after sleep restriction, an effect that persisted for 4 weeks. Intracerebroventricular infusion of an adenosine A1 receptor antagonist produced a similar decrease in sensitivity to alcohol. These results suggest that chronic sleep restriction induces a sustained impairment in adenosine-regulated sleep homeostasis and consequentially impacts the response to alcohol.

The sleep EEG topography in children and adolescents shows sex differences in language areas

The topographic distribution of slow wave activity (SWA, EEG power between 0.75 and 4.5Hz) during non-rapid eye movement (NREM) sleep was proposed to mirror cortical maturation with a typical age-related pattern. Here, we examined whether sex differences occur in SWA topography of children and adolescents (22 age-matched subjects, 11 boys, mean age 13.4years, range: 8.7–19.4, and 11 girls, mean age 13.4years, range: 9.1–19.0years). In females, SWA during the first 60min of NREM sleep was higher over bilateral cortical areas that are related to language functions, while in males SWA was increased over the right prefrontal cortex, a region also involved in spatial abilities. We conclude that cortical areas governing functions in which one sex outperforms the other exhibit increased sleep SWA and, thus, may indicate maturation of sex-specific brain function and higher cortical plasticity during development.

Topography of sleep slow wave activity in children with attention-deficit/hyperactivity disorder

IntroductionSleep slow wave activity (SWA, EEG power between 1 and 4.5 Hz) is a major characteristic of non-rapid eye movement (NREM) sleep, which seems to be critically involved in cortical plasticity. Studies using high-density electroencephalography (hd-EEG) showed that the topographical distribution of SWA mirrors cortical maturation, expressing a local maximum that is characteristic for a certain age range. We compared the sleep EEG of children with attention-deficit/hyperactivity disorder (ADHD) with healthy controls to explore differences in sleep SWA. MethodsAll-night hd-EEG recordings (128 electrodes) were performed in a group of nine children diagnosed with ADHD and nine age- and sex-matched healthy controls. SWA topography was calculated and contrasted between the groups. ResultsWe found a local increase of SWA in a cluster of six electrodes over central regions in children with ADHD compared to control children (+17% ± 6% SE, p < .01). This group difference was specific for the SWA range and stable across the night. ConclusionsChildren with ADHD showed a less mature topographical SWA distribution in comparison to healthy children of the same age and sex. This neuromaturational delay in ADHD is in accordance with neuroimaging and behavioral studies. Thus, our study supports the use of sleep SWA topography as a reliable imaging tool for the study of cortical plasticity.

Mapping the electrophysiological marker of sleep depth reveals skill maturation in children and adolescents

Electroencephalographically (EEG) recorded slow wave activity (SWA, 1-4.5Hz), reflecting the depth of sleep, is suggested to play a crucial role in synaptic plasticity. Mapping of SWA by means of high-density EEG reveals that cortical regions showing signs of maturational changes (structural and behavioral) during childhood and adolescence exhibit more SWA. Moreover, the maturation of specific skills is predicted by the topographical distribution of SWA. Thus, SWA topography may serve as a promising neuroimaging tool with prognostic potential. Finally, our data suggest that deep sleep SWA in humans is involved in cortical development that optimizes performance.

Sleep Homeostasis and Cortical Synchronization: II. A Local Field Potential Study of Sleep Slow Waves in the Rat

Sleep slow-wave activity (SWA, EEG power between 0.5 and 4.0 Hz) decreases homeostatically in the course of non-rapid eye movement sleep (NREM) sleep. According to a recent hypothesis, the homeostatic decrease of sleep SWA is due to a progressive decrease in the strength of corticocortical connections. This hypothesis was evaluated in a large-scale thalamocortical model, which showed that a decrease in synaptic strength, implemented through a reduction of postsynaptic currents, resulted in lower sleep SWA in simulated local field potentials (LFP). The decrease in SWA was associated with a decreased proportion of high-amplitude slow waves, a decreased slope of the slow waves, and an increase in the number of multipeak waves. Here we tested the model predictions by obtaining LFP recordings from the rat cerebral cortex and comparing conditions of high homeostatic sleep pressure (early sleep) and low homeostatic sleep pressure (late sleep). Intracortical LFP recordings during baseline sleep and after 6 hours of sleep deprivation. Basic sleep research laboratory. WKY adult male rats. N/A. Early sleep (sleep at the beginning of the major sleep phase, sleep immediately after sleep deprivation) was associated with (1) high SWA, (2) many large slow waves, (3) steep slope of slow waves, and (4) rare occurrence of multipeak waves. By contrast, late sleep (sleep at the end of the major sleep phase, sleep several hours after the end of sleep deprivation) was associated with (1) low SWA, (2) few high-amplitude slow waves, (3) reduced slope of slow waves, and (4) more frequent multipeak waves. In rats, changes in sleep SWA are associated with changes in the amplitude and slope of slow waves, and in the number of multi-peak waves. Such changes in slow-wave parameters are compatible with the hypothesis that average synaptic strength decreases in the course of sleep.

Sleep Homeostasis and Cortical Synchronization: I. Modeling the Effects of Synaptic Strength on Sleep Slow Waves

Sleep slow-wave activity (SWA, electroencephalogram [EEG] power between 0.5 and 4.0 Hz) is homeostatically regulated, increasing with wakefulness and declining with sleep. Sleep SWA is thought to reflect sleep need, but the mechanisms of its homeostatic regulation remain unknown. Based on a recent hypothesis, we sought to determine whether a decrease in cortical synaptic strength can account for changes in sleep SWA. A large-scale computer model of the sleeping thalamocortical system was used to reproduce in detail the cortical slow oscillations underlying EEG slow waves. N/A. N/A. Simulated reductions in the strength of corticocortical synapses. Decreased synaptic strength led to (1) decreased single cell membrane potential oscillations and reduced network synchronization, (2) decreased rate of neural recruitment and decruitment, and (3) emergence of local clusters of synchronized activity. These changes were reflected in the local EEG as (1) decreased incidence of high-amplitude slow waves, (2) decreased wave slope, and (3) increased number of multipeak waves. Spectral analysis confirmed that these changes were associated with a decrease in SWA. A decrease in cortical synaptic strength is sufficient to account for changes in sleep SWA and is accompanied by characteristic changes in slow-wave parameters. Experimental results from rat cortical depth recordings and human high-density EEG show similar changes in slow-wave parameters with decreasing SWA, suggesting that the underlying mechanism may indeed be a net decrease in synaptic strength.

Exploratory Behavior, Cortical BDNF Expression, and Sleep Homeostasis

Slow-wave activity (SWA; 0.5-4.0 Hz) during non-rapid eye movement (NREM) sleep is a reliable indicator of sleep need, as it increases with the duration of prior wakefulness and decreases during sleep. However, which biologic process occurring during wakefulness is responsible for the increase of sleep SWA remains unknown. The aim of the study was to determine whether neuronal plasticity underlies the link between waking activities and the SWA response. We manipulated, in rats, the amount of exploratory activity while maintaining the total duration of waking constant. We then measured the extent to which exploration increases cortical expression of plasticity-related genes (BDNF, Arc, Homer, NGFI-A), and the SWA response once the animals were allowed to sleep. Basic neurophysiology and molecular laboratory. Male Wistar Kyoto rats (250-300 g; 2-3 month old). None. We found that, within the same animal, the amount of exploratory behavior during wakefulness could predict the extent to which BDNF was induced, as well as the extent of the homeostatic SWA response during subsequent sleep. This study suggests a direct link between the synaptic plasticity triggered by waking activities and the homeostatic sleep response and identifies BDNF as a major mediator of this link at the molecular level.