Wake EEG oscillation dynamics reflect both sleep need and brain maturation across childhood and adolescence.

An objective measure of brain maturation is highly insightful for monitoring both typical and atypical development. Slow wave activity, recorded in the sleep electroencephalogram (EEG), reliably indexes changes in brain plasticity with age, as well as deficits related to developmental disorders such as attention-deficit hyperactivity disorder (ADHD). Unfortunately, measuring sleep EEG is resource-intensive and burdensome for participants. We therefore aimed to determine whether wake EEG could likewise index developmental changes in brain plasticity. We analyzed high-density wake EEG collected from 163 participants 3-25 years old, before and after a night of sleep. We compared two measures of oscillatory EEG activity, amplitudes and density, as well as two measures of aperiodic activity, intercepts and slopes. Furthermore, we compared these measures in patients with ADHD (8-17 y.o., N=58) to neurotypical controls. We found that wake oscillation amplitudes behaved the same as sleep slow wave activity: amplitudes decreased with age, decreased after sleep, and this overnight decrease decreased with age. Oscillation densities were also substantially age-dependent, decreasing overnight in children and increasing overnight in adolescents and adults. While both aperiodic intercepts and slopes decreased linearly with age, intercepts decreased overnight, and slopes increased overnight. Overall, our results indicate that wake oscillation amplitudes track both development and sleep need, and overnight changes in oscillation density reflect some yet-unknown shift in neural activity around puberty. No wake measure showed significant effects of ADHD, thus indicating that wake EEG measures, while easier to record, are not as sensitive as those during sleep.

Associations between Social Contact, Sleep and Dietary Patterns among Children: A Cross-Sectional Study.

Social isolation in adults can be associated with altered sleep and eating behavior. This study aimed to investigate the interactions between the extent of social contact, eating behavior and sleep in infants and preschool children. In an observational study, 439 caregivers of 562 children aged 0-6 years provided information on sleep (i.e., duration, latency, bedtimes and nighttime awakenings), eating behaviors (i.e., meal size, consumption of sweet snacks, salty snacks, fruits and vegetables) and social contact (i.e., quarantine status, household size, social activities) during the COVID-19 pandemic (April 2020). In infants (0-3 years), the change in meal size and consumption of snacks, fruits, and vegetables did not significantly relate to the extent of social contact. For preschool children (3-6 years), a trend was observed, suggesting that quarantine status was associated with increased meal size. Changes in sleep duration, sleep latency, bedtimes and nighttime awakenings from before to during the pandemic were not significantly linked to the three variables quantifying social contact in both age groups. This study highlights that, contrary to expectations, the extent of social contact has negligible associations with infants' and preschool children's sleep and eating behaviors. These findings indicate that other factors beyond social isolation play a role in shaping children's eating habits and sleep patterns.

Bedtime to the brain: how infants' sleep behaviours intertwine with non-rapid eye movement sleep electroencephalography features.

Adequate sleep is critical for development and facilitates the maturation of the neurophysiological circuitries at the basis of cognitive and behavioural function. Observational research has associated early life sleep problems with worse later cognitive, psychosocial, and somatic health outcomes. Yet, the extent to which day-to-day sleep behaviours (e.g., duration, regularity) in early life relate to non-rapid eye movement (NREM) neurophysiology-acutely and the long-term-remains to be studied. We measured sleep behaviours in 32 healthy 6-month-olds assessed with actimetry and neurophysiology with high-density electroencephalography (EEG) to investigate the association between NREM sleep and habitual sleep behaviours. Our study revealed four findings: first, daytime sleep behaviours are related to EEG slow-wave activity (SWA). Second, night-time movement and awakenings from sleep are connected with spindle density. Third, habitual sleep timing is linked to neurophysiological connectivity quantified as delta coherence. And lastly, delta coherence at 6 months predicts night-time sleep duration at 12 months. These novel findings widen our understanding that infants' sleep behaviours are closely intertwined with three particular levels of neurophysiology: sleep pressure (determined by SWA), the maturation of the thalamocortical system (spindles), and the maturation of cortical connectivity (coherence). The crucial next step is to extend this concept to clinical groups to objectively characterise infants' sleep behaviours 'at risk' that foster later neurodevelopmental problems.

Not simply a matter of parents-Infants' sleep-wake patterns are associated with their regularity of eating.

In adults there are indications that regular eating patterns are related to better sleep quality. During early development, sleep and eating habits experience major maturational transitions. Further, the bacterial landscape of the gut microbiota undergoes a rapid increase in complexity. Yet little is known about the association between sleep, eating patterns and the gut microbiota. We first hypothesized that higher eating regularity is associated with more mature sleep patterns, and second, that this association is mediated by the maturational status of the gut microbiota. To test this hypothesis, we performed a longitudinal study in 162 infants to assess actigraphy, diaries of sleep and eating times, and stool microbiota composition at ages 3, 6 and 12 months. To comprehensively capture infants' habitual sleep-wake patterns, 5 sleep composites that characterize infants' sleep habits across multiple days in their home environment were computed. To assess timing of eating habits, we developed an Eating Regularity Index (ERI). Gut microbial composition was assessed by 16S rRNA gene amplicon sequencing, and its maturation was assessed based on alpha diversity, bacterial maturation index, and enterotype. First, our results demonstrate that increased eating regularity (higher ERI) in infants is associated with less time spent awake during the night (sleep fragmentation) and more regular sleep patterns. Second, the associations of ERI with sleep evolve with age. Third, the link between infant sleep and ERI remains significant when controlling for parents' subjectively rated importance of structuring their infant's eating and sleeping times. Finally, the gut microbial maturational markers did not account for the link between infant's sleep patterns and ERI. Thus, infants who eat more regularly have more mature sleep patterns, which is independent of the maturational status of their gut microbiota. Interventions targeting infant eating rhythm thus constitute a simple, ready-to-use anchor to improve sleep quality.

Lack of association between behavioral development and simplified topographical markers of the sleep EEG in infancy.

The sleep EEG mirrors neuronal connectivity, especially during development when the brain undergoes substantial rewiring. As children grow, the slow-wave activity (SWA; 0.75-4.25 Hz) spatial distribution in their sleep EEG changes along a posterior-to-anterior gradient. Topographical SWA markers have been linked to critical neurobehavioral functions, such as motor skills, in school-aged children. However, the relationship between topographical markers in infancy and later behavioral outcomes is still unclear. This study aims to explore reliable indicators of neurodevelopment in infants by analyzing their sleep EEG patterns. Thirty-one 6-month-old infants (15 female) underwent high-density EEG recordings during nighttime sleep. We defined markers based on the topographical distribution of SWA and theta activity, including central/occipital and frontal/occipital ratios and an index derived from local EEG power variability. Linear models were applied to test whether markers relate to concurrent, later, or retrospective behavioral scores, assessed by the parent-reported Ages & Stages Questionnaire at ages 3, 6, 12, and 24 months. Results indicate that the topographical markers of the sleep EEG power in infants were not significantly linked to behavioral development at any age. Further research, such as longitudinal sleep EEG in newborns, is needed to better understand the relationship between these markers and behavioral development and assess their predictive value for individual differences.

Sleep spindles across youth affected by schizophrenia or anti-N-methyl-D-aspartate-receptor encephalitis.

Background: Sleep disturbances are intertwined with the progression and pathophysiology of psychotic symptoms in schizophrenia. Reductions in sleep spindles, a major electrophysiological oscillation during non-rapid eye movement sleep, have been identified in patients with schizophrenia as a potential biomarker representing the impaired integrity of the thalamocortical network. Altered glutamatergic neurotransmission within this network via a hypofunction of the N-methyl-D-aspartate receptor (NMDAR) is one of the hypotheses at the heart of schizophrenia. This pathomechanism and the symptomatology are shared by anti-NMDAR encephalitis (NMDARE), where antibodies specific to the NMDAR induce a reduction of functional NMDAR. However, sleep spindle parameters have yet to be investigated in NMDARE and a comparison of these rare patients with young individuals with schizophrenia and healthy controls (HC) is lacking. This study aims to assess and compare sleep spindles across young patients affected by Childhood-Onset Schizophrenia (COS), Early-Onset Schizophrenia, (EOS), or NMDARE and HC. Further, the potential relationship between sleep spindle parameters in COS and EOS and the duration of the disease is examined. Methods: Sleep EEG data of patients with COS (N = 17), EOS (N = 11), NMDARE (N = 8) aged 7-21 years old, and age- and sex-matched HC (N = 36) were assessed in 17 (COS, EOS) or 5 (NMDARE) electrodes. Sleep spindle parameters (sleep spindle density, maximum amplitude, and sigma power) were analyzed. Results: Central sleep spindle density, maximum amplitude, and sigma power were reduced when comparing all patients with psychosis to all HC. Between patient group comparisons showed no differences in central spindle density but lower central maximum amplitude and sigma power in patients with COS compared to patients with EOS or NMDARE. Assessing the topography of spindle density, it was significantly reduced over 15/17 electrodes in COS, 3/17 in EOS, and 0/5 in NMDARE compared to HC. In the pooled sample of COS and EOS, a longer duration of illness was associated with lower central sigma power. Conclusions: Patients with COS demonstrated more pronounced impairments of sleep spindles compared to patients with EOS and NMDARE. In this sample, there is no strong evidence that changes in NMDAR activity are related to spindle deficits.

An infant sleep electroencephalographic marker of thalamocortical connectivity predicts behavioral outcome in late infancy.

Infancy represents a critical period during which thalamocortical brain connections develop and mature. Deviations in the maturation of thalamocortical connectivity are linked to neurodevelopmental disorders. There is a lack of early biomarkers to detect and localize neuromaturational deviations, which can be overcome with mapping through high-density electroencephalography (hdEEG) assessed in sleep. Specifically, slow waves and spindles in non-rapid eye movement (NREM) sleep are generated by the thalamocortical system, and their characteristics, slow wave slope and spindle density, are closely related to neuroplasticity and learning. Spindles are often subdivided into slow (11.0-13.0 Hz) and fast (13.5-16.0 Hz) frequencies, for which not only different functions have been proposed, but for which also distinctive developmental trajectories have been reported across the first years of life. Recent studies further suggest that information processing during sleep underlying sleep-dependent learning is promoted by the temporal coupling of slow waves and spindles, yet slow wave-spindle coupling remains unexplored in infancy. Thus, we evaluated three potential biomarkers: 1) slow wave slope, 2) spindle density, and 3) the temporal coupling of slow waves with spindles. We use hdEEG to first examine the occurrence and spatial distribution of these three EEG features in healthy infants and second to evaluate a predictive relationship with later behavioral outcomes. We report four key findings: First, infants' EEG features appear locally: slow wave slope is maximal in occipital and frontal areas, whereas slow and fast spindle density is most pronounced frontocentrally. Second, slow waves and spindles are temporally coupled in infancy, with maximal coupling strength in the occipital areas of the brain. Third, slow wave slope, fast spindle density, and slow wave-spindle coupling are not associated with concurrent behavioral status (6 months). Fourth, fast spindle density in central and frontocentral regions at age 6 months predicts overall developmental status at age 12 months, and motor skills at age 12 and 24 months. Neither slow wave slope nor slow wave-spindle coupling predict later behavioral development. We further identified spindle frequency as a determinant of slow and fast spindle density, which accordingly, also predicts motor skills at 24 months. Our results propose fast spindle density, or alternatively spindle frequency, as early EEG biomarker for identifying thalamocortical maturation, which can potentially be used for early diagnosis of neurodevelopmental disorders in infants. These findings are in support of a role of sleep spindles in sensorimotor microcircuitry development. A crucial next step will be to evaluate whether early therapeutic interventions may be effective to reverse deviations in identified individuals at risk.

The sleeping brain's connectivity and family environment: characterizing sleep EEG coherence in an infant cohort.

Brain connectivity closely reflects brain function and behavior. Sleep EEG coherence, a measure of brain's connectivity during sleep, undergoes pronounced changes across development under the influence of environmental factors. Yet, the determinants of the developing brain's sleep EEG coherence from the child's family environment remain unknown. After characterizing high-density sleep EEG coherence in 31 healthy 6-month-old infants by detecting strongly synchronized clusters through a data-driven approach, we examined the association of sleep EEG coherence from these clusters with factors from the infant's family environment. Clusters with greatest coherence were observed over the frontal lobe. Higher delta coherence over the left frontal cortex was found in infants sleeping in their parents' room, while infants sleeping in a room shared with their sibling(s) showed greater delta coherence over the central parts of the frontal cortex, suggesting a link between local brain connectivity and co-sleeping. Finally, lower occipital delta coherence was associated with maternal anxiety regarding their infant's sleep. These interesting links between sleep EEG coherence and family factors have the potential to serve in early health interventions as a new set of targets from the child's immediate environment.

Sleep as a protective factor of children's executive functions: A study during COVID-19 confinement.

Confinements due to the COVID-19 outbreak affected sleep and mental health of adults, adolescents and children. Already preschool children experienced acutely worsened sleep, yet the possible resulting effects on executive functions remain unexplored. Longitudinally, sleep quality predicts later behavioral-cognitive outcomes. Accordingly, we propose children's sleep behavior as essential for healthy cognitive development. By using the COVID-19 confinement as an observational-experimental intervention, we tested whether worsened children's sleep affects executive functions outcomes 6 months downstream. We hypothesized that acutely increased night awakenings and sleep latency relate to reduced later executive functions. With an online survey during the acute confinement phase we analyzed sleep behavior in 45 children (36-72 months). A first survey referred to the (retrospective) time before and (acute) situation during confinement, and a follow-up survey assessed executive functions 6 months later (6 months retrospectively). Indeed, acutely increased nighttime awakenings related to reduced inhibition at FOLLOW-UP. Associations were specific to the confinement-induced sleep-change and not the sleep behavior before confinement. These findings highlight that specifically acute changes of children's nighttime sleep during sensitive periods are associated with behavioral outcome consequences. This aligns with observations in animals that inducing poor sleep during developmental periods affects later brain function.

Association of transportation noise with sleep during the first year of life: A longitudinal study.

STUDY OBJECTIVES: During infancy, adequate sleep is crucial for physical and neurocognitive development. In adults and children, night-time noise exposure is associated with sleep disturbances. However, whether and to what extent infants' sleep is affected, is unknown. Thus, this study investigated the relationship between nocturnal transportation noise and actimetry-derived habitual sleep behavior across the first year of life. METHODS: In 144 healthy infants (63 girls), nocturnal (23:00-7:00) transportation noise (i.e., road, railway, and aircraft) was modelled at the infants' individual places of residence. Using actimetry, we recorded movement patterns for 11 days in a longitudinal design at 3, 6, and 12 months of age and derived the recently proposed core sleep composites of night-time sleep duration, activity, and variability. Using linear mixed-effects models, we determined associations between noise exposure and sleep composites. Sex, gestational age, parents' highest educational level, infants' age, and the existence of siblings served as control variables. RESULTS: In models without interactions, night-time transportation noise was unrelated to sleep composites across the first year of life (p > .16). Exploratory analyses of an interaction between noise and the existence of siblings yielded an association between night-time transportation noise and sleep duration in infants without siblings only (p = .004). CONCLUSION: In our study, sleep in infants during the first year of life was relatively robust against external perturbation by night-time transportation noise. However, particularly in children without siblings increasing night-time transportation noise reduced sleep duration. This suggests that the habitual noise environment may modulate individual susceptibility to adverse effects of noise on sleep.

Sleep behavior of infants with infantile hemangioma treated with propranolol-a cohort study.

Sleep problems are frequently reported in infants treated with propranolol for infantile hemangiomas, possibly serving as a marker for a negative impact on central nervous system function. In this cohort study, we objectively investigate the sleep behavior of infants with infantile hemangiomas on propranolol compared to a healthy, untreated control group. Sleep of propranolol-treated infants and controls was investigated using ankle actigraphy and a 24-h diary for 7-10 days at ages 3 and 6 months. The main outcome measures were the Number of Nighttime Awakenings and Sleep Efficiency. The main secondary outcome measures included 24-hour Total Sleep, daytime sleep behavior, and parent-rated infant sleep quality and behavioral development based on the Brief Infant Sleep Questionnaire (BISQ) and the age-appropriate Ages-and-Stages Questionnaire (ASQ), respectively. Fifty-four term-born infants were included in each cohort. No group difference in any investigated parameter was seen at age 3 months. At age 6 months, the propranolol group exhibited a decrease in Sleep Efficiency and a trend towards an increased Number of Nighttime Awakenings compared to the control group. Treated infants at 6 months also had shorter daytime waking periods. 24-hour Total Sleep was unaffected by propranolol. No negative impact of propranolol on subjective sleep quality and behavioral development was noted.Conclusion: Propranolol exerts a measurable yet mild impact on objectively assessed infants' sleep measures. Behavioral developmental scores were unaffected. Our results support propranolol as first-line therapy for complicated infantile hemangiomas. What is Known: • Sleep disorders are frequently reported in infants with infantile hemangiomas treated with propranolol and often lead to treatment discontinuation. • Investigations of the sleep pattern in this patient group using objective measures are lacking. What is New: • The sleep pattern of propranolol-treated infants is assessed using actigraphy and a 24-h sleep diary and compared to healthy, untreated controls. • Propranolol leads to a decreased sleep efficiency at night and an increased demand of daytime sleep, yet effects are mild overall.

Altered EEG markers of synaptic plasticity in a human model of NMDA receptor deficiency: Anti-NMDA receptor encephalitis.

Plasticity of synaptic strength and density is a vital mechanism enabling memory consolidation, learning, and neurodevelopment. It is strongly dependent on the intact function of N-Methyl-d-Aspartate Receptors (NMDAR). The importance of NMDAR is further evident as their dysfunction is involved in many diseases such as schizophrenia, Alzheimer's disease, neurodevelopmental disorders, and epilepsies. Synaptic plasticity is thought to be reflected by changes of sleep slow wave slopes across the night, namely higher slopes after wakefulness at the beginning of sleep than after a night of sleep. Hence, a functional NMDAR deficiency should theoretically lead to altered overnight changes of slow wave slopes. Here we investigated whether pediatric patients with anti-NMDAR encephalitis, being a very rare but unique human model of NMDAR deficiency due to autoantibodies against receptor subunits, indeed show alterations in this sleep EEG marker for synaptic plasticity. We retrospectively analyzed 12 whole-night EEGs of 9 patients (age 4.3-20.8 years, 7 females) and compared them to a control group of 45 healthy individuals with the same age distribution. Slow wave slopes were calculated for the first and last hour of Non-Rapid Eye Movement (NREM) sleep (factor 'hour') for patients and controls (factor 'group'). There was a significant interaction between 'hour' and 'group' (p = 0.013), with patients showing a smaller overnight decrease of slow wave slopes than controls. Moreover, we found smaller slopes during the first hour in patients (p = 0.022), whereas there was no group difference during the last hour of NREM sleep (p = 0.980). Importantly, the distribution of sleep stages was not different between the groups, and in our main analyses of patients without severe disturbance of sleep architecture, neither was the incidence of slow waves. These possible confounders could therefore not account for the differences in the slow wave slope values, which we also saw in the analysis of the whole sample of EEGs. These results suggest that quantitative EEG analysis of slow wave characteristics may reveal impaired synaptic plasticity in patients with anti-NMDAR encephalitis, a human model of functional NMDAR deficiency. Thus, in the future, the changes of sleep slow wave slopes may contribute to the development of electrophysiological biomarkers of functional NMDAR deficiency and synaptic plasticity in general.

Severe effects of the COVID-19 confinement on young children's sleep: A longitudinal study identifying risk and protective factors.

The COVID-19 confinement has dramatically altered daily routines, causing decreased sleep quality in adults. This necessitates careful observation, as sleep plays a crucial role in brain maturation and poor sleep increases the risk of psychopathology, particularly in the young population. Through an online survey with one baseline (April 2020) and two follow-up assessments (May and June 2020), we examined the effect of confinement on sleep quality in 452 babies (0-35 months) and 412 preschool children (36-71 months) from several, mainly European, countries. An acute decrease in sleep quality was found in both groups of children. However, at follow-up assessments, this effect rebounded to the level reported for the period before the confinement. Importantly, caregiver's stress level was identified as a substantial risk factor determining lower sleep quality in both groups of children across assessments. Protective factors conserving children's sleep quality included caregiver's engagement in mindfulness techniques or childcare, and the presence of siblings and pets. In the near future, we may repeatedly experience the circumstances of abruptly enforced confinement. Our findings reveal promising pathways of action to protect young children's sleep, with which to essentially mitigate the long-term consequences of the pandemic on brain development and mental health.

Actigraphy in sleep research with infants and young children: Current practices and future benefits of standardized reporting.

Actigraphy is a cost-efficient method to estimate sleep-wake patterns over long periods in natural settings. However, the lack of methodological standards in actigraphy research complicates the generalization of outcomes. A rapidly growing methodological diversity is visible in the field, which increasingly necessitates the detailed reporting of methodology. We address this problem and evaluate the current state of the art and recent methodological developments in actigraphy reporting with a special focus on infants and young children. Through a systematic literature search on PubMed (keywords: sleep, actigraphy, child *, preschool, children, infant), we identified 126 recent articles (published since 2012), which were classified and evaluated for reporting of actigraphy. Results show that all studies report on the number of days/nights the actigraph was worn. Reporting was good with respect to device model, placement and sleep diary, whereas reporting was worse for epoch length, algorithm, artefact identification, data loss and definition of variables. In the studies with infants only (n = 58), the majority of articles (62.1%) reported a recording of actigraphy that was continuous across 24 hr. Of these, 23 articles (63.9%) analysed the continuous 24-hr data and merely a fifth used actigraphy to quantify daytime sleep. In comparison with an evaluation in 2012, we observed small improvements in reporting of actigraphy methodology. We propose stricter adherence to standards in reporting methodology in order to streamline actigraphy research with infants and young children, to improve comparability and to facilitate big data ventures in the sleep community.

Which are the Central Aspects of Infant Sleep? The Dynamics of Sleep Composites across Infancy.

Sleep during infancy is important for the well-being of both infant and parent. Therefore, there is large interest in characterizing infant sleep with reliable tools, for example by combining actigraphy with 24-h-diaries. However, it is critical to select the right variables to characterize sleep. In a longitudinal investigation, we collected sleep data of 152 infants at ages 3, 6, and 12 months. Using principal component analysis, we identified five underlying sleep composites from 48 commonly-used sleep variables: Sleep Night, Sleep Day, Sleep Activity, Sleep Timing, and Sleep Variability. These composites accurately reflect known sleep dynamics throughout infancy as Sleep Day (representing naps), Sleep Activity (representing sleep efficiency and consolidation), and Sleep Variability (representing day-to-day stability) decrease across infancy, while Sleep Night (representing nighttime sleep) slightly increases, and Sleep Timing becomes earlier as one ages. We uncover interesting dynamics between the sleep composites and demonstrate that infant sleep is not only highly variable between infants but also dynamic within infants across time. Interestingly, Sleep Day is associated with behavioral development and therefore a potential marker for maturation. We recommend either the use of sleep composites or the core representative variables within each sleep composite for more reliable research.

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

OBJECTIVE/BACKGROUND: Learning 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/METHODS: Participants 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. RESULTS: Healthy 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. CONCLUSIONS: Our 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.

Spatio-temporal properties of sleep slow waves and implications for development.

Objective sleep quality can be measured by electroencephalography (EEG), a non-invasive technique to quantify electrical activity generated by the brain. With EEG, sleep depth is measured by appearance and an increase in slow wave activity (scalp-SWA). EEG slow waves (scalp-SW) are the manifestation of underlying synchronous membrane potential transitions between silent (DOWN) and active (UP) states. This bistable periodic rhythm is defined as slow oscillation (SO). During its "silent state" cortical neurons are hyperpolarized and appear inactive, while during its "active state" cortical neurons are depolarized, fire spikes and exhibit continuous synaptic activity, excitatory and inhibitory. In adults, data from high-density EEG revealed that scalp-SW propagate across the cortical mantle in complex patterns. However, scalp-SW propagation undergoes modifications across development. We present novel data from children, indicating that scalp-SW originate centro-parietally, and emerge more frontally by adolescence. Based on the concept that SO and SW could actively modify neuronal connectivity, we discuss whether they fulfill a key purpose in brain development by actively conveying modifications of the maturing brain.

Characterization of overnight slow-wave slope changes across development in an age-, amplitude-, and region-dependent manner.

STUDY OBJECTIVES: The restorative function of sleep has been linked to a net reduction in synaptic strength. The slope of slow-waves, a major characteristic of non-rapid eye movement (NREM) sleep, has been shown to directly reflect synaptic strength, when accounting for amplitude changes across the night. In this study, we aimed to investigate overnight slope changes in the course of development in an age-, amplitude-, and region-dependent manner. METHODS: All-night high-density electroencephalography data were analyzed in a cross-sectional population of 60 healthy participants in the age range of 8-29 years. To control for amplitude changes across the night, we matched slow-waves from the first and the last hour of NREM sleep according to their amplitude. RESULTS: We found a reduction of slow-wave slopes from the first to the last hour of NREM sleep across all investigated ages, amplitudes, and most brain regions. The overnight slope change was largest in children and decreased toward early adulthood. A topographical analysis revealed regional differences in slope change. Specifically, for small amplitude waves the decrease was smallest in an occipital area, whereas for large amplitude waves, the decrease was smallest in a central area. CONCLUSIONS: The larger slope decrease in children might be indicative of a boosted renormalization of synapses during sleep in childhood, which, in turn, might be related to increased plasticity during brain maturation. Regional differences in the extent of slow-wave slope reduction may reflect a "smart" down-selection process or, alternatively, indicate amplitude-dependent differences in the generation of slow-waves.

Sleep EEG slow-wave activity in medicated and unmedicated children and adolescents with attention-deficit/hyperactivity disorder.

Slow waves (1-4.5 Hz) are the most characteristic oscillations of deep non-rapid eye movement sleep. The EEG power in this frequency range (slow-wave activity, SWA) parallels changes in cortical connectivity (i.e., synaptic density) during development. In patients with attention-deficit/hyperactivity disorder (ADHD), prefrontal cortical development was shown to be delayed and global gray matter volumes to be smaller compared to healthy controls. Using data of all-night recordings assessed with high-density sleep EEG of 50 children and adolescents with ADHD (mean age: 12.2 years, range: 8-16 years, 13 female) and 86 age- and sex-matched healthy controls (mean age: 12.2 years, range: 8-16 years, 23 female), we investigated if ADHD patients differ in the level of SWA. Furthermore, we examined the effect of stimulant medication. ADHD patients showed a reduction in SWA across the whole brain (-20.5%) compared to healthy controls. A subgroup analysis revealed that this decrease was not significant in patients who were taking stimulant medication on a regular basis at the time of their participation in the study. Assuming that SWA directly reflects synaptic density, the present findings are in line with previous data of neuroimaging studies showing smaller gray matter volumes in ADHD patients and its normalization with stimulant medication.

Endocrine responses during CPAP withdrawal in obstructive sleep apnoea: data from two randomised controlled trials.

The aim of this investigation was to elucidate the effect of CPAP withdrawal on neurometabolic and cardiometabolic markers in patients with obstructive sleep apnoea. We evaluated 70 patients (mean age 61±10 years, 82% men) treated with CPAP in two 2-week, parallel, randomised controlled trials. CPAP withdrawal resulted in elevated 3,4-dihydroxyphenylglycol, norepinephrine and cortisol after 2 weeks of CPAP withdrawal; however, no statistically significant changes of the renin-angiotensin-aldosterone system (RAAS) determinants were documented. In summary, CPAP withdrawal may be more prominently linked to short-term increases in sympathetic activation than hypothalamic-pituitary-adrenal axis or RAAS activation. ClinicalTrials.gov Identifier: NCT02493673 and NCT02050425.