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.

Uncoupling of behavioral and metabolic 24-h rhythms in reindeer.

Reindeer in the Arctic seasonally suppress daily circadian patterns of behavior present in most animals.1 In humans and mice, even when all daily behavioral and environmental influences are artificially suppressed, robust endogenous rhythms of metabolism governed by the circadian clock persist and are essential to health.2,3 Disrupted rhythms foster metabolic disorders and weight gain.4 To understand circadian metabolic organization in reindeer, we performed behavioral measurements and untargeted metabolomics from blood plasma samples taken from Eurasian tundra reindeer (Rangifer tarandus tarandus) across 24 h at 2-h intervals in four seasons. Our study confirmed the absence of circadian rhythms of behavior under constant darkness in the Arctic winter and constant daylight in the Arctic summer, as reported by others.1 We detected and measured the intensity of 893 metabolic features in all plasma samples using untargeted ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS). A core group of metabolites (66/893 metabolic features) consistently displayed 24-h rhythmicity. Most metabolites displayed a robust 24-h rhythm in winter and spring but were arrhythmic in summer and fall. Half of all measured metabolites displayed ultradian sleep-wake dependence in summer. Irrespective of the arrhythmic behavior, metabolism is rhythmic (24 h) in seasons of low food availability, potentially favoring energy efficiency. In seasons of food abundance, 24-h rhythmicity in metabolism is drastically reduced, again irrespective of behavioral rhythms, potentially fostering weight gain.

Reindeer in the Arctic reduce sleep need during rumination.

Timing and quantity of sleep depend on a circadian (∼24-h) rhythm and a specific sleep requirement.1 Sleep curtailment results in a homeostatic rebound of more and deeper sleep, the latter reflected in increased electroencephalographic (EEG) slow-wave activity (SWA) during non-rapid eye movement (NREM) sleep.2 Circadian rhythms are synchronized by the light-dark cycle but persist under constant conditions.3,4,5 Strikingly, arctic reindeer behavior is arrhythmic during the solstices.6 Moreover, the Arctic's extreme seasonal environmental changes cause large variations in overall activity and food intake.7 We hypothesized that the maintenance of optimal functioning under these extremely fluctuating conditions would require adaptations not only in daily activity patterns but also in the homeostatic regulation of sleep. We studied sleep using non-invasive EEG in four Eurasian tundra reindeer (Rangifer tarandus tarandus) in Tromsø, Norway (69°N) during the fall equinox and both solstices. As expected, sleep-wake rhythms paralleled daily activity distribution, and sleep deprivation resulted in a homeostatic rebound in all seasons. Yet, these sleep rebounds were smaller in summer and fall than in winter. Surprisingly, SWA decreased not only during NREM sleep but also during rumination. Quantitative modeling revealed that sleep pressure decayed at similar rates during the two behavioral states. Finally, reindeer spent less time in NREM sleep the more they ruminated. These results suggest that they can sleep during rumination. The ability to reduce sleep need during rumination-undisturbed phases for both sleep recovery and digestion-might allow for near-constant feeding in the arctic summer.

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

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/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.

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.

Reduced sleep spindle density in adolescent patients with early-onset schizophrenia compared to major depressive disorder and healthy controls.

OBJECTIVES: During adolescence schizophrenia and major depressive disorder (MDD) increasingly emerge. Overlapping symptomatology during first presentation challenges the diagnostic process. Reduced sleep spindle density (SSD) was suggested as a biomarker in adults, discerning patients with schizophrenia from patients with depression or healthy controls (HC). We aimed to compare SSD in early-onset schizophrenia (EOS), with MDD, and HC, and to analyse associations of SSD with symptomatology and neurocognitive measures. METHODS: Automatic sleep spindle detection was performed on all-night high-density EEG (128 electrodes) data of 12 EOS, 19 MDD, and 57 HC (age range 9.8-19), allowing an age- and sex-matching of 1:2 (patients vs. HC). Severity of current symptoms and neurocognitive variables were assessed in all patients. RESULTS: SSD was defined between 13.75 and 14.50 Hz as within this frequency range SSD differed between EOS vs. HC in bin by bin analyses (12-15 Hz). In EOS, SSD was lower over 27 centro-temporal electrodes compared to HC and over 9 central electrodes compared to MDD. Reduced SSD in EOS compared to MDD and HC was accompanied by a high variability of SSD in all adolescents. SSD did not differ between MDD and HC. In the pooled sample of patients, lower SSD was associated with more severe Positive and Negative Symptoms Scale total score, more impaired memory consolidation and processing speed. CONCLUSION: A high variability of SSD in all adolescents may reflect the evolving character of SSD. The association of reduced SSD with the symptom dimension of impaired cognition cuts across diagnostical entities.

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.

Diurnal changes in human brain glutamate + glutamine levels in the course of development and their relationship to sleep.

Sleep slow waves during non-rapid eye movement (NREM) sleep play a crucial role in maintaining cortical plasticity, a process that is especially important in the developing brain. Children show a considerably larger overnight decrease in slow wave activity (SWA; the power in the EEG frequency band between 1 and 4.5 â€‹Hz during NREM sleep), which constitutes the primary electrophysiological marker for the restorative function of sleep. We previously demonstrated in adults that this marker correlates with the overnight reduction in cortical glutamate â€‹+ â€‹glutamine (GLX) levels assessed by magnetic resonance spectroscopy (MRS), proposing GLX as a promising biomarker for the interplay between cortical plasticity and SWA. Here, we used a multimodal imaging approach of combined MRS and high-density EEG in a cross-sectional cohort of 46 subjects from 8 to 24 years of age in order to examine age-related changes in GLX and its relation to SWA. Gray matter volume, GLX levels and SWA showed the expected age-dependent decrease. Unexpectedly, the overnight changes in GLX followed opposite directions when comparing children to adults. These age-related changes could neither be explained by the overnight decrease in SWA nor by circadian factors.