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.

The Swiss Primary Hypersomnolence and Narcolepsy Cohort study (SPHYNCS): Study protocol for a prospective, multicentre cohort observational study.

Narcolepsy type 1 (NT1) is a disorder with well-established markers and a suspected autoimmune aetiology. Conversely, the narcoleptic borderland (NBL) disorders, including narcolepsy type 2, idiopathic hypersomnia, insufficient sleep syndrome and hypersomnia associated with a psychiatric disorder, lack well-defined markers and remain controversial in terms of aetiology, diagnosis and management. The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a comprehensive multicentre cohort study, which will investigate the clinical picture, pathophysiology and long-term course of NT1 and the NBL. The primary aim is to validate new and reappraise well-known markers for the characterization of the NBL, facilitating the diagnostic process. Seven Swiss sleep centres, belonging to the Swiss Narcolepsy Network (SNaNe), joined the study and will prospectively enrol over 500 patients with recent onset of excessive daytime sleepiness (EDS), hypersomnia or a suspected central disorder of hypersomnolence (CDH) during a 3-year recruitment phase. Healthy controls and patients with EDS due to severe sleep-disordered breathing, improving after therapy, will represent two control groups of over 50 patients each. Clinical and electrophysiological (polysomnography, multiple sleep latency test, maintenance of wakefulness test) information, and information on psychomotor vigilance and a sustained attention to response task, actigraphy and wearable devices (long-term monitoring), and responses to questionnaires will be collected at baseline and after 6, 12, 24 and 36 months. Potential disease markers will be searched for in blood, cerebrospinal fluid and stool. Analyses will include quantitative hypocretin measurements, proteomics/peptidomics, and immunological, genetic and microbiota studies. SPHYNCS will increase our understanding of CDH and the relationship between NT1 and the NBL. The identification of new disease markers is expected to lead to better and earlier diagnosis, better prognosis and personalized management of CDH.

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.

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.

How do children fall asleep? A high-density EEG study of slow waves in the transition from wake to sleep.

INTRODUCTION: Slow waves, the hallmarks of non-rapid eye-movement (NREM) sleep, are thought to reflect maturational changes that occur in the cerebral cortex throughout childhood and adolescence. Recent work in adults has revealed evidence for two distinct synchronization processes involved in the generation of slow waves, which sequentially come into play in the transition to sleep. In order to understand how these two processes are affected by developmental changes, we compared slow waves between children and young adults in the falling asleep period. METHODS: The sleep onset period (starting 30s before end of alpha activity and ending at the first slow wave sequence) was extracted from 72 sleep onset high-density EEG recordings (128 electrodes) of 49 healthy subjects (age 8-25). Using an automatic slow wave detection algorithm, the number, amplitude and slope of slow waves were analyzed and compared between children (age 8-11) and young adults (age 20-25). RESULTS: Slow wave number and amplitude increased linearly in the falling asleep period in children, while in young adults, isolated high-amplitude slow waves (type I) dominated initially and numerous smaller slow waves (type II) with progressively increasing amplitude occurred later. Compared to young adults, children displayed faster increases in slow wave amplitude and number across the falling asleep period in central and posterior brain regions, respectively, and also showed larger slow waves during wakefulness immediately prior to sleep. CONCLUSIONS: Children do not display the two temporally dissociated slow wave synchronization processes in the falling asleep period observed in adults, suggesting that maturational factors underlie the temporal segregation of these two processes. Our findings provide novel perspectives for studying how sleep-related behaviors and dreaming differ between children and adults.

Theta waves in children's waking electroencephalogram resemble local aspects of sleep during wakefulness.

Vyazovskiy and colleagues found in rats' multi-unit recordings brief periods of silence (off-states) in local populations of cortical neurons during wakefulness which closely resembled the characteristic off-states during sleep. These off-states became more global and frequent with increasing sleep pressure and were associated with the well-known increase of theta activity under sleep deprivation in the surface EEG. Moreover, the occurrence of such off-states was related to impaired performance. While these animal experiments were based on intracranial recordings, we aimed to explore whether the human surface EEG may also provide evidence for such a local sleep-like intrusion during wakefulness. Thus, we analysed high-density wake EEG recordings during an auditory attention task in the morning and evening in 12 children. We found that, theta waves became more widespread in the evening and the occurrence of widespread theta waves was associated with slower reaction times in the attention task. These results indicate that widespread theta events measured on the scalp might be markers of local sleep in humans. Moreover, such markers of local sleep, seem to be related to the well described performance decline under high sleep pressure.

High-Density Electroencephalographic Recordings During Sleep in Children and Adolescents With Acquired Brain Injury.

BACKGROUND: Acquired brain injuries (ABI) such as traumatic brain injury (TBI) or stroke can result in motor, language, or cognitive impairments. Although a considerable number of studies have investigated functional recovery, underlying brain reorganization remains poorly understood. Accumulating evidence indicates that plastic processes in the brain are linked to changes in electroencephalographic (EEG) slow wave activity (SWA) during deep sleep (EEG spectral power 1-4.5 Hz). OBJECTIVE: We investigated sleep SWA in children and adolescents with ABI. METHODS: We used high-density EEG (128 electrodes) to record sleep in 22 young patients with ABI (age range = 4-16 years). We compared patients to 52 previously measured typically developing children and adolescents (age range = 4-16 years). RESULTS: The pattern of alterations in SWA differed between particular patient groups. In patients with bilateral stroke, SWA was globally reduced across the entire scalp. Patients with unilateral stroke showed a local reduction in SWA over lesion areas and an increase over perilesional and contralateral brain areas. In patients with severe TBI, we found a reduction in SWA over the midline and an increase over lateral brain areas. We found no consistent pattern in patients with mild to moderate TBI. CONCLUSIONS: Sleep SWA seems to be a sensitive measure to assess individual alterations in neural activity after ABI. Deviations from age norms might indirectly indicate plastic processes that have occurred since injury. Improving our understanding of neural activity after ABI could optimize clinical prognosis and guide the development of novel therapeutic interventions.

Developmental trajectories of EEG sleep slow wave activity as a marker for motor skill development during adolescence: a pilot study.

Reliable markers for brain maturation are important to identify neural deviations that eventually predict the development of mental illnesses. Recent studies have proposed topographical EEG-derived slow wave activity (SWA) during NREM sleep as a mirror of cortical development. However, studies about the longitudinal stability as well as the relationship with behavioral skills are needed before SWA topography may be considered such a reliable marker. We examined six subjects longitudinally (over 5.1 years) using high-density EEG and a visuomotor learning task. All subjects showed a steady increase of SWA at a frontal electrode and a decrease in central electrodes. Despite these large changes in EEG power, SWA topography was relatively stable within each subject during development indicating individual trait-like characteristics. Moreover, the SWA changes in the central cluster were related to the development of specific visuomotor skills. Taken together with the previous work in this domain, our results suggest that EEG sleep SWA represents a marker for motor skill development and further supports the idea that SWA mirrors cortical development during childhood and adolescence.

High-density electroencephalographic recordings during sleep in children with disorders of consciousness.

INTRODUCTION: A large number of studies have investigated neural correlates of consciousness in adults. However, knowledge about brain function in children with disorders of consciousness (DOC) is very limited. We suggest that EEG recordings during sleep are a promising approach. In healthy adults as well as in children, it has been shown that the activity of sleep slow waves (EEG spectral power 1-4.5 Hz), the primary characteristic of deep sleep, is dependent on use during previous wakefulness. Thus the regulation of slow wave activity (SWA) provides indirect insights into brain function during wakefulness. METHODS: In the present study, we investigated high-density EEG recordings during sleep in ten healthy children and in ten children with acquired brain injury, including five children with DOC and five children with acquired brain injury without DOC. We used the build-up of SWA to quantify SWA regulation. RESULTS: Children with DOC showed a global reduction in the SWA build-up when compared to both, healthy children and children with acquired brain injury without DOC. This reduction was most pronounced over parietal brain areas. Comparisons within the group of children with DOC revealed that the parietal SWA build-up was the lowest in patients showing poor outcome. Longitudinal measurements during the recovery period showed an increase in parietal SWA build-up from the first to the second sleep recording. CONCLUSIONS: Our results suggest that the reduced parietal SWA regulation may represent a characteristic topographical marker for brain network dysfunction in children with DOC. In the future, the regulation of SWA might be used as a complementary assessment in adult and paediatric patients with DOC.

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.

Spike wave location and density disturb sleep slow waves in patients with CSWS (continuous spike waves during sleep).

OBJECTIVE: In CSWS (continuous spike waves during sleep) activation of spike waves during slow wave sleep has been causally linked to neuropsychological deficits, but the pathophysiologic mechanisms are still unknown. In healthy subjects, the overnight decrease of the slope of slow waves in NREM (non-rapid eye movement) sleep has been linked to brain recovery to regain optimal cognitive performance. Here, we investigated whether the electrophysiologic hallmark of CSWS, the spike waves during sleep, is related to an alteration in the overnight decrease of the slope, and if this alteration is linked to location and density of spike waves. METHODS: In a retrospective study, the slope of slow waves (0.5-2 Hz) in the first hour and last hour of sleep (19 electroencephalography [EEG] electrodes) of 14 patients with CSWS (3.1-13.5 years) was calculated. The spike wave "focus" was determined as the location of highest spike amplitude and the density of spike waves as spike wave index (SWI). RESULTS: There was no overnight change of the slope of slow waves in the "focus." Instead, in "nonfocal" regions, the slope decreased significantly. This difference in the overnight course resulted in a steeper slope in the "focus" compared to "nonfocal" electrodes during the last hour of sleep. Spike wave density was correlated with the impairment of the overnight slope decrease: The higher the SWI, the more hampered the slope decrease. SIGNIFICANCE: Location and density of spike waves are related to an alteration of the physiologic overnight decrease of the slow wave slope. This overnight decrease of the slope was shown to be closely related to the recovery function of sleep. Such recovery is necessary for optimal cognitive performance during wakefulness. Therefore we propose the impairment of this process by spike waves as a potential mechanism leading to neuropsychological deficits in CSWS. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

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 4.5 Hz) 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 13.4 years, range: 8.7-19.4, and 11 girls, mean age 13.4 years, range: 9.1-19.0 years). In females, SWA during the first 60 min 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.

INTRODUCTION: Sleep 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. METHODS: All-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. RESULTS: We 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. CONCLUSIONS: Children 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 electroencephalography topography and children's intellectual ability.

The aim of the study was to investigate the relationship between regional aspects of the children's sleep electroencephalogram (EEG) (high-density EEG recordings) and their intellectual ability. The spectral power in the α, σ, and ß frequency ranges of 109 EEG derivations was correlated with the scores of full-scale intelligence quotient, fluid intelligence quotient, and working memory (14 participants, mean age: 10.5±1.0 years; six girls). The previously reported relationship (derivation C3/A2) between spectral band power and intellectual ability could further be refined, particular spatial patterns over central and parietal areas with positive correlations were found. Thus, neurobiological correlates of intelligence during sleep may exhibit brain region-specific patterns.

Long-term exposure to music enhances the sensitivity of the auditory system in children.

This event-related brain potential study aims to contribute to the present debate regarding the effect of musical training on the maturation of the human auditory nervous system. To address this issue, we recorded the mismatch negativity (MMN) evoked by violin and pure sine-wave tones in a group of 7.5- to 12-year-old children who had either several years of musical experience with Suzuki violin lessons, or no musical training. The strength of the MMN responses to violin tones evident in the Suzuki students clearly surpassed responses in controls; the reverse pattern was observed for sine-wave tones. Suzuki students showed significantly shorter MMN latencies to violin tones than to pure tones; the MMN latency did not differ significantly between pure tones and violin sounds in the control group. Thus, our data provide general evidence of how and to what extent extensive musical experience affects the maturation of human auditory function at multiple levels, namely, accuracy and speed of auditory discrimination processing. Our findings add to the present understanding of neuroplastic organization and function of the mammalian nervous system. Furthermore, behavioural recordings obtained from the participating children provide corroborating evidence for a relationship between the duration and intensity of training, the specific sensitivity to instrumental timbre, and pitch recognition abilities.

Developmental aspects of sleep slow waves: linking sleep, brain maturation and behavior.

Sleep slow waves are the major electrophysiological features of non-rapid eye movement (NREM) sleep. Although there is growing understanding of where slow waves originate and how they are generated during sleep, the function of slow waves is still largely unclear. A recently proposed hypothesis relates slow waves to the homeostatic regulation of synaptic plasticity. While several studies confirm a correlation between experimentally triggered synaptic changes and slow-wave activity (SWA), little is known about its association to synaptic changes occurring during cortical maturation. Interestingly, slow waves undergo remarkable changes during development that parallel the time course of cortical maturation. In a recent cross-sectional study including children and adolescents, the topographical distribution of SWA was analyzed with high-density electroencephalography. The results showed age-dependent differences in SWA topography: SWA was highest over posterior regions during early childhood and then shifted over central derivations to the frontal cortex in late adolescence. This trajectory of SWA topography matches the course of cortical gray maturation. In this chapter, the major changes in slow waves during development are highlighted and linked to cortical maturation and behavior. Interestingly, synaptic density and slow-wave amplitude increase during childhood are highest shortly before puberty, decline thereafter during adolescence, reaching overall stable levels during adulthood. The question arises whether SWA is merely reflecting cortical changes or if it plays an active role in brain maturation. We thereby propose a model, by which sleep slow waves may contribute to cortical maturation. We hypothesize that while there is a balance between synaptic strengthening and synaptic downscaling in adults, the balance of strengthening/formation and weakening/elimination is tilted during development.

Anatomical markers of sleep slow wave activity derived from structural magnetic resonance images.

Sleep studies often observe differences in slow wave activity (SWA) during non-rapid eye movement sleep between subjects. This study investigates to what extent these absolute differences in SWA can be explained with differences in grey matter volume, white matter volume or the thickness of skull and outer liquor rooms. To do this, we selected the 10-min interval showing maximal SWA of 20 young adult subjects and correlated these values lobe-wise with grey matter, skull and liquor thickness and globally with white matter as well as segments of the corpus callosum. Whereas grey matter, skull thickness and liquor did not correlate significantly with maximal slow wave activity, there were significant correlations with the anterior parts of the corpus callosum and with one other white matter region. In contrast, electroencephalogram power of higher frequencies correlates positively with grey matter volumes and cortical surface area. We discuss the possible role of white matter tracts on the synchronization of slow waves across the cortex.

The sleep EEG as a marker of intellectual ability in school age children.

STUDY OBJECTIVES: To investigate the within-subject stability in the sleep EEG and the association between the sleep EEG and intellectual abilities in 9- to 12-year-old children. DESIGN: Intellectual ability (WISC-IV, full scale, fluid, and verbal IQ, working memory, speed of processing) were examined and all-night polysomnography was performed (2 nights per subject). SETTING: Sleep laboratory. PARTICIPANTS: Fourteen healthy children (mean age 10.5 ± 1.0 years; 6 girls). MEASUREMENTS AND RESULTS: Spectral analysis was performed on artifact-free NREM sleep epochs (C3/A2). To determine intra-individual stability and inter-individual variability of the sleep EEG, power spectra were used as feature vectors for the estimation of Euclidean distances, and intraclass correlation coefficients (ICC) were calculated for the 2 nights. Sleep spindle peaks were identified for each individual and individual sigma band power was determined. Trait-like aspects of the sleep EEG were observed for sleep stage variables and spectral power. Within-subject distances were smaller than between-subject distances and ICC values ranged from 0.72 to 0.96. Correlations between spectral power in individual frequency bins and intelligence scores revealed clusters of positive associations in the alpha, sigma, and beta range for full scale IQ, fluid IQ, and working memory. Similar to adults, sigma power correlated with full scale (r = 0.67) and fluid IQ (r = 0.65), but not with verbal IQ. Spindle peak frequency was negatively related to full scale IQ (r = -0.56). CONCLUSIONS: The sleep EEG during childhood shows high within-subject stability and may be a marker for intellectual ability.

EEG sleep slow-wave activity as a mirror of cortical maturation.

Deep (slow wave) sleep shows extensive maturational changes from childhood through adolescence, which is reflected in a decrease of sleep depth measured as the activity of electroencephalographic (EEG) slow waves. This decrease in sleep depth is paralleled by massive synaptic remodeling during adolescence as observed in anatomical studies, which supports the notion that adolescence represents a sensitive period for cortical maturation. To assess the relationship between slow-wave activity (SWA) and cortical maturation, we acquired sleep EEG and magnetic resonance imaging data in children and adolescents between 8 and 19 years. We observed a tight relationship between sleep SWA and a variety of indexes of cortical maturation derived from magnetic resonance (MR) images. Specifically, gray matter volumes in regions correlating positively with the activity of slow waves largely overlapped with brain areas exhibiting an age-dependent decrease in gray matter. The positive relationship between SWA and cortical gray matter was present also for power in other frequency ranges (theta, alpha, sigma, and beta) and other vigilance states (theta during rapid eye movement sleep). Our findings indicate a strong relationship between sleep EEG activity and cortical maturation. We propose that in particular, sleep SWA represents a good marker for structural changes in neuronal networks reflecting cortical maturation during adolescence.