Maya Ringli

Mapping of Cortical Activity in the First Two Decades of Life: A High-Density Sleep Electroencephalogram Study

Evidence that electroencephalography (EEG) slow-wave activity (SWA) (EEG spectral power in the 1–4.5 Hz band) during non-rapid eye movement sleep (NREM) reflects plastic changes is increasing (Tononi and Cirelli, 2006). Regional assessment of gray matter development from neuroimaging studies reveals a posteroanterior trajectory of cortical maturation in the first three decades of life (Shaw et al., 2008). Our aim was to test whether this regional cortical maturation is reflected in regional changes of sleep SWA. We evaluated all-night high-density EEG (128 channels) in 55 healthy human subjects (2.4–19.4 years) and assessed age-related changes in NREM sleep topography. As in adults, we observed frequency-specific topographical distributions of sleep EEG power in all subjects. However, from early childhood to late adolescence, the location on the scalp showing maximal SWA underwent a shift from posterior to anterior regions. This shift along the posteroanterior axis was only present in the SWA frequency range and remained stable across the night. Changes in the topography of SWA during sleep parallel neuroimaging study findings indicating cortical maturation starts early in posterior areas and spreads rostrally over the frontal cortex. Thus, SWA might reflect the underlying processes of cortical maturation. In the future, sleep SWA assessments may be used as a clinical tool to detect aberrations in cortical maturation.

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.

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.

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.

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.

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.

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.

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

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.

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 &agr;, &sgr;, and &bgr; 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.

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.