Abstract
BackgroundAngelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, speech and motor impairments, epilepsy, abnormal sleep, and phenotypic overlap with autism. Individuals with AS display characteristic EEG patterns including high-amplitude rhythmic delta waves. Here, we sought to quantitatively explore EEG architecture in AS beyond known spectral power phenotypes. We were motivated by studies of functional connectivity and sleep spindles in autism to study these EEG readouts in children with AS.MethodsWe analyzed retrospective wake and sleep EEGs from children with AS (age 4–11) and age-matched neurotypical controls. We assessed long-range and short-range functional connectivity by measuring coherence across multiple frequencies during wake and sleep. We quantified sleep spindles using automated and manual approaches.ResultsDuring wakefulness, children with AS showed enhanced long-range EEG coherence across a wide range of frequencies. During sleep, children with AS showed increased long-range EEG coherence specifically in the gamma band. EEGs from children with AS contained fewer sleep spindles, and these spindles were shorter in duration than their neurotypical counterparts.ConclusionsWe demonstrate two quantitative readouts of dysregulated sleep composition in children with AS—gamma coherence and spindles—and describe how functional connectivity patterns may be disrupted during wakefulness. Quantitative EEG phenotypes have potential as biomarkers and readouts of target engagement for future clinical trials and provide clues into how neural circuits are dysregulated in children with AS.
Highlights
Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, speech and motor impairments, epilepsy, abnormal sleep, and phenotypic overlap with autism
Long-range coherence is increased in Angelman syndrome during wakefulness During wakefulness, overall (1–50 Hz) short-range coherence (Fig. 2a) was not statistically different between children with AS and neurotypical controls (Fig. 2b, “overall”; p = 0.1887, Student’s t test)
While two-way ANOVA revealed a statistically significant main effect of genotype (Fig. 2b; F(1, 390) = 8.32, p = 0.0041), there was no genotype × frequency interaction (F(4, 390) = 0.0702, p = 0.9910) and short-range coherence was not increased within any specific frequency band
Summary
Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, speech and motor impairments, epilepsy, abnormal sleep, and phenotypic overlap with autism. We were motivated by studies of functional connectivity and sleep spindles in autism to study these EEG readouts in children with AS. Symptoms of AS include severe intellectual disability, impaired speech and motor function, epilepsy, sleep abnormalities, and some phenotypic overlap with autism [1,2,3]. We were motivated to study coherence in AS by the observation that individuals with autism show altered coherence patterns [9,10,11,12,13,14,15,16,17]. Specific connectivity patterns remain unclear, there is widespread consensus that EEG coherence is altered in autism. The phenotypic and genetic links between AS and autism led us to hypothesize that children with AS might display irregularities in the relationship between long-range and short-range coherence
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