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.Electronic supplementary materialThe online version of this article (10.1186/s13229-018-0214-8) contains supplementary material, which is available to authorized users.
Previous studies have highlighted an important role for hippocampal sharp-wave ripples in spatial alternation learning, as well as modulating activity in the medial prefrontal cortex (mPFC). However, no study so far has investigated the direct influence of hippocampal sharp-wave ripples on mPFC activity during spatial alternation learning. Long Evans rats were trained on a three-arm radial maze to perform a sequence of alternations. Three different alternation sequences needed to be learnt, and while learning a new sequence, the activity in the mPFC was inhibited either directly following sharp-wave ripples in the hippocampus (on-time condition) or with a randomized delay (delayed condition). In the on-time condition the behavioral performance was significantly worse compared to the same animals in the delayed inhibition condition, as measured by a lower correct alternation performance and more perseverative behavior. This indicates that the activity in the mPFC directly following hippocampal sharp-wave ripples is necessary for spatial rule switching.
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