Increased overall cortical connectivity with syndrome specific local decreases suggested by atypical sleep-EEG synchronization in Williams syndrome

Ferenc Gombos,Ilona Kovács,Róbert Bódizs

doi:10.1038/s41598-017-06280-2

Ferenc Gombos, Ilona Kovács + Show 1 more

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https://doi.org/10.1038/s41598-017-06280-2

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Abstract

Williams syndrome (7q11.23 microdeletion) is characterized by specific alterations in neurocognitive architecture and functioning, as well as disordered sleep. Here we analyze the region, sleep state and frequency-specific EEG synchronization of whole night sleep recordings of 21 Williams syndrome and 21 typically developing age- and gender-matched subjects by calculating weighted phase lag indexes. We found broadband increases in inter- and intrahemispheric neural connectivity for both NREM and REM sleep EEG of Williams syndrome subjects. These effects consisted of increased theta, high sigma, and beta/low gamma synchronization, whereas alpha synchronization was characterized by a peculiar Williams syndrome-specific decrease during NREM states (intra- and interhemispheric centro-temporal) and REM phases of sleep (occipital intra-area synchronization). We also found a decrease in short range, occipital connectivity of NREM sleep EEG theta activity. The striking increased overall synchronization of sleep EEG in Williams syndrome subjects is consistent with the recently reported increase in synaptic and dendritic density in stem-cell based Williams syndrome models, whereas decreased alpha and occipital connectivity might reflect and underpin the altered microarchitecture of primary visual cortex and disordered visuospatial functioning of Williams syndrome subjects.

Highlights

Neurodevelopmental disorders are caused by significant and persistent disruption of the dynamic inter-relationship between genetic, brain, cognitive, emotional, and behavioural processes across the developmental lifespan[1]
Statistical analyses aiming to unravel the Williams syndrome vs. typically developing group differences were performed in a stepwise manner starting from the tests of regional unspecific and broadband effects, gradually attaining region- and frequency-specific peculiarities in the synchronization of sleep EEG in Williams syndrome
Post-hoc tests (Fisher Least Square Differences) indicated a significantly increased non- rapid eye movement (NREM) sleep EEG broadband-1 Weighted Phase Lag Index (WPLI) mean in Williams syndrome as compared to the typically developing group (p = 0.0003), and the lack of a significant group difference in the broadband-2 range (p = 0.1651)

Summary

Introduction

Neurodevelopmental disorders are caused by significant and persistent disruption of the dynamic inter-relationship between genetic, brain, cognitive, emotional, and behavioural processes across the developmental lifespan[1]. Sigma waves, as well as accelerations of sigma peak frequencies[8, 10, 12] These sleep macrostructural and EEG alterations are present both in children and young adults with Williams syndrome. Recent findings suggest that NREM sleep EEG coherence reflects the programmed unfolding of neuronal networks during ontogenetic development in children[13]. Altered network connectivity, longer total dendrites, as well as an increased number of spines and synapses are characteristic features of a Williams syndrome model based on human induced pluripotent stem cells[22]. Evidence suggests the correlation between structural and functional connectivity of neuronal structures[26, 27] Despite all these convergent findings, sleep-state-dependent neural synchronization/ connectivity has not been tested in Williams syndrome before

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