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Molecular Autism
Published in: Molecular Autism 1/2017

Open Access 01-12-2017 | Research

Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome

Authors: Lauren E. Ethridge, Stormi P. White, Matthew W. Mosconi, Jun Wang, Ernest V. Pedapati, Craig A. Erickson, Matthew J. Byerly, John A. Sweeney

Published in: Molecular Autism | Issue 1/2017

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Abstract

Background

Studies in the fmr1 KO mouse demonstrate hyper-excitability and increased high-frequency neuronal activity in sensory cortex. These abnormalities may contribute to prominent and distressing sensory hypersensitivities in patients with fragile X syndrome (FXS). The current study investigated functional properties of auditory cortex using a sensory entrainment task in FXS.

Methods

EEG recordings were obtained from 17 adolescents and adults with FXS and 17 age- and sex-matched healthy controls. Participants heard an auditory chirp stimulus generated using a 1000-Hz tone that was amplitude modulated by a sinusoid linearly increasing in frequency from 0–100 Hz over 2 s.

Results

Single trial time-frequency analyses revealed decreased gamma band phase-locking to the chirp stimulus in FXS, which was strongly coupled with broadband increases in gamma power. Abnormalities in gamma phase-locking and power were also associated with theta-gamma amplitude-amplitude coupling during the pre-stimulus period and with parent reports of heightened sensory sensitivities and social communication deficits.

Conclusions

This represents the first demonstration of neural entrainment alterations in FXS patients and suggests that fast-spiking interneurons regulating synchronous high-frequency neural activity have reduced functionality. This reduced ability to synchronize high-frequency neural activity was related to the total power of background gamma band activity. These observations extend findings from fmr1 KO models of FXS, characterize a core pathophysiological aspect of FXS, and may provide a translational biomarker strategy for evaluating promising therapeutics.
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Metadata
Title
Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome
Authors
Lauren E. Ethridge
Stormi P. White
Matthew W. Mosconi
Jun Wang
Ernest V. Pedapati
Craig A. Erickson
Matthew J. Byerly
John A. Sweeney
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2017
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-017-0140-1

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