A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome.
BACKGROUND
Cortical hyperexcitability due to abnormal fast-spiking inhibitory interneuron function has been documented infmr1KO mice, a mouse model of the fragile X syndrome which is the most common single gene cause of autism and intellectual disability.


METHODS
We collected resting state dense-array electroencephalography data from 21 fragile X syndrome (FXS) patients and 21 age-matched healthy participants.


RESULTS
FXS patients exhibited greater gamma frequency band power, which was correlated with social and sensory processing difficulties. Second, FXS patients showed increased spatial spreading of phase-synchronized high frequency neural activity in the gamma band. Third, we observed increased negative theta-to-gamma but decreased alpha-to-gamma band amplitude coupling, and the level of increased theta power was inversely related to the level of resting gamma power in FXS.


CONCLUSIONS
Increased theta band power and coupling from frontal sources may represent a mechanism providing compensatory inhibition of high-frequency gamma band activity, potentially contributing to the widely varying level of neurophysiological and behavioral abnormalities and treatment response seen in full-mutation FXS patients. These findings extend preclinical observations and provide new mechanistic insights into brain alterations and their variability across FXS patients. Electrophysiological measures may provide useful translational biomarkers for advancing drug development and individualizing treatments for neurodevelopmental disorders with associated neuronal hyperexcitability.
Department of Psychology, Zhejiang Normal University, 688 Yingbin Road, Jinhua, Zhejiang China 321004.
Jun
J
Wang
Department of Pediatrics, Section of Developmental and Behavioral Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK USA.|Department of Psychology, University of Oklahoma, Norman, OK USA.
Lauren E
LE
Ethridge
Clinical Child Psychology Program and Schiefelbusch Institute for Life Span Studies, University of Kansas, Lawrence, KS USA.
Matthew W
MW
Mosconi
Department of Psychiatry, Center for Autism and Developmental Disabilities, University of Texas Southwestern Medical Center, Dallas, TX USA.
Stormi P
SP
White
Center for Glial-Neuronal Interactions, Neuroscience Graduate Program, Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA USA.
Devin K
DK
Binder
Department of Psychiatry and Behavioral Neuroscience and Division of Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH USA.
Ernest V
EV
Pedapati
Department of Psychiatry and Behavioral Neuroscience and Division of Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH USA.
Craig A
CA
Erickson
Center for Mental Health Research and Recovery, Montana State University, Bozeman, MT USA.
Matthew J
MJ
Byerly
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH USA.
John A
JA
Sweeney
Cross-frequency coupling; EEG; Fragile X syndrome; Gamma; Hyperexcitability; Top-down modulation