Reduced habituation of auditory evoked potentials indicate cortical hyper-excitability in Fragile X Syndrome

• Published in: Translational psychiatry Vol. 6; no. 4; p. e787
• Main Authors: Ethridge, L E, White, S P, Mosconi, M W, Wang, J, Byerly, M J, Sweeney, J A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.04.2016; Nature Publishing Group
• Subjects: 631/378; 692/53; Adolescent; Adult; Behavioral Sciences; Biological Psychology; Cerebral Cortex - physiopathology; Cortical Excitability - physiology; Electroencephalography; Evoked Potentials, Auditory - physiology; Female; Fragile X Syndrome - physiopathology; Habituation, Psychophysiologic - physiology; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Neurosciences; Original; original-article; Pharmacotherapy; Psychiatry; Young Adult
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/tp.2016.48

Sensory hypersensitivities are common, clinically distressing features of Fragile X Syndrome (FXS). Preclinical evidence suggests this abnormality may result from synaptic hyper-excitability in sensory systems. This model predicts reduced sensory habituation to repeated stimulus presentation. Fourteen adolescents and adults with FXS and 15 age-matched controls participated in a modified auditory gating task using trains of 4 identical tones during dense array electroencephalography (EEG). Event-related potential and single trial time–frequency analyses revealed decreased habituation of the N1 event-related potential response in FXS, and increased gamma power coupled with decreases in gamma phase-locking during the early-stimulus registration period. EEG abnormalities in FXS were associated with parent reports of heightened sensory sensitivities and social communication deficits. Reduced habituation and altered gamma power and phase-locking to auditory cues demonstrated here in FXS patients parallels preclinical findings with Fmr1 KO mice. Thus, the EEG abnormalities seen in FXS patients support the model of neocortical hyper-excitability in FXS, and may provide useful translational biomarkers for evaluating novel treatment strategies targeting its neural substrate.