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

Transl Psychiatry. 2016 Apr 19;6(4):e787. 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Cerebral Cortex / physiopathology*
  • Cortical Excitability / physiology
  • Electroencephalography
  • Evoked Potentials, Auditory / physiology*
  • Female
  • Fragile X Syndrome / physiopathology*
  • Habituation, Psychophysiologic / physiology*
  • Humans
  • Male
  • Middle Aged
  • Young Adult