Reliability of resting-state electrophysiology in fragile X syndrome

Fragile X Syndrome (FXS) is the leading monogenic cause of intellectual disability and autism spectrum disorder. Currently, there are no established biomarkers for predicting and monitoring drug effects in FXS, and no approved therapies are available. Previous studies have shown electrophysiological changes in the brain using electroencephalography (EEG) in individuals with FXS and animal models. These changes may be influenced by drug therapies. In this study, we aimed to assess the reliability of resting-state EEG measures in individuals with FXS, which could potentially serve as a biomarker for drug discovery. We collected resting-state EEG data from 35 individuals with FXS participating in placebo-controlled clinical trials (23 males, 12 females; visit age mean+/-std 25.6+/-8.3). The data were analyzed for various spectral features using intraclass correlation analysis to evaluate test-retest reliability. The intervals between EEG recordings ranged from same-day measurements to up to six weeks apart. Our results showed high reliability for most spectral features, with same-day reliability exceeding 0.8. Features of interest demonstrated ICC values of 0.60 or above at longer intervals. Among the features, alpha band relative power exhibited the highest reliability. These findings indicate that resting-state EEG can provide consistent and reproducible measures of brain activity in individuals with FXS. This supports the potential use of EEG as an objective biomarker for evaluating the effects of new drugs in FXS. The reliable measurements obtained from power spectrum-based resting-state EEG make it a promising tool for assessing the impact of small molecule drugs in FXS.