biostudies-literatureElmaghraby RNational Institutes of Health (NIH) Fragile X Centers49https://www.ebi.ac.uk/biostudies/studies/S-EPMC12486676biostudies-literatureUnknown16(1)<h4>Background</h4>Fragile X syndrome (FXS) is characterized by cortical hyperexcitability, a core neurophysiological feature that contributes to sensory hypersensitivity, cognitive dysfunction, and other disabling symptoms. This disruption in excitatory-inhibitory balance is a key pharmacological target, yet reliable biomarkers to quantify it noninvasively remain limited. Spectral slope, derived from the aperiodic component of the EEG power spectrum, has emerged as a potential index of cortical excitability. Here, we evaluated spectral slope and theta-alpha peak frequency in individuals with FXS to assess their utility as candidate neurophysiological biomarkers.<h4>Methods</h4>Five minutes of resting state EEG data were collected from 70 subjects with FXS (mean age 20.5 ± 10 years; 32 femMolecular autismDivergent aperiodic slope and alpha dynamics expose cortical excitability gradients in fragile X syndrome.PMC12486676U54HD082008 and U54HD104461Liu YErickson CAPedapati EVWu SWNelson MAElmaghraby RWesterkamp GSmith ELarsh TRamesh PGilbert DLfalseDivergent aperiodic slope and alpha dynamics expose cortical excitability gradients in fragile X syndrome.<h4>Background</h4>Fragile X syndrome (FXS) is characterized by cortical hyperexcitability, a core neurophysiological feature that contributes to sensory hypersensitivity, cognitive dysfunction, and other disabling symptoms. This disruption in excitatory-inhibitory balance is a key pharmacological target, yet reliable biomarkers to quantify it noninvasively remain limited. Spectral slope, derived from the aperiodic component of the EEG power spectrum, has emerged as a potential index of cortical excitability. Here, we evaluated spectral slope and theta-alpha peak frequency in individuals with FXS to assess their utility as candidate neurophysiological biomarkers.<h4>Methods</h4>Five minutes of resting state EEG data were collected from 70 subjects with FXS (mean age 20.5 ± 10 years; 32 fem2025-01-01T00:00:00Z2025 Oct2026-06-04T00:34:35.157Z2026-05-03T03:12:11.958ZS-EPMC124866764102947410.1186/s13229-025-00682-0