Alpha Reactivity Dynamics Reveal Multi-System Variability Without Global Alpha Slowing in Fragile X Syndrome.

Fragile X syndrome (FXS) is associated with alterations in alpha-band activity recorded using electroencephalography (EEG), including reports of alpha slowing, that may reflect impaired inhibitory regulation and network-level dysfunction. However, it remains unclear whether these abnormalities represent a global shift in oscillatory frequency or dissociable disruptions across distinct systems. In the present study, we leveraged alpha reactivity dynamics, defined as eyes-open to eyes-closed modulation, to probe alpha function in 23 individuals with FXS and 23 typically developing controls using both absolute and relative spectral measures. In FXS, absolute alpha reactivity showed a robust, region-specific reduction localized to occipital cortex, consistent with impaired sensory-inhibitory modulation. While relative alpha reactivity revealed more widespread attenuation across regions, indicating broader network alterations. Peak reactivity frequency showed no evidence of global slowing but was consistent with localized shifts toward lower frequencies. These effects were region- and sex-specific, with females showing reduced frontal relative peak frequency and males showing associations between lower relative peak frequency in non-occipital regions and higher IQ. These findings support a multi-system model of alpha dysfunction in FXS, characterized by posterior inhibitory deficits and distributed network alterations, and highlight alpha reactivity dynamics as a promising translational biomarker.