Temporal and frontal lobe contributions to neural synchronization dysfunction and auditory attention in Fragile X Syndrome

Fragile X syndrome (FXS) is a trinucleotide repeat disorder and the most common hereditary form of intellectual disability. Patients with FXS are commonly impaired by sensory hypersensitivity. Compared to cognition, neural correlates of sensory responses can be studied more objectively and across species. Alterations in auditory processing in FXS measured by scalp electroencephalography (EEG) are well documented. However, the orientation of the auditory cortex in humans introduces significant confounding between temporal and frontal sources. Herein, we conducted EEG source analysis in 36 participants with FXS and 39 matched controls to localize known alterations to the auditory chirp stimulus. The key findings in participants with FXS include 1) distinct contributions of frontal and temporal sources to the onset and intrastimulus neural synchronization, 2) moderation of abnormal neural responses in females with FXS, 3) evidence of deep brain sources contributing to impairments in synchronization, and 4) presence of robust region-specific clinical correlations. The synchronous and asynchronous gamma activity (SA ratio) ratio may further represent a clinically relevant biomarker of the efficiency of auditory processing in FXS. Findings from this study have implications for back translation and relevance for signal-to-noise conceptual frameworks in understanding neural activity in neurodevelopmental disorders.