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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The present study was federally funded by National Institutes of Health (NIH) Fragile X Center (U54HD082008). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of Cincinnati Children's Hospital Medical Center gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors