Sex-Dependent Alterations in Fusiform Face Area Activation During Emotional Face Processing in Autism

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Abstract Atypical processing of emotional faces has been proposed as a characteristic of Autism Spectrum Disorder (ASD), but functional neuroimaging research has yielded inconsistent findings. Prior work is limited in generalizability due to methodological heterogeneity, imbalanced or small sample sizes, and underrepresentation of females. The present study examined functional brain activation during the Hariri Emotional Face-Matching Task (EFMT) in a large, sex-balanced sample of both typically developing and ASD participants (n=295, 8-18 years old) from the multi-site Autism Center of Excellence GENDAAR project. Using an ROI-driven approach, we targeted the right FFA, right OFA, right pSTS, and bilateral amygdala, we investigated whether ASD diagnosis was associated with atypical regional activation when viewing emotional faces, and if these differences were generalizable across sexes. Results revealed a group-by-sex interaction in the right FFA, driven by divergence of ASD males from the ASD female and typically developing participants. Generally, ASD females did not diverge greatly from typically developing populations. These findings suggest that atypical face processing is present, but meaningfully modulated by sex, underscoring the importance of sex-balanced, well-powered developmental samples in autism.

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