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bioRxiv · 10.1101/2025.08.28.672884

Brain morphology network alterations in adolescents with autism spectrum disorder: a sex-stratified study

Safari, N.·Levy, I.·Zhang, A.·Agarwal, C.·Cortes, J. M.·Pelphrey, K. A.·Van Horn, J. D.·Rasero, J.
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Abstract

Neuroimaging studies based on altered functional and structural networks have contributed to better characterizing males and females with Autism Spectrum Disorder (ASD), advancing our understanding of the male prevalence in diagnosis. However, much less is known about how brain networks are altered from a morphological perspective, and whether these alterations may help explain sex-related characteristics in ASD. Here, we used structural MRI from a sex- and diagnosis-balanced sample of 337 individuals in typical neurodevelopmental ages (8-18 years) from the Autism Center of Excellence to elucidate sex-specific alterations in morphology-based connectivity, calculated as the similarity between region-wise multivariate morphological signatures. Network-based statistics showed that ASD males had significantly increased connectivity involving the fusiform gyrus, medial orbitofrontal, entorhinal, and parahippocampal cortices. This network profile was further linked to a core social-communication trait within the autistic group. In females with ASD, increased connectivity was found in a subnetwork primarily implicating the entorhinal cortex, followed by the inferior parietal lobule and lateral occipital cortex. In contrast to males, females fusiform gyrus showed decreased connectivity with the superior temporal sulcus. No overlap between male- and female-specific profiles was found. Together, these findings offer new insights into the neurobiology underlying sex differences in autism.

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Safari, N., Levy, I., Zhang, A., Agarwal, C., Cortes, J. M., Pelphrey, K. A., Van Horn, J. D., Rasero, J.. 2025-08-28. Brain morphology network alterations in adolescents with autism spectrum disorder: a sex-stratified study. https://doi.org/10.1101/2025.08.28.672884

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