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Sex-related brain connectivity correlates of compensation in adults with autism: insights into female protection.

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The male preponderance in autism spectrum disorder (ASD) led to the hypothesis that aspects of female biology are protective against ASD. Females with ASD (ASD-F) report more compensatory behaviors (i.e.… Click to show full abstract

The male preponderance in autism spectrum disorder (ASD) led to the hypothesis that aspects of female biology are protective against ASD. Females with ASD (ASD-F) report more compensatory behaviors (i.e. "camouflaging") to overcome ASD-related social differences, which may be a mechanism of protection. No studies have examined sex-related brain pathways supporting camouflaging in ASD-F, despite its potential to inform mechanisms underlying the ASD sex bias. We used functional connectivity (FC) to investigate "sex-atypical" and "sex-typical" FC patterns linked to camouflaging in adults with ASD and examined multimodal coherence of findings via structural connectometry. Exploratory associations with cognitive/emotional functioning examined the adaptive nature of FC patterns. We found (i) "sex-atypical" FC patterns linked to camouflaging in the hypothalamus and precuneus and (ii) "sex-typical" patterns in the right anterior cingulate and anterior parahippocampus. Higher hypothalamic FC with a limbic reward cluster also correlated with better cognitive control/emotion recognition. Structural connectometry validated FC results with consistent brain pathways/effect patterns implicated in ASD-F. In summary, "male-typical" and "female-typical" brain connectivity patterns support camouflaging in ASD-F in circuits implicated in reward, emotion, and memory retrieval. "Sex-atypical" results are consistent with fetal steroidogenic/neuroinflammatory hypotheses. However, female genetics/biology may contribute to "female-typical" patterns implicated in camouflaging.

Keywords: connectivity; related brain; sex; sex related; biology

Journal Title: Cerebral cortex
Year Published: 2022

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