biostudies-literatureWalsh MJMArizona Biomedical Research CommissionNIMH NIH HHSNational Institute of Mental HealthDepartment of Defense316-329https://www.ebi.ac.uk/biostudies/studies/S-EPMC9837609biostudies-literatureUnknown33(2)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.Cerebral cortex (New York, N.Y. : 1991)Sex-related brain connectivity correlates of compensation in adults with autism: insights into female protection.PMC98376091F31MH122107K01 MH116098AR140105ADHS16-1624131K01MH116098Pagni BBaxter LDelaney SBraden BBWalsh MJMSmith CJMonahan LfalseSex-related brain connectivity correlates of compensation in adults with autism: insights into female protection.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.2022-01-01T00:00:00Z2022 Dec2024-11-12T12:56:20.564Z2024-11-12T12:56:20.564ZS-EPMC98376093521237310.1093/cercor/bhac069