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

Melissa J.M. Walsh, Broc Pagni, Leanna Monahan, Shanna Delaney, Christopher J. Smith, Leslie Baxter, B. Blair Braden

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)316-329
Number of pages14
JournalCerebral Cortex
Issue number2
StatePublished - Jan 15 2023
Externally publishedYes


  • autism
  • camouflaging
  • DTI
  • MRI
  • resting-state
  • sex/gender

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience


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