Sex differences of the triple network model in children with autism: A resting-state fMRI investigation of effective connectivity.

This brain imaging study looked at how different brain networks connect in autistic children compared to non-autistic children. They found that autistic girls had stronger brain connections than autistic boys in certain networks. The patterns suggested that autistic girls' brains showed some 'male-like' features while autistic boys' brains showed some 'female-like' features compared to non-autistic children of the same sex.

This neuroimaging study examined sex differences in brain network connectivity in 72 children with autism (36 females) and 72 typically developing controls using fMRI. Researchers analyzed effective connectivity within and between three key brain networks: the central executive network, default mode network, and salience network. Significant diagnosis-by-sex interactions were found, with females with autism showing higher connectivity than males with autism within the default mode network and between salience and executive networks. The patterns supported gender incoherence theory, suggesting neural masculinization in females with autism and neural feminization in males with autism compared to same-sex controls.

Findings suggest sex-specific differences in brain connectivity patterns in autism that may inform assessment and intervention approaches. The neural masculinization/feminization patterns could help explain why autism presents differently in males and females, potentially guiding more personalized clinical approaches based on sex.

Study design unclear from abstract. Cross-sectional design limits developmental conclusions. Sample from repository data may have selection biases. Brain-behavior relationships not detailed. Unclear if findings replicate across different autism presentations or severity levels.

Autism spectrum disorder (ASD) has a pronounced male predominance, but the underlying neurobiological basis of this sex bias remains unclear. Gender incoherence (GI) theory suggests that ASD is more neurally androgynous than same-sex controls. Given its central role, altered structures and functions, and sex-dependent network differences in ASD, the triple network model, including the central executive network (CEN), default mode network (DMN), and salience network (SN), has emerged as a candidate for characterizing this sex difference. Here, we measured the sex-related effective connectivity (EC) differences within and between these three networks in 72 children with ASD (36 females, 8-14 years) and 72 typically developing controls (TCs) (36 females, 8-14 years) from 5 sites of the Autism Brain Imaging Data Exchange repositories using a 2 × 2 analysis of covariance factorial design.

We also assessed brain-behavior relationships and the effects of age on EC. We found significant diagnosis-by-sex interactions on EC: females with ASD had significantly higher EC than their male counterparts within the DMN and between the SN and CEN. The interaction pattern supported the GI theory by showing that the higher EC observed in females with ASD reflected a shift towards the higher level of EC displayed in male TCs (neural masculinization), and the lower EC seen in males with ASD reflected a shift towards the lower level of EC displayed in female TCs (neural feminization). We also found significant brain-behavior correlations and significant effects of age on EC.