Sex differences of the triple network model in children with autism: A resting-state fMRI investigation of effective connectivity.
Autistic girls' brain networks shift toward typical-boy patterns, while autistic boys shift toward typical-girl patterns inside the triple-network system.
01Research in Context
What this study did
Li et al. (2023) scanned kids with autism while they rested. They looked at how three big brain networks talk to each other. They asked: do boys and girls with autism show different wiring?
The team used a fancy MRI tool that tracks which way signals flow. They compared 20 girls with autism, 20 boys with autism, and 20 typical kids of each sex.
What they found
Girls with autism had 'boy-like' strong connections. Boys with autism had 'girl-like' weak connections. The swap happened inside the triple-network system that controls focus and self-thought.
The pattern fits the gender-incoherence idea: autistic brains shift toward the opposite sex's typical wiring.
How this fits with other research
Yang et al. (2018) first saw the flip: autistic boys were over-connected, girls under-connected, in mentalizing hubs. Cuicui moves the same story into the triple network and shows the flip holds for signal direction, not just strength.
Payne et al. (2020) found autistic boys link sensory problems to salience wiring, while girls link them to prefrontal wiring. Cuicui agrees: sex shapes network jobs, even when behavior looks the same.
Lin et al. (2025) pooled 26 studies and say autism usually means weak network links. Cuicui does not fight this; it adds that the weakness is sex-flipped, so the average hides opposite patterns in boys and girls.
Why it matters
Stop using one-size-fits-all brain profiles. When you read an MRI report or pick a social skills target, ask: was the reference group mostly boys? If you work with autistic girls, expect their neural 'hot spots' to look more like typical boys, and vice versa. Build assessments and interventions that honor this wiring swap.
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02At a glance
03Original abstract
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.
Autism research : official journal of the International Society for Autism Research, 2023 · doi:10.1002/aur.2991