Sex heterogeneity of functional brain network dynamics in autism spectrum disorder based on the high-amplitude...

Autism spectrum disorder (ASD) is a neurodevelopmental condition exhibiting marked sex heterogeneity in functional connectivity. Given that high-amplitude co-fluctuation patterns dominate whole-brain functional connectivity, this study investigated sex heterogeneity in these patterns in ASD from the perspective of temporal variability. Resting-state functional magnetic resonance imaging data were obtained from the Autism Brain Imaging Data Exchange database, comprising 284 males/65 females with ASD and 340 male/119 female typical controls. High-amplitude co-fluctuation patterns were obtained using an edge time series analysis, and temporal variability of intra-network and inter-network functional architecture was calculated to characterize functional brain network dynamics. A two-way analysis of variance was further conducted to explore sex heterogeneity of functional brain network dynamics in ASD. At the intra-network level, significant diagnosis-by-sex interactions were observed in the default-mode network (DMN), salience network (SAN), cingulo-opercular network (CO), motor and somatosensory network (SMN), subcortical network (SUB), and visual network (VN). In ASD, sex differences in temporal variability were reduced in the DMN, SMN, and VN, increased in the CO and SUB, and an additional sex difference emerged in the SAN relative to controls. In contrast, at the inter-network level, all brain networks showed varying degrees of diagnosis-by-sex interaction effects. Moreover, network-level functional connectivity dynamics predicted the severity of social interaction impairments in females with ASD and social communication impairments in males with ASD, respectively. These findings reveal the sex heterogeneity of functional brain network dynamics in ASD, and highlight the potential role of altered high-amplitude co-fluctuations in the sex-specific neural mechanism underlying ASD.