Sex differences in the flexibility of dynamic network reconfiguration of autism spectrum disorder based on multilayer network

Dynamic network reconfiguration alterations in the autism spectrum disorder (ASD) brain have been frequently reported. However, since the prevalence of ASD in males is approximately 3.8 times higher than that in females, and previous studies of dynamic network reconfiguration of ASD have predominantly used male samples, it is unclear whether sex differences exist in dynamic network reconfiguration in ASD. This study used resting-state functional magnetic resonance imaging data from the Autism Brain Imaging Data Exchange database, which included balanced samples of 64 males and 64 females with ASD, along with 64 demographically-matched typically developing control (TC) males and 64 TC females. The multilayer network analysis was used to explore the flexibility of dynamic network reconfiguration. The two-way analysis of variance was further performed to examine the sex-related changes in ASD in flexibility of dynamic network reconfiguration. A diagnosis-by-sex interaction effect was identified in the cingulo-opercular network (CON), central executive network (CEN), salience network (SN), and subcortical network (SUB). Compared with TC females, females with ASD showed lower flexibility in CON, CEN, SN, and SUB. The flexibility of CEN and SUB in males with ASD was higher than that in females with ASD. In addition, the flexibility of CON, CEN, SN, and SUB predicted the severity of social communication impairments and stereotyped behaviors and restricted interests only in females with ASD. These findings highlight significant sex differences in the flexibility of dynamic network reconfiguration in ASD and emphasize the importance of further study of sex differences in future ASD research.