Enhancement of indirect functional connections with shortest path length in the adult autistic brain

Autism is a neurodevelopmental condition characterized by atypical brain functional organization. Here we investigated the intrinsic indirect (semi-metric) connectivity of the functional connectome associated with autism. Resting-state functional magnetic resonance imaging scans were acquired from 65 neurotypical adults (33 males/32 females) and 61 autistic adults (30 males/31 females). From functional connectivity networks, semi-metric percentages (SMPs) were calculated to assess the proportion of indirect shortest functional pathways at global, hemisphere, network, and node levels. Group comparisons were then conducted to ascertain differences between autism and neurotypical control groups. Finally, the strength and length of edges were examined to explore the patterns of semi-metric connections associated with autism. Compared with neurotypical controls, autistic adults displayed significantly higher SMP at all spatial scales, similar to prior observations in adolescents. Differences were primarily in weaker, longer-distance edges in the majority between networks. However, no significant diagnosis-by-sex interaction effects were observed on global SMP. These findings suggest increased indirect functional connectivity in the autistic brain is persistent from adolescence to adulthood and is indicative of reduced functional network integration.