Altered Relationship between Functional Connectivity and Fiber-Bundle Structure in High-Functioning Male Adults with Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by abnormalities in structure and function of the brain. However, how ASD affects the relationship between fiber-bundle microstructures and functional connectivity (FC) remains unclear. Here, we analyzed structural and functional images of 26 high-functioning adult males with ASD, alongside 26 age-, gender-, and full-scale IQ-matched typically developing controls (TDCs) from the BNI dataset in the ABIDE database. We utilized fixel-based analysis to extract microstructural information from fiber tracts, which was then used to predict FC using a multilinear model. Our results revealed that the structure–function relationships in both ASD and TDC cohorts were strongly aligned in the primary cortex but decoupled in the high-order cortex, and the ASD patients exhibited reduced structure–function relationships throughout the cortex compared to the TDCs. Furthermore, we observed that the disrupted relationships in ASD were primarily driven by alterations in FC rather than fiber-bundle microstructures. The structure–function relationships in the left superior parietal cortex, right precentral and inferior temporal cortices, and bilateral insula could predict individual differences in clinical symptoms of ASD patients. These findings underscore the significance of altered relationships between fiber-bundle microstructures and FC in the etiology of ASD.