Exploring atypical spatial-functional coupling in adolescent autism spectrum disorder: insights from neurodevelopment and transcriptomic architecture

Abstract

Autism Spectrum Disorder (ASD) is associated with atypical large-scale brain network organization, yet how spatial-functional dependencies relate to clinical features and molecular reference maps remains incompletely understood. To quantify spatial functional heterogeneity (Sill) and coherence persistence (Range), we analyzed resting-state fMRI data from 162 ASD and 175 TD adolescents, all aged 12–18. Compared with TD, adolescents with ASD exhibited significantly increased Sill within higher-order association networks, including the left Language and right Posterior Multimodal networks, whereas no group differences in Range survived multiple-comparison correction. Within the ASD group, elevated Sill was selectively associated with greater social-affective symptom severity but not restricted and repetitive behaviors. To explore potential biological correlates, we integrated cortical gene expression reference data and identified transcriptomic patterns associated with regional Sill differences. These genes showed enrichment for synaptic signaling, mitochondrial processes, and glial-related functions, highlighting multiscale correspondence between spatial-functional organization and molecular reference maps. Together, these results demonstrate statistical associations among altered spatial-functional properties, clinical severity, and transcriptomic profiles related to synaptic signaling, mitochondrial processes, and glial-related functions in ASD, providing a complementary spatial perspective on large-scale functional organization.