Hierarchical distortions in structure-function coupling linked to multiscale neurobiological characteristics in autism

Abstract Autism spectrum disorder is associated with widespread alterations in brain connectivity, but how structural and functional networks are jointly reorganized remains unclear. Here, we show that autism is associated with altered structure-function coupling, particularly in the hierarchical organization of sensory and association systems. Using brain imaging data from 91 individuals with autism and 67 typically developing controls, we model functional connectivity from structural networks using Riemannian optimization and examine communication across multiple steps. In the resulting simulated networks, hierarchical organization is comparable between groups at lower communication steps but becomes less differentiated in autism as communication extends across multiple steps. These alterations are associated with excitation/inhibition alterations, neurotransmitter distributions, gene expression, and multisensory processing. We also identify atypical connectivity involving the thalamus and putamen. Importantly, greater hierarchical distortion predicts more severe autistic symptoms, linking macroscale network organization with neurobiology and behavior. These findings highlight hierarchical structure-function coupling as a potential framework for understanding biological and behavioral characteristics in autism.