Structure–function coupling reveals the excitation–inhibition imbalance in autism spectrum disorder: A perspective from large-scale whole-brain network modeling

Excitation-inhibition (E-I) imbalance is a core pathological mechanism in autism spectrum disorder (ASD). However, current research on how E-I balance changes in ASD remains highly controversial. In this study, we integrate structural and functional magnetic resonance imaging data from the UCLA Multimodal Connectivity Database to construct a large-scale whole-brain network model, aiming to investigate the potential neural mechanism of E-I imbalance in ASD. We find that compared with healthy controls, patients with ASD exhibit stronger structural-functional connectivity (SC-FC) coupling, suggesting impaired cognitive flexibility. Model analysis demonstrates altered network dynamics in ASD, characterized by reduced optimal coupling strength between empirical and simulated FC and a lower small-world index in simulated functional networks. Furthermore, a marked shift in neural oscillations is observed in ASD, including increased activity in the δ band and decreased activity in the α band, consistent with clinical findings. More importantly, our study reveals heterogeneous reductions of the E-I ratio in ASD across multiple spatial scales, spanning from local brain regions to large-scale networks, particularly highlighting a significant negative correlation between E-I ratio and SC-FC coupling. These findings establish a direct link between E-I dysregulation and abnormal structure-function integration in brain networks, providing novel insights into the complex pathogenesis underlying ASD.