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.
Si et al. (2025) studied this question.