While direct brain connection differences are well-documented in Autism Spectrum Disorder (ASD), brain function also critically depends on indirect, higher-order structural connections (hSC). Understanding the influence of these connections on functional relationships is key to unraveling the neural mechanisms of ASD. This study included 76 participants with ASD and 64 typically development (TD). We utilized the node2vec embedding method to characterize brain nodes and construct hSC networks, which were then differentiated into direct and indirect connectivity networks. The structural-functional coupling (SC-FC coupling) method was subsequently employed to quantify the relationship between structural and functional connectivity. Our findings demonstrated significant differences in SC-FC coupling within the ASD group. These alterations were particularly evident in rich club connections and within specific modules, including the default mode network and visual network. Furthermore, the coupling strengths of several brain regions—specifically the left dorsolateral superior frontal gyrus, left middle orbital gyrus, left olfactory cortex, and right superior temporal gyrus—were found to be associated with the severity of ASD symptoms. These results underscore the importance of considering higher-order network interactions when analyzing structural and functional relationships in neurodevelopmental disorders. This study offers new insights into the neural mechanisms of ASD by highlighting the role of hSC and its coupling with functional connectivity.
Dai et al. (2026) studied this question.