Dynamic Inter-Modality Source Coupling Reveals Sex Differences in Children based on Brain Structural-Functional Network Connectivity: A Multimodal MRI Study of the ABCD Dataset

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Abstract

Background: Sex differences in brain development are well-documented, yet the dynamic coupling between structure and function remains underexplored. We introduce dynamic inter-modality source coupling (dIMSC), extending our previous work to link structural MRI source-based morphometry (SBM) with dynamic functional network connectivity (dFNC). Methods: We used data from the Adolescent Brain Cognitive Development (ABCD) study (ages 9-11) and combined SBM-derived gray matter sources with sliding-window dFNC. dIMSC was computed as the time-resolved cross-correlation between these modalities to quantify structure-function coupling strength. We evaluated sex differences in these profiles and their interaction with cognitive performance. Results: Significant sex-specific patterns emerged: males exhibited stronger positive coupling in sensorimotor regions (postcentral gyrus), while females showed stronger coupling in higher-order associative regions (inferior parietal lobule). These configurations were functionally distinct: higher positive coupling occupancy predicted better crystallized cognition (vocabulary) in females, whereas it predicted better fluid cognition (working memory) in males. Conclusion: Together, these findings suggest that males and females utilize distinct structural-functional configurations to support cognitive processing, males relying on a sensorimotor-anchored organization and females on an associative-anchored one. The dIMSC method advances our earlier work by enabling time-resolved analysis of brain coupling, providing a powerful framework for investigating sex-specific neurodevelopmental mechanisms.

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