Tract-explainable and underexplained synchrony play complementary roles in the functional organization of the brain

Authors

Luo, J., Zeng, X., Xiong, Y., Xu, Y., Zhou, C., Wang, Y., Yao, D., Guo, D.

Abstract

Macroscale functional connectivity is jointly shaped by structural wiring and non-tract influences. Because these contributions are intrinsically entangled, their distinct roles remain unclear. Here, we introduce a large-scale brain modeling-based framework that disentangles functional synchrony into two components: tract-explainable and underexplained synchrony. Across two independent human cohorts (total n = 1214) and a marmoset dataset (n = 24), both components were highly reproducible and played distinct roles in shaping network architecture. Tract-explainable synchrony closely aligned with tractography and supported global integration, whereas underexplained synchrony was associated with multiscale cortical similarity features, including microstructure, receptor, and gene-expression patterns, and exhibited higher modularity. Crucially, these components dissociated along the sensorimotor-to-association hierarchy. Tract-underexplained synchrony became increasingly prominent in higher-order regions, exhibiting greater individual variability, behavioral relevance, and clinical sensitivity. Ultimately, tract-based and non-tract-mediated mechanisms serve distinct yet complementary roles in driving functional organization.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 21 Mar 2026.

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