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

AbstractMacroscale 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.