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bioRxiv · 10.64898/2026.03.19.712967

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

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

Macroscale functional connectivity emerges from a complex interplay between structural wiring and non-tract-mediated mechanisms. However, the intrinsic entanglement of these contributions obscures their specific roles in brain organization. Here, we introduce a computational modeling framework to disentangle functional synchrony into two fundamentally distinct components: tract-explainable and tract-underexplained synchrony. Validated across two large-scale human cohorts (n = 1214) and an independent marmoset dataset (n = 24), this dissociation reveals an evolutionarily conserved architectural principle. We show that tract-explainable synchrony aligns closely with structural connectomes to facilitate global integration. Conversely, tract-underexplained synchrony drives local modularity and is anchored by multiscale cortical similarity, encompassing microstructural, receptor, and transcriptomic profiles. Crucially, these components gradually dissociate from sensori-motor to higher-order association cortices, with the importance of tract-underexplained synchrony progressively increasing. Furthermore, the tract-underexplained synchrony exhibits greater individual variability and demonstrates a stronger association with individual cognitive performance. Ultimately, tract-based and non-tract-mediated mechanisms serve distinct yet complementary roles, jointly shaping a functional organization that balances conserved macroscopic stability with higher-order cognitive flexibility.

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Luo, J., Zeng, X., Xiong, Y., Xu, Y., Zhou, C., Wang, Y., Yao, D., Guo, D.. 2026-03-20. Tract-explainable and underexplained synchrony play complementary roles in the functional organization of the brain. https://doi.org/10.64898/2026.03.19.712967

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