Abstract
The brain is a complex network of neuronal populations interconnected by white matter tracts. The composition of these white matter connections (SC) shapes inter-regional signaling dynamics giving rise to spatial patterns of synchronous functional connectivity (FC). Several modeling approaches have proven useful for studying the mechanisms underlying the relationship between SC and FC. However, despite being a major component of white matter connectivity, the myelination of white matter tracts is not accounted for by conventional SC networks and has therefore largely been excluded from models of FC. Here, we expand structure-function brain modeling by integrating a multi-feature white matter SC network. We use multi-modal MRI to compute an SC network with connections (edges) weighted by the caliber, myelination, and length of white matter tracts. We investigate the relationship of this multi-feature SC network with both haemodynamic and electromagnetic FC. Edge myelin was strongly predictive of FC in a pattern that was heterogeneous across brain regions and timescales of neural function. Edge myelin showed strong, frequency-specific interactions with both edge caliber and length suggesting a modulatory role for white matter myelin in structure-function coupling. This was further supported by antagonistic gradients of white matter myelin and structure-function coupling along the sensory-association axis. We describe in detail the individual and joint relationships between these major white matter features and multi-frequency FC. These results illustrate the advantage of a more comprehensive characterization of white matter in structure-function models and establish how white matter myelin—known for roles in conduction velocity, plasticity, and metabolic support at the microscale—shapes brain function at the systems-level.
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Data availability
All data necessary to replicate this work are freely available for download at https://github.com/TardifLab/Modeling-Myelin-FC. Source data for all plots shown here can be found in Supplementary Data.
Code availability
All code necessary to replicate this work are freely available for download at https://github.com/TardifLab/Modeling-Myelin-FC. We provide the MATLAB code directly used in this analysis, along with a translated Python library for user convenience.
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Acknowledgements
The authors acknowledge research support from the National Science and Engineering Research Council of Canada (NSERC), the Canadian Institutes for Health Research (CIHR), Fonds de recherche du Québec—Santé (FRQ-S), CFREF Healthy Brains for Healthy Lives, the Killam Trusts, and Brain Canada.
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Conceptualization and methodology: M.C.N. and C.L.T. Data curation: M.C.N., W.D.L., I.R.L., H.A.H., and C.D.R. Formal analysis: M.C.N. Funding acquisition, resources, and supervision: C.L.T. Visualization and writing—original draft: M.C.N. Writing—review and editing: M.C.N., W.D.L., I.R.L., H.A.H., C.D.R., B.M., and C.L.T.
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Nelson, M.C., Da Lu, W., Leppert, I.R. et al. The role of white matter myelin in structural-functional network coupling. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09813-6
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DOI: https://doi.org/10.1038/s42003-026-09813-6
