The Human Brain Connectome Weighted by the Myelin Content and Total Intra-Axonal Cross-Sectional Area of White Matter Tracts

ABSTRACT A central goal in neuroscience is the development of a comprehensive mapping between structural and functional brain features. Computational models support in vivo investigation of the mechanisms mediating this relationship but currently lack the requisite biological detail. Here, we characterize human structural brain networks weighted by multiple white matter microstructural features to assess their potential joint utilization in computational models. We report edge-weight-dependent spatial distributions, variance, small-worldness, rich club, hubs, as well as relationships with function, edge length and myelin. Contrasting networks weighted by the total intra-axonal cross-sectional area and myelin content of white matter tracts, we find opposite relationships with functional connectivity, an edge-length-independent inverse relationship with each other, and the lack of a canonical rich club in myelin-weighted networks. When controlling for edge length, tractometry-derived networks weighted by either tensor-based metrics or neurite density show no relationship with whole-brain functional connectivity. We conclude that structure-function brain models are likely to be improved by the co-utilization of structural networks weighted by total intra-axonal cross-sectional area and myelin content. We anticipate that the proposed microstructure-weighted computational modeling approach will support mechanistic understanding of the structure-function relationship of the human brain. AUTHOR SUMMARY For computational network models to provide mechanistic links between brain structure and function, they must be informed by networks in which edge weights quantify structural features relevant to brain function. Here, we characterized several weighted structural networks capturing multiscale features of white matter connectivity. We describe these networks in terms of edge weight distribution, variance and network topology, as well as their relationships with each other, edge length and function. Overall, these findings support the joint use of structural networks weighted by the total intra-axonal cross-sectional area and myelin content of white matter tracts in structure-function models. This thorough characterization serves as a benchmark for future investigations of weighted structural brain networks.