The human brain connectome weighted by the myelin content and total intra-axonal cross-sectional area of white matter tracts

Mark C Nelson; Jessica Royer; Wen Da Lu; Ilana R Leppert; Jennifer S W Campbell; Simona Schiavi; Hyerang Jin; Shahin Tavakol; Reinder Vos de Wael; Raul Rodriguez-Cruces; G Bruce Pike; Boris C Bernhardt; Alessandro Daducci; Bratislav Misic; Christine L Tardif

doi:10.1162/netn_a_00330

The human brain connectome weighted by the myelin content and total intra-axonal cross-sectional area of white matter tracts

Netw Neurosci. 2023 Dec 22;7(4):1363-1388. doi: 10.1162/netn_a_00330. eCollection 2023.

Authors

Mark C Nelson^{1

2}, Jessica Royer^{1

2}, Wen Da Lu^{2

3}, Ilana R Leppert², Jennifer S W Campbell², Simona Schiavi⁴, Hyerang Jin^{1

2}, Shahin Tavakol^{1

2}, Reinder Vos de Wael^{1

2}, Raul Rodriguez-Cruces^{1

2}, G Bruce Pike⁵, Boris C Bernhardt^{1

2}, Alessandro Daducci⁴, Bratislav Misic^{1

2}, Christine L Tardif^{1

2

3}

Affiliations

¹ Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
² McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, Montreal, QC, Canada.
³ Department of Biomedical Engineering, McGill University, Montreal, QC, Canada.
⁴ Department of Computer Science, University of Verona, Verona, Italy.
⁵ Hotchkiss Brain Institute and Departments of Radiology and Clinical Neuroscience, University of Calgary, Calgary, Canada.

Abstract

A central goal in neuroscience is the development of a comprehensive mapping between structural and functional brain features, which facilitates mechanistic interpretation of brain function. However, the interpretability of structure-function brain models remains limited by a lack of biological detail. Here, we characterize human structural brain networks weighted by multiple white matter microstructural features including total intra-axonal cross-sectional area and myelin content. 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, networks weighted by either fractional anisotropy, radial diffusivity, or neurite density show no relationship with whole-brain functional connectivity. We conclude that the co-utilization of structural networks weighted by total intra-axonal cross-sectional area and myelin content could improve our understanding of the mechanisms mediating the structure-function brain relationship.

Keywords: Connectomics; Functional connectivity; Microstructure-weighted imaging; Myelin; Network neuroscience; Structural connectivity; White matter.