A Data-Driven Method to Map the Functional Organisation of Human Brain White Matter

TL;DR

This paper introduces a data-driven framework combining diffusion MRI and functional MRI to map the functional organization of white matter in the human brain, revealing age-related declines and links to cognitive performance.

Contribution

It presents a novel method called Track-DFC that models functional coupling of white matter pathways, advancing understanding of brain connectivity and aging effects.

Findings

White matter pathways show age-related declines in functional coupling.

Specific white matter clusters mediate age-related cognitive decline.

The framework effectively identifies functionally coherent white matter clusters.

Abstract

The white matter of the brain is organised into axonal bundles that support long-range neural communication. Although diffusion MRI (dMRI) enables detailed mapping of these pathways through tractography, how white matter pathways directly facilitate large-scale neural synchronisation remains poorly understood. We developed a data-driven framework that integrates dMRI and functional MRI (fMRI) to model the dynamic coupling supported by white matter tracks. Specifically, we employed track dynamic functional connectivity (Track-DFC) to characterise functional coupling of remote grey matter connected by individual white matter tracks. Using independent component analysis followed by k-medoids clustering, we derived functionally-coherent clusters of white matter tracks from the Human Connectome Project young adult cohort. When applied to the HCP ageing cohort, these clusters exhibited widespread age-related declines in both functional coupling strength and temporal variability. Importantly, specific clusters encompassing pathways linking control, default mode, attention, and visual systems significantly mediated the relationship between age and cognitive performance. Together, these findings depict the functional organisation of white matter tracks and provide a powerful tool to study brain ageing and cognitive decline.