White-Matter BOLD Mediates Time-Varying Cortico-Cortical Functional Connectivity

Area of Science:

• Neuroimaging
• Brain Connectivity
• White Matter Function

Background:

• Functional connectivity (FC) studies using BOLD fMRI typically focus on gray matter (GM) signals.
• The role of white matter (WM) in neural network organization and cortico-cortical communication is often overlooked.

Purpose of the Study:

• To investigate whether WM pathways mediate GM-GM functional associations.
• To explore the relationship between dynamic WM BOLD signals and time-varying intra-cortical FC.

Main Methods:

• Utilized a tract-informed mediation framework on resting-state fMRI data from the Human Connectome Project.
• Quantified pathway-level mediation effects across gray matter-white matter-gray matter (GM-WM-GM) units.
• Analyzed the relationship between temporal dynamics of WM BOLD signals and fluctuating GM-GM connectivity.

Main Results:

• WM BOLD signals were found to significantly mediate GM-GM associations, exhibiting tract-dependent heterogeneity.
• Temporal variability in WM signals, rather than mean amplitude, correlated with dynamic GM-GM connectivity (r ≈ 0.4).
• Specific WM tracts showed distinct relationships with cortico-cortical coupling.

Conclusions:

• WM BOLD signals play an integral role in large-scale brain network organization.
• WM pathways contribute to how cortical regions interact, challenging the exclusive focus on GM in FC studies.
• The dynamic properties of WM are crucial for understanding time-varying brain network function.