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Association Areas of the Cortex01:21

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

Lyuan Xu1,2, Yurui Gao1,3, Muwei Li1,4

  • 1Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN USA.

Biorxiv : the Preprint Server for Biology
|December 22, 2025
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Summary
This summary is machine-generated.

White matter (WM) BOLD signals significantly mediate brain gray matter (GM) associations, influencing how cortical regions interact. Temporal variability in WM signals, not amplitude, tracks dynamic GM-GM connectivity, revealing WM

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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.