Apparent Diffusion Coefficient fMRI shines light on white matter resting-state connectivity compared to BOLD

Resting-state functional magnetic resonance imaging (fMRI) is used to derive functional connectivity (FC) between brain regions. Typically, blood oxygen level-dependent (BOLD) contrast is used. However, BOLD's reliance on neurovascular coupling poses challenges in reflecting brain activity accurately, leading to reduced sensitivity in white matter (WM). WM BOLD signals have long been considered physiological noise, although recent evidence shows that both stimulus-evoked and resting-state WM BOLD signals resemble those in gray matter (GM), albeit smaller in amplitude. We introduce apparent diffusion coefficient fMRI (ADC-fMRI) as a promising functional contrast for GM and WM FC, capturing activity-driven neuromorphological fluctuations. Our study compares BOLD-fMRI and ADC-fMRI FC in GM and WM, showing that ADC-fMRI mirrors BOLD-fMRI connectivity in GM, while capturing more robust FC in WM. ADC-fMRI displays higher average clustering and average node strength in WM, and higher inter-subject similarity, compared to BOLD. Taken together, this suggests that ADC-fMRI is a reliable tool for exploring FC that incorporates gray and white matter nodes in a novel way.