# Biophysical basis of functional MRI of white matter

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $480,997

## Abstract

Abstract
The proposed research aims to measure blood oxygenation level dependent (BOLD) signals in white matter
(WM) using functional magnetic resonance imaging (fMRI), validate their relationships to cortical neural activity,
and quantify their characteristics and their underlying biophysical origins. BOLD signals have previously been
robustly detected in gray matter (GM) in response to stimuli in a very large number of studies. In addition,
correlations of signal fluctuations between cortical regions in a resting state have been analyzed to derive
functional connectivity. However, whether such signals reliably arise in WM remains controversial, and their
interpretation is unclear. We have previously shown that BOLD signals can be reliably detected in WM if
appropriate detection and analysis methods are used, and that in a resting state they exhibit anisotropic
temporal correlations that largely align with WM tracts. Multiple such lines of evidence converge to suggest that
WM BOLD signals are related to intrinsic, function-dependent neural activity and are apparent only in tracts
engaged in specific functions. However, the precise relationships between WM and corresponding GM signals
have not been established, and neither the characteristics nor origins of the hemodynamic response function
(HRF) of WM have been elucidated. We hypothesize that BOLD signal variations in WM tracts are directly
related to corresponding variations in neural activity in GM volumes to which they connect and/or which share
specific functional roles, and that further studies will provide a new basis for more fully integrating structural
and functional aspects of neural organization. In the proposed research we will [1] demonstrate and measure
the relationships between BOLD signals in WM tracts (identified using diffusion imaging) and GM volumes in
response to parametric stimuli whose variations modulate the degree of neural activity in specific cortical
areas; [2] measure and characterize the HRF in specific WM tracts using event-related fMRI, and modify
conventional models of BOLD responses to explain and fit those data; [3] establish the biophysical basis of
stimulus-evoked BOLD activations in white matter by comparing data from different imaging sequences and
field strengths, and by measuring BOLD signals in the brains of non-human primates with and without an
intravascular susceptibility contrast agent to separate contributions from changes in blood volume vs blood
oxygenation. Overall, these studies will validate the nature of WM BOLD effects, demonstrate their relevance
in neural processing, and provide a basis for future studies of functional changes in a broad range of WM-
associated disorders as well as development and degeneration.

## Key facts

- **NIH application ID:** 10333348
- **Project number:** 5R01NS113832-03
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** John C Gore
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $480,997
- **Award type:** 5
- **Project period:** 2020-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10333348

## Citation

> US National Institutes of Health, RePORTER application 10333348, Biophysical basis of functional MRI of white matter (5R01NS113832-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10333348. Licensed CC0.

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