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Reliance on the hemodynamic response as a surrogate marker of neural activity imposes an intrinsic limit on the spatial specificity of functional MRI. An alternative approach based on diffusion-weighted functional MRI (DfMRI) has been reported as a contrast less reliant on hemodynamic effects, however current evidence suggests that both hemodynamic and unique neural sources contribute to the diffusion signal. Here we compare activation patterns obtained with the standard blood oxygenation level-dependent (BOLD) contrast to DfMRI in order to gain a deeper understanding of how the BOLD proportion contributes to the observable diffusion signal. Both individual and group-level activation patterns obtained with DfMRI and BOLD to a visual field stimulation paradigm were analyzed. At the individual level, the DfMRI contrast showed a strong, positive relationship between the volumes of cortex activated in response to quadrant- and hemi-field visual stimulation. This was not observed in the corresponding BOLD experiment. Overall, the DfMRI response indicated less between-subject variability, with random effects analyses demonstrating higher statistical values at the peak voxel for DfMRI. Furthermore, the spatial extent of the activation was more restricted to the primary visual region for DfMRI than BOLD. However, the diffusion signal was sensitive to the hemodynamic response in a manner dependent on experimental manipulation. It was also limited by its low signal-to-noise ratio (SNR), demonstrating lower sensitivity than BOLD. Together these findings both support DfMRI as a contrast that bears a closer spatial relationship to the underlying neural activity than BOLD, and raise important caveats regarding its utilization. Models explaining the DfMRI signal change need to consider the dynamic vascular contributions that may vary with neural activity.

Influence of BOLD Contributions to Diffusion fMRI Activation of the Visual Cortex