Evidence for a vascular contribution to diffusion FMRI at high b value

Recent work has suggested that diffusion-weighted functional magnetic resonance imaging (FMRI) with strong diffusion weighting (high b value) detects neuronal swelling that is directly related to neuronal firing. This would constitute a much more direct measure of brain activity than current methods and represent a major advance in neuroimaging. However, it has not been firmly established that the observed signal changes do not reflect residual vascular effects, which are known to exist at low b value. This study measures the vascular component of diffusion FMRI directly by using hypercapnia, which induces blood flow changes in the absence of a change in neuronal firing. Hypercapnia elicits a similar diffusion FMRI response to a visual stimulus including a rise in percent signal change with increasing b value, which was reported for visual activation. Analysis of the response timing found no evidence for an early response at high b value, which has been reported as evidence for a nonhemodynamic response. These results suggest that a large component of the diffusion FMRI signal at high b value is vascular rather than neuronal.