Diffusion-weighted functional magnetic resonance imaging (DfMRI) is based on a novel contrast mechanism sensitised to changes in water diffusion induced by neuronal activation. Initial evidence suggests that diffusion changes precede the haemodynamic response, and thus may reflect neuronal activity more directly than blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI), the dominant technique for functional neuroimaging. However, the extent to which early diffusion changes and residual BOLD effects influence the signal observed in DfMRI and whether residual BOLD effects are dependent on experimental design are unclear. The aim of this thesis was to determine the extent to which DfMRI reflects neural changes that are separate from BOLD effects and whether BOLD contributions to DfMRI are influenced by experimental design.
Visual stimulation paradigms known to activate well-defined regions of cerebral cortex were employed to directly compare DfMRI and BOLD in neurologically normal individuals using within-subjects designs. By manipulating the region of visual cortex stimulated, the spatial concordance between the fMRI response and the expected locus of neural activity was investigated. The influence of block and event-related experimental designs was also assessed. In the block design, tasks engaged sustained neural activity whereas in the event-related design, transient stimulation events were employed.
Spatial coupling with underlying neural activity, both within the primary and extrastriate visual cortices, was stronger for DfMRI than for BOLD fMRI. DfMRI demonstrated lower intra-individual variance in spatial activation patterns and in signal magnitude change than BOLD fMRI, despite the limitation of a low signal-to-noise ratio (SNR). These findings, however, were influenced by experimental design. In block design DfMRI, BOLD contributions were greater than for event-related designs.
Together, these results suggest that DfMRI and BOLD reflect distinct mechanisms related to neuronal activation. DfMRI provides a more direct view of in vivo neuronal activity; however its sensitivity to residual BOLD effects varies with experimental manipulation. These results, while outlining the strengths and efficacy of DfMRI, also highlight the need for further research identifying optimal experimental designs.