Cortical depth dependence and implications on the neuronal specificity of the functional apparent diffusion coefficient contrast

Although the blood oxygenation level-dependent (BOLD) contrast is widely used in functional MRI (fMRI), its spatial specificity is compromised by the diversity of the participating vasculature, including large draining veins. Previous studies have shown that an alternative contrast mechanism based on functional changes of the apparent diffusion coefficient (ADC) can be sensitized to small vessels more closely tied to the sites of neural activity. Such an improved functional localization, however, has not yet been demonstrated at the cortical level in humans. Here, we investigate the cortical depth dependence and neuronal specificity of the functional ADC contrast in the human primary visual cortex by performing high-resolution BOLD and ADC imaging during visual stimulation at 4 T. Our results show that, by using optimal parameters, the functional ADC changes are significantly higher in the middle cortical layers, whereas the BOLD signal changes are higher at the cortical surface and vary much less significantly across the cortex. These results are in good agreement with previous studies performed in anesthetized cats at 9.4 T and demonstrate the improved spatial specificity of the functional ADC contrast as compared to the BOLD contrast.