Spatiotemporal characteristics and vascular sources of neural-specific and -nonspecific fMRI signals at submillimeter columnar resolution

The neural specificity of hemodynamic-based functional magnetic resonance imaging (fMRI) signals is dependent on both the vascular regulation and the sensitivity of the applied fMRI technique to different types and sizes of blood vessels. In order to examine the specificity of MRI-detectable hemodynamic responses, submillimeter blood oxygenation level-dependent (BOLD) and cerebral blood volume (CBV) fMRI studies were performed in a well-established cat orientation column model at 9.4 T. Neural-nonspecific and -specific signals were separated by comparing the fMRI responses of orthogonal orientation stimuli. The BOLD response was dominantly neural-nonspecific, mostly originating from pial and intracortical emerging veins, and thus was highly correlated with baseline blood volume. Uneven baseline CBV may displace or distort small functional domains in high-resolution BOLD maps. The CBV response in the parenchyma exhibited dual spatiotemporal characteristics, a fast and early neural-nonspecific response (with 4.3-s time constant) and a slightly slower and delayed neural-specific response (with 9.4-s time constant). The nonspecific CBV signal originates from early-responding arteries and arterioles, while the specific CBV response, which is not correlated with baseline blood volume, arises from late-responding microvessels including small pre-capillary arterioles and capillaries. Our data indicate that although the neural specificity of CBV fMRI signals is dependent on stimulation duration, high-resolution functional maps can be obtained from steady-state CBV studies.