Temporal evolution and spatial heterogeneity of cerebral cortical-depth profiles of the BOLD-fMRI response

Functional MRI measures brain activity by tracking the associated hemodynamic response, which is shaped by the vascular anatomy. Microscopy studies have shown that the hemodynamic response initiates within the cerebral cortex then spreads upwards to the pial surface, where the largest fMRI signal changes are seen, however responses at the cortical surface exhibit poor neuronal specificity. Motived by this, we characterized the time-evolution of the fMRI response in humans. At some cortical locations the fMRI response peaked at the pial surface but in others it peaked within the cortex, likely due to the sparsity of large pial vessels and the dense capillary bed in middle cortical layers. We observed the earliest response onset in middle cortical depths, which is also the site of thalamocortical input. Standard approaches that aggregate fMRI responses over space and time may therefore lose meaningful information, and "physiologically-informed" strategies may enhance neuronal specificity of fMRI measurements.