Distinct subtypes of the negative hemodynamic response function across cortical distance and depth in human visual...

The negative blood-oxygenation-level-dependent (BOLD) response (NBR) and its origins have been investigated for over a decade. However, the temporal characteristics and spatial organization of the NBR are not fully understood. Previous studies by our group and others have shown that the negative HRF (nHRF)-the NBR evoked by a brief stimulus-exhibits substantial spatial variability. To investigate this spatial variability in greater detail, we used a unilateral parafoveal visual stimulus and examine nHRF temporal dynamics as a function of cortical distance from the stimulus representation (SR) and throughout cortical depth in both the contralateral and ipsilateral visual cortex. We identified two temporally distinct patterns of nHRF dynamics and defined the corresponding subtypes: 1) a transient nHRF (T-nHRF), characterized by a weak but significant initial negative response (INR) followed by a prominent positive peak, and 2) a fully developed nHRF (FD-nHRF), characterized by a delayed and strong INR followed by a weak or absent positive peak. We observed that the two subtypes coexisted throughout visual cortex in regionally varying proportions. T-nHRFs predominated near the SR while FD-nHRFs predominated in more peripheral contralateral regions and homologous ipsilateral regions. Response magnitudes increased toward the superficial gray matter, with pronounced depth dependence in the positive peak for T-nHRFs and in the INR for FD-nHRFs. For each subtype, depth dependence was most consistent in regions where that subtype predominated. The regional distributions and depth-dependent response profiles of two nHRF subtypes showed systematic nHRF organization with respect to cortical distance from the SR and cortical depth. This organization suggests that distinct NBR mechanisms may contribute to the two subtypes, with their relative contributions varying cortical locations.