Negative hemodynamic response in the cortex: evidence opposing neuronal deactivation revealed via optical imaging and electrophysiological recording

Functional brain imaging techniques depend on the relationship between regional hemodynamic responses and neural activity. The positive hemodynamic response (PHR) has widely been discussed and has generally been associated with an increase in neuronal signals. In contrast, the negative hemodynamic response (NHR) has not been investigated extensively, and its underlying nature is highly controversial. In the present study, we employed an optical imaging (OI) technique and microelectrode array (MEA) recordings in the rat cortex to examine the NHR to hindlimb electrical stimulation; we primarily focused on the NHR adjacent to a PHR region. We determined that the dynamics of the total blood volume signal in the NHR regions lagged slightly behind those in the PHR areas. Additionally, the deoxyhemoglobin signal in the PHR areas increased immediately after stimulation and the deoxyhemoglobin signal in the NHR regions remained unchanged or increased. Consistent with the change in the deoxyhemoglobin signal, the MEA recordings demonstrated that neural activity in the PHR regions was elevated and that activity in the NHR areas was unchanged or increased during stimulation, implying that the NHR occurred in the absence of neural deactivation. These results suggest that the NHR may be explained by purely hemodynamic contributions, specifically "blood stealing" or increased neural activity, and indicate that caution should be exercised when interpreting the NHR as a decrease in neural activity, especially when the NHR is adjacent to a PHR.