The post-stimulation undershoot in BOLD fMRI of human brain is not caused by elevated cerebral blood volume

Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) contrast is the most widely used technique for imaging human brain function. However, the dynamic interplay of altered cerebral blood flow (CBF), cerebral blood volume (CBV), and oxidative metabolism (CMRO2) is not yet fully understood. One of the characteristics of the BOLD response is the post-stimulation undershoot, that is increased deoxyhemoglobin, which has been suggested to originate from a delayed recovery of elevated CBV or CMRO2 to baseline. To investigate the CBV contribution to the post-stimulation BOLD undershoot, we performed bolus-tracking experiments using a paramagnetic contrast agent in eight healthy subjects at 3 T. In an initial BOLD experiment without contrast agent, we determined the individual hemodynamic responsiveness. In two separate experiments, we then evaluated the relative CBV (rCBV) during visual stimulation and the post-stimulation undershoot, respectively. The results confirm a pronounced rCBV increase during stimulation (31.4 ± 8.6%), but reveal no change in rCBV relative to baseline in the post-stimulation phase (0.7 ± 7.2%). This finding renders a CBV contribution to the BOLD MRI undershoot unlikely and - in conjunction with a rapid post-stimulation return of CBF to baseline - supports the idea of a prolonged elevation of oxidative metabolism.