Hemodynamic changes after visual stimulation and breath holding provide evidence for an uncoupling of cerebral blood flow and volume from oxygen metabolism

Functional neuroimaging is most commonly performed using the blood-oxygenation-level-dependent (BOLD) approach, which is sensitive to changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and the cerebral metabolic rate of oxygen (CMRO2). However, the precise mechanism by which neuronal activity elicits a hemodynamic response remains controversial. Here, visual stimulation (14 secs flashing checkerboard) and breath-hold (4 secs exhale + 14 secs breath hold) experiments were performed in alternating sequence on healthy volunteers using BOLD, CBV-weighted, and CBF-weighted fMRI. After visual stimulation, the BOLD signal persisted for 33 +/- 5 secs (n = 9) and was biphasic with a negative component (undershoot), whereas CBV and CBF returned to baseline without an undershoot at 20 +/- 5 and 20 +/- 3 secs, respectively. After breath hold, the BOLD signal returned to baseline (23 +/- 7 secs) at the same time (P > 0.05) as CBV (21 +/- 6 secs) and CBF (18 +/- 3 secs), without a poststimulus undershoot. These data suggest that the BOLD undershoot after visual activation reflects a persistent increase in CMRO2. These observations support the view that CBV and CBF responses elicited by neuronal activation are not necessarily coupled to local tissue metabolism.