Hemodynamic Changes Following Visual Stimulation and Breath-holding Provide Evidence for an Uncoupling of Cerebral Blood Flow and Volume from Oxygen Metabolism

摘要

Functional neuroimaging is most commonly performed using the blood-oxygenation-level-depend (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, separate visual stimulation (14s flashing checkerboard) and breath-hold (4s exhale + 14s breath-hold) experiments were performed in parallel on healthy volunteers using BOLD, CBV-weighted (CBVw) and CBF-weighted (CBFw) fMRI. Following visual stimulation, the BOLD signal persisted for 33±5s (n=9) and was bi-phasic with a negative component (undershoot), whereas CBV and CBF returned to baseline without an undershoot at 20±5s and 20±3s, respectively. Following breath-hold, the BOLD signal returned to baseline (23±7s) at the same time (p>0.05) as CBV (21±6s) and CBF (18±3s), without a post-stimulus undershoot. These data indicate that following visual activation, the BOLD undershoot is likely due to continued elevated CMRO2. Furthermore, persisting elevated CMRO2 is found when CBF and CBV have returned to baseline levels, providing evidence for an uncoupling of CBV and CBF responses from CMRO2 changes. Persisting elevated CMRO2 following elevated neuronal activity may be necessary to reverse neurotransmitter movements arising from excitatory postsynaptic currents.