Coupling of cerebral blood flow and oxygen consumption during physiological activation and deactivation measured with fMRI

The physiological basis of the blood oxygenation level dependent (BOLD) signal and its dependence on baseline cerebral blood flow (CBF) were investigated by comparing responses to a visual stimulus after physiological changes of the baseline. Eight human subjects were imaged with 3 and 4 T MRI scanners, and both BOLD signal and CBF were simultaneously measured. Subjects viewed a flickering radial checkerboard in a block design experiment, alternating between eyes open or closed during the off periods. Compared to a baseline state with eyes open in a darkened room, substantial deactivation (average change: 2.9 ± 0.3% BOLD, 22 ± 2.1% CBF) in the occipital cortex was observed when the eyes were closed. The absolute response during stimulation (average change: 4.4 ± 0.4% BOLD, 36.3 ± 3.1% CBF) was independent of the preceding resting condition. We estimated the fractional change in CBF to be approximately 2.2 ± 0.15 times greater than the fractional change in metabolic rate of oxygen (CMRO 2). The changes in CBF and CMRO 2 were consistently linearly coupled during activation and deactivation with CBF changes being between approximately 60% and 150% compared to baseline with eyes open. Relative to an assumed baseline oxygen extraction fraction (OEF) of 40%, the estimated OEF decreased to 33 ± 1.4% during activation and increased to 46 ± 1.2% during rest with eyes closed. In conclusion, we found that simply closing the eyes creates a large physiological deactivation in the visual cortex, and provides a robust paradigm for studying baseline effects in fMRI. In addition, we propose a feed-forward model for neurovascular coupling which accounts for the changes in OEF seen following baseline changes, including both the current physiological perturbations as well as previously reported pharmacologically induced changes.