Model of blood-brain transfer of oxygen explains nonlinear flow-metabolism coupling during stimulation of visual cortex

Abstract

The coupling between cerebral metabolic rate of oxygen (CMRO2) and blood flow (CBF) in response to visual stimulation was evaluated by means of a model of oxygen delivery. The model predicted a nonlinear relationship between stimulus-evoked changes of oxygen consumption and blood flow. The magnitude of the CMRO2/CBF ratio index (IO2) was used to indicate the degree of flow-metabolism coupling prevailing in specific areas of the brain during physiological stimulation. Therefore, the index provided a measure of the blood oxygenation level dependent (BOLD) magnetic resonance contrast. To evaluate the changes of IO2 in response to visual stimulation, the model was applied to the effect of a changing flicker rate of a visual stimulus on the magnitudes of CBF, CMRO2, and oxygen diffusion capacity, in the human brain. Positron emission tomography (PET) was used to measure the CBF and the CMRO2 in 12 healthy volunteers who viewed a cross-hair (baseline) or a yellow-blue annular checkerboard reversing at frequencies of 1, 4, or 8 Hz. The magnitude of CBF in the primary visual cortex increased as a function of the checkerboard reversal rate and reached a maximum at the frequency of 8 Hz (z=16.0), while the magnitude of CMRO2 reached a maximum at 4 Hz (z=4.0). Therefore, the calculated IO2 was lower at 8 Hz than at 1 and 4 Hz, in contrast to the oxidative metabolic rate that reached its maximum at 4 Hz. The model explained the increase of oxygen consumption as the combined effect of increased blood flow and increased oxygen diffusion capacity in the region of visual activation.