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

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.