Blood flow and oxygen delivery to human brain during functional activity: Theoretical modeling and experimental data

Coupling of cerebral blood flow (CBF) and cerebral metabolic rate for oxyge n (CMRO2) in physiologically activated brain states remains the subject of debates. Recently it was suggested that CBF is tightly coupled to oxidative metabolism in a nonlinear fashion. As part of this hypothesis, mathematica l models of oxygen delivery to the brain have been described in which dispr oportionately large increases in CBF are necessary to sustain even small in creases in CMRO2 during activation. We have explored the coupling of CBF an d oxygen delivery by using two complementary methods. First, a more complex mathematical model was tested that differs from those recently described i n that no assumptions were made regarding tissue oxygen level, Second, [O-1 5] water CBF positron emission tomography (PET) studies in nine healthy sub jects were conducted during states of visual activation and hypoxia to exam ine the relationship of CBF and oxygen delivery. In contrast to previous re ports, our model showed adequate tissue levels of oxygen could be maintaine d without the need for increased CBF or oxygen delivery. Similarly, the PET studies demonstrated that the regional increase in CBF during visual activ ation was not affected by hypoxia. These findings strongly indicate that th e increase in CBF associated with physiological activation is regulated by factors other than local requirements in oxygen.