In human brain, short-term physiological stimulation results in dramatic and proportional increase in blood flow and metabolic rate of glucose but minimal change in oxygen utilization, however, with continuing stimulation, we have observed that blood flow response diminishes and oxygen utilization increases. Given the temporal limitation of conventional methods to measure glucose metabolism in the human brain, we modified [(18)F]fluorodeoxyglucose (FDG) PET paradigm to evaluate the short-term and long-term effects of visual stimulation on human brain glucose metabolism. In the present study, seven healthy volunteers each underwent three dynamic FDG PET studies: at rest and after 1 min and 15 min of visual stimulation (using reversing black-white checkerboard) which continued for only 5 min after FDG injection. We found that increase in FDG uptake in the visual cortex was attenuated by 28% when preceded by 15 min of continuous visual stimulation (p<0.001). This decline in metabolism occurred in the absence of any behavior changes in task performance. The similarity in behavior of blood flow and glucose metabolism over time supports the hypothesis that, in activated brain, blood flow is modulated by changes in cytosolic free NADH/NAD(+) ratio related to increased glycolysis. Furthermore, the observed decline in glucose metabolism may reflect a shift from glycolytic to oxidative glucose metabolism with continued activation.