Caffeine is the most widely used neurostimulant in the world, and it has been shown that 79% of the population in the United States drinks coffee at least occasionally. This high incidence of use is of considerable significance because caffeine can modulate multiple physiological imaging measures. The effects of caffeine are due to the nonselective antagonism of adenosine receptors, acting not only as a vasoconstrictor but also as a neurostimulant. It has been proposed that the caffeine-induced decrease in resting cerebral perfusion will allow for a greater difference between resting and active states in a BOLD study, thus increasing the magnitude of the signal. However, it is well known that chronic caffeine use causes an upregulation of adenosine receptors. Thus, the administration of caffeine as a BOLD signal enhancer is likely complicated by neural and vascular responses and by differences in receptor numbers dependent on the individual's dietary caffeine consumption. In fact, resting perfusion decreases have been found to produce variable effects including both increases, decreases, or no consistent change in the BOLD signal amplitude. The conflicting results are likely due the fact that previous studies have either not controlled for caffeine consumption or have been limited to withdrawal states. The broad, long-term objective of this project is to gain a more thorough understanding of the effects of caffeine and adenosine on brain activity and blood flow, and how such effects modulate physiological brain imaging measures. Our primary hypothesis is that caffeine modulates neural activity-induced changes in regional cerebral blood flow through 2 mechanisms: 1.) caffeine indirectly increases blood flow by blocking neural receptors and increasing neural activity and 2.) caffeine directly decreases blood flow by producing vasoconstriction through the blockade of vascular receptors.
