Effect of Caffeine on Functional and Perfusion MRI

描述（由申请人提供）：咖啡因是世界上使用最广泛的神经兴奋剂，有研究表明，79%的美国人至少偶尔喝咖啡。如此高的使用发生率是相当重要的，因为咖啡因可以调节多种生理成像指标。咖啡因的作用是由于腺苷受体的非选择性拮抗作用，不仅作为血管收缩剂，而且作为神经兴奋剂。有人提出，在BOLD研究中，咖啡因诱导的静息脑灌注减少将允许静息和活动状态之间的更大差异，从而增加信号的幅度。然而，众所周知，长期摄入咖啡因会导致腺苷受体的上调。因此，咖啡因作为BOLD信号增强剂的作用可能因神经和血管反应以及依赖于个体膳食咖啡因摄入量的受体数量差异而变得复杂。事实上，已经发现静息灌注减少会产生不同的影响，包括BOLD信号幅度的增加、减少或没有一致的变化。这些相互矛盾的结果很可能是由于之前的研究要么没有控制咖啡因的摄入，要么仅限于戒断状态。这个项目的长远目标是更深入地了解咖啡因和腺苷对大脑活动和血流的影响，以及这种影响如何调节大脑的生理成像测量。我们的主要假设是咖啡因通过两种机制调节神经活动引起的局部脑血流量的变化：1.)咖啡因通过阻断神经受体和增加神经活动间接增加血流量；2.)咖啡因通过阻断血管受体产生血管收缩直接减少血流量。

DESCRIPTION (provided by applicant): 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.