Effect of Caffeine on Functional and Perfusion MRI

描述(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，美国79%的人口至少偶尔喝咖啡。咖啡因的高使用率具有相当重要的意义，因为咖啡因可以调节多种生理成像措施。咖啡因的作用是由于腺苷受体的非选择性拮抗作用，腺苷受体不仅起到血管收缩的作用，还起到神经刺激剂的作用。一项大胆的研究提出，咖啡因导致的静息脑灌注减少将导致静息状态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，长期使用咖啡因会导致腺苷受体上调。因此，作为一种大胆的信号增强剂，咖啡因的服用可能会因神经和血管反应以及依赖于个人饮食咖啡因摄入量的受体数量的差异而变得复杂。事实上，已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可能是因为之前的研究要么没有控制咖啡因的摄入量，要么只限于戒断状态。该项目的广泛、长期目标是更彻底地了解咖啡因和腺苷对大脑活动和血液流动的影响，以及这些影响如何调节生理脑成像指标。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感受器和增加神经活动间接增加血流量。咖啡因通过阻断血管受体产生血管收缩，从而直接减少血液流量。

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.