FMRI STUDY OF CNS PHYSIOLOGY DURING COCAINE RESPONSE

描述（申请人摘要）： 这项提案，“脑卒中期间生理耦合的功能磁共振成像研究 响应”，是为了响应NIDA计划宣布， 指导研究科学家发展奖（K 01）。 候选人寻求 接受药物滥用神经生物学方面的培训， 这项研究增强了我们对可卡因引起的大脑变化的理解 生理学和功能磁共振成像信号的解释方面的这些变化。 凭借其独特的高空间和时间分辨率组合， 通过磁共振成像（fMRI）进行的功能性脑成像具有很大的 有助于我们理解药物的神经生物学 成瘾 急性药物研究的早期fMRI经验表明， 只有T2* 变体的fMRI血氧水平依赖（BOLD） 信号和CBV加权信号-具有检测的功能灵敏度 个体中由于药物刺激引起的小脑区域的局灶性激活 科目 BOLD信号和CBV的不确定解释， 血流灌注是代谢的最佳血流动力学预测因子， 重大问题。 本提案涉及多步骤链接的一部分 神经元活动和功能磁共振成像信号之间的关系-功能磁共振成像 信号和潜在的代谢和血液动力学改变， 可卡因的管理。 拟议研究的目标是 分别测量fMRI可观察值的基本集合- CBF，CBV，BOLD信号， 和CMR 02-在大鼠模型中对可卡因的功能反应期间，以及 确定每个量与葡萄糖代谢的关系。 基本假设是脑血流动力学和代谢 对精神活性药物的改变以可识别的方式耦合，并且 BOLD信号的测量-这些变量的复杂组合， 是目前人类功能磁共振成像的首选工具-可以可靠地与 灌注和葡萄糖代谢的变化。 将进行测量 在两种大鼠模型中：1）用氟烷麻醉的幼稚大鼠， 急性可卡因中毒后局部葡萄糖代谢增加 给药与清醒的未处理大鼠中的类似测量相关， 2)长期暴露于可卡因的大鼠，这是一种预期表现出 改变了生理机能 这些研究试图验证生理基础 研究精神活性药物在脑内作用的一种有前途的新技术 并增加我们对可卡因神经生物学的理解。

DESCRIPTION (Applicant's Abstract): This proposal, "fMRI Study of Physiological Couplings During Cocaine Response", is submitted in response to the NIDA program anouncement for Mentored Research Scientist Development Awards (K01). The Candidate seeks to gain training in the neurobiology of drug abuse while contributing research that enhances our understanding of cocaine-induced changes in brain physiology and the interpretation of fMRI signal in terms of those changes. With its unique combination of high spatial and temporal resolution, functional brainmapping by magnetic resonance imaging (fMRI) has great potential to contribute to our understanding of the neurobiology of drug addiction. The early fMRI experience in acute drug studies suggests that only the T2* variants of fMRI blood oxygenation level dependent (BOLD) signal and CBV-weighted signal - have the functional sensitivity to detect focal activation in small brain regions due to drug stimuli in individual subjects. The uncertain interpretation of BOLD signal and CBV in terms of perfusion, the best hemodynamic predictor of metabolism, remains a significant issue. This proposal addresses one part of the multi-step link between neuronal activity and fMRI signal - the relationship between fMRI signal and underlying metabolic and hemodynamic alterations due to administration of cocaine. The goal of the proposed research is to separately measure the base set of fMRI observables - CBF, CBV, BOLD signal, and CMR02 - during a functional response to cocaine in a rat model, and to determine the relationships that couple each quantity to glucose metabolism. The fundamental hypothesis is that cerebral hemodynamic and metabolic alterations to a psychoactive drug are coupled in identifiable ways, and measurements of BOLD signal - a complex combination of these variables which is currently the fMRI tool of choice in humans- can be reliably related to changes in perfusion and glucose metabolism. Measurements will be performed in two rat models: 1) naive rats anesthetized by halothane, a model in which regional increases in glucose metabolism following acute cocaine administration correlate with similar measurements in awake, naive rats, and 2) rats chronically exposed to cocaine, a model which is expected to exhibit altered physiology. These studies seek to validate the physiological basis of a promising new technology for study of psychoactive drug action in brain and to increase our understanding of the neurobiology of cocaine.