fMRI Technique Development for Substance Abuse Research

描述：(申请人提供) 这是一项为期5年的资助申请，通过“指导性量化 研究事业奖“(K25)机制。申请人，a 生物物理学家/电气工程师，提出了一项培训计划 神经科学和药理学。申请者的长期目标是成为 独立和跨学科的调查员，熟练应用 核磁共振方法用于物质滥用研究的研究。这个 该奖项的研究部分将开发和改进功能磁学 磁共振成像(FMRI)技术用于研究药物滥用和 人类受试者的毒瘾。这些技术将被应用于研究 可卡因对人类的影响。可卡因滥用是一个严重的公共问题 有重要的精神、医疗和药物滥用政策的健康问题 这意味着什么。急性注射可卡因改变中枢神经系统 (中枢神经系统)神经元活动和脑血流量；长期使用可卡因可以 导致长期的神经元和行为变化，以及 脑血管功能。功能磁共振成像使用血氧变化来估计 神经元活动，时间分辨率为几秒，空间分辨率为 分辨率只有几毫米。然而，信噪比(SNR)和 时间分辨率限制对当前可以 在活体内进行测量。提出了三种不同的技术开发努力。 首先，相控阵回波平面成像系统，优化研究 可能调节可卡因奖赏效应的大脑区域将是 在4特斯拉磁共振扫描仪上实现。这一系统将显著增加 FMRI的信噪比，并允许检测可卡因诱导的脑组织改变 大鼠腹侧纹状体、丘脑和后部新皮质神经元活动 个别受试者。二是一种快速同步考核的方法 由蓝光和红光引起的相对大胆的激活将是 具有至少一次多色测量的时间分辨率 确定可卡因对颜色视觉影响之间的关系的分钟数 处理(多巴胺能改变的代用品)和其他大脑中的激活 地区。第三，将进行一系列实验研究，以确定 脑电α活动(脑电替代标记物)之间的关系 药物诱导的欣快感)和大胆的光反应。这项研究可能有助于 用于评估EEGα活性的磁共振方法的发展， 客观地衡量了各种药物的催眠效果。这个 这项研究的长期目标是更好地了解 让可卡因滥用现象得到更好的预防和治疗策略 可以被开发和评估。

DESCRIPTION: (provided by applicant) This is a request for 5 years of funding through the "Mentored Quantitative Research Career Award" (K25) mechanism. The applicant, a biophysicist/electrical engineer, proposes a program of training in neuroscience and pharmacology. The long term goal of the applicant is to become an independent and interdisciplinary investigator, skilled in the application of magnetic resonance methods for the study of substance abuse research. The research component of this award will develop and improve functional magnetic resonance imaging (fMRI) techniques for the study of substance abuse and addiction in human subjects. These techniques will be applied to study the effects of cocaine administration in humans. Cocaine abuse is a serious public health problem having important psychiatric, medical, and drug abuse policy implications. Acute administration of cocaine alters central nervous system (CNS) neuronal activity and cerebral blood flow; chronic use of cocaine can lead to long term neuronal and behavioral changes, as well as to alterations in cerebral vascular function. fMRI uses blood oxygenation changes to estimate neuronal activity, with a temporal resolution of several seconds and spatial resolution of a few millimeters. However, signal to noise ratio (SNR) and temporal resolution limits put constraints on the parameters that can currently be measured in vivo. Three separate technical development efforts are proposed. First, a phased array echoplanar imaging system, optimized for the study of brain regions which may mediate the rewarding effects of cocaine, will be implemented on a 4 Tesla MR scanner. This system will significantly increase the SNR of fMRI, and allow the detection of cocaine-induced alterations in neuronal activity in ventral striatum, thalamus, and posterior neocortex in individual subjects. Second, a method for rapidly and simultaneously assessing the relative BOLD activation resulting from blue and red light will be developed with a time resolution of at least one multicolor measurement per minute to determine the relationship between cocaine's effects on color visual processing (a proxy for dopaminergic alterations) and activation in other brain regions. Third, a set of experimental studies will be conducted to determine the relationship between EEG alpha activity (a surrogate marker for drug-induced euphoria) and the BOLD photic response. This study may aid in the development of magnetic resonance methods for assessing EEG alpha activity, giving an objective measure of the euphorigenic effects of various drugs. The long term goals of this research are to provide a better understanding of the phenomenon of cocaine abuse so that better prevention and treatment strategies can be developed and evaluated.