Core 3: Translational Neuroimaging Core

核心 3：转化神经影像核心

• 批准号: 10090538
• 负责人: Christopher D Kroenke
• 金额: $ 16.07万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-15 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10090538
• 关键词: Abstinence; Address; Affect; Age; Alcohol abuse; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Anatomy; Animals; Appearance; Area; Autopsy; Biological; Brain; Chronic; Control Animal; Corpus striatum structure; Data; Data Analyses; Diffusion Magnetic Resonance Imaging; Ethanol; Ethics; Frequencies; Functional Magnetic Resonance Imaging; Glucocorticoids; Goals; Grant; Human; Knowledge; Ligands; Link; Logistics; Macaca mulatta; Magnetic Resonance Imaging; Measurement; Measures; Methods; Monitor; Monkeys; Motor; Nature; Neurobiology; Neurons; Neurophysiology - biologic function; Oregon; Pattern; Pharmaceutical Preparations; Physiological; Plague; Primates; Procedures; Recovery; Research; Research Personnel; Research Subjects; Rest; Rodent; Self Administration; Series; Signal Transduction; Stress; Structure; Techniques; Translating; Validation; Withdrawal; alcohol abstinence; alcohol effect; alcohol exposure; alcohol use initiation; blood oxygen level dependent; brain circuitry; brain health; brain tissue; cohort; data acquisition; design; designer receptors exclusively activated by designer drugs; drinking; drinking behavior; experimental study; flexibility; human subject; in vivo; indexing; insight; multiple drug use; neural stimulation; neuroimaging; neuromechanism; neurophysiology; nonhuman primate; nutrition; problem drinker; putamen; receptor; relating to nervous system; response; tool; white matter

Project Summary Non-invasive neuroimaging procedures have provided instrumental insights into our understanding of how chronic exposure to ethanol can affect brain structure and function. Through comparisons of brain macroscopic structure in alcoholics and age-matched controls, it has been possible to detect changes in brain tissue volume, and its recovery following abstinence from alcohol. Diffusion tensor imaging (DTI) experiments have provided information on cellular-level changes in white matter microstructure that result from chronic exposure to ethanol, often prior to the appearance of macroscopic changes. In addition to these structural changes, it has also been possible to characterize physiological changes associated with brain function in functional MRI experiments. However, in all of these neuroimaging approaches, consistent systematic confounding factors plague the biological interpretations of findings. First, it is not possible to accurately quantify ethanol exposure, beginning at the initiation of drinking, in human subjects. Second, confounding factors such as polydrug use, nutrition, frequency of withdrawals, and other environmental insults are difficult to discern from the effects of ethanol exposure on brain structure and function. Third, the interpretation of functional neuroimaging experiments can be difficult to cast in terms of neural function, e.g., as measured using traditional neurophysiological methods. In order to address these deficits in knowledge, we propose a Translational Neuroimaging Core to perform MRI experiments on nonhuman primate research subjects at the Oregon National Primate Research Center's nonhuman-primate-dedicated MRI facility. These experiments have been designed to directly support projects in the INIA-S as well as the INIA-N consortia. Aim 1 is to provide data to buttress INIA-S project 8, in which glucocorticoid antagonists will be administered to nonhuman primate research subjects, and the resting-state functional MRI changes associated with the resulting changes in drinking patterns will be determined. Aim 2 is to support an INIA-N project proposed by A. Pfefferbaum, E. Sullivan, and N. Zahr, in which brain structural and functional changes associated with repeated episodes of abstinence and drinking will be determined in rhesus macaques to bridge data acquired in rodent and human species. Aim 3 is to support INIA-S project 7, to use functional MRI to directly monitor changes in brain circuitry induced through the influence of designer receptors exclusively activated by designer drugs (DREADDs) in the striatum, and to characterize the effects of DREADDs-induced neural activity changes on functional connectivity measurements. Last, in a subset of control animals, quantitative comparisons will be performed between MRI-determined functional connectivity and connectivity assessed with focal infrared neural stimulation of regions known to be sensitive to previous exposure to ethanol, with the goal of assessing the validity of common interpretations of resting-state fMRI experiments.

项目概要 非侵入性神经影像学程序为我们理解如何 长期接触乙醇会影响大脑结构和功能。通过大脑宏观比较 通过研究酗酒者和年龄匹配的对照组的结构，可以检测到脑组织的变化 体积及其在戒酒后的恢复。扩散张量成像（DTI）实验 提供了长期暴露导致的白质微结构细胞水平变化的信息 乙醇，通常在宏观变化出现之前。除了这些结构性变化外， 还可以在功能性 MRI 中表征与大脑功能相关的生理变化 实验。然而，在所有这些神经影像学方法中，一致的系统混杂因素 困扰着研究结果的生物学解释。首先，不可能准确量化乙醇暴露， 从人类受试者开始饮酒时开始。其次，混杂因素，例如多种药物的使用、 营养、戒断频率和其他环境损害很难从影响中辨别出来。 乙醇暴露对大脑结构和功能的影响。三、功能神经影像解读 就神经功能而言，实验可能很难进行预测，例如，使用传统方法测量的 神经生理学方法。为了解决这些知识缺陷，我们提出了一个转化 神经影像核心将在俄勒冈州对非人类灵长类动物研究对象进行 MRI 实验 国家灵长类动物研究中心的非人类灵长类动物专用 MRI 设施。这些实验已 旨在直接支持 INIA-S 以及 INIA-N 联盟的项目。目标 1 是提供数据 支持 INIA-S 项目 8，其中将给非人类灵长类动物施用糖皮质激素拮抗剂 研究对象，以及与由此产生的变化相关的静息态功能 MRI 变化 饮酒方式将被确定。目标 2 是支持 A. Pfefferbaum、E. 提出的 INIA-N 项目。 Sullivan 和 N. Zahr，其中大脑结构和功能的变化与反复发作有关 将确定恒河猴的禁欲和饮酒情况，以将啮齿动物和人类获得的数据联系起来 物种。目标3是支持INIA-S项目7，利用功能性MRI直接监测大脑回路的变化 通过专门由设计药物（DREADD）激活的设计受体的影响而诱导 纹状体，并表征 DREADD 诱导的神经活动变化对功能的影响 连接测量。最后，在对照动物的子集中，将进行定量比较 MRI 确定的功能连接与通过聚焦红外神经评估的连接之间的关系 刺激已知对先前接触乙醇敏感的区域，目的是评估 静息态功能磁共振成像实验的常见解释的有效性。