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.

项目摘要 非侵入性神经成像程序为我们对我们如何理解的理解提供了工具见解 长期暴露于乙醇会影响大脑的结构和功能。通过比较大脑宏观 酗酒和年龄匹配的对照中的结构，可以检测脑组织的变化 体积及其对酒精禁欲后的恢复。扩散张量成像（DTI）实验具有 提供了有关由慢性暴露引起的白质微观结构中细胞级变化的信息 到乙醇，通常是在出现宏观变化之前。除了这些结构性变化之外， 还可以表征功能MRI中与大脑功能相关的生理变化 实验。但是，在所有这些神经影像学方法中，一致的系统混杂因素 困扰发现的生物学解释。首先，无法准确量化乙醇暴露， 从饮酒开始，在人类受试者中。其次，混淆因素，例如使用多药物， 营养，提取频率和其他环境侮辱很难与 大脑结构和功能上的乙醇暴露。第三，功能神经影像的解释 实验可能很难根据神经功能进行，例如使用传统的 神经生理方法。为了解决这些知识的这些缺陷，我们提出了翻译 神经影像学核心以对俄勒冈州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青睐的MRI设施。这些实验已经 旨在直接支持INIA-S和INIA-N-N联盟中的项目。目的1是提供数据 Buttress Inia-S项目8，其中糖皮质激素拮抗剂将用于非人类灵长类动物 研究对象以及与由此产生的变化相关的静止状态功能MRI变化 将确定饮酒方式。 AIM 2是支持A. Pfefferbaum提出的INIA-N项目。 Sullivan和N. Zahr，其中大脑结构和功能变化与重复发作相关 戒酒和饮酒将在恒河猕猴中确定，以桥接啮齿动物和人类获得的数据 物种。 AIM 3是支持INIA-S项目7，使用功能性MRI直接监测脑电路的变化 通过专门由设计师药物（Dreadds）激活的设计器受体的影响。 纹状体，并表征可怕的神经活动变化对功能的影响 连通性测量。最后，在对照动物的一部分中，将进行定量比较 在MRI确定的功能连接性与用焦点红外神经评估的连接性之间 刺激已知对先前暴露于乙醇敏感的区域，目的是评估 静止状态fMRI实验的共同解释的有效性。