Advancing Neuroimaging in Nonhuman Primates

推进非人类灵长类动物的神经影像学

• 批准号: 9978306
• 负责人: JAMES B DAUNAIS
• 金额: $ 21.23万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-15 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978306
• 关键词: Address; Affect; Alcohol abuse; Alcohol consumption; Anatomy; Anesthesia procedures; Animals; Applications Grants; Area; Attention; Behavioral; Brain; Brain region; Cercopithecus tantalus; Characteristics; Chronic; Clinical; Cognition; Cognitive; Conscious; Controlled Study; Data; Development; Disease model; Dose; Environment; Ethanol; Female; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Future; Goals; Grant; Hippocampus (Brain); Human; Image; Magnetoencephalography; Maps; Measures; Methods; Modeling; Monkeys; Morphologic artifacts; Motor; Movement; Performance; Phenotype; Prefrontal Cortex; Procedures; Reporting; Research; Rest; Sampling; Scanning; Self Administration; Signal Transduction; Task Performances; Time; Training; Work; alcohol effect; alcohol exposure; animal imaging; awake; base; behavior measurement; brain behavior; chronic alcohol ingestion; drinking; frontal eye fields; habituation; human disease; human imaging; human model; imaging study; information processing; insight; neuroimaging; nonhuman primate; programs; tool

PROJECT SUMMARY The overall objective of this exploratory R21 is to establish proof of principle for developing neuroimaging in conscious monkeys using magnetoencephalography (MEG). We will focus on image acquisition in the MEG environment since the MEG operates silently. This developmental project is a logical extension of our ongoing work, which has proven the feasibility of acquiring MEG in anesthetized monkeys. We recently reported that chronic ethanol (EtOH) self-administration significantly altered signal power of multiple bandwidths across the brain in a vervet monkey model of EtOH abuse (Rowland et al., 2017a). More recent MEG data suggest that Rich Club characteristics of baseline, pre-exposure functional networks predict future drinking phenotypes and power spectral analyses found that resting state brain activity also predicts future drinking. Early exposure to EtOH during a 3-month EtOH induction procedure (Grant et al., 2008) appears to affect predominantly frontal regions and these effects expand to more caudal and subcortical areas with continued drinking. These studies however were conducted under anesthesia, which can complicate interpretation of the results, making it difficult to disentangle the effects of EtOH alone from potential EtOH-anesthesia interactions. We propose to compare brain activity and functional connectivity in fully conscious monkeys to characterize baseline, pre- ethanol brain function and functional networks and then to identify which brain regions are more vulnerable to the early effects of EtOH. Female vervet monkeys will be scanned in the fully conscious state using habituation procedures as outlined in this application. While the monkeys are habituated to conscious imaging, they will be trained to perform a delayed-match-to-sample (DMS) behavioral task as a behavioral measure of EtOH's effects on cognition and motor function. DMS performance measures will be collected throughout the study. Monkeys will be scanned while EtOH naïve, in the task-free state and then during active DMS performance. After baseline MEG acquisition in the pre-EtOH state, the monkeys will begin to drink EtOH using a well- characterized induction procedure during which monkeys drink escalating doses (0.5, 1.0 and 1.5 g/kg) EtOH for 30 days at each dose. MEG will be repeated after completion of each 30 day epoch to determine how dose- and time of exposure (30 days at each dose) affect brain function. The monkeys will be trained to perform a delayed match to sample behavioral task to track how EtOH affects cognitive and motor function as it relates to brain function. During each MEG recording session (EtOH naïve state and after each dose of EtOH), resting state brain function will be recorded followed by acquisition during task performance. The overarching goal of this developmental project is to extend conscious imaging combined with performance on behavioral tasks in our current research program to investigate how and when voluntary alcohol consumption affects functional brain networks in monkeys.

项目概要 该探索性 R21 的总体目标是建立在以下领域开发神经影像学的原理证明： 使用脑磁图（MEG）观察有意识的猴子。我们将重点关注 MEG 中的图像采集 环境，因为 MEG 运行无声。这个开发项目是我们正在进行的项目的逻辑延伸 工作，证明了在麻醉猴子中获取 MEG 的可行性。我们最近报道说 慢性乙醇（EtOH）自我给药显着改变了多个带宽的信号功率 滥用乙醇的黑长尾猴模型中的大脑（Rowland 等人，2017a）。最近的 MEG 数据表明 基线、暴露前功能网络的丰富俱乐部特征可预测未来的饮酒表型和 功率谱分析发现，静息状态下的大脑活动也可以预测未来的饮酒情况。早期接触 在为期 3 个月的乙醇诱导程序中（Grant 等，2008），乙醇似乎主要影响额叶 随着持续饮酒，这些影响会扩大到更多的尾部和皮质下区域。这些研究 然而，这是在麻醉下进行的，这可能会使结果的解释变得复杂，使其 很难将单独使用乙醇的影响与潜在的乙醇-麻醉相互作用分开。我们建议 比较完全清醒的猴子的大脑活动和功能连接，以表征基线、预 乙醇大脑功能和功能网络，然后确定哪些大脑区域更容易受到影响 乙醇的早期影响。雌性黑长尾猴将在完全清醒的状态下使用习惯进行扫描 本申请中概述的程序。虽然猴子已经习惯了有意识的成像，但它们会 接受训练以执行延迟匹配样本 (DMS) 行为任务，作为 EtOH 的行为测量 对认知和运动功能的影响。 DMS 绩效指标将在整个研究过程中收集。 猴子将在 EtOH 天真的状态下、无任务状态下以及活跃的 DMS 性能期间进行扫描。 在乙醇前状态下获取基线 MEG 后，猴子将开始使用良好的饮水器饮用乙醇。 特征性诱导程序，在此过程中猴子饮用逐渐增加剂量（0.5、1.0 和 1.5 g/kg）的 EtOH 每次剂量持续 30 天。每 30 天的时期完成后将重复 MEG 以确定剂量- 暴露时间（每次剂量 30 天）会影响大脑功能。这些猴子将被训练来表演 延迟匹配样本行为任务，以跟踪乙醇如何影响认知和运动功能，因为它与 大脑功能。在每次 MEG 记录期间（EtOH 初始状态和每次 EtOH 剂量后），休息 大脑功能状态将被记录，然后在任务执行过程中获取。总体目标是 这个开发项目旨在扩展意识成像与行为任务的表现相结合 我们目前的研究计划旨在调查自愿饮酒如何以及何时影响功能 猴子的大脑网络。