Advancing Neuroimaging in Nonhuman Primates

推进非人类灵长类动物的神经影像学

基本信息

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
项目类别：
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

项目摘要

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。由于 MEG 默默运行，因此该开发项目是我们正在进行的项目的逻辑延伸。我们最近报道了这一工作，证明了在麻醉猴子中获取 MEG 的可行性。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早期饮酒情况。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这些研究表明，随着持续饮酒，这些影响会扩展到更多的尾部和皮质下区域。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。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雌性黑长尾猴的早期影响将在完全清醒的状态下使用习惯进行扫描。虽然猴子已经习惯了有意识的成像，但它们仍将是本申请中概述的程序。接受训练以执行延迟匹配样本 (DMS) 行为任务，作为 EtOH 的行为测量在整个研究过程中将收集对认知和运动功能的影响。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 30 天，在每个 30 天周期完成后重复 MEG，以确定如何剂量。暴露时间（每次剂量 30 天）会影响大脑功能。猴子将接受训练以执行以下操作。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，因为它与在每次 MEG 记录期间（乙醇初始状态和每次服用乙醇后），休息。大脑功能状态将被记录，然后在任务执行过程中获取。这个联合开发项目旨在通过行为任务的表现来扩展意识成像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。