Advancing Neuroimaging in Nonhuman Primates

项目总结 这个探索性的R21的总体目标是建立开发神经成像的原则证据 意识清醒的猴子使用脑磁图(MEG)。我们将专注于脑磁图中的图像采集 环境，因为脑磁图是静默运行的。这个开发项目是我们正在进行的 这项工作已经证明了在麻醉猴子身上获得MEG的可行性。我们最近报道说 慢性乙醇(Etoh)自我给药显著改变了 酒精滥用的马鞭猴模型中的大脑(Rowland等人，2017a)。最近的脑磁图数据表明 基线、暴露前功能网络的丰富俱乐部特征预测未来饮酒表型和 功率谱分析发现，静息状态的大脑活动也预示着未来的饮酒。早期接触 在为期3个月的无水乙醇诱导过程中(Grant等人，2008年)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，他们是在麻醉下进行的，这可能会使结果的解释复杂化，使 很难将乙醇单独作用与潜在的乙醇-麻醉相互作用分开。我们建议 比较全意识猴子的脑活动和功能连接，以表征基线、预 酒精的大脑功能和功能网络，然后确定大脑的哪些区域更容易受到 乙醇的早期效应。雌性黑猩猩将在全意识状态下使用习惯化进行扫描 本申请书中概述的程序。虽然猴子习惯于有意识的想象，但它们将 接受培训以执行延迟匹配到样本(DMS)行为任务，作为Etoh的行为测量 对认知和运动功能的影响。将在整个研究过程中收集DMS绩效衡量标准。 猴子将在Etoh幼稚、无任务状态和活动DMS执行期间进行扫描。 在酒精前状态下获得基线脑磁图后，猴子将开始使用井-水饮用酒精- 表征了猴子饮用递增剂量(0.5、1.0和1.5g/kg)乙醇的诱导过程 每次剂量30天。脑磁图将在每个30天周期结束后重复，以确定如何剂量- 以及暴露时间(每次30天)会影响大脑功能。这些猴子将接受训练，以执行一项 延迟匹配以采样行为任务，以跟踪乙醇如何影响认知和运动功能 大脑功能。在每一次脑磁图记录期间(无水乙醇状态和每次无水乙醇后)，休息 状态脑功能将被记录下来，然后在任务执行期间进行获取。的首要目标是 这个开发项目是将意识成像与行为任务的表现结合在一起 我们目前的研究项目是调查自愿饮酒如何以及何时影响功能 猴子的大脑网络。

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.