Advancing Neuroimaging in Nonhuman Primates

项目摘要 这项探索性R21的总体目标是为开发神经影像学建立原则证据， 意识清醒的猴子使用脑磁图（MEG）。我们将重点介绍MEG中的图像采集 环境，因为MEG默默地工作。这个发展项目是我们正在进行的 这项工作已经证明了在麻醉的猴子中获得MEG的可行性。我们最近报道说， 慢性乙醇（EtOH）自我管理显着改变了信号功率的多个带宽跨 在EtOH滥用的长尾猴模型中的脑（Rowland等人，2017年a）。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预测未来的饮酒表型， 功率谱分析发现，静息状态下的大脑活动也预示着未来的饮酒。早期接触 在3个月的EtOH诱导过程中使用EtOH（Grant等人，2008年）似乎主要影响正面 这些影响扩大到更多的尾部和皮层下区域，继续饮酒。这些研究 然而，在麻醉下进行，这可能使结果的解释复杂化， 难以将单独的EtOH效应与潜在的EtOH-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， 乙醇脑功能和功能网络，然后确定哪些大脑区域更容易受到 EtOH的早期影响。雌性黑长尾猴将在全意识状态下使用习惯化进行扫描 如本申请中所述的程序。当猴子习惯于有意识的想象时， 接受培训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将在整个研究期间收集DMS性能指标。 将在未使用EtOH、处于无任务状态以及随后在激活DMS性能期间对猴进行扫描。 在EtOH前状态下的基线MEG采集后，猴将开始使用孔- 表征的诱导程序，在此过程中，猴饮用递增剂量（0.5、1.0和1.5 g/kg）EtOH 每次给药30天。每30天完成后将重复MEG，以确定剂量- 和暴露时间（每次剂量30天）影响脑功能。这些猴子将被训练来表演 延迟匹配样本行为任务，以跟踪EtOH如何影响认知和运动功能，因为它涉及 大脑功能在每次MEG记录期间（EtOH初始状态和每次EtOH给药后），静息 状态脑功能将被记录，然后在任务执行期间进行采集。的首要目标 这个发展项目是将意识成像与行为任务的表现相结合， 我们目前的研究计划，以调查如何以及何时自愿饮酒影响功能 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.