Impact of Timing, Targeting, and Brain State on rTMS of Human and Non-Human Primates

刺激人脑的非侵入性方法为安全、有效的治疗提供了巨大的希望。 精神和运动障碍，被广泛用于人类行为和运动的基础研究 认知力。一种这样的方法，经颅磁刺激(TMS)是时变的应用 头皮上方的磁场会在大脑中产生瞬变电场。TMS明显刺激了 大脑并影响行为，但我们不知道它为什么起作用；它对大脑区域内神经活动的影响 而网络并不是在生物学层面上被理解的。这个项目试图确定效应的神经基础。 由脉冲序列中应用的TMS引起的，称为重复TMS(RTMS)，这是一种由 美国食品和药物管理局治疗抑郁症。利用我们在并发单点期间应用TMS方法方面的专业知识 非人灵长类的神经元记录技术和人类的成像和头皮电位技术 (fMRI和EEG)，我们的目标是解决rTMS设计和应用中的三个互锁问题：定时， 空间目标，以及与大脑状态的互动。在所有研究中，神经元对rTMS的反应将是 在人类和非人类灵长类动物执行视觉运动任务时被量化，这使得系统性 大脑活动和认知状态的操控。在这两个物种中，我们将专注于一种特定的运动选择 大脑区域，MT，以及与之相连的电路。首先，我们将确定定时对脉冲的影响 在rtms期间传递的序列。我们将系统地权衡频率和传输的脉冲数量 当人类和非人类灵长类动物执行任务时，大脑活动和行为表现 被监视着。将为两者建立rTMS时间参数的最终剂量-反应关系 物种。其次，我们将评估分布式网络空间目标的简单但原则性的方法。 基于白质连接的成像和rTMS诱导的神经激活的计算模型， 我们将研究TMS线圈的位置和方向如何不同地招募两条主要路径 从它发出的视觉系统的背侧和腹侧的流。三是抓好根本性攻坚 RTMS如何与大脑中的内源性活动相互作用的问题。通过操纵任务需求，我们将 系统地控制大脑状态，并量化这如何改变rTMS对神经活动和 认知表现。综上所述，该项目将产生一个多尺度数据集，将来自非 通过人类灵长类动物到人类的实验，应该能很好地推广到对其他大脑的研究 大脑皮层回路。这些结果将有助于将rTMS从依赖于试错测试的方法向前推进 朝着一个建立在明确的生物学原则上的方向发展。

Non-invasive methods for stimulating the human brain show great promise for safe, effective treatments of psychiatric and motor disorders, and are in widespread use for basic research on human behavior and cognition. One such method, transcranial magnetic stimulation (TMS), is the application of time-varying magnetic fields above the scalp that induce transient electrical fields in the brain. TMS clearly stimulates the brain and affects behavior, but we do not know why it works; its effects on neural activity within brain regions and networks are not understood at a biological level. This project seeks to determine the neural basis of effects caused by TMS as applied in sequences of pulses, known as repetitive TMS (rTMS), a technique approved by the FDA for depression. Leveraging our expertise in application of TMS methodology during concurrent single neuron recording techniques in non-human primates and imaging and scalp potential techniques in humans (fMRI and EEG), we aim to resolve three interlocking problems in the design and application of rTMS: timing, spatial targeting, and interactions with brain state. In all studies, neuronal responses to rTMS will be quantified in human and non-human primates as they perform a visual motion task that allows systematic manipulation of brain activity and cognitive state. In both species, we will focus on a specific motion-selective brain area, MT, and the circuits that connect with it. First, we will determine the effects of timing on the pulse sequences delivered during rTMS. We will systematically trade off frequency with number of pulses delivered as human and non-human primates perform the task and brain activity and behavioral performance are monitored. Definitive dose-response relationships for rTMS temporal parameters will be established for both species. Second, we will assess simple but principled methods for spatial targeting of distributed networks. Based on imaging of white-matter connectivity and computational models of rTMS-induced neural activation, we will examine how location and orientation of the TMS coil differentially recruits two major pathways that emanate from it, the dorsal and ventral streams of the visual system. Third, we will tackle the fundamental question of how rTMS interacts with endogenous activity in the brain. By manipulating task demands, we will systematically control brain state and quantify how this alters the influence of rTMS on neural activity and cognitive performance. Taken together, this project will yield a multi-scale data set that links results from non- human primates to humans through experiments that should generalize well to the study of other cerebral cortical circuits. The results will help to advance rTMS from a method that relies on trial-and-error testing toward one that is founded on clear biological principles.