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显示出安全、有效的治疗脑缺血的巨大希望。 精神和运动障碍，并广泛用于人类行为的基础研究， 认知.一种这样的方法，即经颅磁刺激（TMS），是应用时变磁刺激。 头皮上方的磁场在大脑中产生瞬时电场。TMS明显刺激了 大脑和影响行为，但我们不知道为什么它的工作;它对大脑区域内的神经活动的影响 网络在生物学层面上是不被理解的。该项目旨在确定影响的神经基础 在脉冲序列中应用TMS引起的，称为重复TMS（rTMS），这是一种由 FDA的抑郁症。利用我们在TMS方法应用方面的专业知识， 非人类灵长类动物的神经元记录技术和人类的成像和头皮电位技术 (fMRI和脑电图），我们的目标是解决三个联锁问题的设计和应用的rTMS：时间， 空间定位以及与大脑状态的相互作用。在所有的研究中，神经元对rTMS的反应将是 在人类和非人类灵长类动物中，当它们执行视觉运动任务时， 操纵大脑活动和认知状态。在这两个物种中，我们将重点关注一种特定的运动选择性 首先，我们将确定时间对脉搏的影响， 在rTMS期间递送的序列。我们将系统地权衡频率与脉冲数的传递 当人类和非人类灵长类动物执行任务时， 监测。将为两者建立rTMS时间参数的确定剂量-反应关系 物种其次，我们将评估简单但有原则的分布式网络空间定位方法。 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募集两个主要途径， 视觉系统的背侧流和腹侧流。第三，我们将从根本上解决 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对神经活动的影响， 认知绩效总之，这个项目将产生一个多尺度的数据集，从非 人类灵长类动物对人类的研究，通过实验，应该推广到其他大脑的研究， 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中发展出来 一个建立在明确的生物学原理上的系统。

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.