Investigating the Effects of Transcranial Magnetic Stimulation with Intracranial EEG in Humans

项目总结/摘要 经颅磁刺激（TMS）是一种非侵入性的局部刺激大脑的方法， 电磁感应，不需要手术。人们乐观地认为，TMS将彻底改变我们如何 治疗神经和精神疾病，证明了超过1000临床试验注册使用TMS。多 这种乐观情绪的一部分源于经颅磁刺激治疗抑郁症的成功应用。尽管有大批 使用TMS的临床试验数量的治疗适应症的数量一直停滞不前，仅限于主要 抑郁症和最近的强迫症。有一些基本的问题 TMS的潜在作用机制，这对于理解以推进这种治疗至关重要 模态在这里，我们提出了一个独特的神经病学和神经外科之间的合作项目， 这是了解TMS如何影响人类大脑的前所未有的窗口。具体来说，我们将执行 TMS在神经外科患者颅内脑电图（iEEG）监测中的真实的记录时间 TMS对局部和远程大脑区域的影响具有无与伦比的空间和时间组合 相对于其他人类研究的分辨率。我们已经使用一个 基于凝胶的体模脑，并有来自七名患者的结果，证明了安全性和初步结果。 对于目前的建议，我们的目标是：1）表征TMS对人脑的反应，如从 活动和假手术条件之间的iEEG，以及2）由 TMS用于测量静息状态下评估的刺激和记录部位之间的脑连接 功能连接性MRI（rs-fcMRI）。这将使我们能够评估TMS诱发的 iEEG反应和回归模型中刺激部位的功能连接强度。我们 假设：1）TMS将具有从刺激下的表面电极检测到的焦点效应 站点以及在远程站点检测到的网络级参与，2）重复TMS将导致频率- 在0.5和10 Hz刺激方案之间不同的特定效果，以及3）重复性的幅度 跨电极的TMS诱发的iEEG响应将与刺激之间的rs-fcMRI的强度相关。 和记录网站。通过研究高时空分辨率TMS的电生理反应， 这项研究将为TMS对靶细胞的影响提供新的机制见解， 并将这些发现与已经广泛使用的成像方法联系起来。此外，TMS将 通过在用于以下的方案中靶向左背外侧前额叶皮质，以具有临床意义的方式应用 治疗抑郁症为这些目标产生结果将是促进我们理解TMS如何 利用大脑网络，可以合理地开发个性化的， 经颅磁刺激治疗抑郁症和其他疾病

PROJECT SUMMARY / ABSTRACT Transcranial magnetic stimulation (TMS) is a noninvasive method of focally stimulating the brain that uses electromagnetic induction and does not require surgery. There is optimism that TMS will revolutionize how we treat neurological and psychiatric disorders, evidenced by over 1000 clinical trials registered using TMS. Much of this optimism stems from the successful use of TMS as a treatment for depression. Despite the large number of clinical trials using TMS the number of therapeutic indications has been stagnant, limited to major depression and more recently obsessive-compulsive disorder. There are fundamental questions about the underlying mechanisms of action for TMS that will be critical to understand in order to advance this treatment modality. Here, we propose a unique collaborative project between neurology and neurosurgery that will allow an unprecedented window into understanding how TMS impacts the human brain. Specifically, we will perform TMS in neurosurgical patients with intracranial electroencephalography (iEEG) monitoring to record real time effects of TMS on local and remote brain areas with an unparalleled combination of spatial and temporal resolution relative to other human studies. We have already demonstrated the safety of this approach using a gel-based phantom brain and have results from seven patients demonstrating safety and preliminary results. For the current proposal we aim to: 1) characterize the response of TMS on the human brain as recorded from iEEG between active and sham conditions, and 2) relate remote electrophysiological responses induced by TMS to measures of brain connectivity between the stimulation and recording sites assessed with resting state functional connectivity MRI (rs-fcMRI). This will allow us to evaluate the relationship between TMS-evoked iEEG responses and the strength of functional connectivity to the stimulation site in a regression model. We hypothesize that: 1) TMS will have focal effects detected from surface electrodes underlying the stimulation site as well as network-level engagement detected at remote sites, 2) Repetitive TMS will induce frequency- specific effects that differ between 0.5 and 10 Hz stimulation protocols, and 3) the magnitude of repetitive TMS-evoked iEEG responses across electrodes will relate to the strength of rs-fcMRI between the stimulation and recording sites. By investigating the electrophysiological responses of TMS with high spatiotemporal precision in humans, this study will provide new mechanistic insights into the effects of TMS on target engagement and relate these findings to imaging methods already in widespread use. Moreover, the TMS will be applied in a clinically meaningful way by targeting the left dorsolateral prefrontal cortex in a protocol used to treat depression. Generating results for these aims will be key to advancing our understanding of how TMS engages brain networks, which can be leveraged to rationally develop personalized, imaging-guided therapeutic TMS for depression and other disorders.