Defining Targets for Tic Detection and Suppression in Tourette Syndrome Deep Brain Stimulation

项目总结 抽动秽语综合征(TS)是一种持续终生的疾病，高度流行，社交障碍，在一些严重的情况下 案件，对身体造成伤害。DBS已经成为一种很有前途的治疗方案，用于解决医学上无法控制的抽搐 难治性和重症TS患者常有自残行为。我们已经进行了一项重大的信息学研究 通过建立国际TS DBS注册和数据库的倡议，一个多国财团已经捕获了Long 277名TS-DBS患者的远期结局占全球TS-DBS病例的50%-75%。从这些结果中，有两个 大脑深层靶点已经成为潜在的有效靶点：丘脑的中央正中核区(CM)，以及 苍白内球前叶(AGPI)。然而，我们目前对tic产生的认识受到许多因素的限制。 包括缺乏TS的动物模型，结构成像上看起来正常的大脑结构，以及 用功能成像研究不自主运动痉挛。下一代闭环式DBS系统可以记录大脑活动 并确定抽搐的神经生理学相关因素。此外，这些设备可以在 对病人症状状态的反应。我们的总体目标是发展神经生理学驱动和连接引导 用于改进TS治疗的闭环式DBS系统。为此，我们将植入8名具有药物耐药性的TS患者 在CM和aGPI中有双边引线。在目标1中，我们将从CM和aGPI中确定结构网络投影，以指导 术前手术计划和术后刺激参数的选择。在目标2中，我们将确定 CM和aGPI中TIC发生的神经生理学相关性。我们还将研究丘脑-苍白球网络的相互作用 导致抽搐和抽搐期间。在目标3中，我们将测试闭环式TS DBS的可行性、安全性和有效性。我们期待着 闭合环路刺激将提供更有效和个性化的治疗选择，电池寿命更长，而且更少 不良影响。

PROJECT SUMMARY Tourette syndrome (TS) is a continuous lifelong condition that is highly prevalent, socially disabling, and in some severe cases, physically injurious. DBS has emerged as a promising treatment option for addressing uncontrollable tics in medically resistant and severe cases of TS frequently involving self-injurious behavior. We have undertaken a major informatics initiative by establishing the International TS DBS Registry and Database, a multi-country consortium that has captured long term outcomes of 277 TS DBS patients representing 50-75% of all TS DBS cases worldwide. From these outcomes, two deep brain targets have emerged as potentially effective: the centromedian nucleus region (CM) of the thalamus, and the anterior globus pallidus internus (aGPi). However, our current understanding of tic generation is limited by many factors including a lack of animal models for TS, apparently normal brain structure on structural imaging, and the impracticality of studying involuntary motor tics with functional imaging. Next generation closed-loop DBS systems can record brain activity in patients with TS and identify the neurophysiological correlates of tics. Moreover, these devices can deliver stimulation in response to a patient's symptomatic state. Our overall goal is to develop neurophysiology driven and connectivity-guided closed-loop DBS systems for the improved treatment of TS. To this end, we will implant 8 medically resistant TS patients with bilateral leads in the CM and aGPi. In Aim 1, we will identify structural network projections from CM and aGPi to guide pre-operative surgical planning and post-operative selection of stimulation parameters. In Aim 2, we will identify neurophysiologic correlates of tic genesis in the CM and aGPi. We will also study thalamo-pallidal network interactions leading to and during tics. In Aim 3, we will test the feasibility, safety, and efficacy of closed-loop TS DBS. We expect that closed-loop stimulation will provide more effective and personalized treatment options with longer battery life and fewer adverse effects.