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

项目摘要 图雷特综合征（TS）是一种持续终身的疾病，非常普遍，社会残疾，在一些严重的 案件，身体伤害。DBS已成为一种有前途的治疗选择，用于解决医学上无法控制的抽搐。 顽固性和严重的TS病例经常涉及自我伤害行为。我们进行了一项重大的信息学研究， 通过建立国际TS DBS登记和数据库，这是一个多国联盟， 277例TS DBS患者的长期结局，占全球所有TS DBS病例的50-75%。从这些结果来看，两个 脑深部靶点已经成为潜在的有效靶点：丘脑的中央中核区（CM）， 内苍白球前区（aGPi）。然而，我们目前对抽动产生的认识受到许多因素的限制 包括缺乏TS的动物模型，结构成像上明显正常的大脑结构，以及 用功能成像研究无意识运动抽搐下一代闭环DBS系统可以记录大脑活动 并确定抽搐的神经生理学相关性。此外，这些设备可以在不影响患者的情况下递送刺激。 对患者症状状态的反应。我们的总体目标是开发神经生理学驱动和连接引导的 闭环DBS系统用于改善TS的治疗。为此，我们将植入8名耐药性TS患者 CM和aGPi的双侧导联在目标1中，我们将从CM和aGPi中识别结构网络投影，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中抽动发生的神经生理学相关性。我们也将研究丘脑-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TS DBS的可行性、安全性和有效性。我们预计 闭环刺激将提供更有效和个性化的治疗选择，电池寿命更长， 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.