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

定义抽动秽语综合征抽动检测和抑制的目标深部脑刺激

• 批准号: 10490272
• 负责人: CHRISTOPHER R BUTSON
• 金额: $ 111.51万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10490272
• 关键词: Address; Adverse effects; Adverse event; Affect; Animal Model; Anterior; Basal Ganglia; Behavior Therapy; Behavioral tic; Bilateral; Brain; Centromedian Thalamic Nucleus; Characteristics; Chronic; Clinical; Country; Data; Databases; Deep Brain Stimulation; Detection; Development; Devices; Disease; Electrophysiology (science); FDA approved; Follow-Up Studies; Foundations; Functional Imaging; Generations; Gilles de la Tourette syndrome; Globus Pallidus; Goals; Hour; Human; Image; Implant; Informatics; International; Investigation; Knowledge; Lead; Life; Location; Longitudinal Studies; Maps; Medical; Methods; Monitor; Motor Tics; Movement; Operative Surgical Procedures; Outcome; Pathologic; Patients; Pharmaceutical Preparations; Physiological; Physiology; Postoperative Period; Public Health; Publications; Quality of life; Registries; Research; Resistance; Safety; Self-Injurious Behavior; Severities; Signal Transduction; Stigmatization; Structure; Symptoms; Syndrome; System; Testing; Thalamic structure; Time; Vocal Tics; base; connectome; data repository; effective therapy; experience; feasibility testing; improved; neurophysiology; neuroregulation; next generation; novel; personalized medicine; primary outcome; prospective; relating to nervous system; response; safety and feasibility; safety outcomes; safety testing; social; tic suppression

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.

项目概要 抽动秽语综合症 (TS) 是一种持续终生的疾病，非常普遍，具有社交障碍，在某些严重的情况下 情况下，身体受到伤害。 DBS 已成为解决医疗领域无法控制的抽动的一种有前途的治疗选择 抵抗性和严重的 TS 病例经常涉及自残行为。我们进行了一项重大的信息学研究 通过建立国际 TS DBS 注册和数据库来发起倡议，这是一个多国联盟，长期致力于 277 名 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 深部大脑目标已成为潜在有效的：丘脑的中心正中核区域（CM）和 苍白球内部前部（aGPi）。然而，我们目前对抽动产生的理解受到许多因素的限制 包括缺乏 TS 动物模型、结构成像上明显正常的大脑结构以及不切实际的 通过功能成像研究不自主运动抽动。下一代闭环 DBS 系统可以记录大脑活动 TS 患者并确定抽动的神经生理学相关性。此外，这些设备可以提供刺激 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 用于改善 TS 治疗的闭环 DBS 系统。为此，我们将植入8名具有耐药性的TS患者 CM 和 aGPi 双侧导联。在目标 1 中，我们将识别 CM 和 aGPi 的结构网络投影，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。我们还将研究丘脑-苍白球网络相互作用 导致抽动和抽动期间。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。我们期望 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，更少 不良影响。