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.

项目总结