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

基本信息

批准号：
10290544
负责人：
CHRISTOPHER R BUTSON
金额：
$ 87.2万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
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/10290544
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

项目摘要

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.