Closing the Loop on Tremor: A Responsive Deep Brain Stimulator for the Treatment of Essential Tremor

关闭震颤循环：用于治疗特发性震颤的响应性深部脑刺激器

基本信息

批准号：
10663159
负责人：
Kelly D Foote
金额：
$ 37.05万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-30 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10663159
关键词：
Adverse effects Area BRAIN initiative Biological Markers Brain Brain Diseases Cell Nucleus Cells Central Nervous System Cerebellum Characteristics Chronic Clinical Clinical Research Contralateral Data Deep Brain Stimulation Detection Development Device Designs Devices Disease Electrodes Electrophysiology (science)Essential Tremor Feasibility Studies Frequencies Funding Opportunities Future Gait Ataxia Generations Gilles de la Tourette syndrome Goals Hand Head Hour Human Implant Implanted Electrodes Intention Intention Tremor Ipsilateral Lead Limb Tremors Link Measures Medical Mental Depression Mission Modality Motor Motor Cortex Movement Movement Disorders Muscle National Institute of Neurological Disorders and Stroke Neurons Occupations Operative Surgical Procedures Pathologic Patients Persons Pharmaceutical Preparations Physiologic pulse Population Population Study Production Public Health Refractory Reporting Research Rest Retirement Safety Schedule Signal Transduction Speech System Thalamic structure Therapeutic Tremor United States National Institutes of Health Upper Extremity Voice Walking Work arm battery life cohort deep brain stimulator design economic impact effective therapy experience functional disability improved individualized medicine neural circuit neural correlate neurophysiology next generation novel side effect social

项目摘要

PROJECT SUMMARY Essential tremor (ET) is an incurable, degenerative brain disorder that results in increasingly debilitating tremor, and afflicts an estimated 7 million people in the US (2.2% of the population). While the economic impact of ET is indeterminate, it is surely quite substantial. In one study, 25% of ET patients were forced to change jobs or take early retirement because of tremor. ET is directly linked to progressive functional impairment, social embarrassment, and even depression. The tremor associated with ET is typically slow (~5 Hz), involves the hands (and sometimes the head and voice), worsens with intentional movements, and is insidiously progressive over many years. Deep Brain Stimulation (DBS) has emerged as a highly effective treatment for intractable, debilitating ET. However, since the intention tremor of ET is typically intermittent, and commonly absent at rest, the currently available continuous DBS may be delivering unnecessary current to the brain that increases undesirable side effects such as slurred speech and walking difficulty, and hastens the depletion of device batteries, necessitating more frequent surgical procedures to replace spent pulse generators. The overall objective of this early feasibility study is to provide preliminary data on the safety and efficacy of “closed-loop” DBS for intention tremor using novel DBS devices capable of continuously sensing brain activity and delivering therapeutic stimulation only when necessary to suppress tremor. We will measure and compare the power usage and the assessment of side-effects with adaptive (closed-loop) vs. continuous (open-loop) DBS. In Aim 1, we will identify the neural correlates of movement intention in local field potential (LFP) recordings from subdural electrode arrays implanted over the premotor hand cortex. In Aim 2, we will first determine the neural correlates of hand tremor from the primary motor hand cortex and in the ventral intermediate (Vim) nucleus LFPs. We will then use these markers to actuate therapeutic DBS when intention and/or tremor is detected, and terminate DBS when absence of tremor is detected. These aims will be achieved using first generation Medtronic Activa PC+S devices, which are capable stimulation and recording simultaneously. The proposed project is expected to provide proof-of-concept for the first chronic closed-loop DBS system for the treatment of a debilitating movement disorder in humans. We expect that this project will also lead the way for future closed-loop adaptive DBS systems designed for other movement disorders.

项目概要特发性震颤 (ET) 是一种无法治愈的退行性脑部疾病，会导致日益衰弱的震颤，并且据估计，美国有 700 万人受到影响（占人口的 2.2%），而 ET 的经济影响是不确定，但肯定是相当大的。在一项研究中，25% 的 ET 患者被迫换工作或提早上班。因震颤而退休与进行性功能障碍、社交尴尬、甚至与 ET 相关的震颤通常是缓慢的（~5 Hz），涉及手（和）。有时是头部和声音），随着有意的运动而恶化，并且在许多情况下会不知不觉地进展。多年来，深部脑刺激 (DBS) 已成为治疗顽固性、衰弱性病症的高效方法。然而，由于 ET 的意向性震颤通常是间歇性的，并且在休息时通常不存在，因此目前可用的连续 DBS 可能会向大脑传递不必要的电流，从而增加不良副作用，例如言语不清和行走困难，并加速设备的耗尽电池，需要更频繁的外科手术来更换用过的脉冲发生器。这项早期可行性研究的目的是提供有关“闭环”安全性和有效性的初步数据 DBS 使用新颖的 DBS 设备持续感知大脑活动并传递信息，用于意向性震颤仅当需要抑制震颤时，我们才会测量和比较治疗刺激的强度。自适应（闭环）与连续（开环）DBS 的使用和副作用评估。 1，我们将识别局部场电位（LFP）记录中运动意图的神经相关性硬膜下电极阵列植入前运动手皮层在目标 2 中，我们将首先确定神经元。手部初级运动皮层和腹侧中间 (Vim) 核的手部震颤的相关性然后，当检测到意向和/或震颤时，我们将使用这些标记来启动治疗性 DBS，当检测到不存在震颤时终止 DBS 这些目标将通过使用第一代来实现。美敦力 Activa PC+S 设备，能够同时进行刺激和记录。该项目预计将为第一个慢性闭环 DBS 系统提供概念验证我们预计该项目也将引领人类衰弱性运动障碍的治疗。为未来专为其他运动障碍设计的闭环自适应 DBS 系统。