Dual Lead Thalamic DBR-DBS Interface for Closed Loop Control of Severe Essential Tremor

双导联丘脑 DBR-DBS 接口，用于严重特发性震颤的闭环控制

• 批准号: 10468601
• 负责人: Kelly D Foote
• 金额: $ 77.72万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10468601
• 关键词: Activities of Daily Living; Address; Adverse effects; Affect; Algorithm Design; Algorithms; Anterior; Biological Markers; Brain; Cerebellum; Chronic; Clinical; Data; Deep Brain Stimulation; Development; Disparate; Dysarthria; Engineering; Essential Tremor; Failure; Feasibility Studies; Feedback; Functional disorder; Globus Pallidus; Goals; Human; Hybrids; Impairment; Implant; Intention Tremor; Knowledge; Lead; Medical Device; Microelectrodes; Modeling; Motor; Motor Cortex; Movement; Multiple Sclerosis; Neurosciences; Operative Surgical Procedures; Parkinson Disease; Pathologic; Patients; Persons; Population; Progressive Disease; Public Health; Quality of life; Refractory; Research Personnel; Safety; Second Look Surgery; Severities; Signal Transduction; Solid; Spinal cord injury; Stroke; Structure; System; Techniques; Technology; Thalamic Nuclei; Thalamic structure; Therapeutic; Time; Titrations; Tremor; Upper limb movement; Use Effectiveness; Work; arm function; arm movement; battery life; clinical application; disability; effective therapy; effectiveness evaluation; efficacy evaluation; experience; flexibility; functional restoration; human subject; improved; industry partner; limb movement; migration; multiple sclerosis patient; neural; neural circuit; neural network; neurophysiology; neuroregulation; receptor; side effect; symposium

Project Abstract Essential Tremor (ET) is a progressive disease that leads to significant disability and markedly diminished quality of life. Deep brain stimulation (DBS) in the ventralis intermedius (VIM) thalamus has been an effective treatment for ET control, but is associated with problematic side effects (e.g. dysarthia, imbalance) and may lose efficacy over time in people with severe ET. The ability to improve tremor control and reduce side effects with multifocal, current steering DBS techniques will be an important advance to the field. Furthermore, the ability to concurrently perform Deep Brain Recording (DBR) during DBS is of critical importance for characterizing both the pathologic neural circuitry of tremor and network mechanisms of DBS. We seek to restore optimal tremor control to subjects with refractory ET by replacing a failing single lead VIM thalamic DBS system with a dual lead (VIM + Ventralis Oralis (VOP)) thalamic DBS system in patients seeking revision surgery. The dual lead system will not only offer an effective rescue strategy for patients with severe tremor (open loop) and failure of standard VIM DBS, but the optional use of a DBR-capable system will also afford us an unprecedented opportunity to explore closed loop, on-demand, patient-specific tremor control. We propose to conduct this clinical feasibility study in 10 human subjects. Our specific aims are: Aim 1: Evaluate the efficacy and safety of dual lead thalamic DBS for treatment of severe essential tremor that has failed standard VIM DBS; Aim 2: Identify neurophysiologic markers of action tremor using a dual lead DBS/DBR system Aim 3: Develop neural decoding and control strategies for closed loop dual lead stimulation The proposal addresses what are arguably some of the most important limitations of currently available treatment for severe ET patients. We have assembled a highly experienced team of investigators and established an exclusive industrial partnership with Medtronic to fulfill the goals of this project. The proposed plan is driven by solid neuroscience and engineering principles that may have overarching impact on clinical applications of DBS technology for years to come.

项目摘要 特发性震颤 (ET) 是一种进行性疾病，可导致严重残疾和 生活质量明显下降。中间腹肌深部脑刺激 (DBS) (VIM) 丘脑一直是 ET 控制的有效治疗方法，但与 有问题的副作用（例如构音障碍、失衡），并且随着时间的推移可能会对人们失去功效 患有严重的 ET。能够通过多焦点改善震颤控制并减少副作用， 目前的转向 DBS 技术将是该领域的重要进步。此外， 在 DBS 期间同时进行深脑记录 (DBR) 的能力至关重要 用于表征震颤的病理神经回路和 DBS 的网络机制。 我们寻求通过更换失效的 ET 来恢复难治性 ET 受试者的最佳震颤控制。 单导联 VIM 丘脑 DBS 系统，带双导联 (VIM + Ventralis Oralis (VOP)) 丘脑 DBS 系统用于寻求修复手术的患者。双导联系统不仅提供 对严重震颤（开环）和标准 VIM 失败患者的有效抢救策略 DBS，但可选地使用具有 DBR 功能的系统也将为我们提供前所未有的 有机会探索闭环、按需、针对患者的震颤控制。我们建议 在 10 名人类受试者中进行这项临床可行性研究。我们的具体目标是： 目标 1：评估双导丘脑 DBS 治疗重症肌无力的有效性和安全性 标准 VIM DBS 失败的特发性震颤； 目标 2：使用双导联 DBS/DBR 识别动作性震颤的神经生理学标志物 系统 目标 3：开发闭环双导联的神经解码和控制策略 刺激 该提案解决了可以说是一些最重要的限制 目前可用于治疗严重 ET 患者。我们组建了一支经验丰富的 研究人员团队并与美敦力建立了独家工业合作伙伴关系，以实现 该项目的目标。拟议的计划由扎实的神经科学和工程学驱动 多年来可能对 DBS 技术的临床应用产生总体影响的原则 来。