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: 10023956
• 负责人: Kelly D Foote
• 金额: $ 76.28万
• 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/10023956
• 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; Dysarthria; Engineering; Essential Tremor; Failure; Feasibility Studies; Feedback; Functional disorder; Globus Pallidus; Goals; Human; Hybrids; Impairment; Implant; Intention Tremor; Knowledge; Lead; Life; 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; Severities; Signal Transduction; Solid; Spinal cord injury; Stroke; Structure; System; Techniques; Technology; Thalamic Nuclei; Thalamic structure; Therapeutic; Time; Tremor; Upper limb movement; Use Effectiveness; Work; arm function; arm movement; base; clinical application; disability; effective therapy; effectiveness evaluation; efficacy evaluation; experience; flexibility; functional restoration; human subject; improved; industry partner; limb movement; multiple sclerosis patient; neural circuit; neural network; neurophysiology; neuroregulation; receptor; relating to nervous system; 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）是一种导致严重残疾的进行性疾病， 生活质量明显下降。腹中间肌脑深部电刺激（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），并且可能随着时间的推移在人群中失去疗效 严重的ET。改善震颤控制和减少多灶性副作用的能力， 电流导向DBS技术将是该领域的重要进展。而且 在DBS期间同时执行脑深部记录（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。 我们试图通过更换失败的震颤控制系统来恢复难治性ET受试者的最佳震颤控制。 单导联Vim丘脑DBS系统，双导联（Vim +口脑（VOP））丘脑 DBS系统用于寻求翻修手术的患者。双导系统不仅提供 严重震颤（开环）和标准Vim失败患者的有效抢救策略 DBS，但可选择使用具有DBR功能的系统也将为我们提供前所未有的 探索闭环、按需、患者特异性震颤控制的机会。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： 目的1：评价双电极丘脑DBS治疗重度脑梗死的有效性和安全性 标准Vim DBS失败的特发性震颤; 目的2：使用双导线DBS/DBR识别动作性震颤的神经生理学标志物 系统 目标3：为闭环双导联开发神经解码和控制策略 刺激 该提案解决了一些可以说是最重要的限制， 目前治疗严重ET患者的有效方法。我们召集了一位经验丰富的 研究者团队，并与美敦力建立了独家工业合作伙伴关系， 这个项目的目标。拟议的计划是由坚实的神经科学和工程驱动的 多年来可能对DBS技术的临床应用产生总体影响的原则 来的