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

项目总结 原发性震颤(ET)是一种无法治愈的退行性大脑疾病，会导致日益衰弱的震颤， 据估计，美国有700万人(占总人口的2.2%)受到这种疾病的困扰。虽然外星人的经济影响是 不确定，它肯定是相当可观的。在一项研究中，25%的ET患者被迫换工作或提前接受治疗 因震颤而退休。ET与进行性功能障碍、社交尴尬、 甚至是抑郁症。与ET相关的震颤通常是缓慢的(~5赫兹)，涉及手(和 有时是头部和声音)，随着有意的动作而恶化，并在许多情况下潜伏地进行 好几年了。脑深部刺激(DBS)已成为治疗顽固性、衰弱的一种非常有效的方法。 Et.然而，由于ET的意向震颤通常是间歇性的，通常在休息时不存在， 目前可用的连续DBS可能正在向大脑提供不必要的电流，从而增加 不良副作用，如说话含糊和行走困难，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。整体而言 这项早期可行性研究的目的是提供有关“闭环系统”安全性和有效性的初步数据。 意向性震颤的DBS治疗使用新型DBS设备，能够连续感知大脑活动并提供 只有在必要时才能进行治疗性刺激以抑制震颤。我们将测量和比较这些能量 适应性(闭环系统)与连续(开环系统)DBS的使用和副作用评估。在AIM 1，我们将在局部场电位(LFP)记录中识别运动意图的神经关联 硬膜下电极阵列植入运动前手部皮质。在目标2中，我们将首先确定神经 手部震颤与手部初级运动皮质和腹侧中间核(Vim)的相关性 LFP。当检测到意图和/或震颤时，我们将使用这些标记来启动治疗性DBS， 并在检测到没有震动时终止DBS。这些目标将通过使用第一代来实现 美敦力Activa PC+S装置，可同时刺激和记录。建议数 该项目预计将为第一个慢性闭环式DBS系统提供概念验证 治疗人类一种令人衰弱的运动障碍。我们预计这个项目也将引领这一进程 用于未来针对其他运动障碍设计的闭环式自适应DBS系统。

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.