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

项目摘要 特发性震颤（ET）是一种无法治愈的退行性脑部疾病，导致越来越衰弱的震颤， 在美国，估计有700万人（占人口的2.2%）受到影响。虽然经济影响是 不确定的，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服用 因地震退休。ET与进行性功能障碍、社交尴尬、 甚至抑郁症。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），与有意的运动相结合，并且在许多方面都是不知不觉地进行的。 年脑深部电刺激（DBS）已成为一种非常有效的治疗顽固性，衰弱， ET.然而，由于ET的意向性震颤通常是间歇性的，并且通常在休息时不存在， 目前可用的连续DBS可能会向大脑输送不必要的电流， 不希望的副作用，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。整体 这项早期可行性研究的目的是提供关于“闭环”的安全性和有效性的初步数据， 使用能够连续感测大脑活动并递送的新型DBS装置的用于意向性震颤的DBS 仅在必要时进行治疗性刺激以抑制震颤。我们将测量和比较 自适应（闭环）与连续（开环）DBS的使用和副作用评估。在Aim中 1，我们将从局部场电位（LFP）记录中识别运动意图的神经相关物， 硬脑膜下电极阵列植入在前运动手皮质上。在目标2中，我们将首先确定神经 初级运动手皮层和腹侧中间核（Vim）中手震颤的相关性 LFP。然后，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， 并在检测到没有震颤时终止DBS。这些目标将通过第一代 Medtronic Activa PC+S器械，能够同时刺激和记录。拟议 该项目预计将为第一个慢性闭环DBS系统提供概念验证， 治疗人类的衰弱性运动障碍。我们预计，该项目也将引领 用于未来为其他运动障碍设计的闭环自适应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.