Scalar Closed-Loop STN/GPi DBS Based on Evoked and Spontaneous Potentials

基于诱发电位和自发电位的标量闭环 STN/GPi DBS

• 批准号: 9564229
• 负责人: DENNIS Alan TURNER
• 金额: $ 54.38万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9564229
• 关键词: Affect; Algorithms; Axon; Basal Ganglia; Bilateral; Biological Markers; Bradykinesia; Brain; Chronic; Clinical; Clinical Markers; Clinical Research; Complex; Deep Brain Stimulation; Development; Devices; Disease Progression; Dopamine; Dyskinetic syndrome; Early Intervention; Electrodes; Evaluation; Evoked Potentials; Evolution; FDA approved; Feedback; Human; Implant; Lead; Location; Manuals; Medical Device; Morphologic artifacts; Motor; Nature; Onset of illness; Operative Surgical Procedures; Outcome; Parkinson Disease; Patients; Pattern; Persons; Pharmaceutical Preparations; Physiological; Postoperative Period; Public Health; Research; Signal Transduction; Site; Surrogate Markers; Symptoms; Synapses; System; Technology; Testing; Thalamic structure; Time; Tremor; base; clinical efficacy; experience; experimental study; first-in-human; improved; motor symptom; novel; novel strategies; programs; reduce symptoms; relating to nervous system; response; synergism; systems research; treatment effect

Abstract DBS therapy for Parkinson's disease is now the primary surgical approach for Parkinson's disease, recently FDA approved at 4 years after onset of disease. However, this therapy is still limited to treatment of a subset of motor symptoms (ie, tremor, rigidity, bradykinesia and dyskinesias) and requires considerable postoperative clinical adjustment to program and maintain function. A number of improvements to DBS for PD are being tested, including changes in patterns of stimulation and specific targets. However, a major new approach involves internal parameter adjustment using a surrogate physiological marker of clinical symptoms, useful for confirming initial electrode placement, programming, and also long-term optimization of parameters. Several research systems have been suggested and are in testing for development of closed loop systems, including systems based on recording beta-band oscillations. Closed loop control involving recording a surrogate signal relevant to PD could improve DBS therapy on several time scales, including short-term dynamics (ie, over minutes), initial programming (over weeks to months), and long-term, depending on the time course of response to STN DBS. In addition to spontaneous beta band recording we have also implemented direct evoked potential recording using the stimulating DBS electrode, requiring suppression of the DBS-induced artifact. These intraoperative DBS recordings during STN DBS implants have revealed a complex evoked potential likely reflecting GPe/GPi activation, which may provide an excellent surrogate marker. This complex evoked potential changes over a short-term time period as the treatment effect of STN DBS comes on, indicating that the evoked potential likely reflects DBS effects on a larger motor circuit as the circuit dynamically is altered to an improved state. We hypothesize that this surrogate marker (in addition to beta band oscillations) may provide a key feedback signal for scalar, graded (proportional) closed loop DBS control, highly relevant to DBS effects on PD circuitry. To test this hypothesis we will perform long-term recording of this signal from humans (in either STN or GPe/GPi) together with DBS stimulation (in STN and/or GPi), using a novel DBS recording/stimulation device (Medtronics RC+S). These clinical experiments will focus on a small, pilot clinical study (n = 6 patients) to implant bilateral STN + GPe/GPi DBS electrodes in Parkinson's patients eligible for DBS using conventional stereotactic localization, connecting to Medtronics RC+S IPGs. Patients will benefit from either ordinary STN or GPi DBS stimulation and then we will also test the possibility of synergism between the two electrodes for clinical efficacy. Additionally, we will analyze the motor efficacy of both an external (using recording and modifying the parameters manually) and internal (using an algorithm for providing parameters automatically) scalar, closed loop response to these recorded surrogate markers. We will take advantage of the graded nature of the spontaneous and evoked responses to construct a proportional control feedback system, and to specifically delineate the time constants of the closed loop system to be able to define optimally damped control of PD symptoms. These experiments will provide a number of novel outcomes, including a direct, within-person comparison of STN and GPe/GPi DBS efficacy, development of an optimal surrogate parameter for detecting DBS efficacy using spontaneous and evoked physiological responses in direct comparison to clinical symptoms, and defining an optimal, scalar feedback, proportional control system for treatment on various time scales.

抽象的 近年来，DBS治疗帕金森病现已成为治疗帕金森病的主要手术方法 FDA 在疾病发病 4 年后批准。然而，这种疗法仍然仅限于治疗一个子集 运动症状（即震颤、强直、运动迟缓和运动障碍），需要大量的术后恢复 临床调整以规划和维持功能。针对 PD 的 DBS 正在进行多项改进 测试，包括刺激模式和特定目标的变化。然而，一个重要的新方法 涉及使用临床症状的替代生理标记进行内部参数调整，可用于 确认初始电极放置、编程以及参数的长期优化。一些 已提出研究系统，并正在测试闭环系统的开发，包括 基于记录β带振荡的系统。涉及记录代理信号的闭环控制 与 PD 相关的研究可以在多个时间尺度上改善 DBS 治疗，包括短期动态（即超过 分钟）、初始规划（数周至数月）和长期（取决于时间进程） 对 STN DBS 的响应。除了自发的 beta 频段录音外，我们还实施了直接录音 使用刺激 DBS 电极进行诱发电位记录，需要抑制 DBS 诱发的电位 人工制品。 STN DBS 植入过程中的这些术中 DBS 记录揭示了复杂的诱发因素 潜力可能反映 GPe/GPi 激活，这可能提供一个极好的替代标记。这个综合体 随着 STN DBS 治疗效果的出现，在短期内引起潜在的变化， 表明诱发电位可能反映了 DBS 对较大运动电路的影响，因为该电路 动态地改变为改进的状态。我们假设这个替代标记（除了 beta 带振荡）可以为标量、分级（比例）闭环 DBS 控制提供关键反馈信号， 与 DBS 对 PD 电路的影响高度相关。为了检验这个假设，我们将进行长期记录 该信号来自人类（在 STN 或 GPe/GPi 中）以及 DBS 刺激（在 STN 和/或 GPi 中），使用 新型 DBS 记录/刺激装置 (Medtronics RC+S)。 这些临床实验将重点关注一项植入双侧 STN + 的小型试点临床研究（n = 6 名患者） 适合使用传统立体定向定位进行 DBS 的帕金森病患者的 GPe/GPi DBS 电极， 连接到 Medtronics RC+S IPG。患者将受益于普通 STN 或 GPi DBS 刺激 然后我们还将测试两个电极之间协同作用的可能性以达到临床疗效。 此外，我们将分析外部的运动功效（使用记录和修改 手动参数）和内部（使用自动提供参数的算法）标量，封闭 对这些记录的替代标记的循环响应。我们将利用分级性质 自发反应和诱发反应，构建比例控制反馈系统，并具体 描述闭环系统的时间常数，以便能够定义 PD 的最佳阻尼控制 症状。这些实验将提供许多新颖的结果，包括直接的、人体内的 STN 和 GPe/GPi DBS 功效的比较，开发用于检测的最​​佳替代参数 DBS 疗效使用自发和诱发的生理反应，与临床直接比较 症状，并定义最佳的标量反馈比例控制系统，用于不同时间的治疗 秤。