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: 10219364
• 负责人: DENNIS Alan TURNER
• 金额: $ 41.97万
• 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 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10219364
• 关键词: Affect; Algorithms; Axon; Basal Ganglia; Bilateral; Biological Markers; Bradykinesia; Brain; Chronic; Clinical; 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; dopamine replacement therapy; 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 帕金森氏病的DBS治疗现在是帕金森氏病的主要手术方法，最近 FDA在疾病发作后4年批准。但是，这种疗法仍然仅限于子集的治疗 运动症状（即震颤，僵硬，胸肌和运动障碍），需要术后相当大 临床调整程序和维护功能。 PD的DBS有很多改进 经过测试，包括刺激模式和特定目标的变化。但是，一种主要的新方法 涉及使用临床症状的替代生理标记的内部参数调整，可用于 确认参数的初始电极放置，编程以及长期优化。一些 研究系统已被建议，并正在测试开发封闭循环系统，包括 基于记录β波段振荡的系统。封闭循环控制涉及记录替代信号 与PD有关 分钟），初始编程（超过几周到几个月），并长期，具体取决于时间课程 对STN DBS的响应。除了自发的beta频段录制，我们还直接实施了 使用刺激的DBS电极诱发潜在记录，需要抑制DBS诱导的 人工制品。 STN DBS植入物期间的这些术中DBS记录显示了一个复杂的诱发 可能反映GPE/GPI激活的可能可能提供出色的替代标记。这个复合物 随着STN DBS的治疗效果的出现，诱发的潜在变化在短期内， 表明诱发的潜在可能反映了DBS对较大电机电路的影响 动态变为改进的状态。我们假设这个替代标记（除了beta 频段振荡）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。为了检验这一假设，我们将执行长期记录 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）。 这些临床实验将集中于植入双侧STN +的小型试验临床研究（n = 6例） 帕金森氏症患者中的GPE/GPI DBS电极有资格使用常规立体定位的DBS， 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的协同作用的可能性。 此外，我们将分析外部的电动机功效（使用记录和修改 参数手动）和内部（使用算法自动提供参数），封闭 对这些记录的替代标记的循环响应。我们将利用 自发和诱发的响应，以构建比例控制反馈系统，特别是 描述闭环系统的时间常数，能够定义PD的最佳抑制控制 症状。这些实验将提供许多新的结果，包括直接的，人工 STN和GPE/GPI DBS功效的比较，开发用于检测的最​​佳替代参数 与临床直接比较的自发和诱发生理反应的DBS功效 症状，并定义最佳的标量反馈，在不同时间进行治疗的比例控制系统 秤。

项目成果

Treatment of diaphragmatic dystonia with pallidal deep brain stimulation.

用苍白球深部脑刺激治疗膈肌肌张力障碍。

• DOI: 10.1136/bcr-2020-240510
• 发表时间: 2021
• 期刊: BMJ case reports
• 影响因子: 0.9
• 作者: Rahimpour,Shervin;Calakos,Nicole;Turner,DennisA;Mitchell,KyleT
• 通讯作者: Mitchell,KyleT

Deep brain stimulation and electromagnetic interference.

• DOI: 10.1016/j.clineuro.2021.106577
• 发表时间: 2021-04
• 期刊: Clinical neurology and neurosurgery
• 影响因子: 1.9
• 作者: Rahimpour S;Kiyani M;Hodges SE;Turner DA
• 通讯作者: Turner DA

Comparative efficacy of surgical approaches to disease modification in Parkinson disease.

• DOI: 10.1038/s41531-022-00296-w
• 发表时间: 2022-03-25
• 期刊: NPJ Parkinson's disease
• 作者: Rahimpour S;Zhang SC;Vitek JL;Mitchell KT;Turner DA
• 通讯作者: Turner DA

Freezing of Gait in Parkinson's Disease: Invasive and Noninvasive Neuromodulation.

• DOI: 10.1111/ner.13347
• 发表时间: 2021-07
• 期刊: Neuromodulation : journal of the International Neuromodulation Society
• 作者: Rahimpour S;Gaztanaga W;Yadav AP;Chang SJ;Krucoff MO;Cajigas I;Turner DA;Wang DD
• 通讯作者: Wang DD