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

摘要 最近，DBS治疗帕金森氏症是帕金森氏症的主要外科治疗方法 FDA在发病4年后批准。然而，这种疗法仍然局限于对子集的治疗。 运动症状(即震颤、僵直、运动迟缓和运动障碍)，需要相当长的术后时间 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 使用临床症状的替代生理标记物进行内部参数调整，对于 确定初始电极放置、编程以及参数的长期优化。几个 已经提出了研究系统，并正在测试闭环系统的开发，包括 基于记录贝塔频段振荡的系统。涉及记录替代信号的闭环控制 与帕金森病相关的可以在几个时间尺度上改进DBS治疗，包括短期动态(即 几分钟)、初始规划(几周到几个月)和长期规划，具体取决于 对STN DBS的回应。除了自发的Beta乐队录音外，我们还实现了直接 使用刺激DBS电极记录诱发电位，需要抑制DBS诱导的诱发电位 神器。在STN DBS植入期间的这些术中DBS记录显示，复杂的诱发 潜在的可能反映GPE/GPI激活，这可能是一个很好的替代标记。这个建筑群 随着STN DBS治疗效果的显现，诱发电位在短期内发生变化， 这表明诱发电位可能反映了DBS对较大马达电路的影响 动态地改变为改进的状态。我们假设这个代理标记(除了测试版之外 频带振荡)可以提供用于标量、分级(比例)闭环DBS控制的关键反馈信号， 与局部放电电路上的DBS效应高度相关。为了验证这一假设，我们将对 这种来自人类的信号(STN或GPE/GPI)与DBS刺激(STN和/或GPI)一起，使用 新型DBS记录/刺激装置(美敦力RC S)。 这些临床实验将集中于一项植入双侧STN的小型先导性临床研究(n=6名患者)。 采用常规立体定向定位的帕金森病患者的GPE/GPI DBS电极 连接到美敦力RC S IPGS。患者将从普通的STN或GPI DBS刺激中受益 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，我们还将分析外部(使用录音和修改 参数手动)和内部(使用自动提供参数的算法)标量、关闭 对这些记录的代理标记的循环响应。我们将利用 自发和诱发的反应，以构建比例控制反馈系统，并具体 描绘闭环系统的时间常数，以便能够定义PD的最优阻尼控制 症状。这些实验将提供许多新的结果，包括直接的、面对面的 STN与GPE/GPI DBS检测效果比较及最佳替代检测参数的建立 使用自发和诱发生理反应的DBS疗效与临床的直接比较 症状，并定义一个最佳的，标量反馈，比例控制系统，用于不同时间的治疗 比例。

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.