Recording Evoked Potentials for Closed-Loop DBS

描述（由申请人提供）：脑深部电刺激是一种临床有效的治疗方法，但刺激参数的选择仍然是一项重大的临床挑战，许多接受者因非最佳参数选择而无法获益。该项目将提出一种创新的方法，根据刺激过程中大脑中神经信号的监测自动选择刺激参数。我们建议首先在人类中记录大脑信号，并将其作为脑深部电刺激（DBS）有效性的可能生物标志物进行评估。DBS是一种植入式脑起搏器，是治疗原发性震颤和帕金森病的有效方法。目前的DBS系统以开环方式操作;临床医生设置刺激参数，并且患者无限期地接收24小时/天的不变刺激。刺激参数的选择是一个非系统的过程，需要大量的时间和临床专业知识，并且通常会导致次优结果。此外，在如癫痫或抑郁症的治疗的应用中，可能没有明显或立即的变化来指导刺激参数的选择。闭环DBS系统自动调整参数，并以响应患者需求的方式进行调整，有可能通过在药物状态波动期间、随着疾病进展或随着DBS响应随时间变化而维持治疗来改善结局。该项目的目的是确定使用神经记录的可行性， 活动，使用植入的相同电极提供刺激，作为DBS闭环控制的反馈信号。我们将在DBS过程中记录EEG样脑活动，并将这些信号的振幅和特征的变化与症状的变化相关联。这些实验使用了我们在动物研究中开发和验证的创新硬件，以及允许直接连接DBS脑电极导线的新型术中设置。结果将提供脑电活动作为DBS有效性生物标志物的适用性的临床验证。我们还将进行补充动物研究和计算建模，以确定构成生物标志物的神经信号的来源。结果将提供深入了解DBS的作用机制相关的未来DBS系统的设计。

DESCRIPTION (provided by applicant): Deep brain stimulation is a clinically effective treatment, but the selection of the parameters of stimulation remains a significant clinical challenge and many recipients are deprived of benefit due to non-optimal parameter selection. This project will advance an innovative approach to automatic selection of stimulation parameters based on monitoring of neural signals in the brain during stimulation. We propose to conduct first in human recordings of brain signals and evaluate them as a possible biomarker for the effectiveness of deep brain stimulation (DBS). DBS - an implanted brain pacemaker - is an effective therapy for essential tremor and Parkinson's disease. Present DBS systems operate in an open-loop fashion; a clinician sets the stimulation parameters, and patients receive invariant stimulation 24 h/day indefinitely. Selection of stimulation parameters is a non- systematic process that requires substantial time and clinical expertise and often results in sub-optimal outcomes. Further, in applications like treatment of epilepsy or depression, there may be no overt or immediate changes to guide selection of stimulation parameters. Closed-loop DBS, where the system adjusts parameters automatically and in a manner responsive to the needs of the patient, has the potential to improve outcomes by maintaining treatment during fluctuations in medication status, as the disease progresses, or as the response to DBS changes over time. The objective of the proposed project is to determine the feasibility of using recordings of neural activity, obtained using the same electrodes implanted to deliver stimulation, as a feedback signal for closed-loop control of DBS. We will conduct recordings of EEG-like brain activity during DBS and correlate changes in the amplitude and character of these signals with changes in symptoms. These experiments use innovative hardware that we developed and validated in animal studies and a novel intraoperative setting that allows direct connection to the DBS brain lead. The outcome will provide clinical validation of the suitability of brain electrical activity s a biomarker for the effectiveness of DBS. We will also conduct complementary animal studies and computational modeling to determine the source(s) of the neural signals constituting the biomarker. The outcome will provide insight into the mechanisms of action of DBS relevant to the design of future DBS systems.