Recording Evoked Potentials for Closed-Loop DBS

描述(申请人提供)：脑深部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个重大的临床挑战，许多接受者由于参数选择不佳而无法受益。该项目将推进一种创新的方法，基于对刺激过程中大脑中神经信号的监测，自动选择刺激参数。我们建议首先进行人类大脑信号的记录，并将其作为脑深部刺激(DBS)有效性的可能生物标志物进行评估。DBS是一种植入的脑起搏器，是治疗特发性震颤和帕金森病的有效疗法。目前的DBS系统以开环方式运行；由临床医生设置刺激参数，患者无限期地接受24小时不变的刺激。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，而且往往导致不太理想的结果。此外，在癫痫或抑郁症的治疗中，可能没有明显或立即的变化来指导刺激参数的选择。闭环式DBS系统以响应患者需求的方式自动调整参数，有可能通过在药物状态波动期间、随着疾病进展或随着DBS的反应随时间变化而保持治疗来改善结果。拟议项目的目标是确定使用神经记录的可行性。 使用植入的相同电极来提供刺激的活动，作为对DBS进行闭环控制的反馈信号。我们将在DBS期间进行脑电样脑活动的记录，并将这些信号的幅度和特征的变化与症状的变化联系起来。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，以及允许直接连接到DBS脑导线的新颖术中设置。这一结果将为脑电活动的适宜性提供临床验证，S是星展银行有效性的生物标志物。我们还将进行互补的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(S)。研究结果将有助于深入了解与未来发展支持系统设计相关的发展援助的作用机制。

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.