Biophysical Characterization of Subthalamic Local Field Potentials in Parkinson's Disease

帕金森病下丘脑局部场电位的生物物理特征

• 批准号: 10543713
• 负责人: Cameron McIntyre
• 金额: $ 45.81万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10543713
• 关键词: Address; Algorithms; Anatomy; Biological Models; Biomedical Engineering; Biophysics; Boston; Characteristics; Chronic; Clinical; Computer Models; Custom; Data; Deep Brain Stimulation; Development; Devices; Dissection; Dorsal; Electrodes; Evaluation; Functional disorder; Goals; Human; Image; Implant; Infrastructure; Investigation; Lateral; Lead; Location; Measurable; Measurement; Modeling; Neurons; Parkinson Disease; Patients; Physiological; Play; Population; Population Study; Positioning Attribute; Quality of life; Research; Research Project Grants; Research Subjects; Role; Signal Transduction; Structure of subthalamic nucleus; Synapses; System; Technology; Time; Walkers; base; biophysical properties; computer infrastructure; engineering design; experimental study; improved; motor symptom; patient population; relating to nervous system; symposium; tool

PROJECT SUMMARY Subthalamic deep brain stimulation (DBS) can significantly improve the motor symptoms and quality of life of patients with Parkinson’s disease (PD). Recent advances in DBS technology are providing new opportunities to interrogate and characterize the pathophysiology of PD using local field potential (LFP) recordings. Previous LFP investigations brought to light the important role of beta-band (12-30 Hz) activity in PD. However, we are still faced with a wide range of questions on the biophysics of subthalamic LFPs. For example, How many subthalamic nucleus (STN) neurons need to be synchronized to generate a clinically measurable LFP signal? What are the synaptic input characteristics responsible for that synchronization? Where are those neurons located in the STN? The McIntyre lab has spent the last decade developing the computational infrastructure to address these questions within the context of the human STN implanted with clinical DBS electrodes. Therefore, we propose the integration of those advanced modeling tools with ongoing human studies (directional STN LFP recordings – Dr. Walker, and chronic STN LFP recordings – Dr. Bronte- Stewart) that are defining the clinical cutting edge of DBS LFP studies. The goal of this Bioengineering Research Grant (PAR-19-158) is to apply the latest advances in patient- specific LFP modeling to the analysis of directional STN recordings and chronic STN recordings in PD patients. These analyses will allow us to address fundamental questions on the size and location of synchronous neural populations in the STN, which have important implications for understanding the pathophysiology of PD. In addition, our models will enable us to evaluate the variance in STN neural synchrony across populations of patients, and over long periods of time within the same patient, both of which have important implications for the engineering design of LFP-based DBS algorithms. The first step of this project will focus on evolving the patient-specific LFP modeling infrastructure to accommodate directional DBS electrodes and adapt to different electrode positions in each patient-specific STN volume. The second step of this project will use the patient- specific LFP model system to identify the size and location of beta synchrony in 10 PD patients using directional DBS recordings acquired during intra-operative experiments. Finally, we will quantify the modulation of the size and location of the beta synchrony in 5 PD patients using chronic LFP recordings and measurements taken at 4 different time points over a 1 year period.

项目摘要 亚丘脑深脑刺激（DBS）可以显着改善运动症状和生活质量 帕金森氏病（PD）的患者。 DBS技术的最新进展正在提供新的 使用局部现场潜力（LFP）询问和表征PD的病理生理学的机会 录音。以前的LFP调查揭示了Beta波段（12-30 Hz）活性在 PD。但是，我们仍然面临着丘脑下LFP的生物物理学的广泛问题。为了 例如，需要同步多少丘脑核（STN）神经元以产生临床 可测量的LFP信号？哪些合成输入特性是什么原因导致该同步？ 这些神经元位于STN中的哪里？麦金太尔实验室在过去的十年中已经开发了 计算基础架构在植入人类的背景下解决这些问题 临床DBS电极。因此，我们建议将这些高级建模工具与持续的集成 人类研究（定向STN LFP录音 - Walker博士和慢性STN LFP录音 - Bronte-博士 Stewart）正在定义DBS LFP研究的临床尖端。 这项生物工程研究补助金（Par-19-158）的目标是应用患者的最新进展 - 特定的LFP建模，以分析PD患者的定向性STN记录和慢性STN记录。 这些分析将使我们能够解决有关同步中性的大小和位置的基本问题 STN中的种群，对理解PD的病理生理具有重要意义。 此外，我们的模型将使我们能够评估在 患者以及同一患者的长时间时间内，这两者都对 基于LFP的DBS算法的工程设计。该项目的第一步将着重于发展 患者特定的LFP建模基础架构可容纳定向DBS电子并适应不同的 每个患者特异性STN体积中的电极位置。该项目的第二步将使用患者 - 特定的LFP模型系统，以使用10个PD患者中β同步的大小和位置 在术中实验中获得的定向DBS记录。最后，我们将量化 使用慢性LFP记录和 在1年期间在4个不同时间点进行的测量。