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

项目摘要 丘脑底脑深部电刺激（DBS）可明显改善患者的运动症状和生活质量 帕金森病（PD）患者的情况。DBS技术的最新进展正在提供新的 使用局部场电位（LFP）询问和表征PD病理生理学的机会 录音.以前的LFP研究揭示了β波段（12-30 Hz）活动在 警局然而，我们仍然面临着一个广泛的问题，对生物物理学的丘脑底LFPs。为 例如，需要多少丘脑底核（subthalamic nucleus，简称NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN 可测量的LFP信号？负责这种同步的突触输入特征是什么？ 这些神经元位于大脑的什么位置？麦金太尔实验室在过去的十年里一直在开发 计算基础设施，以解决这些问题的背景下，人类植入 临床DBS电极。因此，我们建议将这些先进的建模工具与正在进行的 人体研究（定向LFP记录-步行者博士，和慢性LFP记录-勃朗特博士， Stewart），定义了DBS LFP研究的临床前沿。 该生物工程研究资助（PAR-19-158）的目标是将最新进展应用于患者， 特异性LFP建模用于分析PD患者中的定向EEG记录和慢性EEG记录。 这些分析将使我们能够解决同步神经元的大小和位置的基本问题。 人群中，这对理解PD的病理生理学具有重要意义。在 此外，我们的模型将使我们能够评估不同人群的神经同步性的差异。 患者，以及在同一患者体内的长时间内，这两者都对 基于LFP的DBS算法的工程设计。该项目的第一步将侧重于发展 患者特定的LFP建模基础设施，以适应定向DBS电极并适应不同的 每个患者特定的MRI体积中的电极位置。这个项目的第二步将使用病人- 使用特定LFP模型系统在10名PD患者中鉴定β同步的大小和位置 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记录对5名PD患者的β同步的大小和位置进行调制， 在1年期间的4个不同时间点进行测量。

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.