Circuit-based deep brain stimulation for Parkinson's disease

明尼苏达大学（UMN）Udall中心的总体目标是开发新颖的，基于电路的深 脑刺激（DBS）治疗帕金森病（PD）的基础上的变化的理解 在基底神经节丘脑皮质-脑干（BGTC-B）通路中发生的病理生理活动模式中。 项目1（人类）将描述振荡活动的作用，耦合和连接在更广泛的 BGTC网络，包括丘脑底核（subthalamic nucleus，简称BGTC）、苍白球内侧核（globus pallidus internus，简称GPi）、感觉核、运动核、 前运动区和背外侧前额叶皮层这些记录将在休息和认知期间进行- 运动任务，有和没有治疗干预（DBS，左旋多巴，DBS+左旋多巴）。它还将澄清相对 在运动和认知功能上，在运动神经元和GPi的不同功能子区域中的刺激的影响。 项目2（人类）将探索苍白球DBS对左旋多巴抵抗运动体征的机制和影响 使用MRI衍生的计算模型和fMRI来检查介导这些变化的途径。它将 使用新的传感技术（Percept）来识别GP的生理变化并将其与恶化相关联 或改善步态功能障碍。项目3（非人类灵长类动物）将检查电生理 苍白球参与脚、苍白球→板内和苍白球→缰活动的变化与 认知运动症状提供了对认知运动步态障碍、任务 转移困难，失去动力，这将补充项目中人类研究的结果 1和2.中心的所有组成部分都与催化剂项目进行协同互动， 一位有前途的早期研究者的研究工作，他将使用一种新的闭环DBS方法来探索 PD患者的回路动力学及其与PD运动体征的关系。成像核心将获取状态- 最先进的，高场结构MRI以及项目1和2中PD患者的休息和基于任务的fMRI（使用 7 T扫描仪）和项目3中NHP的结构MRI（使用首台10.5T扫描仪）。 核心将获得临床和定量运动和神经心理学评估，这些评估将与 在手术室中急性获得的生理数据，在外部DBS电极导线患者中亚急性获得的生理数据 和皮质电图阵列，并通过术后使用Percept进行长期记录。的 生物统计核心将提供全面的数据管理，质量控制，统计和机器学习 分析并将数据输入NINDS数据管理资源。行政核心将协调 UMN Udall中心的所有方面，实施和支持患者教育和公共外展工作，以及 为下一代PD研究人员制定和监控个性化的职业发展计划。 总之，这些方法将为开发和翻译新的患者提供关键数据， 特定DBS疗法。

The overall goal of the University of Minnesota (UMN) Udall Center is to develop novel, circuit based deep brain stimulation (DBS) therapies for Parkinson’s disease (PD) based on an understanding of the changes in pathophysiological activity patterns that occur in basal ganglia thalamocortical-brainstem (BGTC-B) pathways. Project 1 (human) will characterize the role of oscillatory activity, coupling and connectivity across the broader BGTC network, including the subthalamic nucleus (STN), globus pallidus internus (GPi), sensory, motor, premotor and dorsolateral prefrontal cortices. These recordings will be performed at rest and during cognitive- motor tasks, with and without therapeutic interventions (DBS, L-dopa, DBS+L-dopa). It will also clarify the relative effect of stimulation in different functional subregions of the STN and GPi on motor and cognitive function. Project 2 (human) will explore the mechanisms and effects of pallidal DBS on levodopa resistant motor signs using MRI-derived computational models and fMRI to examine the pathways mediating these changes. It will use new sensing technology (Percept) to identify and correlate the physiological changes in the GP to worsening of, or improvement in, gait dysfunction. Project 3 (non-human primate) will examine the electrophysiological changes in pallido↔peduncular, pallido→intralaminar, and pallido→habenular activity that are related to cognitive-motor symptoms providing further network-level insights into cognitive motor gait impairments, task shifting difficulties, and loss of motivation, which will complement the results from the human studies in Projects 1 and 2. All center components have synergistic interactions with the Catalyst Project, which will support research efforts of a promising Early Stage Investigator who will use a novel closed-loop DBS approach to probe circuit dynamics in PD patients and their relationship to PD motor signs. The Imaging Core will acquire state- of-the-art, high-field structural MRI as well as rest and task-based fMRI for PD patients in Projects 1 and 2 (using 7T scanner) and structural MRI for the NHPs in Project 3 (using the first of its kind 10.5T scanner).The Clinical Core will obtain clinical and quantitative motor and neuropsychological assessments that will be correlated to physiological data obtained acutely in the operating room, subacutely in patients with externalized DBS leads and electrocorticography arrays, and chronically through postoperative recordings using Percept. The Biostatistics Core will provide overall data management, quality control, statistical and machine learning analysis and data entry into the NINDS Data Management Resource. The Administrative Core will orchestrate all aspects of the UMN Udall Center, implement and support patient education and public outreach efforts, and develop and monitor individualized career enhancement plans for the next generation of PD researchers. Together, these approaches will provide critical data towards the development and translation of novel patient- specific DBS therapies.