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基于电路的新型深度 基于对变化的理解的脑刺激(DBS)治疗帕金森病(PD) 在发生在基底节、丘脑皮质-脑干(BGTC-B)通路的病理生理活动模式中。 项目1(人类)将描述振荡活动、耦合和连接在更广泛范围内的作用 BGTC网络包括丘脑底核(STN)、苍白球内侧核(GPI)、感觉、运动、 前额叶皮质和背外侧前额叶皮质。这些录音将在休息和认知过程中进行- 运动任务，有无治疗干预(DBS、L-多巴、DBS+L-多巴)。它还将澄清相关的 刺激STN和GPI不同功能区对运动和认知功能的影响 项目2(人类)将探索苍白球DBS对左旋多巴抵抗运动体征的作用机制和效果。 使用磁共振成像衍生的计算模型和功能磁共振成像来检查调节这些变化的通路。会的 使用新的传感技术(Percept)识别GP中的生理变化并将其与恶化相关 步态障碍的或改善的。项目3(非人灵长类)将检查电生理学。 苍白球↔足部、板层内苍白球→和苍白球→缰核活动的变化 认知运动症状提供了对认知运动步态障碍、任务的进一步网络层面的洞察 转移困难和丧失动力，这将补充项目中人体研究的结果 1和2.所有中心组件都与Catalyst项目有协同作用，这将支持 一位有前途的早期研究员的研究工作，他将使用一种新的闭环式DBS方法来探测 帕金森病患者的电路动力学及其与帕金森病运动体征的关系。成像核心将获得状态- 项目1和2中最先进的高场结构磁共振成像以及针对PD患者的休息和基于任务的功能磁共振成像(使用 7T扫描仪)和结构磁共振成像(使用首台10.5T扫描仪)。临床 CORE将获得临床和量化的运动和神经心理学评估，这些评估将与 生理数据在手术室中获得，在外置DBS导联的患者中亚急性获得 和皮层脑电图仪阵列，并通过使用Percept的术后记录进行慢性记录。这个 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宣传努力，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型患者提供关键数据- 特定的星展银行疗法。

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.