Circuit-based deep brain stimulation for Parkinson's disease

基于电路的深部脑刺激治疗帕金森病

基本信息

批准号：
10489820
负责人：
Jerrold L Vitek
金额：
$ 226.42万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-17 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10489820
关键词：
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Acute Affect Algorithms Animals Awareness Basal Ganglia Biological Markers Biostatistics Core Bradykinesia Brain Stem Brain region Caring Chronic Clinical Cognitive Communities Complement Computer Models Coupling Data Data Management Resources Databases Deep Brain Stimulation Development Diffusion Magnetic Resonance Imaging Dopa Dyskinetic syndrome Electrocorticogram Electrophysiology (science)Equilibrium Frequencies Functional Magnetic Resonance Imaging Functional disorder Gait General Population Globus Pallidus Goals Human Image Impairment Individual Infrastructure Lead Leg Levodopa Location MPTP model Magnetic Resonance Magnetic Resonance Imaging Mediating Midwestern United States Minnesota Modeling Monitor Motivation Motor Motor Cortex National Institute of Neurological Disorders and Stroke Neuropsychology Operating Rooms Outcome Parkinson Disease Parkinsonian Disorders Pathway interactions Patient Education Patient Recruitments Patients Pattern Physiological Postoperative Period Prefrontal Cortex Property Quality Control Research Research Personnel Research Support Resistance Resolution Rest Role Sensory Severities Site Structure of subthalamic nucleus Techniques Testing Therapeutic Therapeutic Effect Therapeutic Intervention Translations United States National Institutes of Health Universities base brain circuitry career catalyst cognitive function cognitive impairment in Parkinson&apos s cohort community engagement data management data quality implantation improved insight motor disorder motor symptom multimodal data neural circuit neuroimaging neurophysiology next generation nonhuman primate novel outreach preimplantation sensor technology statistical and machine learning symposium symptomatology treatment optimization

项目摘要

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.

明尼苏达大学 (UMN) 尤德尔中心的总体目标是开发新颖的、基于电路的深度学习基于对变化的了解，针对帕金森病 (PD) 进行脑刺激 (DBS) 疗法基底节丘脑皮质-脑干 (BGTC-B) 通路中发生的病理生理活动模式。项目 1（人类）将描述振荡活动、耦合和连接在更广泛的范围内的作用。 BGTC网络，包括丘脑底核（STN）、苍白球内部核（GPi）、感觉、运动、这些记录将在休息和认知过程中进行。运动任务，有或没有治疗干预（DBS、左旋多巴、DBS+左旋多巴）它还将澄清相关关系。 STN 和 GPi 不同功能分区的刺激对运动和认知功能的影响。项目2（人类）将探索苍白球DBS对左旋多巴抵抗性运动体征的机制和影响使用 MRI 衍生的计算模型和功能磁共振成像来检查介导这些变化的途径。使用新的传感技术 (Percept) 来识别 GP 的生理变化并将其与病情恶化相关联步态功能障碍的改善或改善项目 3（非人类灵长类动物）将检查电生理学。苍白球↔脚、苍白球→板内和苍白球→缰核活动的变化与认知运动症状提供了对认知运动步态障碍、任务的进一步网络级见解转移困难和失去动力，这将补充项目中人类研究的结果 1 和 2. 所有中心组件都与 Catalyst 项目具有协同作用，这将支持对一项有前途的早期研究工作的研究，该研究将使用一种新颖的闭环 DBS 方法来探索 PD 患者的回路动态及其与 PD 运动体征的关系将获得状态 - 项目 1 和 2 中为 PD 患者提供最先进的高场结构 MRI 以及基于休息和任务的 fMRI（使用 7T 扫描仪）和项目 3 中 NHP 的结构 MRI（使用第一台 10.5T 扫描仪）。临床核心将获得与以下相关的临床和定量运动和神经心理学评估在手术室中急性获得的生理数据，在使用外置 DBS 导线的患者中亚急性获得的生理数据和皮层电图阵列，并使用 Percept 进行术后长期记录。生物统计核心将提供全面的数据管理、质量控制、统计和机器学习管理核心将协调分析和数据输入 NINDS 数据管理资源。 UMN Udall 中心的各个方面，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，这些方法将为新型患者的开发和转化提供关键数据。特定的 DBS 疗法。