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

• 批准号: 10703235
• 负责人: Jerrold L Vitek
• 金额: $ 226.53万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 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/10703235
• 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; MPTP non-human primate; 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; brain circuitry; career; catalyst; cognitive function; cognitive impairment in Parkinson' 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; sensor technology; statistical and machine learning; symposium; symptomatology; treatment optimization

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）Udall中心的总体目标是开发基于巡回赛的小说深度 基于对变化的理解，帕金森氏病（PD）的脑刺激（DBS）疗法 在基底神经节丘脑皮层脑（BGTC-B）途径中发生的病理生理活性模式。 项目1（人类）将表征振荡活动，耦合和连通性在更广泛的 BGTC网络，包括丘脑下核（STN），Globus pallidus internus（GPI），感觉，运动，运动， 前前额叶皮层。这些录音将在静止和认知期间进行 运动任务，没有治疗干预措施（DBS，L-DOPA，DBS+L-DOPA）。它也将阐明亲戚 STN和GPI不同功能子区域刺激对运动和认知功能的影响。 项目2（人类）将探索苍白的DBS对左旋多巴电动机标志的机制和影响 使用MRI衍生的计算模型和fMRI检查介导这些变化的途径。会 使用新的灵敏度技术（感知）来识别和关联GP的物理变化以担心 步态功能障碍或改进。项目3（非人类灵长类动物）将检查电生理学 pallido↔phecular，pallido→层内的变化和pallido→Habenular活性与之相关 认知运动符号为认知运动步态障碍提供进一步的网络级别的见解，任务 转移困难和动力丧失，这将完成项目中人类研究的结果 1和2。所有中心组件都与催化剂项目具有协同的相互作用，该项目将支持 诺言的早期研究员的研究工作将使用新颖的闭环DBS方法证明 PD患者的电路动力学及其与PD电机标志的关系。成像核心将获得状态 - 项目1和2（使用）的PD患者的ART，高场结构MRI以及REST和基于任务的fMRI 项目3中NHP的7T扫描仪和结构性MRI（使用此类扫描仪的第一个扫描仪）。临床 核心将获得临床和定量运动和神经心理学评估，这将与 在手术室中敏锐地获得的物理数据，在具有外部DBS铅的患者中脱粒 和皮质学阵列，以及使用感知术后记录。 生物统计学核心将提供总体数据管理，质量控制，统计和机器学习 分析和数据输入NINDS数据管理资源。行政核心将编排 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研究人员制定和监视个性化的职业增强计划。 这些方法一起将提供关键数据，以开发和翻译新的患者 - 特定的DBS疗法。

项目成果

Modulation of Beta Oscillations in the Pallidum During Externally Cued Gait.

外部提示步态期间苍白球中 Beta 振荡的调节。

• DOI: 10.3389/frsip.2022.813509
• 发表时间: 2022
• 期刊: Frontiers in signal processing
• 作者: Lu,Chiahao;Amundsen-Huffmaster,SommerL;Louie,KennethH;Petrucci,MatthewN;Palnitkar,Tara;Patriat,Remi;Harel,Noam;Park,MichaelC;Vitek,JerroldL;MacKinnon,ColumD;Cooper,ScottE
• 通讯作者: Cooper,ScottE

Overground versus treadmill walking in Parkinson's disease: Relationship between speed and spatiotemporal gait metrics.

• DOI: 10.1016/j.gaitpost.2022.01.020
• 发表时间: 2022-03
• 期刊: Gait & posture
• 影响因子: 2.4
• 作者: Lu C;Louie KH;Twedell EL;Vitek JL;MacKinnon CD;Cooper SE
• 通讯作者: Cooper SE

Postural instability in Parkinson's disease assessed with clinical "pull test" and standardized postural perturbations: effect of medication and body weight support.

• DOI: 10.1007/s00415-022-11375-6
• 发表时间: 2023-01
• 期刊: JOURNAL OF NEUROLOGY
• 影响因子: 6
• 作者: Lu, Chiahao;Louie, Kenneth H.;Stutz, Amber M.;MacKinnon, Colum D.;Cooper, Scott E.
• 通讯作者: Cooper, Scott E.