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: 10282956
• 负责人: Jerrold L Vitek
• 金额: $ 228.69万
• 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/10282956
• 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; 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' 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

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