Spatiotemporal optimization of deep brain stimulation for Parkinson's Disease

帕金森病脑深部刺激的时空优化

• 批准号: 9278298
• 负责人: Matthew Douglas Johnson
• 金额: $ 53.59万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9278298
• 关键词: Acute; Affect; Algorithms; Animals; Area; Basal Ganglia; Behavioral; Bradykinesia; Brain; Brain Stem; Cell Nucleus; Clinical; Complementary therapies; Computer Simulation; Coupled; Coupling; Data; Deep Brain Stimulation; Development; Dopamine; Drug-Induced Dyskinesia; Electric Stimulation; Electrodes; Electrophysiology (science); Frequencies; Functional disorder; Future; Gait; Globus Pallidus; High Frequency Oscillation; Impairment; Implant; Individual; Injection of therapeutic agent; Internal Capsule; Lead; Magnetic Resonance Imaging; Microelectrodes; Modeling; Monkeys; Motor; Motor Cortex; Motor Pathways; Muscle Contraction; Neurotoxins; Parkinson Disease; Parkinsonian Disorders; Pathologic; Pathway interactions; Patients; Pattern; Pharmaceutical Preparations; Phase; Physiological; Process; Replacement Therapy; Severities; Site; Stimulus; Structure; Structure of subthalamic nucleus; Symptoms; Technology; Testing; Thalamic structure; Therapeutic; Therapeutic Effect; Time; Translating; Translations; Treatment Efficacy; Tremor; base; behavioral outcome; density; experimental study; improved; individual patient; motor control; nonhuman primate; novel; novel strategies; signal processing; spatiotemporal; symptomatology; targeted treatment

PROJECT SUMMARY AND ABSTRACT The basal ganglia have a rich, functional topography composed of motor subcircuits and oscillatory networks that are thought to be critically important to the pathophysiology of Parkinson's disease (PD) and the successful application of deep brain stimulation therapy (DBS) in managing each cardinal motor sign of PD. There is a strong clinical need to better understand these processes and in turn harness them to deliver therapy that is tailored to an individual patient and a patient's own symptomatology. In this project, we seek to develop a novel spatiotemporally optimized DBS therapy and evaluate its efficacy in a non-human primate model of PD. The optimization approach leverages the unique capabilities of (1) high-field MR imaging (7T and 10.5T), (2) subject-specific computational models of DBS, (3) a high-density DBS lead with electrodes arranged along and around the lead shank, and (4) a real-time signal processing interface that can readily adapt stimulation parameters on the DBS array based on analysis of ongoing oscillatory activity at and downstream of the site of stimulation. High-density DBS arrays spanning the subthalamic nucleus (STN) and thalamic fasciculus (Array A) and the external and internal globus pallidus (GP) (Array B) will be implanted in each subject. Aim 1 will characterize the magnitude and time course of therapeutic effects on each parkinsonian motor sign when targeting electrical stimulation within and around the STN and GP. Aim 2 will investigate how targeted stimulation differentially affects oscillatory activity at and downstream of the site of stimulation and relates to improvement in each parkinsonian motor sign. Aim 3 will develop and apply a novel set of optimization algorithms, including chaotic desynchronization and real-time closed-loop phasic stimulation, to test the hypothesis that optimizing suppression of exaggerated phase amplitude coupling in the STN and GP will further increase the overall magnitude of DBS therapy. Together, this project will enhance our understanding of the pathophysiology of PD and provide critical data towards translating a patient-optimized DBS therapy that integrates high-density DBS leads with novel closed-loop stimulation.

项目概要和摘要 基底神经节具有丰富的功能性拓扑结构，由运动子电路和振荡网络组成 被认为对帕金森病 (PD) 的病理生理学至关重要 成功应用深部脑刺激疗法（DBS）来管理帕金森病的每个主要运动体征。 临床迫切需要更好地理解这些过程，并利用它们来实现 针对个体患者和患者自身症状的治疗。在这个项目中，我们力求 开发一种新型时空优化 DBS 疗法并评估其在非人类灵长类动物中的疗效 PD 模型。该优化方法利用了 (1) 高场 MR 成像（7T 和 10.5T), (2) DBS 特定学科计算模型，(3) 带电极的高密度 DBS 导联 沿着引导杆和围绕引导杆布置，以及（4）实时信号处理接口，可以很容易地 根据对 和 处持续振荡活动的分析，调整 DBS 阵列上的刺激参数 刺激部位的下游。高密度 DBS 阵列跨越丘脑底核 (STN) 和 丘脑束（阵列 A）以及外部和内部苍白球（GP）（阵列 B）将被植入 每个科目。目标 1 将描述每种治疗效果的大小和时间进程 针对 STN 和 GP 内部及其周围的电刺激时出现帕金森病运动征兆。目标2将 研究目标刺激如何不同地影响该部位及其下游的振荡活动 刺激并与每个帕金森运动体征的改善有关。目标3将开发并应用一部小说 一组优化算法，包括混沌去同步和实时闭环相位 刺激，以检验优化抑制夸大相位幅度耦合的假设 STN和GP将进一步增加DBS治疗的总体规模。总之，这个项目将增强我们的 了解 PD 的病理生理学并为转化患者优化方案提供关键数据 DBS 疗法将高密度 DBS 导联与新型闭环刺激相结合。