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.

项目总结和摘要 基底神经节有丰富的功能地形组成的运动亚回路和振荡网络 被认为是至关重要的病理生理学帕金森病（PD）和 成功应用脑深部电刺激治疗（DBS）管理PD的每个主要运动体征。 有一个强烈的临床需要更好地了解这些过程，并反过来利用它们来提供 根据患者个体和患者自身的病理学量身定制的治疗。在这个项目中，我们力求 开发一种新的时空优化DBS疗法，并评估其在非人类灵长类动物中的疗效 PD模型优化方法利用了以下独特功能：（1）高场MR成像（7T和 10.5T），（2）DBS的受试者特定计算模型，（3）带电极的高密度DBS电极导线 沿沿着并围绕引线柄布置，以及（4）实时信号处理接口，其可以容易地 根据对持续振荡活动的分析，调整DBS阵列上的刺激参数， 刺激位点的下游。高密度DBS阵列跨越丘脑底核（STN）， 丘脑束（阵列A）和外部和内部苍白球（GP）（阵列B）将植入 每个主题。目标1将描述治疗效果的大小和时间过程， 帕金森氏症的运动迹象时，针对电刺激内和周围的脊髓和GP。目标2将 研究靶向刺激如何不同地影响振荡活动在和下游的网站， 刺激，并涉及每一个帕金森运动体征的改善。目标3将开发和应用一种新的 一套优化算法，包括混沌去噪和实时闭环相位 刺激，以测试优化抑制放大的相位振幅耦合的假设， DBS和GP将进一步增加DBS治疗的整体规模。这个项目将加强我们的 了解PD的病理生理学，并提供关键数据，以将患者优化的 DBS治疗将高密度DBS电极导线与新型闭环刺激相结合。