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: 10680463
• 负责人: Matthew Douglas Johnson
• 金额: $ 61.42万
• 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: 2016-07-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680463
• 关键词: Action Potentials; Affect; Algorithms; Anatomic Models; Anatomy; Area; Autopsy; Axon; Basal Ganglia; Behavioral; Bradykinesia; Brain; Cell Nucleus; Cells; Chronic; Clinical; Computer Models; Data; Data Set; Deep Brain Stimulation; Distal; Electrodes; Electrophysiology (science); Elements; Face; Fingerprint; Frequencies; Functional disorder; Funding; Globus Pallidus; Goals; Grant; Image; Implant; Individual; Injections; Lead; Lesion; Macaca mulatta; Magnetic Resonance Imaging; Maps; Methods; Microelectrodes; Modeling; Motor; Motor Cortex; Movement; Neural Pathways; Neurons; Neurotoxins; Optical Coherence Tomography; Outcome; Parkinson Disease; Parkinsonian Disorders; Pathway interactions; Patients; Pattern; Phase; Physiologic pulse; Population; Primates; Process; Resolution; Severities; Site; Stimulus; Structure of subthalamic nucleus; Symptoms; Synaptic Transmission; Thalamic structure; Therapeutic; Therapeutic Effect; Time; Tissues; Translating; Tremor; Visit; Visualization; Width; Work; behavioral outcome; density; dopamine replacement therapy; electric field; improved; in vivo; innovation; insight; instrument; motor control; multidisciplinary; neurosurgery; next generation; nonhuman primate; novel; parkinsonian non-human primate; personalized medicine; posture instability; predictive modeling; response; spatiotemporal; symptomatology; targeted treatment; tractography; translational approach; transmission process

PROJECT SUMMARY AND ABSTRACT The basal ganglia have a rich somatotopy and functional topography composed of motor subcircuits that are thought to be critically important to the pathophysiology of Parkinson's disease (PD) and successful application of deep brain stimulation therapy (DBS) for 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 a patient's own symptomatology and motor control needs on a moment by moment basis. This project will investigate how spatiotemporal optimization of DBS settings can differentially affect neural pathway activation through the brain's motor control network and how those results translate to improving each of the four cardinal motor signs of PD (bradykinesia, rigidity, tremor, and postural instability). Aim 1 will investigate at the single cell, ensemble, and network levels how spatiotemporal parameters of DBS influence information transmission, and critically how the motor control network is able to produce naturalistic movements despite information lesions induced by high-frequency stimulation. Aim 2 will develop and apply a Bayesian Dual Adaptive Control algorithm to investigate how spatiotemporal DBS settings affect electrically-evoked compound action potentials and how those features map onto modulating individual motor signs. Aim 3 will leverage the ground-truth electrophysiological data from high-density microelectrode array recordings at the site of DBS and within the motor control network to validate key parameters used in computational models of neural pathway activation with DBS therapy. The proposed study integrates innovative high-density microelectrode array recordings, closed-loop optimization algorithms, micron-resolution anatomical pathway imaging, and subject-specific computational models of DBS. Together, this project will enhance our understanding of the pathophysiology of PD and provide critical data towards translating next generation personalized and responsive DBS therapies.

项目总结和摘要 基底神经节具有丰富的躯体形态和功能地形，由运动子回路组成， 被认为是至关重要的帕金森病（PD）的病理生理和成功的应用 脑深部电刺激治疗（DBS）用于管理PD的每个主要运动体征。有一个强大的临床 我们需要更好地了解这些过程，并反过来利用它们来提供针对特定人群的治疗。 患者自身的神经病学和运动控制需求。该项目将 研究DBS设置的时空优化如何不同地影响神经通路激活 通过大脑的运动控制网络，以及这些结果如何转化为改善四个基本的 PD的运动体征（运动迟缓、僵硬、震颤和姿势不稳定）。目标1将在单一的调查 单元、系综和网络级DBS的时空参数如何影响信息传输， 以及运动控制网络如何能够在信息不对称的情况下产生自然的运动， 高频刺激引起的损伤。目标2将开发和应用贝叶斯对偶自适应控制 研究时空DBS设置如何影响电诱发复合动作电位的算法 以及这些特征如何映射到调制个体运动信号上。目标3将利用地面实况 来自DBS部位和脑内高密度微电极阵列记录的电生理数据 运动控制网络用于验证神经通路激活计算模型中使用的关键参数 DBS治疗。这项研究整合了创新的高密度微电极阵列记录， 闭环优化算法、微米分辨率解剖通路成像和特定受试者 DBS的计算模型。总之，这个项目将提高我们对糖尿病的病理生理学的理解。 PD，并为下一代个性化和响应性DBS治疗提供关键数据。

项目成果

Individual Magnetoencephalography Response Profiles to Short-Duration L-Dopa in Parkinson's Disease.

• DOI: 10.3389/fnhum.2021.640591
• 发表时间: 2021
• 期刊: Frontiers in human neuroscience
• 影响因子: 2.9
• 作者: Peña E;Mohammad TM;Almohammed F;AlOtaibi T;Nahrir S;Khan S;Poghosyan V;Johnson MD;Bajwa JA
• 通讯作者: Bajwa JA