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.

项目总结与摘要