The effects of parkinsonism and deep brain stimulation on basal ganglia-thalamocortical circuitry during sleep-wake behavior

帕金森症和深部脑刺激对睡眠-觉醒行为期间基底节-丘脑皮质回路的影响

• 批准号: 10374059
• 负责人: LUKE Aaron JOHNSON
• 金额: $ 60.28万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10374059
• 关键词: Affect; Animals; Basal Ganglia; Behavior; Biological Markers; Brain; Chronic; Coupled; Coupling; Data; Decision Making; Deep Brain Stimulation; Development; Disease; Dose; Evolution; Excessive Daytime Sleepiness; Exhibits; Foundations; Functional disorder; Future; Globus Pallidus; Goals; Home; Human; Individual; Intervention; Knowledge; Lesion; MPTP non-human primate; Maintenance; Measures; Modeling; Motor; Motor Activity; Motor Cortex; Neurodegenerative Disorders; Neurons; Neurotoxins; Output; Parkinson Disease; Parkinsonian Disorders; Patient Care; Patients; Pattern; Persons; Physiological; Play; Polysomnography; Protocols documentation; Quality of life; REM Sleep; Reporting; Resistance; Role; STN stimulation; Severities; Signal Transduction; Sleep; Sleep Architecture; Sleep Disorders; Sleep Disorders Therapy; Sleep Fragmentations; Sleep Stages; Sleep Wake Cycle; Sleep disturbances; Structure; Structure of subthalamic nucleus; Substantia nigra structure; Technology; Thalamic structure; Therapeutic; Therapeutic Effect; Therapeutic Intervention; Time; base; behavior observation; brain circuitry; clinical care; design; improved; individual patient; insight; invention; motor symptom; nervous system disorder; neurophysiology; nonhuman primate; novel; sleep behavior; sleep physiology; sleep quality; sleep regulation; targeted treatment; wireless

PROJECT SUMMARY/ABSTRACT Over 75% of people with Parkinson's disease (PD) have significant sleep-wake disturbances that are major contributors to decreased quality of life that can be more disabling and resistant to treatment than the motor symptoms of PD. Currently, the mechanisms contributing to disordered sleep in people with PD are poorly understood and there is a critical need for therapeutic inventions to improve sleep quality. Studies suggest that the basal ganglia thalamo-cortical (BGTC) circuit plays an important role in maintaining normal sleep-wake behavior, and the observation that MPTP non-human primate models of PD with selective basal ganglia dopaminergic lesions have extensive sleep alterations further implicates the BGTC circuitry in playing an important mechanistic role in sleep physiology. This project will provide new insight into the pathophysiology of sleep-wake disturbances in PD by characterizing the changes in sleep-related neuronal activity and physiological interactions that occur between subcortical and cortical structures in the BGTC circuit during progressively more severe parkinsonian states. It will compare how deep brain stimulation (DBS) in the subthalamic nucleus and pallidum modifies these interactions to influence sleep-wake behavior, providing data with immediate translational value by identifying whether DBS in one target is more effective than another in normalizing sleep- related neuronal activity and improving sleep-wake behavior. Furthermore, knowledge about how changes in neuronal activity across the BGTC correlates with altered sleep from normal, parkinsonian, and parkinsonian+DBS conditions will provide the basis to develop more effective stimulation strategies that utilize target-specific physiological biomarkers and closed-loop control paradigms tailored to individual patient's sleep disturbances.

项目总结/文摘