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: 10601010
• 负责人: LUKE Aaron JOHNSON
• 金额: $ 55.24万
• 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 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10601010
• 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; 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; Rodent; 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; brain circuitry; clinical care; design; improved; improvement on sleep; 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/摘要 超过75%的帕金森病（PD）患者有严重的睡眠-觉醒障碍， 导致生活质量下降的因素，可能比运动更致残和更难治疗 PD的症状目前，导致PD患者睡眠障碍的机制尚不清楚， 这是可以理解的，并且迫切需要改善睡眠质量的治疗发明。研究表明 基底神经节丘脑-皮层（BGTC）回路在维持正常睡眠-觉醒中起重要作用 行为，并观察MPTP非人灵长类动物模型的PD与选择性基底神经节 多巴胺能损伤有广泛的睡眠改变，进一步暗示BGTC回路在发挥作用， 睡眠生理学中重要的机械作用。该项目将提供新的见解的病理生理学 通过表征睡眠相关神经元活动和生理学变化， BGTC回路中皮质下和皮质结构之间发生的相互作用， 严重的帕金森症它将比较丘脑底核的深部脑刺激（DBS）和 苍白球改变这些相互作用，影响睡眠-觉醒行为，提供数据， 通过确定一个目标中的DBS是否比另一个目标在正常化睡眠方面更有效， 相关的神经元活动和改善睡眠-觉醒行为。此外，关于如何改变 跨BGTC的神经元活动与从正常、帕金森病患者和 帕金森病+DBS条件将为开发更有效的刺激策略提供基础， 目标特异性生理生物标志物和针对个体患者睡眠定制闭环控制范例 干扰.

项目成果

Role of Microelectrode Recording in Deep Brain Stimulation of the Pedunculopontine Nucleus: A Physiological Study of Two Cases.

微电极记录在脑深部刺激桥脚核中的作用：两个病例的生理学研究。

• DOI: 10.1111/ner.13479
• 发表时间: 2022
• 期刊: Neuromodulation : journal of the International Neuromodulation Society
• 作者: Yako,Takehiro;Kitazawa,Kazuo;Kobayashi,Shigeaki;Yomo,Shoji;Sato,Hiromasa;Johnson,LukeA;Vitek,JerroldL;Hashimoto,Takao
• 通讯作者: Hashimoto,Takao