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.

项目摘要/摘要 超过75％的帕金森氏病（PD）患有严重的睡眠障碍，这是重大的 与电动机相比，降低生活质量的降低质量可能更残疾和对治疗能力 PD的症状。目前，PD患者导致睡眠不足的机制很差 理解，并且迫切需要治疗发明以提高睡眠质量。研究表明 基底神经节丘脑皮层（BGTC）电路在维持正常睡眠效果中起着重要的作用 行为以及具有选择性基底神经节的MPTP非人类灵长类动物模型的观察 多巴胺能病变具有广泛的睡眠改变，进一步暗示了BGTC电路 睡眠生理中的重要机械作用。该项目将提供有关对病理生理学的新见解 通过表征与睡眠相关的神经元活性的变化和生理学的变化，在PD中的睡眠效果干扰 在逐渐逐步的更多 严重的帕金森氏派国家。它将比较丘脑下核中的大脑刺激（DB）和 Pallidum修改了这些相互作用以影响睡眠效果行为，并立即提供数据 通过识别一个目标中的DB是否比另一个目标的DB在标准化睡眠方面更有效 - 相关的神经元活动和改善睡眠效果行为。此外，了解如何变化 跨BGTC的神经元活性与正常，帕金森尼和 帕金森氏症+DBS条件将为制定利用更有效的刺激策略提供基础 针对个体患者睡眠的靶标特异性生理生物标志物和闭环控制范例 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