Sleep-specific DBS therapy in Parkinson's disease

帕金森病的睡眠特异性 DBS 疗法

• 批准号: 10635548
• 负责人: LUKE Aaron JOHNSON
• 金额: $ 62.61万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10635548
• 关键词: Affect; Basal Ganglia; Behavior; Biological Markers; Brain; Characteristics; Clinical; Clinical Data; Coupling; Data; Deep Brain Stimulation; Development; Diffusion; Disease; Electrocorticogram; Electrophysiology (science); Excessive Daytime Sleepiness; Frequencies; Goals; Individual; Infrastructure; Knowledge; Magnetic Resonance; Magnetic Resonance Imaging; Maintenance; Measures; Minnesota; Modeling; Motor; Neural Pathways; Neurodegenerative Disorders; Neurons; Operative Surgical Procedures; Outcome; Parkinson Disease; Pathologic; Pathway interactions; Patients; Pattern; Persons; Physiologic pulse; Physiological; Play; Prefrontal Cortex; Quality of life; REM Sleep; Reporting; Research; Resistance; Resolution; Role; Sleep; Sleep Disorders; Sleep Fragmentations; Sleep Wake Cycle; Sleep disturbances; Therapeutic; Therapeutic Effect; Therapeutic Intervention; Universities; actigraphy; biophysical model; brain circuitry; design; imaging facilities; improved; improvement on sleep; individual patient; insight; invention; motor disorder; motor symptom; nervous system disorder; neurophysiology; neuroregulation; non rapid eye movement; novel; pre-clinical; sleep behavior; sleep quality; sleep regulation; targeted treatment; tractography

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 and 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. Deep brain stimulation (DBS) has been shown to improve sleep in PD however effects are highly variable across patients. A better understanding of the neuronal mechanisms underlying sleep dysfunction in PD, how DBS affects sleep quality, and the neurophysiological changes and patterns of pathway activation with DBS that underlie these changes would provide the rationale for development of circuit-based DBS approaches to the treatment of sleep disorders in PD. The goal of this proposal is to: (1) characterize the changes in oscillatory activity and connectivity in the basal ganglia-thalamocortical network during disturbances in sleep in PD patients; (2) examine the relative effects of DBS in the STN or GPi on these changes; (3) identify the neural pathways that are preferentially activated (or avoided) in patients with improved or impaired sleep after STN or GPi DBS. We will leverage the well-established infrastructure at the University of Minnesota to externalize DBS leads and perform electrophysiology recordings and stimulation studies in PD patients prior to pulse generator placement (Specific Aims 1 and 2). We will also use high-resolution 7 Tesla (T) MRI, diffusion tractography, and subject-specific computational biophysical modeling to associate pathway activation patterns with quantitative and qualitative measures of sleep outcomes in the year following DBS surgery (Specific Aim 3). This project will increase our understanding of the role of BG-cortical activity patterns on sleep and provide new insights into the mechanisms by which DBS impacts sleep. It will inform the development of more effective stimulation strategies to normalize sleep activity that utilize physiological biomarkers and closed-loop control paradigms tailored to individual patient's sleep-wake cycle. These data will provide the basis to target specific pathways with DBS to optimize sleep-related outcomes in PD.

项目概要/摘要 超过 75% 的帕金森病 (PD) 患者存在严重的睡眠-觉醒障碍 导致生活质量下降，并且比运动更容易造成残疾和对治疗产生抵抗力 PD 的症状。目前，导致帕金森病患者睡眠障碍的机制尚不明确。 已被理解，并且迫切需要改善睡眠质量的治疗发明。脑深部刺激 DBS 已被证明可以改善 PD 患者的睡眠，但不同患者的效果差异很大。更好的 了解 PD 睡眠功能障碍的神经机制、DBS 如何影响睡眠质量、 以及这些变化背后的神经生理学变化和 DBS 通路激活模式 将为开发基于回路的 DBS 方法来治疗睡眠障碍提供依据 在PD。该提案的目标是：（1）表征振荡活动和连通性的变化 PD患者睡眠障碍期间的基底节-丘脑皮质网络； （二）考察亲属 STN 或 GPi 中的 DBS 对这些变化的影响； (3) 确定优先的神经通路 STN 或 GPi DBS 后睡眠改善或受损的患者被激活（或避免）。我们将利用 明尼苏达大学完善的基础设施可将星展银行的领先优势外部化并执行 在放置脉冲发生器之前对 PD 患者进行电生理学记录和刺激研究（具体 目标 1 和 2)。我们还将使用高分辨率 7 Tesla (T) MRI、扩散纤维束成像和特定主题 计算生物物理模型将通路激活模式与定量和定性相关联 DBS 手术后一年的睡眠结果测量（具体目标 3）。这个项目将增加我们的 了解 BG 皮质活动模式对睡眠的作用并提供对其机制的新见解 DBS 影响睡眠的方式。它将为制定更有效的刺激策略以实现正常化提供信息 利用生理生物标志物和针对个人量身定制的闭环控制范式的睡眠活动 患者的睡眠-觉醒周期。这些数据将为 DBS 优化特定路径提供基础 PD 中睡眠相关的结果。