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; 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 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。深脑刺激 （DBS）已证明可以改善PD的睡眠，但是在患者中的影响较大。更好 了解PD中睡眠功能障碍的神经元机制，DBS如何影响睡眠质量， 以及使用这些变化的DBS激活途径激活的神经生理学变化和途径模式 将为开发基于电路的DBS方法来治疗睡眠障碍的理由 在PD中。该建议的目的是：（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础神经节 - 丘脑皮质网络； （2）检查亲戚 DBS在STN或GPI中对这些变化的影响； （3）确定优先的神经途径 STN或GPI DBS后睡眠改善或睡眠不足的患者激活（或避免）。我们将利用 明尼苏达大学建立的基础设施良好 在脉冲发生器放置之前，PD患者的电生理记录和刺激研究（特定 目标1和2）。我们还将使用高分辨率7特斯拉（T）MRI，扩散术和特定于主题 计算生物物理建模将途径激活模式与定量和定性相关联 DBS手术后一年的睡眠结局度量（特定目标3）。这个项目将增加我们的 了解BG - 皮层活动模式在睡眠中的作用，并提供有关机制的新见解 DBS会影响睡眠。它将告知开发更有效的刺激策略以正常化 使用生理生物标志物和针对个体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。这些数据将为针对特定途径的DBS提供基础，以优化 PD中与睡眠有关的结果。