Sleep-specific DBS therapy in Parkinson's disease

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，并且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。脑深部电刺激 (DBS)已显示可改善PD患者的睡眠，但效果在患者之间差异很大。更好的 了解帕金森病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DBS的神经生理学变化和通路激活模式 将为开发基于电路的DBS方法治疗睡眠障碍提供理论基础 在警局该建议的目标是：（1）表征振荡活动和连通性的变化， PD患者睡眠障碍时基底节-丘脑皮质网络的变化;（2）检查PD患者睡眠障碍时基底节-丘脑皮质网络的相关性。 DBS对这些变化的影响;（3）识别优先 在DBS或GPi DBS后睡眠改善或受损的患者中激活（或避免）。我们将利用 明尼苏达大学完善的基础设施，使DBS电极导线外部化， 在脉冲发生器放置之前，PD患者的电生理学记录和刺激研究（特定 目标1和2）。我们还将使用高分辨率7特斯拉（T）MRI，弥散纤维束成像和特定主题 将途径激活模式与定量和定性 DBS手术后一年内的睡眠结果指标（具体目标3）。该项目将增加我们的 了解BG皮质活动模式对睡眠的作用，并提供新的见解的机制 DBS会影响睡眠它将为制定更有效的刺激策略提供信息， 睡眠活动利用生理生物标记和为个体定制闭环控制范例 病人的睡眠-觉醒周期这些数据将为DBS靶向特定通路提供基础， PD中的睡眠相关结果。

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.