Sleep-specific DBS therapy in Parkinson's disease

项目摘要/摘要 超过75%的帕金森氏症(PD)患者有严重的睡眠-唤醒障碍 导致生活质量下降的因素，可能比马达更残疾和更耐受治疗 帕金森病的症状。目前，导致帕金森病患者睡眠障碍的机制尚不清楚 认识到这一点，而且迫切需要治疗性发明来改善睡眠质量。脑深部刺激 (DBS)已被证明可以改善帕金森病患者的睡眠，但不同患者的效果差异很大。更好的 了解帕金森病患者睡眠障碍的神经机制，DBS如何影响睡眠质量， 以及作为这些变化基础的神经生理学变化和DBS的通路激活模式 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。这项提议的目标是：(1)描述在振荡活动和连通性方面的变化 帕金森病患者睡眠障碍时的基底节-丘脑皮质网络；(2)相关检查 DBS在STN或GPI中对这些变化的影响；(3)确定优先于 STN或GPI DBS后睡眠改善或受损的患者激活(或避免)。我们将利用 明尼苏达大学完善的基础设施，将星展银行的销售线索和业绩外部化 脉冲发生器放置前帕金森病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)磁共振成像、扩散束成像和特定受试者 将通路激活模式与定量和定性联系起来的计算生物物理模型 衡量DBS手术后一年的睡眠结果(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，并为其机制提供新的见解 DBS对睡眠的影响。它将为制定更有效的刺激战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做的闭环控制范例的睡眠活动 病人的睡眠-觉醒周期。这些数据将为针对DBS的特定路径进行优化提供基础 帕金森病患者的睡眠相关结局。

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.