The effects of parkinsonism and deep brain stimulation on basal ganglia-thalamocortical circuitry during sleep-wake behavior

项目概要/摘要 超过75%的帕金森病（PD）患者有严重的睡眠-觉醒障碍， 导致生活质量下降的因素，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。研究表明 基底神经节丘脑-皮层（BGTC）回路在维持正常睡眠-觉醒中起重要作用 行为，并观察MPTP非人灵长类动物模型的PD与选择性基底神经节 多巴胺能损伤有广泛的睡眠改变，进一步暗示BGTC回路在发挥作用， 睡眠生理学中重要的机械作用。该项目将提供新的见解的病理生理学 通过表征睡眠相关神经元活动和生理学变化， BGTC回路中皮质下和皮质结构之间发生的相互作用， 严重的帕金森症它将比较丘脑底核的深部脑刺激（DBS）和 苍白球改变这些相互作用，影响睡眠-觉醒行为，提供数据， 通过确定一个目标中的DBS是否比另一个目标在正常化睡眠方面更有效， 相关的神经元活动和改善睡眠-觉醒行为。此外，关于如何改变 跨BGTC的神经元活动与从正常、帕金森病患者和 帕金森病+DBS条件将为开发更有效的刺激策略提供基础， 目标特异性生理生物标志物和针对个体患者睡眠定制闭环控制范例 干扰.

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.