Characterizing the interaction between neural attention and somato-motor systems in non-demented patients with Parkinson's disease

帕金森病（PD）是一种进行性神经退行性疾病，在美国和世界范围内提出了迫在眉睫的经济和社会挑战。尽管主要是运动系统的障碍（即，控制运动的大脑系统），PD患者也被认为表现出严重的注意力缺陷，这是我们将大脑资源引导到环境重要方面的能力。重要的是，这些问题并非彼此孤立，因为注意力问题与PD患者的福尔斯风险密切相关，这是该人群住院和重大损伤的最常见原因。事实上，基于注意力的治疗已经为PD患者开发，并取得了一定的成功，但患者结局存在很大的差异。这种变异性在很大程度上是由于这些疗法缺乏特定的神经生理学和认知靶点，因此更好地了解受影响的大脑系统对于改善患者预后至关重要。目前的项目旨在识别和量化PD患者注意力障碍的大脑基础，以及这些缺陷的注意力子系统和躯体运动系统之间相互作用的神经生理学基础。这项研究的主要目标是为增强临床干预提供新的目标，如大脑刺激和注意力训练疗法。该项目的第二个目标是提供一个数据驱动的框架，用于评估PD患者大脑中的注意力训练，以及这种训练对控制运动的大脑回路（即，躯体运动网络）。为了实现这些目标，将利用一系列创新的认知神经科学实验，结合先进的脑成像技术。这些数据将使用蒙特利尔现有的扩展数据库（魁北克帕金森网络和蒙特利尔神经学研究所临床生物成像和遗传库）收集，并使用Sylvain Baillet教授在其麦吉尔大学实验室中最先进的软件中开发的许多高度创新的信号处理技术进行分析（Brainstorm;全球超过23，000名用户）。这些研究将允许PD患者的注意力和躯体运动网络之间和内部的动态脑活动模式的作用进行新的调查。这将为注意力训练和脑刺激疗法提供新的靶点，同时也增强了我们对导致PD的神经生物学畸变的理解。我的研究项目的目的是了解（1）哪些注意力神经子系统优先受到PD的影响，以及（2）这些注意力子系统如何与已建立的PD相关的躯体运动系统畸变相互作用。这些发现将为评估治疗效果提供关键指标，以及治疗干预的目标。随着PD的患病率在全国和全球范围内的上升，迫切需要具体的干预目标，以尽量减少这种使人衰弱的疾病的影响，无论是对受影响的人的个人水平，还是广泛的社会经济规模。

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that presents a looming economic and societal challenge in the United States and worldwide. Despite being primarily a disorder of the motor system (i.e., the brain systems controlling movement), patients with PD are also known to exhibit profound deficits in attention, which is our ability to direct brain resources towards important aspects of the environment. Importantly, these issues are not isolated from one another, as attentional issues are robustly linked to risk of falls in patients with PD, which are the most common reason for hospitalization and major injury in this population. Indeed, attention-based therapies have been developed for patients with PD and have been moderately successful, but a great deal of variability exists in patient outcomes. This variability is largely due to the lack of specific neurophysiological and cognitive targets of these therapies, so a better understanding of the brain systems being affected is essential to improving patient outcomes. The current project aims to identify and quantify the brain- basis of attentional impairments in patients with PD, as well as the neurophysiology underlying the interactions between these deficient attentional sub-systems and somato-motor systems. The primary goal of this research will be to provide novel targets for enhanced clinical interventions, such as brain stimulation and attention-training therapies. A secondary goal of this project is to provide a data-driven framework for the assessment of attention- training in the brains of patients with PD, and the impact of this training on the brain circuits that control movement (i.e., somato-motor networks). To reach these goals, a series of innovative cognitive neuroscience experiments will be utilized, combined with advanced brain imaging techniques. These data will be collected using expansive data repositories available in Montreal (the Quebec Parkinson Network and the Montreal Neurological Institute Clinical Biological Imaging and Genetic Repository) and analyzed using a number of highly innovative signal processing techniques developed by Professor Sylvain Baillet in his state-of-the-art software housed in his laboratory at McGill University (Brainstorm; > 23,000 users worldwide). These studies which will allow for novel investigations of the role of dynamic brain activity patterns between and within attention and somato-motor networks in patients with PD. This will provide new targets for attention- training and brain stimulation therapies, while also enhancing our understanding of the neurobiological aberrations that contribute to PD. The aim of my research project is to understand (1) which attentional neural sub-systems are being preferentially affected by PD, and (2) how these attentional sub-systems interact with established PD-related somato-motor system aberrations. These findings will then provide key metrics for the assessment of treatment efficacy, as well as targets for therapeutic intervention. With the prevalence of PD rising both nationally and worldwide, concrete targets for intervention are desperately needed to minimize the impact of this debilitating disorder, both on the personal level for those affected, and broadly on a socio-economic scale.