Working Memory in Parkinson Disease: A Cognitive & Systems Neuroscience Approach

认知障碍和痴呆是帕金森病最具破坏性的症状之一s病（PD）。 早期PD患者表现出轻微的认知功能障碍，通常在出现运动症状时已经存在 超过15%的PD患者在治疗时将符合轻度认知障碍（PD-MCI）的标准。 PD的初步诊断。在PD中观察到的认知缺陷中，许多患者具有特定的 工作记忆（WM），它在几乎所有的高级认知功能中起着重要的作用。这里我们 建议启动对PD患者WM功能障碍的系统研究。本研究的总体目标是 是为了确定大脑激活，网络连接和因果神经动力学的变化， PD患者的WM缺陷，将这些变化与遗忘型MCI（aMCI）患者的WM缺陷进行对比， 确定与多巴胺能相关的激活，连接和因果动力学的变化 药物治疗在目标1中，我们将在功能性磁共振成像（fMRI）过程中使用WM任务， 确定PD-MCI和aMCI中WM期间脑激活的差异模式。在目标2中，我们将 我们使用无任务功能磁共振成像来概括我们在目标1中的发现，以确定 两组中与WM相关的脑区。最后，在目标3中，我们将研究 PD中与皮质多巴胺代谢和口服多巴胺相关的激活和内在连接 更换.我们将检验弱皮质-纹状体网络相互作用是显著特征的假设 的WM赤字PD，这些相互作用的强度与赤字的个体差异。 我们提出的研究将导致新的和更好的理解的机制，认知 帕金森病和阿尔茨海默病损害s病，这两种最常见的神经退行性疾病在老龄化 人口 我们研究的长期目标是更好地理解工作记忆和执行认知 缺陷及其神经生物学基础，的疾病。我们建议的研究将提供 帕金森氏症患者工作记忆缺陷的系统和详细分析s疾病患者。表征 这些赤字对于减少与以下方面有关的大量人力和财力成本至关重要： 认知功能障碍，并最终促进更好的治疗患者。

Cognitive impairment and dementia are among the most devastating symptoms of Parkinsons disease (PD). Early PD patients exhibit subtle cognitive dysfunction that is often already present by the time motor symptoms develop, and over 15% of PD patients will fulfill criteria for Mild Cognitive Impairment (PD-MCI) at the time of the initial PD diagnosis. Among the cognitive deficits seen in PD, many patients have specific impairment of Working Memory (WM), which plays an important role in virtually all higher-order cognitive functions. Here, we propose to initiate a systematic study of WM dysfunction in PD patients. The overarching goals of this study are to determine changes in brain activation, network connectivity, and causal neural dynamics associated with WM deficits in patients with PD, contrast these changes with WM deficits in amnestic-MCI (aMCI) patients, and determine the changes in activation, connectivity, and causal dynamics associated with dopaminergic medications. In Aim 1 we will use a WM task during functional Magnetic Resonance Imaging (fMRI) to determine the differential patterns of brain activation during WM in PD-MCI and aMCI. In Aim 2, we will generalize our findings from Aim 1 using task-free fMRI to determine the intrinsic connectivity differences in brain regions associated with WM in the two groups. Finally, in Aim 3 we will investigate changes in patterns of activation and intrinsic connectivity in PD associated with cortical dopamine metabolism and oral dopamine replacement. We will test the hypothesis that weak cortico-striatal network interactions are prominent features of WM deficits in PD, and that the strength of these interactions is related to individual differences in deficits. Our proposed studies will lead to new and improved understanding of the mechanisms underlying cognitive impairment in PD and Alzheimers disease, the two most common neurodegenerative disorders in the aging population. The long-term goal of our research is to better understand the working memory and executive cognitive deficits, and their neurobiological bases, in people with Parkinsons disease. Our proposed studies will provide a systematic and detailed analysis of working memory deficits in Parkinsons disease patients. Characterizing these deficits is profoundly important to reducing the substantial human and financial costs associated with cognitive dysfunction in PD, and ultimately promoting better treatments for patients.