PC-based Rehabilitation of Motor Planning Deficits in Parkinson Disease

描述(由申请人提供)： 项目摘要：帕金森病是最常见的神经系统疾病之一，美国退伍军人健康管理局每年在全国范围内治疗约4万名退伍军人帕金森病。帕金森病传统上被认为是一种运动障碍，但现在很明显，也有认知症状，至少60%的非痴呆患者在一个或多个认知领域受损。虽然认知功能是正常运动行为的基础，但治疗的发展主要集中在运动症状上。认知康复领域有越来越多的证据表明，侧重于认知的特定方面的训练策略可以改善神经疾病的治疗结果。然而，目前还没有认知障碍的模型来为认知功能障碍分配特定的神经心理康复策略。此外，目前还没有对帕金森病患者认知康复效果的系统评估，帕金森病认知康复的神经机制也不清楚。我们有三个目标，1)系统地评价帕金森病患者的认知康复，2)研究帕金森病认知康复的神经机制，3)评估帕金森病认知康复的生态效度。我们将专注于认知功能的一个方面，即决定发起一项运动。运动可以是内部产生的，也可以是外部提示的，帕金森病的运动障碍通常与内部产生的(IG)运动有关。我们的方法是使用基于PC的适应性训练来改善PD患者的IG运动启动性能。该方案旨在使用类似于在创伤性脑损伤患者中显示出有希望的结果的范例来推动有益的神经整形改变。此外，我们将使用功能磁共振成像来测量潜在的BG-丘脑皮质回路的活动，特别是正常激活和额外大脑区域招募不足的模式，并测量与训练相关的这些模式的变化。最后，由于任何关于疾病病理生理学的研究都是为了改善疾病患者的生活，行为和神经心理测量将与训练前后fMRI测量的功能异常相关。改善内源性动作的启动有可能极大地改善日常功能，包括减少跌倒，改善语言产出，并提高对日常自我发起任务的熟练程度，如打开药瓶或准备食物。为帕金森病提供新的和更好的治疗方法的努力对退伍军人健康管理局的使命至关重要。这项工作的关键贡献在于，我们将提供一种新的辅助疗法来治疗帕金森病的认知症状，该疗法具有非侵入性、无副作用、成本效益高、易于实施的特点。 公共卫生相关性： 叙述性帕金森病(PD)是最常见的神经系统疾病之一。大多数人认为帕金森病是一种导致运动问题的疾病，比如震颤或行走困难，然而，现在很明显，帕金森病也涉及认知、思维和运动问题。这些思维障碍，如计划一个动作，是帕金森氏症运动问题的重要组成部分，但很少有研究了解帕金森病对思维的影响，治疗仍主要集中在运动上。我们将测试PD患者认知康复的有效性，并使用脑成像来衡量与训练相关的脑功能变化。我们还将衡量培训对帕金森病患者日常生活活动的帮助程度。这项工作的关键贡献在于，我们将为帕金森病认知症状的治疗提供一种无创、无副作用、成本效益高、易于实施的新疗法。

DESCRIPTION (provided by applicant): Project Abstract: Parkinson's disease (PD) is one of the most common neurological disorders, and the Veterans Health Administration treats approximately 40,000 veterans with PD each year nationwide. PD has traditionally been considered a motor disorder, but it is now clear that there are cognitive symptoms as well, with at least 60% of non-demented patients impaired in one or more cognitive domains. While cognitive function is fundamental to normal motor behavior, the development of treatment has focused primarily on motor symptoms. There is growing evidence in the field of cognitive rehabilitation that training strategies focused on specific aspects of cognition can improve treatment outcomes in neurological disorders. However, there is no model of cognitive impairment that allocates specific neuropsychological rehabilitation strategies to cognitive dysfunction. In addition, there has been no systematic evaluation of the efficacy of cognitive rehabilitation in PD subjects, and the neural mechanisms underlying cognitive rehabilitation in PD are unknown. We have three aims, 1) to systematically evaluate cognitive rehabilitation in PD subjects, 2) to examine the neural mechanisms underlying cognitive rehabilitation in PD and 3) to assess the ecological validity of cognitive rehabilitation in PD. We will focus on a single aspect of cognitive function, the decision to initiate a movement. Movements can be internally generated or externally cued, and motor deficits in PD are typically linked to internally generated (IG) movements. Our approach is to use PC-based adaptive training to improve performance of IG movement initiation in patients with PD. The protocol is designed to drive beneficial neuroplastic changes using paradigms similar to those that have shown promising results in traumatic brain injury patients. In addition, we will use fMRI to measure activity in underlying BG-thalamocortical circuits, specifically patterns of insufficient normal activation and recruitment of additional brain areas, and measure changes in these patterns related to training. Finally, because the goal of any research regarding the pathophysiology of disease is to improve the lives of patients with the disease, behavioral and neuropsychological measures will be correlated with fMRI measured functional abnormalities before and after training. Improvement in the initiation of internally generated movements has the potential to dramatically improve daily functioning including reducing falls, improving language production and increasing proficiency of daily self initiated tasks such as opening a medication bottle or preparing a meal. Efforts to provide new and better treatment approaches for PD are crucial to the mission of the Veterans Health Administration. The key contribution of this work is that we will provide a novel adjunct therapy in the treatment of the cognitive symptoms of PD that is non-invasive, free from side effects, cost effective, and easily implemented. PUBLIC HEALTH RELEVANCE: Narrative Parkinson's disease (PD) is one of the most common neurological disorders. Most people think of PD as a disease that causes problems with movement, such a tremor or difficulty walking, however, it is now clear that PD also involves problems with cognition, or thinking, as well as movement. These thought disorders, such as planning a movement, are an important part of movement problems in PD, but little research has been done to understand the effects of PD on thinking, and treatment still focuses for the most part on movement. We will test the effectiveness of cognitive rehabilitation in PD patients and use brain imaging to measure changes in brain function related to training. We will also measure how well training helps people with PD to perform activities of daily living. The key contribution of this work is that we will provide a new therapy in the treatment of the cognitive symptoms of PD that is non-invasive, free from side effects, cost effective, and easily implemented.