Effects of Parkinson's Disease on Perception, Cognition, and Gait

描述（由申请人提供）：帕金森病（PD）的非运动方面，如感觉、知觉和认知缺陷，是日常功能和生活质量显著下降的一个原因。PD患者最重要的日常功能之一是视觉空间能力，它使视觉环境的感知和认知理解和导航成为可能。这一领域的缺陷源于大脑高阶关联区域的病理改变，以及来自更基本的视觉处理区域的输入缺陷，反映了皮质纹状体回路特定方面的功能障碍。了解PD的视觉空间后遗症的潜在重要性是考虑初始运动损伤的一面，因为PD几乎总是单侧发病的神经退行性变，右半球尤其参与视觉空间加工的许多方面。我们的目的是定义PD的基本视觉和视觉空间问题之间的关系，并检查潜在的神经变化。特别是，我们的目标是阐明特定皮质纹状体结构在视觉空间认知中的因果作用，并定义特定皮质区域和纹状体区域之间的功能连接。首先，我们假设帕金森病的认知障碍反映了涉及尾状背侧的皮质纹状体回路的功能障碍。其次，我们假设运动症状发作的一侧以及视觉刺激的半野表现可以预测皮质纹状体环的半球侧性，对左身体侧（右侧基底神经节）和左视觉半野表现的患者有更强的影响。我们的第三个重点是视觉和视觉空间障碍与日常功能的关系，包括步态、运动冻结、主观生活质量、幻觉、情绪和其他以患者为中心的PD特征。为了实现我们的目标，我们将汇集来自互补学科的科学家的专业知识，包括神经心理学，视觉心理物理学，认知神经科学和神经影像学，以及临床运动科学。我们提出的fMRI研究为皮质纹状体回路的特定成分，特别是额纹状体和顶纹状体回路的功能障碍是PD患者特定视觉空间和视觉认知任务问题的基础这一假设提供了直接检验。由于大多数皮质区域与纹状体相连，这些研究将填补理解皮质纹状体回路在认知中可能普遍存在的作用的重大空白。应用心理物理、认知和成像技术来预测PD患者高级认知和日常功能的完整性，将在临床上有用，使患者在诊断时能够识别潜在的空间问题。我们的测试针对患者自己报告的视觉、视觉空间和功能症状，确保对机制的阐明具有临床相关性。

DESCRIPTION (provided by applicant): Non-motor aspects of Parkinson's disease (PD) such as deficient sensation, perception, and cognition are a source of a significant decline in everyday function and quality of life. Among the most important of daily functions that is affected in PD is visuospatial ability, which enables the perceptual and cognitive comprehension and navigation of the visual environment. Deficits in this domain arise from pathological changes in high-order association areas of the brain as well as from defective input from more basic visual processing areas, reflecting dysfunction of specific aspects of corticostriatal loops. Of potential importance to understanding the visuospatial sequelae of PD is consideration of the side of initial motor impairment, as PD nearly always has unilateral onset of neurodegeneration, and the right hemisphere is especially engaged in many aspects of visuospatial processing. We aim to define the relation between basic vision and visuospatial problems in PD and to examine underlying neural changes. In particular, we aim to elucidate the causal role of specific corticostriatal structures in visuospatial cognition and to define functional connectivity between specific cortical areas and striatal regions. We hypothesize, first, that cognitive impairments in PD reflect dysfunction in corticostriatal loops involving the rostrodorsal caudate. Second, we hypothesize that side of motor symptom onset as well as hemifield presentation of visual stimuli predict the hemispheric laterality of hypoactivation in corticostriatal loops, with stronger effects for patients with onset on the left body side (LPD) (right basal ganglia) and for left visual hemifield presentation. Our third focus is on the relation of visual and visuospatial impairments to daily function, including gait, motoric freezing, subjective quality of life, hallucinations, mood and other patient-centered features of PD. To accomplish our goals, we will marshal the expertise of scientists from complementary disciplines, including neuropsychology, visual psychophysics, cognitive neuroscience and neuroimaging, and clinical movement science. Our proposed fMRI studies provide a direct test of the hypothesis that dysfunction in specific components of corticostriatal loops, especially frontostriatal and parietostriatal loops, underlie problems on specific visuospatial and visuocognitive tasks in PD. As most cortical regions are connected with the striatum, the studies will fill a significant gap in understanding the likely ubiquitous role of corticostriatal circuits in cognition. The application of psychophysical, cognitive and imaging techniques that could predict the integrity of higher-level cognitive and daily functions in PD will be useful clinically, enabling the identification of potential spatial problems for the patient at diagnosis. Our tests target visual, visuospatial, and functional symptoms reported by the patients themselves, ensuring that the elucidation of mechanisms will have clinical relevance. PUBLIC HEALTH RELEVANCE: A principal goal of the proposed project is to relate the neuroimaging, cognitive, and psychometric findings with patient-centered features of PD, including gait abnormalities and motor freezing, subjective quality of life, visual complaints, hallucinations, mood, and self-reported sleep quality. We plan to bridge the psychometric, cognitive and imaging findings to the functional measures, which we expect will lead to translations to diagnostic and management strategies. If visuospatial differences between PD subgroups (such as left and right symptom onset) distinguish their performance on functional measures, then we should target the more affected subgroup with information on what to expect and how best to manage the symptoms that are part of that subgroup's profile.