Imaging the motor system in Parkinson's disease: identifying network deficits with isolated vs. coordinated movements of the upper and lower limbs

帕金森病的运动系统成像：通过上肢和下肢的孤立运动与协调运动来识别网络缺陷

• 批准号: 10261515
• 负责人: Roxana Gabriela Burciu
• 金额: $ 19.77万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10261515
• 关键词: Address; Affect; Age; Ankle; Area; Basal Ganglia; Behavior; Brain; Brain imaging; Brain region; Cerebellum; Characteristics; Chemicals; Clinical; Complex; Corpus striatum structure; Custom; Data; Deterioration; Development; Devices; Disease; Disease Progression; Dopamine; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Future; Gender; Goals; Hand; Head; Image; Individual; Intervention; Ipsilateral; Isometric Exercise; Knowledge; Lateral; Limb structure; Link; Lobule; Locomotion; Lower Extremity; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Medical; Motion; Motor; Motor Cortex; Movement; Movement Disorders; Muscle Contraction; Neurons; Neurophysiology - biologic function; Parkinson Disease; Parkinsonian Disorders; Patients; Pattern; Performance; Play; Production; Protocols documentation; Public Health; Published Comment; Recurrence; Rehabilitation therapy; Relaxation; Research; Role; Substantia nigra structure; Symptoms; System; Testing; Translating; Upper Extremity; Upper limb movement; Walking; Widespread Disease; base; blood oxygen level dependent; brain circuitry; disability; foot; illness length; imaging biomarker; innovation; instrument; limb movement; motor impairment; nervous system disorder; neuroimaging; relating to nervous system; response; targeted treatment; wearable device

Project Summary/Abstract Parkinson's disease (PD) is a debilitating movement disorder that significantly changes the lives of millions of people worldwide. The conventional viewpoint is that the disease is caused by a selective loss of dopamine- producing neurons in the substantia nigra and subsequent striatal dopamine deficiency, leading to a progressive deterioration of voluntary movements. Thus far, functional neuroimaging has been instrumental in identifying PD-related neural abnormalities following dopamine depletion, but it is important to note that most of our understanding of disease-related brain changes is based on studies of upper limb function. Despite the prolific amount of imaging research carried out to date in PD, we still do not have a clear understanding of the extent to which the brain network controlling lower limb movements is affected by the disease. Also, while brain changes associated with isolated limb control have been consistently investigated, the same is not true for simultaneous movements of limbs which are key to many of our daily behaviors including walking. We propose to address this knowledge gap by using a robust functional imaging protocol sensitive to PD changes that relies on quantifying the blood-oxygen-level dependent (BOLD) MRI response during isometric muscle contraction. We will use a force production task to investigate differences in brain activity during performance of isolated limb movements and ipsilateral coordinated movements between PD and healthy subjects. Of note, we anticipate that an interlimb coordination task will further clarify the role of the cerebellum in the pathophysiology of the disease, a largely unexplored and poorly understood area in PD. To accomplish our goals, we propose two aims. First, determine the patterns of brain activity during lower/upper limb force production and determine whether foot-related deficits in key brain regions across the two subcortical-cortical motor circuits are in a different somatotopic region than hand-related deficits. Second, we will determine differences in brain activity during simultaneous movements of non-homologous limbs between PD and healthy controls. We hypothesize the following changes in PD: extensive reduction in brain activity across the basal ganglia- and cerebello-thalamo-cortical motor circuits during isolated limb movements and in higher-order motor areas (cerebellar hemispheres, supplementary motor area, premotor cortex) during interlimb coordination, changes in somatotopic organization, motor circuit specific correlations between functional brain activity and characteristics of movements derived from wearable technology. By establishing task-specific neural activity patterns, we aim to develop a non-invasive testing platform that would: 1) allow for future assessment of disease progression and responsiveness to interventions, 2) guide future research in identifying new neural targets for therapy, 3) provide objective criteria for subtyping PD, and distinguishing it from atypical parkinsonian syndromes.

项目摘要/摘要 帕金森氏病（PD）是一种使人衰弱的运动障碍，可显着改变数百万的生活 全球人。常规的观点是，该疾病是由多巴胺的选择性丧失引起的 在黑质和随后的纹状体多巴胺缺乏症中产生神经元，导致渐进式 自愿运动的恶化。到目前为止，功能性神经影像学已经在识别 多巴胺耗竭后，与PD相关的神经异常，但重要的是要注意我们的大多数 了解与疾病相关的大脑变化是基于上肢功能的研究。尽管有多产 迄今为止在PD中进行的成像研究数量，我们仍然没有清楚地了解 控制下肢运动的大脑网络受疾病的影响。另外，大脑改变 与孤立的肢体控制有关 四肢运动，这对于我们许多日常行为（包括步行）至关重要。我们建议解决这个问题 通过使用依赖于量化的PD变化敏感的稳健功能成像协议，知识差距 等距肌肉收缩期间的血氧水平依赖性（粗体）MRI反应。我们将使用一个 强迫生产任务以调查孤立肢体运动表现过程中大脑活动的差异 PD和健康受试者之间的同侧协调运动。值得注意的是，我们预计会互动 协调任务将进一步阐明小脑在该疾病的病理生理学中的作用，这在很大程度上是 在PD中未开发且了解不足。为了实现我们的目标，我们提出了两个目标。首先，确定 下肢产生/上肢力量期间大脑活动的模式，并确定是否与脚相关的缺陷 在两个下皮质皮层运动电路的关键大脑区域中，与 与手相关的缺陷。其次，我们将确定同时运动期间大脑活动的差异 PD和健康对照之间的非同源肢体。我们假设PD中的以下更改： 在基底神经节和小脑 - 丘脑 - 皮层运动电路中，大脑活动的大量减少 孤立的肢体运动和高阶运动区域（小脑半球，补充运动区域， 跨越协调期间的前皮层） 功能性大脑活动与可穿戴的运动特征之间的相关性 技术。通过建立特定任务的神经活动模式，我们旨在开发非侵入性测试 平台将：1）允许对疾病进展和对干预措施的反应性进行评估， 2）指导未来的研究识别新的神经靶标，3）提供亚型的客观标准 PD，并将其与非典型帕金森综合症区分开。