Frontal Cortex and Gait Freezing in Parkinson's Disease: Rehabilitation Impact

帕金森病中的额叶皮层和步态冻结：对康复的影响

• 批准号: 8486242
• 负责人: FAY BAHLING HORAK
• 金额: --
• 依托单位: PORTLAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8486242
• 关键词: Acceleration; Affect; Area; Auditory; Back; Basal Ganglia; Biological Markers; Biological Neural Networks; Blinded; Brain; Brain Stem; Camping; Caring; Cell Nucleus; Cerebellum; Chronic Disease; Clinical Trials; Cognitive; Cognitive deficits; Complex; Control Groups; Corpus striatum structure; Data; Ear; Elderly; Equilibrium; Failure; Freezing; Frequencies; Frontal Gait; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Future; Gait; Gait abnormality; Goals; Healthcare Systems; Hour; Impairment; Individual; Intervention; Intervention Studies; Lead; Left; Leg; Levodopa; Link; Matched Group; Measures; Medial; Midbrain structure; Neurodegenerative Disorders; Neurologic; Neurologist; Observational Study; Outcome Measure; Parkinson Disease; Patients; Pharmaceutical Preparations; Physical Rehabilitation; Physical therapy; Physiology; Quality of life; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Rehabilitation therapy; Rest; Self Efficacy; Severities; Sternum; Structure of subthalamic nucleus; Testing; Veterans; Walking; Wireless Technology; age related; base; clinical practice; cognitive disability; cognitive function; cognitive rehabilitation; cognitive testing; disability; efficacy testing; executive function; falls; frontal lobe; high risk; improved; indexing; innovation; instrument; mortality; motor impairment; nervous system disorder; novel; programs; public health relevance; putamen; relating to nervous system; sensor; treatment as usual

DESCRIPTION: Our long-term goal is to develop effective rehabilitation to improve balance and gait in patients with Parkinson's disease (PD). To reach this goal, the purpose of this proposal is to develop a valid, objective measure of 'freezing of gait', relate it to abnormal brain connectivity and [determine the feasibility of using these freezing and brain biomarkers for rehabilitation of gait disorders in PD.] Freezing of gait is the intermittent inability to step and is a common cause of falls in patients with PD and other degenerative neurological diseases in the elderly. The [three] aims of this study are: 1) To objectively characterize freezing in PD with body-worn sensors, 2) To explore how these objective measures of freezing are associated with abnormal functional connectivity in the brain using resting state functional imaging (fMRI), and [3) To determine the number of subjects needed for a future randomized, controlled trial of the ABC rehabilitation intervention on FoG.] We hypothesize that valid, instrumented measures of severity of freezing can be developed from portable, wireless inertial sensors practical for clinical trials and clinica practice. We also hypothesize that freezing severity will be related to abnormal functional connectivity of the medial frontal cortex with the basal ganglia and the brainstem locomotor region. [We predict that use of objective gait and brain connectivity biomarkers will be useful to evaluate how rehabilitation intervention reduces freezing and improves gait and balance in patients with PD.] An observational study will relate quantitative measures of coordination of balance and gait during turning and walking to frontal-subcortical functional connectivity from state-of-the art, resting state fMRI in three matched groups of 30 subjects: PD with freezing, PD without freezing, and elderly control subjects. To evaluate freezing of gait, subjects with idiopathic PD will be tested in the OFF levodopa state after withholding their antiparkinson medication for 12 hours. To develop a 'freezing index', all subjects will turn in place and walk through narrow doorways with auditory tones in their left or right ears to indicate change in direction. Wireless, synchronized inertial sensors on the two shanks, low back and sternum will record angular velocity and linear accelerations. Resting-state (task free) fMRI connectivity will be obtained on the same day and analyzed based on synchronization of low frequency activity in a functional network involving the medial frontal cortex, brainstem locomotor region, the striatum and subthalamic nucleus of the basal ganglia, and the cerebellum. [In addition, a pilot, interventional study will randomize 20 of these PD subjects with freezing of gait into either an 8- week ABC rehabilitation program or usual care. A blinded examiner will conduct objective FoG assessment, rsfMRI, and cognitive tests before and after the 8-week period in both groups as pilot data for a clinical trial in the competing renewal of this proposal.] The results of this stdy will identify the best mobility and brain outcome measures for our long- term goal of a rehabilitation intervention study for FoG in Veterans with PD. Clarifying the relationships between gait deficits and frontal lobe deficits will lead to more effective rehabilitation interventions that can improve both mobility and cognitive function not only in Veterans with PD, but also in many elderly Veterans at high risk of falling due to neurological deficits that affect the frontal lobe of the brain.) PUBLIC HEALTH RELEVANCE: Parkinson's disease (PD) imposes a heavy burden on over 3% of US veterans in the VHA health care system. PD is responsible for major mobility disability as well as cognitive disabilit, resulting in worse quality of life than most other chronic diseases. Freezing of gait is a major reason for mobility disability and associated with cognitive disability, leading to falls and mortality in PD and many other degenerative neurological disorders in the elderly. Over 80% of patients with PD develop this intermittent failure to initiate or maintain walking. The results of this study will identify the best mobility and brain outcome measures for our long-term goal of a rehabilitation intervention study for FoG in Veterans with PD. Clarifying the relationships between gait deficits and frontal lobe deficits will lead to more effective rehabilitation interventions that can improve both mobility and cognitive function not only in Veterans with PD, but also in many elderly Veterans at high risk of falling due to neurological deficits that affect the frontal lobe of the brain.

描述： 我们的长期目标是开发有效的康复，以改善帕金森氏病（PD）患者的平衡和步态。为了实现这一目标，该提案的目的是开发一个有效的，客观的“步态冻结”，将其与大脑连通性异常相关，并[确定使用这些冷冻和脑生物标志物进行步态康复的可行性 [pd。]步态的冻结是间歇性无法踏上的，这是老年人PD患者和其他退行性神经系统疾病的常见原因。 [三个] 这项研究的目的是：1）客观地表征PD与身体磨损的传感器中的冻结，2）探索这些客观的冻结测量如何与使用静止状态功能成像（FMRI）（FMRI）（FMRI）和[3）在大脑中的异常功能连通性相关，并[3）确定对未来的，对未来的试验进行启动的启用启用启用启用启用的受试者的数量。冻结的严重程度可以从可移植的无线惯性传感器进行临床试验和临床实践的实用性开发。我们还假设冻结严重程度将与内侧额叶皮质与基底神经节和脑干运动区域的异常功能连通性有关。 [我们预测，使用客观步态和大脑连通性生物标志物将有用，以评估康复干预如何减少冻结，改善PD患者的步态和步态和平衡。冻结，无冻结的PD和老年人控制的受试者。为了评估步态的冻结，在扣留其抗帕金森药物12小时后，将在左旋多巴州的外左伏田特州进行特发性PD的受试者进行测试。为了开发一个“冻结索引”，所有受试者都会在狭窄的门口穿过狭窄的门口，左耳或右耳有听觉色调，以指示方向的变化。无线，在两个柄上同步的惯性传感器，下背部和胸骨将记录角速度和线性加速度。将在同一天获得静止状态（无任务）fMRI连接性，并基于涉及内侧额叶皮层，脑干运动区域，纹状体和基底神经节的纹状体和下alamic核的功能网络中低频活性的同步进行分析。 [此外，一项试点介入的研究将将步态冻结为8周的ABC康复计划或通常的护理，将这些PD中的20个随机。盲目的审查员将进行客观的雾评估，RSFMRI和两组为期8周之前和之后的认知测试，作为该提案的竞争续签的临床试验的试验数据。]这一stdy的结果将确定我们对fog in veterans in veterans in veterans in verterans for pd in verterans in Rebablitation in velyers的最佳流动性和大脑成果指标。澄清步态缺陷与额叶缺陷之间的关系将导致更有效的康复干预措施，不仅可以在PD的退伍军人中提高活动能力和认知功能，而且在许多老年退伍军人中，由于影响大脑前叶的神经系统缺陷而导致的许多老年退伍军人，也可以提高流动性和认知功能。 公共卫生相关性： 帕金森氏病（PD）在VHA卫生保健系统中对3％的美国退伍军人造成了沉重的负担。 PD负责主要的流动性残疾和认知不稳定，从而使生活质量较差。步态的冻结是流动性残疾的主要原因，并且与认知障碍有关，导致PD的下降和死亡率以及老年人的许多退化性神经系统疾病。超过80％的PD患者发生这种间歇性未能启动或维持步行。结果 这项研究将确定我们对PD退伍军人的康复干预研究的长期康复干预研究的最佳移动性和大脑结局指标。澄清步态缺陷与额叶缺陷之间的关系将导致更有效的康复干预措施，不仅在有PD的退伍军人中，而且在许多由于影响大脑前叶的神经系统缺陷而高的老年退伍军人中，不仅可以改善移动性和认知功能。