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

产品说明： 我们的长期目标是开发有效的康复，以改善帕金森病（PD）患者的平衡和步态。为了实现这一目标，本提案的目的是开发一种有效的、客观的"步态冻结"措施，将其与异常的大脑连接联系起来，并[确定]使用这些冻结和大脑生物标志物进行步态康复的可行性 PD中的疾病]。步态冻结是间歇性无法行走，是PD和其他退行性神经系统疾病老年患者福尔斯的常见原因。 （三） 这项研究的目的是：1）客观地描述使用身体佩戴传感器的PD冻结，2）探索这些冻结的客观测量如何与使用静息状态功能成像（fMRI）的大脑中的异常功能连接相关，以及[3]确定未来ABC康复干预FoG的随机对照试验所需的受试者数量。我们假设，有效的，仪器化的措施冻结的严重程度可以开发从便携式，无线惯性传感器实用的临床试验和clinica实践。我们还假设，冻结的严重程度将与异常功能连接的内侧额叶皮层与基底神经节和脑干运动区。[We预测使用客观步态和大脑连接生物标志物将有助于评估康复干预如何减少PD患者的冻结并改善步态和平衡。 一项观察性研究将在3个匹配组（30例受试者）中将转弯和行走期间平衡和步态协调的定量测量与最新技术水平的额叶-皮质下功能连接性、静息状态fMRI相关联：PD伴冷冻、PD不伴冷冻和老年对照受试者。为了评价步态冻结，特发性PD受试者将在停用抗帕金森药物12小时后在左旋多巴关闭状态下接受测试。为了建立一个“冻结指数”，所有的受试者将在原地转身，穿过狭窄的门口，左耳或右耳的听觉音调指示方向的变化。两个小腿上的无线同步惯性传感器，下背部和胸骨将记录角速度和线性加速度。将在同一天获得静息状态（无任务）fMRI连接，并基于涉及内侧额叶皮质、脑干运动区、基底神经节纹状体和丘脑底核以及小脑的功能网络中低频活动的同步进行分析。[In此外，一项初步的干预性研究将20名患有步态冻结的PD受试者随机分为8周ABC康复计划或常规护理。设盲检查者将在8周期间前后对两组进行客观FoG评估、rsfMRI和认知测试，作为本提案竞争性更新中临床试验的初步数据。 这项研究的结果将确定最佳的流动性和大脑的结果措施，我们的长期目标，康复干预研究的FOG退伍军人与PD。阐明步态缺陷和额叶缺陷之间的关系将导致更有效的康复干预，不仅可以改善PD退伍军人的活动性和认知功能，而且还可以改善许多老年退伍军人由于影响大脑额叶的神经功能缺陷而具有跌倒的高风险。

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.)