强化姿势控制训练改善帕金森病平衡障碍的神经影像学机制研究

Postural instability, without clear neural mechanisms, is the most disabling motor sign for patients with Parkinson's disease (PD) since it directly leads to high incidence rate of falls. Exercise therapy is the most evidence-based intervention that can effectively improve postural instability. Our previous study has found postural control training and muscle strength training are two main domains of exercise therapy for enhancing postural stability, the former generate improvement in more aspects and in longer-term. However, the neural mechanisms underlying the treatment has not been known and the postural control training lacks intensity setting, which impedes the clinical application in a precise manner. Postural control deficit is the core problem of postural instability, which shows inefficacy of postural adjustment at speed and amplitude and deteriorates when attention is distracted as dual-task condition. This project aims to clarify the neural mechanism underlying the postural control of PD patients with postural instability and to investigate the neural mechanism of postural control training effectiveness for PD patients. Functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy(fNIRS) are adopted to measure the whole brain activity by detecting changes associated with blood flow during imagined postural control tasks and assess the cortical activity during real tasks respectively. A series of postural control tasks are designed for fMRI and fNIRS tests in which external temporal, or spatial or attention requirement is assigned none once, one kind once, or two kinds once with intensity increasing. Postural control training with emphasis on these requirements are designed with two intensity levels and strength training are used as the active control. The specific research objectives are: 1) to determine the influence of PD and postural instability on the brain activation during postural control tasks with different temporal, or spatial or attention requirement(s), 2) to clarify the neural mechanism underlying the difference of effectiveness of postural control training at two intensity levels and strength training on improving postural stability, enhancing balance confidence and preventing falls. This project will elucidate the neural mechanism of postural instability and treatment-induced brain reorganization in PD patients which provides theoretical basis for new or more effective treatments development for PD patients. Meanwhile this study will reveal the intensity/dose-effect relationships of postural control training which is helpful for its clinical application in a precise way.

帕金森病（PD）平衡障碍是导致高跌倒发生率的直接原因，其神经机制仍不清晰，在目前主流治疗中无法得到有效改善。运动疗法是具有最多科学依据的有效干预手段，本团队前期研究发现姿势控制训练与力量训练为最常用以改善PD平衡障碍的运动疗法，前者较后者产生更全面且长期的疗效，但疗效的神经机制仍未知，且姿势控制训练目前缺少强度量化，不利于临床推广。本项目拟以姿势控制为主线，针对PD姿势控制障碍特征设计对时空参数以及注意力不同需求强度的姿势控制任务以及训练方案，利用fMRI和fNIRS优势互补，系统研究①PD平衡障碍者姿势控制的神经影像学机制，②不同强度姿势控制训练对改善PD平衡障碍的疗效及其神经影像学机制。本项目对于PD平衡障碍的影像学神经机制及神经修复机制的潜在研究成果将为开发出更多有效的PD治疗或预防手段提供理论依据，弄清姿势控制训练强度与疗效的量效关系将有助于标准化训练方案建立与临床推广。

帕金森病（PD）平衡障碍是导致高跌倒发生率的直接原因，其神经机制仍不清晰，在目前主流治疗中无法得到有效改善。运动疗法是具有最多科学依据的有效干预手段，本团队前期研究发现姿势控制训练与力量训练为最常用以改善PD平衡障碍的运动疗法，前者较后者产生更全面且长期的疗效，但疗效的神经机制仍未知，且姿势控制训练目前缺少强度量化，不利于临床推广。本项目拟以姿势控制为主线，针对PD姿势控制障碍特征设计对时空参数以及注意力不同需求强度的姿势控制任务以及训练方案，利用fMRI和fNIRS优势互补，系统研究①PD姿势控制的神经影像学机制，②不同强度姿势控制训练对改善PD平衡障碍的疗效及其神经影像学机制。本项目发现PD患者静息态时在大脑梭状回、额回、枕中回及小脑等区域的低频振幅较健康人更强，但在大脑楔叶、右中央前回、前扣带回等区域的低频振幅较健康人弱。低强度的常规迈步时，PD患者呈现大脑血流活动的效能不足，在大脑前额叶, 辅助运动区以及感觉联合区呈现明显的代偿性激活增加；中等强度任务中大幅迈步较其它任务对大脑血流活动的激活最为明显；感觉联合脑区对于不同强度任务的反应呈现人群间差异。临床随机对照试验发现高低强度平衡训练均较对照组（手功能训练组）更有效地提升平衡功能，但高低强度训练组之间未呈现显著的组间差异，并且通过fMRI发现中平衡组与手功能训练组对静息态脑功能重组表现出明显差异，前者增加小脑上部、额中回及辅助运动区的ALFF, 减少小脑下部、中央后回及右顶下回的ALFF；后者增加楔前回、梭状回及海马旁回的ALFF, 减少颞中回、前扣带回及中央旁小叶的ALFF。本项目对于PD平衡障碍的影像学神经机制及神经修复机制的潜在研究成果, 为开发出更多有效的PD治疗或预防手段提供理论依据，弄清姿势控制训练强度与疗效的量效关系将有助于标准化训练方案建立与临床推广。