Influence of white matter damage on step initiation

描述(申请人提供)：虽然外周运动和感觉功能对活动能力的影响是众所周知的，但一个相对未被探索的领域是老年人亚临床中枢神经系统功能障碍如何影响活动能力。额叶-皮质下(F-SC)白质束损伤，在MRI上被确认为白质高信号(WMH)，已被认为是与老年人行动能力障碍相关的因素之一。这些通路是F-SC电路的一个组成部分，用于调节姿势任务的电机输出。与运动控制相关的主要F-SC电路是骨骼运动电路，它负责选择和启动运动，并对运动的方向、速度和持续时间进行编码。另一个可能影响活动和平衡功能的F-SC回路是背外侧-前额叶回路，它在执行功能过程中发挥着重要作用，包括选择性注意。重要的是，执行功能的要素被认为在平衡控制中的作用，特别是在老年人中。本研究的目的是更详细地研究F-SC白质束损伤与运动功能障碍之间的关系。社区-将对70-85岁的老年人进行广泛的行动障碍测试。对白质束的损伤将通过应用自动化算法来计算特定纤维束中对马达控制至关重要的白质高强度和分数各向异性的体积来量化。活动障碍将通过实验和临床两种方法进行评估。实验方案将使用选择反应步骤任务来评估骨骼运动和背外侧-前额叶F-SC回路的功能。选择反应步骤任务要求受试者在有和没有执行功能参与的条件下，基于显著的视觉线索，尽可能快地步入两个可能的步骤位置之一。这些测试的主要响应度量是启动该步骤的时间量。为了补充实验测试，受试者将接受临床平衡评估，使用不同复杂程度的测试(例如短物理性能电池、多任务测试)。此外，还将进行执行功能的临床测试。多元线性回归模型将被用来将特定于脑束的白质损伤的测量与实验和临床测量相联系，同时控制混杂变量，如年龄、用药和周围感觉功能。公共卫生相关性：老年人的肢体平衡失调会显著影响功能和生活质量，并增加因跌倒而受伤和死亡的风险。亚临床中枢神经系统疾病对平衡功能障碍和跌倒的作用还知之甚少。这项研究将有助于确定导致年龄相关性活动障碍的潜在病理原因(即脑白质损伤)，并帮助确定未来应作为改善老年人活动能力的干预目标的区域。

DESCRIPTION (provided by applicant): While the influence of peripheral motor and sensory function on mobility is well known, a relatively unexplored area is how subclinical central nervous system dysfunction in older adults affects mobility. Damage to frontal-subcortical (F-SC) white matter tracts, identified as white matter hyperintensities (WMH) on MRI, has been identified as one of the factors associated with mobility impairments in older adults. These pathways are an integral component of F-SC circuits that modulate motor output for postural tasks. The primary F-SC circuit associated with motor control is the skeletomotor circuit, which is responsible for selection and initiation of movement, and encoding of direction, velocity and duration of movement. Another F-SC circuit that may affect mobility and balance function is the dorsolateral-prefrontal circuit, which plays a major role in executive function processes, including selective attention. Importantly, elements of executive function are recognized for their role in balance control, especially in older adults. The goal of this research is to investigate the relationship between damage to F-SC white matter tracts and mobility dysfunction in more detail. Community-ambulating older adults aged 70-85 years across a wide spectrum of mobility impairment will be tested. The damage to white matter tracts will be quantified by applying automated algorithms to compute the volume of white matter hyperintensities and fractional anisotropy in specific fiber tracts important for motor control. Mobility impairment will be assessed using both experimental and clinical measures. The experimental protocols will use choice reaction step tasks to assess the function of the skeletomotor and dorsolateral-prefrontal F-SC circuits. The choice reaction step tasks require subjects to step as quickly as possible to one of two potential step locations based on a salient visual cue under conditions with and without executive function involvement. The primary response measure from these tests is the amount of time to initiate the step. To complement the experimental tests, subjects will undergo a clinical balance assessment that uses tests of varying complexity (e.g. Short Physical Performance Battery, Multiple Tasks Test). In addition, clinical tests of executive function will be performed. Multiple linear regression models will be used to relate the measures of tract-specific white matter damage to the experimental and clinical measures, while controlling for confounding variables such as age medication use, and peripheral sensory function. PUBLIC HEALTH RELEVANCE: stural dysequilibrium in older adults can markedly affect function and quality of life and increases the risk of injury and death due to falls. The contribution of subclinical central nervous system disease to balance dysfunction and falls is less understood. This research will help to identify a potential pathologic cause (i.e. damage to white matter) that contributes to age-related mobility impairment, and help to identify an area that should be a target of future interventions for improving mobility in older adults.