Influence of white matter damage on step initiation

描述（由申请人提供）：虽然周围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。额皮层下（F-SC）白质束的损伤，在MRI上被确定为白质高强度（WMH），已被确定为与老年人行动障碍相关的因素之一。这些通路是调节体位任务的运动输出的F-SC电路的一个组成部分。与运动控制相关的主要F-SC电路是骨骼运动电路，它负责运动的选择和开始，以及运动的方向、速度和持续时间的编码。另一个可能影响移动性和平衡功能的F-SC回路是背外侧-前额叶回路，它在执行功能过程中起主要作用，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起作用，特别是在老年人中。本研究的目的是更详细地探讨F-SC白质束损伤与运动功能障碍之间的关系。将对70-85岁的社区活动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算法来量化，以计算对运动控制重要的特定纤维束的白质高密度和分数各向异性的体积。行动障碍将使用实验和临床措施进行评估。实验方案将使用选择性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或没有执行功能参与的情况下，根据一个显著的视觉线索，尽可能快地走向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所需的时间。为了补充实验测试，受试者将接受临床平衡评估，该评估使用不同复杂性的测试（例如短时间物理性能测试，多任务测试）。此外，还将进行执行功能的临床测试。将使用多元线性回归模型将神经束特异性白质损伤的测量与实验和临床测量相关联，同时控制混杂变量，如年龄、药物使用和外周感觉功能。公共卫生相关性：老年人结构失衡可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尚不清楚。这项研究将有助于确定导致与年龄相关的行动障碍的潜在病理原因（即白质损伤），并有助于确定未来应该作为改善老年人行动能力干预目标的领域。

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.