The effect of aging and cognitive impairment on prefrontal cortical inputs to motor cortical outputs during standing balance control

项目总结/摘要 福尔斯是老年人意外死亡的主要原因。OA是 由于神经典型老化的影响，特别容易受到福尔斯的影响，这改变了重要的神经运动通路 平衡控制。与衰老或病理相关的运动功能下降的个体被认为是利用 前额叶认知区的输入，以支持平衡期间受损的下行皮质运动回路 挑战在平衡受损的成年人中，依赖注意力来控制平衡会造成问题， 个体变得分心，如果他们减少了用于平衡的神经运动资源，情况就更糟了。为 因此，认知功能下降的个体，如轻度认知功能障碍（MCI）的OA， 到福尔斯。尽管MCI患者跌倒风险增加，但很少有有效的策略来恢复MCI患者的平衡， 并且他们的认知能力差降低了许多现有的基于训练的平衡干预的有效性。 需要康复策略来增强潜在的认知运动回路功能，以改善 OA伴和不伴MCI的平衡功能。然而，我们开发更有效的平衡疗法的能力 由于我们对跌倒风险背后的认知-运动通路相互作用缺乏了解，客观 这个F31项目的主要目的是描述在平衡控制中重要的认知-运动回路相互作用。的 拟议的研究将使用非侵入性神经刺激来表征来自主要神经元的有效连接。 认知区，背外侧前额叶皮层（DLPFC），到初级运动皮层（M1），作为年龄的函数， 平衡任务难度、DLPFC参与度和认知障碍。我以前工作的严谨性 赞助者和其他人已经展示了相关的证据，即前额叶皮层和 M1作为平衡任务难度和个体平衡能力的调节因子。我会更直接地关注 识别来自DLPFC的自上而下的输入（涉及注意分配和基于注意的平衡控制） M1的腿部区域。双部位经颅磁刺激（TMS）将用于评估有效性 DLPFC和M1电路之间的因果关系和方向关系（DLPFC→M1）。我 假设前额叶认知区被招募来调节更高水平任务的运动通路 个人平衡和认知能力所必需的困难。我将通过以下方式来检验这个假设：1）测量 平衡挑战和年龄对简单和困难站立平衡任务中DLPFC→M1的影响。2)测试 认知参与和年龄对DLPFC→M1在平衡任务中使用认知运动的影响 双重任务3)测试认知障碍对DLPFC→M1在平衡任务和认知任务中的影响， 运动双重任务这一范例将是DLPFC→下肢M1的首次研究， 功能相关的站立平衡任务。从长远来看，这项工作将有助于发展机制知情 改善平衡控制的神经调节治疗，预测福尔斯风险的神经生理学生物标志物， 康复反应和神经生物学知情的精确（p）康复，以减少OA和MCI的福尔斯跌倒。

PROJECT SUMMARY/ABSTRACT Falls present a significant problem as the leading cause of accidental death in older adults (OA). OA are particularly susceptible to falls due to effects of neurotypical aging, which alters neuromotor pathways important in balance control. Individuals with aging- or pathology-related declines in motor function are thought to leverage inputs from prefrontal cognitive regions to support impaired descending cortical motor circuits during balance challenges. In adults with impaired balance, reliance on attention to control balance poses a problem when the individual becomes distracted, and even more so if they have reduced neuromotor resources for balance. For this reason, individuals with cognitive decline such OA with mild cognitive impairment (MCI) are more susceptible to falls. Despite this increased fall-risk in MCI, there are few effective strategies to rehabilitate balance in MCI, and their poor cognitive abilities reduce the effectiveness of many existing training-based balance interventions. There is a need for rehabilitative strategies to enhance underlying cognitive-motor circuit function to improve balance function in OA with and without MCI. However, our ability to develop more effective balance treatments is limited by our lack of knowledge of the cognitive-motor pathway interactions underlying fall-risk. The objective of this F31 project is to characterize cognitive-motor circuit interactions important in balance control. The proposed research will use non-invasive neurostimulation to characterize effective connectivity from a primary cognitive area, the dorsolateral prefrontal cortex (DLPFC), to the primary motor cortex (M1), as a function of age, balance task difficulty, DLPFC engagement, and cognitive impairment. The rigor of previous work by my sponsors and others has shown correlational evidence that functional connectivity between prefrontal cortex and M1 is modulated as a factor of balance task difficulty in and individual balance ability. I will focus on more directly identifying top-down inputs from the DLPFC (involved in attention allocation and attention-based balance control) to leg areas of M1. Dual-site transcranial magnetic stimulation (TMS) will be used to evaluate effective connectivity, or causal and directional relationships between DLPFC and M1 circuits (DLPFC→M1). I hypothesize that prefrontal cognitive regions are recruited to modulate motor pathways at higher levels of task difficulty as necessitated by individual balance and cognitive ability. I will test this hypothesis by: 1) measuring the effect of balance challenge and aging on DLPFC→M1 in easy and difficult standing balance tasks. 2) Testing the effect of cognitive engagement and aging on DLPFC→M1 across balance tasks using a cognitive-motor dual-task. 3) Testing the effect of cognitive impairment on DLPFC→M1 across balance tasks and cognitive- motor dual-tasks. This paradigm will be the first investigation of DLPFC→ lower limb M1 in the context of functionally relevant standing balance tasks. In the long-term, this work will help develop mechanism-informed neuromodulation treatments to improve balance control, neurophysiological biomarkers to predict falls risk and rehabilitation response, and neurobiology-informed, precision (p)rehabilitation to reduce falls in OA and MCI.