Intracortical Mechanisms of Muscle Weakness

描述(由申请人提供)：与衰老相关的肌肉力量(即虚弱)的丧失是一个巨大的问题，因为它限制了身体的独立性，也是残疾发展的主要因素。随着年龄的增长，伴随着力量丧失的许多变化与固定后观察到的变化一致。因此，固定是一种特别适合于检查老龄化人口中所见的力量损失的模型。肌肉(如萎缩)和神经属性(如皮质抑制)的改变导致了力量的丧失。虽然对肌肉特性进行了广泛的研究，但对与力量丧失相关的皮质特性的变化知之甚少。已知的运动想象对增强力量的影响支持了皮质机制在调节力量方面的潜在作用。更具体地说，皮层内的促进和抑制可能是调节强度的重要神经机制。使用成对脉冲经颅磁刺激来评估皮质内的促进和抑制，我们的试点数据表明，老化和制动都增加了长时间间隔的皮质内抑制(LICI)，而制动诱导的LICI的增加与力量的丧失有关。我们的中心假设是，高水平的LICI是肌肉力量的重要神经生理学决定因素。我们将通过实现以下三个具体目标来验证这一假说：1)确定制动引起的皮质内特性变化与肌肉力量和中枢激活减少之间的联系；2)评估运动表象训练在最小化制动引起的皮质内特性变化和肌肉力量和中枢激活减少方面的效果；以及3)比较年轻人、健康老年人和体弱老年之间皮质内特性的差异，并评估与年龄相关的皮质内特性差异与肌肉力量和中枢激活之间的相互关系。了解肌肉力量丧失背后的特定神经机制对于改进康复策略至关重要。 公共卫生相关性：肌肉无力是一种常见的临床现象，与衰老和停用有关，无力与残疾发展、功能能力降低甚至死亡有关。这项研究将确定皮质内的促进和抑制属性，以调节与制动和老化相关的力量丧失。对调节肌肉无力的神经机制的了解将有助于开发促进肌肉功能的干预措施。

DESCRIPTION (provided by applicant): Loss of muscle strength (i.e. weakness) associated with aging is a huge problem as it limits physical independence and is a major factor in the development of disability. Many of the changes that accompany the loss of strength with aging coincide with those observed following immobilization. Thus, immobilization is a model that is particularly well suited to examine losses in strength seen in an aging population. Losses of strength are mediated by changes in both muscular (e.g. atrophy) and neural properties (e.g. cortical inhibition). While there have been extensive studies examining muscular properties, little is known regarding the changes in cortical properties associated with the loss of strength. The potential role of cortical mechanisms in mediating strength is supported by the known effects of motor imagery on increasing strength. More specifically, intracortical facilitation and inhibition may be important neural mechanisms in mediating strength. Intracortical facilitation and inhibition is assessed using paired-pulse transcranial magnetic stimulation, and our pilot data suggests that both aging and immobilization increases long-interval intracortical inhibition (LICI) and the immobilization-induced increase in LICI is associated with the loss of strength. Our central hypothesis is that a high level of LICI is an important neurophysiologic determinant of muscle strength. We will test this hypothesis by accomplishing the following three specific aims: 1) to determine the association between the immobilization-induced changes in intracortical properties and the reduction in muscle strength and central activation; 2) to evaluate the effect of motor imagery training on minimizing the immobilization-induced changes in intracortical properties and the reduction in muscle strength and central activation; and 3) to compare differences in intracortical properties between young adults, older healthy adults, and prefrail older adults, and evaluate the interrelationship between age-related differences in intracortical properties and muscle strength and central activation. Understanding the specific neural mechanisms underlying the loss of muscle strength is critical to improving rehabilitation strategies. PUBLIC HEALTH RELEVANCE: Muscle weakness is a common clinical phenomena observed in association with aging and disuse, weakness is associated with disability development, reduced functional capacity, and even mortality. This research will identify the intracortical facilitatory and inhibitory properties in mediating the loss of strength associated with both immobilization and aging. Developing an understanding of the neural mechanisms mediating muscle weakness will contribute to the development of interventions to promote muscle function.