Intracortical Mechanisms of Muscle Weakness

描述（由申请人提供）：与年龄相关的肌肉力量丧失（即无力）是一个巨大的问题，因为它限制了身体的独立性，是发展为残疾的主要因素。许多随年龄增长而发生的力量丧失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力量损失的模型。力量的丧失是由肌肉（如萎缩）和神经特性（如皮质抑制）的变化介导的。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。已知的运动意象对增强力量的作用支持了皮层机制在调节力量中的潜在作用。更具体地说，皮质内促进和抑制可能是介导强度的重要神经机制。使用配对脉冲经颅磁刺激评估皮质内促进和抑制，我们的试点数据表明，衰老和固定化都会增加长间隔皮质内抑制（LICI），而固定化诱导的LICI增加与力量丧失有关。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设：1)确定固定诱导的皮质内特性变化与肌肉力量和中枢激活减少之间的关联；2)评估运动想象训练对减少固定运动引起的皮质内特性变化、肌肉力量和中枢激活降低的作用；3)比较青壮年、健康老年人和体衰前期老年人的皮质内特性差异，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改善康复策略至关重要。

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.