Cortical and spinal compensatory mechanisms during neuromuscular fatigue

神经肌肉疲劳被定义为一种活动引起的最大肌肉力量的减少，并与在次最大力量产生过程中增加的努力感有关。疲劳的机制包括肌肉衰竭，以及对肌肉的神经驱动减少（中枢疲劳）。有许多研究充分的脊髓和皮质机制有助于中枢疲劳。相比之下，从大脑到肌肉的神经通路中增加增益以抵消失败的机制尚不清楚。两种可能的代偿系统包括：1)皮质促进和2)脊髓运动神经元（MN）持续内向电流（PIC）。本研究的目的是评估这两种代偿系统的贡献，它们可能有助于增加增益，优化运动输出，减少肌肉活动期间的力量感和努力感。运动皮层的许多区域参与计划随意肌活动，这些大脑区域的最终输出通过初级运动皮层的皮质脊髓神经元传递。皮层促进系统以某种方式增加这些细胞的兴奋性，可能补偿疲劳期间从大脑到肌肉通路上游或下游的失败。这将减少保持输出所需的驱动，然而，增加增益的代价可能是产生力的精度的降低。因此，很可能这些机制的使用方式既依赖于状态（疲劳、非疲劳），也依赖于任务（精确与非精确）。提出的工作的第一个目标是确定当任务要求精度时，皮层促进是否在疲劳期间增加。这将通过在与上肢和下肢肌肉的精确和力量任务相关的运动之前使用经颅磁刺激评估皮质促进来完成。在脊柱水平，持续向内电流（PIC）提供了一种强大的手段来增加控制许多肌肉群的不同MNs池的运动输出。然而，迄今为止还没有研究调查疲劳期间PIC是如何调节的。目前的方法是在坐姿、静态收缩时估计PIC。因此，本研究的第二个目标是开发一种技术来评估与功能相关的姿势任务期间PIC的疲劳相关变化。这将通过在坐姿、静态收缩和站立前倾时肌肉内运动单元对的记录来估计PIC。这项工作将提高我们对人体疲劳时运动输出的任务依赖性调节的理解。这是很重要的，因为直到我们了解了调节健康人运动输出的机制，我们才能完全理解损伤、衰老和疾病中运动功能受损的机制

Neuromuscular fatigue is defined as an activity-induced reduction in maximal muscle force and is associated with an increased sense of effort during submaximal force production. Mechanisms of fatigue include muscle failure, as well as reduced neural drive to muscle (central fatigue). There are a number of well-studied spinal and cortical mechanisms that contribute to central fatigue. In contrast, the mechanisms which serve to increase gain in the neural pathway from brain to muscle to offset failure are not well understood. Two possible compensatory systems include: i) cortical facilitation and ii) spinal motor neuron (MN) persistent inward current (PIC). The purpose of the proposed research is to assess the contribution of these two compensatory systems that may serve to increase gain to optimize motor output and reduce sense of force and effort during muscle activity.  Many regions of the motor cortex contribute to planning voluntary muscle activity, and the final output from these brain regions is delivered via corticospinal neurons of the primary motor cortex. The cortical facilitation system increases the excitability of these cells in a way that may compensate for failure upstream or downstream in the pathway from brain to muscle during fatigue.  This would reduce the drive necessary to maintain output, however, the cost of increased gain may be a reduction in the precision with which force is produced. Thus, it is likely that these mechanisms are employed in a way that is both state-dependent (fatigue, nonfatigued) as well as task-dependent (precision vs. nonprecision).  The 1st objective of the proposed work is to determine whether cortical facilitation is increased during fatigue when the task demands precision. This will be accomplished by assessing cortical facilitation using transcranial magnetic stimulation just prior to movements associated with both precision and power tasks of upper and lower limb muscles. At a spinal level, persistent inward currents (PIC) provide a powerful means to increase motor output across diverse pools of MNs controlling many muscle groups. No studies to date, however, have investigated how PIC is modulated during fatigue.  The current methodology is to estimate PIC during seated, static contractions. Therefore, a 2nd objective of this research is to develop a technique to estimate fatigue-associated changes in PIC during a functionally-relevant postural task. This will be accomplished by estimating PIC using intramuscular recordings of motor unit pairs in seated, static contractions and during standing forward postural-sway. This work will improve our understanding of task-dependent modulation of motor output during human fatigue. This is significant because until we understand the mechanisms that modulate motor output in healthy people, we cannot fully understand the mechanisms of impaired motor function in injury, ageing, and disease.**