Responses to transcranial magnetic stimulation in human subjects (n = 9) were studied during series of intermittent isometric maximal voluntary contractions (MVCs) of the elbow. Stimuli were given during MVCs in four fatigue protocols with different duty cycles. As maximal voluntary torque fell during each protocol, the torque increment evoked by cortical stimulation increased from approximately 1.5 to 7% of ongoing torque. Thus "supraspinal" fatigue developed in each protocol. The motor evoked potential (MEP) and silent period in the elbow flexor muscles also changed. The silent period lengthened by 20-75 ms (lowest to highest duty cycle protocol) and recovered significantly with a 5-s rest. The MEP increased in area by >50% in all protocols and recovered significantly with 10 s, but not 5 s, of rest. These changes are similar to those during sustained MVC. The central fatigue demonstrated by the torque increments evoked by the stimuli did not parallel the changes in the electromyogram responses. This suggests that part of the fatigue developed during intermittent exercise is "upstream" of the motor cortex.

The discharge frequency of human motoneurons declines during a sustained isometric maximal voluntary contraction (MVC) of elbow flexor muscles, but the cause is unresolved. We aimed to determine whether motoneurons were inhibited during a sustained fatiguing contraction of the elbow flexor muscles and whether this inhibition was caused by the discharge of group III and IV muscle afferents. Subjects performed brief MVCs before and after a fatiguing 2 min MVC. During maximal efforts, electromyographic responses recorded from the elbow flexor muscles were evoked by stimulation of the corticospinal tracts at the cervicomedullary level [cervicomedullary motor evoked potentials (CMEPs)] and by supramaximal stimulation over the brachial plexus (Mmax). This revealed a novel decrease in the size of the muscle response to corticospinal tract stimulation during fatigue. During the sustained MVCs, the size of CMEPs decreased to 81 +/- 15 and 78 +/- 15% of the control value for brachioradialis and biceps brachii, respectively (mean +/- SEM; n = 8). This recovered within 15 sec after the fatiguing contraction. In a second set of studies, input from group III and IV muscle afferents was prolonged after the end of the fatiguing contraction by holding the muscle ischemic with a cuff inflated above arterial pressure. Despite the maintained discharge of group III and IV afferents, the CMEPs again recovered within 15 sec of the end of the sustained contraction. These results show a diminished output of spinal motoneurons to stimulation of corticospinal tracts during a fatiguing MVC; however, the mechanisms responsible for this decline are not attributable to activity in group III and IV muscle afferents.

Aging is associated with dramatic reductions in muscle strength and motor control, and many of these age-related changes in muscle function result from adaptations in the central nervous system. Aging is associated with wide-spread qualitative and quantitative changes of the motor cortex. For example, advancing age has been suggested to result in cortical atrophy, reduced cortical excitability, reduced cortical plasticity, as well as neurochemical abnormalities. The associated functional effects of these changes likely influence numerous aspects of muscle performance such as muscle strength and motor control. For example, there is evidence to suggest that the muscle weakness associated with aging is partially due to impairments in the nervous system’s ability to fully activate motor neurons- particularly in the larger proximal muscle groups. In this review article we discuss age-related changes in the motor cortex, as well as the ability- or lack thereof- of older adults to voluntarily activate skeletal muscle. We also provide perspectives on scientific and clinical questions that need to be addressed in the near future.