The rate of motor unit (MU) loss and its influence on the progression of sarcopenia is not well understood. Therefore, the main purpose of this study was to estimate and compare numbers of MUs in the tibialis anterior (TA) of young men ( approximately 25 years) and two groups of older men ( approximately 65 years and >/=80 years). Decomposition-enhanced spike-triggered averaging was used to collect surface and intramuscular electromyographic signals during isometric dorsiflexions at 25% of maximum voluntary contraction. The mean surface-MU potential size was divided into the maximum M wave to calculate the motor unit number estimate (MUNE). The MUNE was significantly reduced in the old (91) compared to young (150) men, and further reduced in the very old men (59). Despite the smaller MUNE at age 65, strength was not reduced until beyond 80 years. This suggests that age-related MU loss in the TA does not limit function until a critical threshold is reached.

During maximal exercise, supraspinal fatigue contributes significantly to the decline in muscle performance but little is known about intracortical inhibition during such contractions. Long-interval inhibition is produced by a conditioning motor cortical stimulus delivered via transcranial magnetic stimulation (TMS) 50-200 ms prior to a second test stimulus. We aimed to delineate changes in this inhibition during a sustained maximal voluntary contraction (MVC). Eight subjects performed a 2 min MVC of elbow flexors. Single test and paired (conditioning-test interval of 100 ms) stimuli were delivered via TMS over the motor cortex every 7-8 s throughout the effort and during intermittent MVCs in the recovery period. To determine the role of spinal mechanisms, the protocol was repeated but the TMS test stimulus was replaced by cervicomedullary stimulation which activates the corticospinal tract. TMS motor evoked potentials (MEPs) and cervicomedullary motor evoked potentials (CMEPs) were recorded from biceps brachii. Unconditioned MEPs increased progressively with fatigue, whereas CMEPs increased initially but returned to the control value in the final 40 s of contraction. In contrast, both conditioned MEPs and CMEPs decreased rapidly with fatigue and were virtually abolished within 30 s. In recovery, unconditioned responses required <30 s but conditioned MEPs and CMEPs required ∼90 s to return to control levels. Thus, long-interval inhibition increased markedly as fatigue progressed. Contrary to expectations, subcortically evoked CMEPs were inhibited as much as MEPs. This new phenomenon was also observed in the first dorsal interosseous muscle. Tested with a high intensity conditioning stimulus during a fatiguing maximal effort, long-interval inhibition of MEPs was increased primarily by spinal rather than motor cortical mechanisms. The spinal mechanisms exposed here may contribute to the development of central fatigue in human muscles.

The responsiveness of the human central nervous system can change profoundly with exercise, injury, disuse, or disease. Changes occur at both cortical and spinal levels but in most cases excitability of the motoneuron pool must be assessed to localize accurately the site of adaptation. Hence, it is critical to understand, and employ correctly, the methods to test motoneuron excitability in humans. Several techniques exist and each has its advantages and disadvantages. This review examines the most common techniques that use evoked compound muscle action potentials to test the excitability of the motoneuron pool and describes the merits and limitations of each. The techniques discussed are the H-reflex, F-wave, tendon jerk, V-wave, cervicomedullary motor evoked potential (CMEP), and motor evoked potential (MEP). A number of limitations with these techniques are presented.

During fatigue caused by a sustained maximal voluntary contraction (MVC), motoneurones become markedly less responsive when tested during the silent period following transcranial magnetic stimulation (TMS). To determine whether this reduction depends on the repetitive activation of the motoneurones, responses to TMS (motor evoked potentials, MEPs) and to cervicomedullary stimulation (cervicomedullary motor evoked potentials, CMEPs) were tested during a sustained submaximal contraction at a constant level of electromyographic activity (EMG). In such a contraction, some motoneurones are repetitively activated whereas others are not active. On four visits, eight subjects performed a 10 min maintained-EMG elbow flexor contraction of 25% maximum. Test stimuli were delivered with and without conditioning by TMS given 100 ms prior. Test responses were MEPs or CMEPs (two visits each, small responses evoked by weak stimuli on one visit and large responses on the other). During the sustained contraction, unconditioned CMEPs decreased ∼20% whereas conditioned CMEPs decreased ∼75 and 30% with weak and strong stimuli, respectively. Conditioned MEPs were reduced to the same extent as CMEPs of the same size. The data reveal a novel decrease in motoneurone excitability during a submaximal contraction if EMG is maintained. Further, the much greater reduction of conditioned than unconditioned CMEPs shows the critical influence of voluntary drive on motoneurone responsiveness. Strong test stimuli attenuate the reduction of conditioned CMEPs which indicates that low-threshold motoneurones active in the contraction are most affected. The equivalent reduction of conditioned MEPs and CMEPs suggests that, similar to findings with a sustained MVC, impaired motoneurone responsiveness rather than intracortical inhibition is responsible for the fatigue-related impairment of the MEP during a sustained submaximal contraction.

We investigated the influence of group III/IV muscle afferents in determining corticospinal excitability during cycling exercise and focused on GABA neuron-mediated inhibition as a potential underlying mechanism. Both under control conditions (CTRL) and with lumbar intrathecal fentanyl (FENT) impairing feedback from group III/IV leg muscle afferents, subjects (n = 11) cycled at a comparable vastus-lateralis EMG signal (∼0.26 mV) before (PRE; 100 W) and immediately after (POST; 90 ± 2 W) fatiguing constant-load cycling exercise (80% Wpeak; 221 ± 10 W; ∼8 min). During, PRE and POST cycling, single and paired-pulse (100 ms interstimulus interval) transcranial magnetic stimulations (TMS) were applied to elicit unconditioned and conditioned motor-evoked potentials (MEPs), respectively. To distinguish between cortical and spinal contributions to the MEPs, cervicomedullary stimulations (CMS) were used to elicit unconditioned (CMS only) and conditioned (TMS+CMS, 100 ms interval) cervicomedullary motor-evoked potentials (CMEPs). While unconditioned MEPs were unchanged from PRE to POST in CTRL, unconditioned CMEPs increased significantly, resulting in a decrease in unconditioned MEP/CMEP (P < 0.05). This paralleled a reduction in conditioned MEP (P < 0.05) and no change in conditioned CMEP. During FENT, unconditioned and conditioned MEPs and CMEPs were similar and comparable during PRE and POST (P > 0.2). These findings reveal that feedback from group III/IV muscle afferents innervating locomotor muscle decreases the excitability of the motor cortex during fatiguing cycling exercise. This impairment is, at least in part, determined by the facilitating effect of these sensory neurons on inhibitory GABA intracortical interneurons.

Key points• Maintained firing of fatigue-sensitive small-diameter muscle afferents is reported to reduce voluntary activation of the homonymous (fatigued) muscle.• Our study determined if firing of fatigue-sensitive afferents from elbow extensor muscles reduces voluntary activation and torque of the non-fatigued elbow flexors.• We examined voluntary activation of the elbow flexors by measuring changes in superimposed twitches evoked by magnetic cortical stimulation during maximal voluntary contractions.• Following a fatiguing contraction of elbow extensors, the voluntary drive to unfatigued flexor muscles was reduced with continued activation of small-diameter muscle afferents produced by a blood pressure cuff inflated to maintain muscle ischaemia.• Continued discharge of small-diameter muscle afferents from one muscle can decrease voluntary drive to another muscle in the same limb and can reduce its maximal voluntary torque.Abstract During muscle fatigue, firing of small-diameter muscle afferents can decrease voluntary activation of the fatigued muscle. However, these afferents may have a more widespread effect on other muscles in the exercising limb. We examined if the firing of fatigue-sensitive afferents from elbow extensor muscles in the same arm reduces torque production and voluntary activation of elbow flexors. In nine subjects we examined voluntary activation of elbow flexors by measuring changes in superimposed twitches evoked by transcranial magnetic stimulation of the motor cortex during brief (2-3 s) maximal voluntary contractions (MVC). Inflation of a blood pressure cuff following a 2-min sustained MVC blocked blood flow to the fatigued muscle and maintained firing of small-diameter afferents. After a fatiguing elbow flexion contraction, maximal flexion torque was lower (26.0 ± 4.4% versus 67.9 ± 5.2% of initial maximal torque; means ± S.D.; P < 0.001) and superimposed twitches were larger (4.1 ± 1.1% versus 1.8 ± 0.2% ongoing MVC, P = 0.01) with than without ischaemia. After a fatiguing elbow extensor contraction, maximal flexion torque was also reduced (82.2 ± 4.9% versus 91.4 ± 2.3% of initial maximal torque; P = 0.007), superimposed twitches were larger (2.7 ± 0.7% versus 1.3 ± 0.2% ongoing MVC; P = 0.02) and voluntary activation lower (81.6 ± 8.2% versus 95.5 ± 6.9%; P = 0.04) with than without ischaemia. After a fatiguing contraction, voluntary drive to the fatigued muscles is reduced with continued input from small-diameter muscle afferents. arm. Therefore, firing of small-diameter muscle afferents from one muscle can affect voluntary activation and hence torque generation of another muscle in the same limb.

Muscle power is more functionally relevant than static muscle strength, particularly with aging. However, the effect of age on power derived from isotonic contractions has been studied sparingly, and it has not been studied at all in subjects >75 yr of age. Thus the purpose was to investigate the magnitude and causes of age-related losses in isotonic power among 13 young (26 yr), 13 old (65 yr), and 13 very old (84 yr) men. Six different loads were employed to create velocity-torque and power-torque relationships. Dorsiflexor cross-sectional area was assessed via magnetic resonance imaging for the calculation of specific power. Electromyographic signals of the tibialis anterior and soleus muscles were recorded to assess agonist activation and antagonist coactivation, respectively. Despite similar contractile masses and levels of voluntary drive and antagonist co-activation, power was significantly impaired in the old vs. young (∼25%), and in the very old relative to both the young (∼60%) and old (∼40%). The novel results punctuate two important considerations for studies concerned with the effect of age on the neuromuscular system. First, the decreased ability of muscles from old men to produce power in the presence of reasonably well-preserved strength indicates the utility of studying isotonic contractions. Second, the precipitous decline in many measures between the seventh and ninth decades underscores the benefit of testing more than one group of aged subjects to improve our understanding of rates of change in key variables.

The documented impact of contractile level on decomposition-enhanced spike-triggered averaging motor unit number estimates (MUNEs) in young adults demonstrates the importance of selecting an objective contraction intensity that yields the most representative MUNE for a given muscle. Whether the same contraction intensity would be ideal in an altered system (e.g., by aging or disease) has yet to be examined. Thus, the main purpose of this study was to compare the effects of contraction intensity on MUNEs from the soleus muscle in young ( approximately 27 years) and old ( approximately 75 years) men. Using decomposition-enhanced spike-triggered averaging, surface and intramuscular electromyographic signals were collected from the soleus during a range of submaximal isometric plantar-flexion contractions (threshold, 10%, 20%, and 30% of maximum voluntary contraction; MVC). Five MUNEs were calculated, one for each of the four contraction intensities and an ensemble MUNE was derived from all MUs collected. Although MUNE decreased similarly with increased effort in both groups, MUNEs were not significantly reduced in the old men compared to the young men. Consequently, the ensemble MUNE was extrapolated to an intensity of approximately 15% MVC in both young and old. The results suggest that, in the soleus, the use of the same contraction intensity across age groups is a valid comparison.