Chris J. McNeil

Motor unit number estimates in the tibialis anterior muscle of young, old, and very old men

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 (∼25 years) and two groups of older men (∼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. Muscle Nerve, 2005

The response to paired motor cortical stimuli is abolished at a spinal level during human muscle fatigue.

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.

Behaviour of the motoneurone pool in a fatiguing submaximal contraction

Non‐technical summary  During a sustained maximal contraction, motoneurones rapidly become less responsive to input. This decrease is ameliorated by a high level of voluntary drive from the cortex. Here, we tested whether the excitability of motor cortical neurones or spinal motoneurones is suppressed during fatigue produced by a sustained submaximal contraction in which only some of the motoneurones are active. We found that motoneurone responses were gradually suppressed as fatigue developed. The results suggest that only the active motoneurones were affected and the decreased responsiveness was less when voluntary drive was present. In contrast, the excitability of the motor cortex appeared unaffected.

Testing the excitability of human motoneurons

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.

Age-related reductions in the estimated numbers of motor units are minimal in the human soleus

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 (≈27 years) and old (≈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 ≈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. Muscle Nerve, 2008

The reduction in human motoneurone responsiveness during muscle fatigue is not prevented by increased muscle spindle discharge

Non‐technical summary The responsiveness of motoneurones within the spinal cord to non‐invasive stimulation is markedly reduced during a fatiguing maximal effort if tested when voluntary drive from the brain is transiently interrupted. We tested a major possible cause of this effect by vibrating the tendon of the contracting muscle to increase excitatory input to the motoneurones. Application of tendon vibration had a negligible effect on the fatigue‐induced reduction of motoneurone responsiveness. Hence, we believe the reduction in responsiveness is caused by changes to the intrinsic properties of motoneurones due to their repetitive activity during the sustained maximal effort.

Firing of antagonist small-diameter muscle afferents reduces voluntary activation and torque of elbow flexors.

•  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.

Effect of experimental muscle pain on maximal voluntary activation of human biceps brachii muscle

Muscle pain has widespread effects on motor performance, but the effect of pain on voluntary activation, which is the level of neural drive to contracting muscle, is not known. To determine whether induced muscle pain reduces voluntary activation during maximal voluntary contractions, voluntary activation of elbow flexors was assessed with both motor-point stimulation and transcranial magnetic stimulation over the motor cortex. In addition, we performed a psychophysical experiment to investigate the effect of induced muscle pain across a wide range of submaximal efforts (5-75% maximum). In all studies, elbow flexion torque was recorded before, during, and after experimental muscle pain by injection of 1 ml of 5% hypertonic saline into biceps. Injection of hypertonic saline evoked deep pain in the muscle (pain rating ∼5 on a scale from 0 to 10). Experimental muscle pain caused a small (∼5%) but significant reduction of maximal voluntary torque in the motor-point and motor cortical studies (P < 0.001 and P = 0.045, respectively; n = 7). By contrast, experimental muscle pain had no significant effect on voluntary activation when assessed with motor-point and motor cortical stimulation although voluntary activation tested with motor-point stimulation was reduced by ∼2% in contractions after pain had resolved (P = 0.003). Furthermore, induced muscle pain had no significant effect on torque output during submaximal efforts (P > 0.05; n = 6), which suggests that muscle pain did not alter the relationship between the sense of effort and production of voluntary torque. Hence, the present study suggests that transient experimental muscle pain in biceps brachii has a limited effect on central motor pathways.

Fatigue-related firing of distal muscle nociceptors reduces voluntary activation of proximal muscles of the same limb.

With fatiguing exercise, firing of group III/IV muscle afferents reduces voluntary activation and force of the exercised muscles. These afferents can also act across agonist/antagonist pairs, reducing voluntary activation and force in nonfatigued muscles. We hypothesized that maintained firing of group III/IV muscle afferents after a fatiguing adductor pollicis (AP) contraction would decrease voluntary activation and force of AP and ipsilateral elbow flexors. In two experiments (n = 10) we examined voluntary activation of AP and elbow flexors by measuring changes in superimposed twitches evoked by ulnar nerve stimulation and transcranial magnetic stimulation of the motor cortex, respectively. Inflation of a sphygmomanometer cuff after a 2-min AP maximal voluntary contraction (MVC) blocked circulation of the hand for 2 min and maintained firing of group III/IV muscle afferents. After a 2-min AP MVC, maximal AP voluntary activation was lower with than without ischemia (56.2 ± 17.7% vs. 76.3 ± 14.6%; mean ± SD; P < 0.05) as was force (40.3 ± 12.8% vs. 57.1 ± 13.8% peak MVC; P < 0.05). Likewise, after a 2-min AP MVC, elbow flexion voluntary activation was lower with than without ischemia (88.3 ± 7.5% vs. 93.6 ± 3.9%; P < 0.05) as was torque (80.2 ± 4.6% vs. 86.6 ± 1.0% peak MVC; P < 0.05). Pain during ischemia was reported as Moderate to Very Strong. Postfatigue firing of group III/IV muscle afferents from the hand decreased voluntary drive and force of AP. Moreover, this effect decreased voluntary drive and torque of proximal unfatigued muscles, the elbow flexors. Fatigue-sensitive group III/IV muscle nociceptors act to limit voluntary drive not only to fatigued muscles but also to unfatigued muscles within the same limb.

Twitch interpolation: superimposed twitches decline progressively during a tetanic contraction of human adductor pollicis

The size of an interpolated muscle twitch during a voluntary muscle contraction is used to assess the extra force that the central nervous system can harness from the muscle with volition. During human exercise, this interpolated twitch commonly increases in size and this reduced voluntary activation of the muscle is termed ‘central’ fatigue. Recent work on isolated mouse muscle fibres suggests an alternative ‘peripheral’ explanation for the increased twitch based on altered sensitivity to intracellular calcium. We tested this possibility with tetanic stimulation of the ulnar nerve while measuring thumb adductor force. During maximal tetani lasting 1 min at 30 Hz (or 3 min at 15 Hz), muscle force declined (i.e. peripheral fatigue developed) but the relative and absolute size of superimposed twitches declined progressively. They did not increase as predicted from the mouse study. Twitch interpolation can reveal central fatigue during voluntary muscle contractions.