Gabrielle M. Allen

Supraspinal factors in human muscle fatigue: evidence for suboptimal output from the motor cortex.

1. Voluntary activation of elbow flexor muscles can be optimal during brief maximal voluntary contractions (MVCs), although central fatigue, a progressive decline in the ability to drive the muscle maximally, develops during sustained or repeated efforts. We stimulated the motor cortex and motor point in human subjects to investigate motor output during fatigue. 2. The increment in force (relative to the voluntary force) produced by stimulation of the motor point of biceps brachii increased during sustained isometric MVCs of the elbow flexors. Motoneuronal output became suboptimal during the contraction, i.e. central fatigue developed and accounted for a small but significant loss of maximal voluntary force. During 3 min MVCs, voluntary activation of biceps fell to an average of 90.7% from an average of > 99%. 3. The increment in force (relative to the voluntary force) produced by magnetic cortical stimulation was initially small (1.0%) but also increased during sustained MVCs to 9.8% (with a 2 min MVC). Thus, cortical output was not optimal at the time of stimulation nor were sites distal to the motor cortex already acting maximally. 4. A sphygmomanometer cuff around the upper arm blocked blood supply to brachioradialis near the end of a sustained MVC and throughout subsequent brief MVCs. Neither maximal voluntary force nor voluntary activation recovered during ischaemia after the sustained MVC. However, fatigue‐induced changes in EMG responses to magnetic cortical stimulation recovered rapidly despite maintained ischaemia. 5. In conclusion, during sustained MVCs, voluntary activation becomes less than optimal so that force can be increased by stimulation of the motor cortex or the motor nerve. Complex changes in excitability of the motor cortex also occur with fatigue, but can be dissociated from the impairment of voluntary activation. We argue that inadequate neural drive effectively ‘upstream’ of the motor cortex must be one site involved in the genesis of central fatigue.

Changes in motor cortical excitability during human muscle fatigue.

1. The excitability of the motor cortex was investigated during fatiguing con of the elbow flexors in human subjects. During sustained contractions at 30 and 1 voluntary force (MVC), the short‐latency electromyographic responses (EMG) evoke brachii and brachioradialis by transcranial magnetic stimulation increased in si EMG in the elbow flexors following the evoked muscle potential (silent period), duration during a sustained MVC but not during 30% MVCs nor during a sustained M muscle (adductor pollicis). 2. When the blood supply to brachioradialis was blocked with sphygmomanometer cuff sustained MVC, the changes in EMG responses to transcranial stimulation rapidly control values, This suggests that changes in these responses during fatigue wer small‐diameter muscle afferents. 3. Tendon vibration during sustained MVCs indicated that the changes in the resp cortial stimulation were not mediated by reduced muscle spindle inputs. 4. Muscle action potentials evoked in brachioradialis by electrical stimulation cervicomedullary junction did not increase in size during sustained MVCs. Thus, cortically evoked responses during sustained MVCs reflects a change in cortical Although the silent period following cervicomedullary stimulation lengthened, it substantially shorter than the cortically evoked silent period. 5. The altered EMG responses to transcranial stimulation during fatigue suggest exitation and increased inhibition in the motor cortex. As these changes were un manipulation of afferent input they presumably result from intrinsic cortical pr altered voluntary drive to the motor cortex.

Twitch interpolation of the elbow flexor muscles at high forces

We investigated factors affecting maximal voluntary torque and the assessment of the level of voluntary drive in the elbow flexor muscles. First, the effective compliance of the system was tested by using single, paired, and trains of four stimuli to measure voluntary activation. At high voluntary torques the responses to all these stimuli were identical, suggesting that single stimuli are adequate for estimating voluntary drive. Second, the contribution of torque from synergist elbow flexor muscles was assessed. In attempted maximal voluntary contractions (MVCs), the voluntary activation of brachioradialis (median 91.5%, range 68.9–100%) was lower than for biceps brachii (median 99.1%, range 78.5–100%; P < 0.01). This suggests extra torque may be generated by brachioradialis during elbow flexion, beyond the torque where biceps brachii is maximally activated. Finally, lengthening of the elbow flexors occurred during MVCs, due to slight shoulder movements. This would allow force to increase independently of an increase in voluntary drive.

Effect of contraction strength on responses in biceps brachii and adductor pollicis to transcranial magnetic stimulation

Abstract The sizes of the motor-evoked potentials (MEPs) and the durations of the silent periods after transcranial magnetic stimulation were examined in biceps brachii, brachioradialis and adductor pollicis in human subjects. Stimuli of a wide range of intensities were given during voluntary contractions producing 0–75% of maximal force (maximal voluntary contraction, MVC). In adductor pollicis, MEPs increased in size with stimulus intensity and with weak voluntary contractions (5% MVC), but did not grow larger with stronger contractions. In the elbow flexors, MEPs grew little with stimulus intensity, but increased in size with contractions of up to 50% of maximal. In contrast, the duration of the silent period showed similar changes in the three muscles. In each muscle it increased with stimulus intensity but was unaffected by changes in contraction strength. Comparison of the responses evoked in biceps brachii by focal stimulation over the contralateral motor cortex with those evoked by stimulation with a round magnetic coil over the vertex suggests an excitatory contribution from the ipsilateral cortex during strong voluntary contractions.

Impaired voluntary drive to breathe: a possible link between depression and unexplained ventilatory failure in asthmatic patients.

BACKGROUND--Although psychological distress predicts mortality in asthma, an underlying physiological link has not been shown. This study examined relations between impaired voluntary drive to breathe and measures of mood states. METHODS--The level of maximal voluntary activation of the diaphragm and elbow flexors was measured in a previous study using a sensitive modification of the twitch interpolation technique in 11 asthmatic and 10 control subjects. In this study psychological distress was assessed using the Profile of Mood States questionnaire and measures of distress were compared with the muscle voluntary activation results. RESULTS--For the asthmatic subjects, depressed mood increased the risk of impaired maximal voluntary activation of the diaphragm by 3.5 times (95% CI 1.09 to 11.3). No such association was observed in control subjects. CONCLUSIONS--These results suggest that depressed mood may predispose an asthmatic patient to impaired voluntary activation of the diaphragm. Such individuals would be at increased risk of rapidly developing ventilatory failure if faced with severe airway narrowing.

Reduced voluntary drive to breathe in asthmatic subjects

Maximal voluntary drive to the diaphragm and a non-respiratory muscle group (elbow flexors) was compared in 10 control subjects and 11 asthmatics who were studied when well. The degree of voluntary activation during repeated attempted maximal quasi-static efforts was determined using the twitch interpolation technique in the absence of contractile fatigue under both control conditions and following bronchial challenge with histamine. Diaphragm activation was assessed using bilateral phrenic stimulation at the normal resting end-expiratory lung volume after exhalation from TLC. Asthmatic subjects showed lower and more variable voluntary activation than control subjects for both diaphragm (82.0% +/- 18.4 [SD], vs 87.8% +/- 12.0, P < 0.01) and elbow flexors (91.3% +/- 7.6 vs 95.8% +/- 4.1, P < 0.01). Histamine challenge decreased FEV1 in asthmatic subjects to 50% of the initial value, but had no significant effect on voluntary activation in either subject group. The decreased voluntary drive to the diaphragm observed in some asthmatic subjects may predispose to rapid development of ventilatory failure during severe airway narrowing.

Reduced voluntary drive to the human diaphragm at low lung volumes

Maximal inspiratory and transdiaphragmatic pressures vary with lung volume but the possibility that some of this variability reflects variable voluntary drive to the diaphragm has not been investigated systematically. We assessed the influence of lung volume on the ability to activate the diaphragm with voluntary effort during maximal Mueller manoeuvres. Voluntary activation of the diaphragm was assessed using twitch interpolation with bilateral phrenic nerve stimulation in 6 subjects. Each performed 10 maximal efforts at lung volumes around functional residual capacity (FRC) and additional efforts at volumes above and below FRC. Voluntary activation of the diaphragm was higher at lung volumes above FRC (> 60% TLC; activation 98.3 +/- 2.6%) than at lung volumes around FRC (45-60% TLC; activation 95.5 +/- 3.5%) and below FRC (< 45% TLC; activation 83.3 +/- 15.8%; p < 0.05). Submaximal diaphragm activation at low lung volumes may reflect differences in the length-tension relationships of the various inspiratory muscles and/or reflex inhibition of phrenic motoneurones at low lung volumes.

Post-polio syndrome: assessments, pathophysiology and progression

While there have been many reports of the decline in motor function in patients with prior-polio, there have been few reports of quantitative changes in muscle function and the pathophysiological mechanisms for the deterioration are poorly understood. This paper describes the establishment of a post-polio clinic and the principles adopted in quantitative muscle testing using twitch interpolation. Peripheral endurance and or voluntary drive to muscles is impaired in about 30% of prior-polio patients attending the clinic. Progression of these deficits is slow and not easily predicted by factors associated with the original illness.

Prediction of voluntary activation, strength and endurance of elbow flexors in postpolio patients

To examine the long‐term effects of polio, maximal voluntary strength and voluntary activation of elbow flexor muscles of 177 patients from a postpolio clinic were investigated using twitch interpolation. Muscle endurance was studied in 142 patients during 45 min of submaximal exercise, and predictors of impaired muscle performance were investigated. Twenty‐nine of 177 patients (16.4%) had impaired voluntary drive to their elbow flexor muscles, but only 16 (9.0%) had markedly reduced elbow flexor strength, despite 74 (41.8%) reporting they were initially affected in their tested limb and 172 (97.2%) patients reporting new generalized symptoms. Seven patients had impaired muscle endurance in the tests of strength and voluntary drive. During the submaximal exercise, 16 patients (11.3%) had impaired peripheral muscle endurance with normal voluntary activation. These results confirm a low incidence of impaired upper‐limb muscle performance in postpolio patients, despite many patients having subjective symptoms consistent with postpolio syndrome. There was an increased relative risk for impaired muscle function in those patients with a subjective decrease in strength in the tested limb, a recent decline in activities of daily living in their tested limb, and who used orthotic devices in their tested limb. Monitoring of function in prior‐polio patients with impaired muscle performance may be useful, particularly when combined with investigation of other potential contributory factors to the functional impairment. Muscle Nerve 30: 172–181, 2004

HUMAN RESPIRATORY MUSCLES: SENSATIONS, REFLEXES AND FATIGUABILITY

1. Given the importance of the ventilatory ‘pump’ muscles, it would not be surprising if they were endowed with both sensory and motor specializations. The present review focuses on some unexpected properties of the respiratory muscle system in human subjects.