Alan J. McComas

Physiological changes in ageing muscles

Physiological studies have been made of extensor digitorum brevis muscles in 28 healthy subjects aged between 60 and 96. Within this elderly population there was evidence of muscle wasting and weakness. These changes were shown to result from a loss of functioning motor units. The surviving motor units were often enlarged and tended to have relatively slow twitches. In some subjects the maximum impulse conduction velocities were reduced in motor nerves; there was evidence that slowing of impulse conduction could be especially marked in distal regions of axons. The findings are considered to indicate the presence of motoneurone dysfunction in old age.

Electrophysiological estimation of the number of motor units within a human muscle

An electrophysiological method is described for estimating the numbers of motor units in the extensor digitorum brevis muscle in man. The results obtained are compared with counts of axons in the nerve to the muscle. The significance of the sizes of the evoked motor unit potentials is discussed.

Twitch potentiation after voluntary contraction

Twitch potentiation was studied in human tibialis anterior (TA) and plantarflexor (PF) muscles after maximal voluntary contractions (MVCs). Potentiation was greater in TA and other dorsiflexor (DF) muscles than in PF and was dependent on the intensity of the voluntary effect. It was also observed that potentiation was maximal after MVCs of approximately 10-s duration; after longer voluntary contractions, the potentiation was partially suppressed by fatigue, especially in the TA. Potentiation was significantly larger when muscles were tested in a shortened position regardless of the position at which the preceding MVCs had been performed.

Reflex inhibition of human soleus muscle during fatigue.

1. Human soleus muscles were fatigued under ischaemic conditions by intermittent stimulation at 15 Hz. When maximal voluntary plantarflexion was then attempted, the loss of torque was found to be associated with a reduction in voluntary EMG activity. 2. The decrease in EMG activity could not have been due to ‘exhaustion’ of descending motor drive in the central nervous system since fatigue had been induced by electrical stimulation of peripheral nerve fibres. Similarly, the decrease could not be explained by changes at the neuromuscular junction or muscle fibre membrane, since changes in the M wave (evoked muscle compound action potential) were relatively modest. 3. When the excitability of the soleus motoneurones was tested during fatigue, using the H (Hoffmann) reflex, it was found to be significantly reduced. Control experiments with ischaemia or electrical stimulation, but without fatigue, failed to demonstrate any significant effects on reflex excitability. 4. The findings in this study favour the concept of reflex inhibition of alpha‐motoneurones during fatigue.

Functional changes in motoneurones of hemiparetic patients

Forty-six patients have been studied after upper motor neurone lesions of cerebrovascular origin. The numbers of functioning motor units in extensor digitorum brevis muscles were reduced to approximately half between the second and sixth months after a hemiplegic episode. The surviving motor units tended to have slow twitches and appeared to increase their sizes after the lesions had been present for about 20 months. The findings are explained on the basis of transsynaptic changes in alpha-motoneurones after degeneration of corticospinal fibres.

Increased sodium pump activity following repetitive stimulation of rat soleus muscles.

1. Soleus muscles of anaesthetized rats were stimulated tetanically (4 s at 20 Hz every 5 s for 5 min), following which the resting and action potentials were measured in surface fibres. 2. At the end of the stimulation period, the mean resting potential was found to have increased from a control value of ‐79.5 +/‐ 4.8 mV (mean +/‐ S.D.) to ‐90.5 +/‐ 6.3 mV. The hyperpolarization started to decline after 9 min but was still present at 15 min. 3. Associated with the membrane hyperpolarization was an increase in the mean amplitude of the muscle fibre action potential, from 82.2 +/‐ 10.8 to 96.8 +/‐ 10.0 mV. 4. Both the hyperpolarization and the enlargement of the muscle fibre action potential were abolished by 1.25 X 10(‐4) M‐ouabain, cooling the bathing fluid to 19 degrees C or removing K+ from the bathing fluid. 5. The results are explained in terms of an increase in electrogenic sodium pump activity resulting from tetanic stimulation. When the bathing fluid contained 20 mM‐K+, the mean resting potential of stimulated fibres was approximately ‐30 mV greater than that calculated from the Goldman‐Hodgkin‐Katz equation. 6. The increase in sodium pumping not only acts to restore the concentrations of Na+ and K+ on either side of the muscle fibre membrane, but, through its electrogenic effect, enables fibres to remain excitable during continuous contractile activity.

Cutaneous reflexes in small muscles of the hand

A study has been made of the responses of motoneurones innervating small muscles of the hand to electrical and mechanical stimulation of the skin. Both excitatory and inhibitory effects could be observed in the same muscle after a single stimulus to a given area of skin. The earliest excitatory and inhibitory responses are probably mediated by group III and the smaller group II afferent nerve fibres. A later inhibition results from activity in the larger group II fibres which are connected to cutaneous mechanoreceptors, especially those in the tips of the fingers and thumb. This late inhibitory reflex may operate through the fusimotor system. The possible roles of these reflexes are discussed in relation to previous investigations in man and the cat.

Functional compensation in partially denervated muscles

In patients with various types of chronic motor denervation, the numbers of surviving motor units have been compared with the twitch tensions developed by the same muscle (extensor digitorum brevis). It was found that functional compensation in partially denervated muscles was often marked; in most patients abnormally small twitches occurred only when fewer than 10% of motor axons remained. The factors responsible for this compensation are considered. The twitch speeds of partially denervated muscles differed markedly, even among patients with the same disorder; there was evidence to suggest that the twitches of some motor units might become slower than those found in normal muscles.

SICK MOTONEURONES: A Unifying Concept of Muscle Disease

Abstract New electrophysiological techniques have demonstrated a loss of motor units in muscular dystrophy and myasthenia gravis; the sizes of the surviving motor units suggest that both diseases result from disordered function of motoneurones. Estimates have been made of the incidence of healthy, sick, and dead motoneurones in these conditions and, for comparison, in recognised denervating processes such as motor-neurone disease and the Kugelberg-Welander syndrome.

Effect of strength training upon motoneuron excitability in man.

Two healthy females and twelve healthy males, aged 19-24 yr, underwent strength training for periods of 9-21 wk. The muscles trained included extensor digitorum brevis (N = 3), soleus (N = 7), brachioradialis (N = 4), and the hypothenar muscles (N = 3). The effect of training on motoneuron excitability was measured as the degree to which two reflex responses (V1 and V2) were potentiated by voluntary effort. Strength training was found to increase V1 and V2 potentiation by 49.7 and 38.9%, respectively, (P less than 0.01) for pooled muscle comparisons with the exception of the soleus V2 wave, which was rarely seen and excluded from this analysis. There was a positive correlation (r = 0.83, P less than 0.01) between the change in the V1 and V2 potentiation. It was argued that strength training may cause an increased ability to raise motoneuron excitability during voluntary effort.