The role of motor neuron drive in muscle fatigue.

Large experimental evidence indicates that motor neuron drive plays an important role in the origin of fatigue. Some key findings from electrophysiological investigations provide evidence for central fatigue during prolonged exercise: (1) maximal voluntary activation is usually below maximal muscle force; (2) the amount of voluntary activation decreases and (3) motor unit firing rate tends to decline during maximal voluntary isometric contractions. Spinal and supra-spinal mechanisms can be involved. A fundamental contribution to the comprehension of these mechanisms is provided by non-invasive brain stimulation techniques, such as transcranial magnetic stimulation. They have revealed a general reduction of motor cortical excitability and central drive during fatiguing exercise, also confirmed by direct recording of corticospinal activity. Additional data suggesting concomitant intracortical inhibitory and facilitatory phenomena during sustained muscle contraction are discussed. The picture is made more complex in all pathological conditions where the motor unit pool is reduced by muscle disease. Recent findings showed the capacity of specific repetitive transcranial magnetic stimulation protocols to reinforce facilitatory processes within the motor cortex and to reduce the loss of muscle force during exercise. This approach might represent a way of access to central processes underlying muscle fatigue in motor neuron and neuromuscular disorders.