Neural Contributions to Muscle Fatigue: From the Brain to the Muscle and Back Again

Abstract

: During exercise, there is a progressive reduction in the ability to produce muscle force. Processes within the nervous system as well as within the muscles contribute to this fatigue. In addition to impaired function of the motor system, sensations associated with fatigue and impairment of homeostasis can contribute to the impairment of performance during exercise. This review discusses some of the neural changes that accompany exercise and the development of fatigue. The role of brain monoaminergic neurotransmitter systems in whole-body endurance performance is discussed, particularly with regard to exercise in hot environments. Next, fatigue-related alterations in the neuromuscular pathway are discussed in terms of changes in motor unit firing, motoneuron excitability, and motor cortical excitability. These changes have mostly been investigated during single-limb isometric contractions. Finally, the small-diameter muscle afferents that increase firing with exercise and fatigue are discussed. These afferents have roles in cardiovascular and respiratory responses to exercise, and in the impairment of exercise performance through interaction with the motor pathway, as well as in providing sensations of muscle discomfort. Thus, changes at all levels of the nervous system, including the brain, spinal cord, motor output, sensory input, and autonomic function, occur during exercise and fatigue. The mix of influences and the importance of their contribution vary with the type of exercise being performed.

Figure 1. Schematic of neural contributions to muscle fatigue in single joint exercise

Peripheral fatigue is attributed to processes at or distal to the neuromuscular junction whereas central fatigue is attributed to processes within the nervous system. In the neuromuscular pathway, force is generated by contraction of the muscle fibers. Strength and timing of contraction are controlled by the firing of the motoneurons. Motoneuron firing is influenced by the properties of the motoneurons, feedback from sensory input and by descending drive. There are fatigue-related changes at all of these levels (Changes in the neuromuscular pathway with fatiguing exercise). As well as influencing the neuromuscular pathway, group III/IV muscle afferent feedback interacts with cardiovascular and respiratory processes via the autonomic nervous system (Feedback from fatigue-sensitive muscle afferents). In addition, departures from homeostasis during whole body exercise influence performance through supraspinal mechanisms (Brain changes associated with performance).

Figure 2. Influences on the firing of spinal motoneurons during fatiguing maximal contractions

During fatiguing maximal contractions, motoneuron firing rates decrease. There are multiple influences on the motoneurons. Those described in the text are illustrated. First, repetitive activation (repeated firing) of motoneurons makes them less excitable, but the precise mechanism is not known. Second, group III and IV muscle afferents are mechanically and/or chemically sensitive, and increase their firing during fatiguing contractions. These afferents inhibit some motoneuron pools but excite others. Third, group Ia muscle afferents (from muscle spindles) are thought to decrease their firing and also to undergo additional presynaptic inhibition. This represents a decrease in excitatory drive to the motoneurons. Fourth, supraspinal fatigue, measured during maximal isometric contractions, suggests that excitatory drive from the motor cortex is also lower than it could be. Finally, it has been proposed that high serotonergic drive from the medulla may result in inhibition of motoneurons through activation of extrasynaptic receptors.

Figure 3. Group III and IV muscle afferents increase central fatigue but attenuate peripheral fatigue

Firing of group III and IV muscle afferents increases during fatiguing contractions. During exercise, these afferents produce reflex increases in heart rate, blood pressure and respiration to improve muscle blood flow and oxygenation. This slows the development of fatigue of the muscle itself (peripheral fatigue). At the same time, the afferent firing also leads to a reduction in voluntary neural drive to the muscle. That is, it contributes to central fatigue. The precise pathway for this effect is not known. The afferents evoke sensations of muscle discomfort and fatigue, increase supraspinal fatigue, presynaptically inhibit Ia input to motoneurons, and have differing actions on different motoneuron pools.