Supraspinal regulation of physical fatigue.

Fatigue, defined as difficulty in initiating or sustaining voluntary activities, can be classified as physical or mental, and physical fatigue can be classified as peripheral or central (spinal or supraspinal). It has been reported that during physical fatigue, sensory input from the peripheral system activates an inhibition system to limit motor output from the primary motor cortex (M1) (supraspinal fatigue) while a motivational input activates a facilitation system to increase motor output from M1 in order to overcome supraspinal fatigue. Hence, the motor output from M1 is primarily determined by the balance between the inhibition and facilitation systems. Here, we review data from behavioral, electrophysiological, and neuroimaging experiments related to supraspinal mechanisms that are thought to regulate motor output from M1 during physical fatigue, and we propose a supraspinal model to regulate physical fatigue as well as a hypothetical model of fatigue in human diseases or syndromes.