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Smith, CM, Housh, TJ, Herda, TJ, Zuniga, JM, Camic, CL, Bergstrom, HC, Smith, DB, Weir, JP, Hill, EC, Cochrane, KC, Jenkins, NDM, Schmidt, RJ, and Johnson, GO. Time course of changes in neuromuscular parameters during sustained isometric muscle actions. J Strength Cond Res 30(10): 2697–2702, 2016—The objective of the present study was to identify the time course of changes in electromyographic (EMG) and mechanomyographic (MMG) time and frequency domain parameters during a sustained isometric muscle action of the leg extensors at 50% maximal voluntary isometric contraction. The EMG and MMG signals were measured from the vastus lateralis of 11 subjects to identify when motor unit activation strategies changed throughout the sustained isometric muscle action. The EMG amplitude (muscle activation) had a positive linear relationship (p = 0.018, r2 = 0.77) that began to increase at the initiation of the muscle action and continued until task failure. Electromyographic frequency (motor unit action potential conduction velocity) and MMG frequency (global motor unit firing rate) had negative quadratic relationships (p = 0.002, R2 = 0.99; p = 0.015, R2 = 0.94) that began to decrease at 30% of the time to exhaustion. The MMG amplitude (motor unit activation) had a cubic relationship (p = 0.001, R2 = 0.94) that increased from 10 to 30% of the time to exhaustion, then decreased from 40 to 70% of the time to exhaustion, and then markedly increased from 70% to task failure. The time course of changes in the neuromuscular parameters suggested that motor unit activation strategies changed at approximately 30 and 70% of the time to exhaustion during the sustained isometric muscle action. These findings indicate that the time course of changes in neuromuscular responses provide insight into the strategies used to delay the effects of fatigue and are valuable tools for quantifying changes in the fatiguing process during training programs or supplementation research.