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The role of the neural stimulus in regulating skeletal muscle hypertrophy


Resistance training is frequently performed with the goal of stimulating muscle hypertrophy. Due to the key roles motor unit recruitment and mechanical tension play to induce muscle growth, when programming, the manipulation of the training variables is oriented to provoke the correct stimulus. Although it is known that the nervous system is responsible for the control of motor units and active muscle force, muscle hypertrophy researchers and trainers tend to only focus on the adaptations of the musculotendinous unit and not in the nervous system behaviour. To better guide resistance exercise prescription for muscle hypertrophy and aiming to delve into the mechanisms that maximize this goal, this review provides evidence-based considerations for possible effects of neural behaviour on muscle growth when programming resistance training, and future neurophysiological measurement that should be tested when training to increase muscle mass. Combined information from the neural and muscular structures will allow to understand the exact adaptations of the muscle in response to a given input (neural drive to the muscle). Changes at different levels of the nervous system will affect the control of motor units and mechanical forces during resistance training, thus impacting the potential hypertrophic adaptations. Additionally, this article addresses how neural adaptations and fatigue accumulation that occur when resistance training may influence the hypertrophic response and propose neurophysiological assessments that may improve our understanding of resistance training variables that impact on muscular adaptations.

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Fig. 1
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High-density surface electromyography


Muscle protein synthesis


Maximum voluntary isometric contraction


Rate of force development


Satellite cells (SC)


One repetition maximum


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CAF had the idea for this article. All authors contributed equally to this work. All authors read and approved the manuscript.

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Correspondence to Carlos Alix-Fages.

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The authors declare that they have no conflict of interest.

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Communicated by Michael Lindinger.

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Alix-Fages, C., Del Vecchio, A., Baz-Valle, E. et al. The role of the neural stimulus in regulating skeletal muscle hypertrophy. Eur J Appl Physiol 122, 1111–1128 (2022).

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