A Comprehensive Model of Human Neuromuscular Function During Repeated Isometric Contractions: Predicting the Effect of Age on Fatigue

Development of joint torque through the voluntary activation of skeletal muscle is the result of a complicated series of events, beginning with the generation of excitatory action potentials in the motor cortex. A theoretical pathway of voluntary joint torque production includes motor neuron recruitment and rate-coding, sarcolemmal depolarization and calcium release by the sarcoplasmic reticulum, and force generation by the contractile proteins. The direct source of energetic support for this process is ATP hydrolysis. Although it is possible to examine portions of this physiologic pathway using various in vivo and in vitro techniques, none provide a complete view of the multiple ways in which features of the pathway interact and ultimately impact joint torque. Computational modeling provides a means to simulate these interactions and their net outcome, and thereby make inferences about key variables of interest. We present a novel, comprehensive computational model of the activated neuromuscular system. Components representing excitatory drive, calcium release, force generation, metabolic perturbations, and torque generated during human voluntary dorsiflexion were constructed from a combination of literature values and experimentally-derived data. Simulations were validated by comparing model output to voluntary and stimulated torque generation conditions in vivo. The model successfully predicted peak torque output, approximated submaximal torque, and the metabolic perturbations associated