Reduced Gibbs free energy supply hinders brain information processing during mental fatigue

Abstract

Background: Brain information processing deteriorates as cortical neurons gradually transition from a rested state into fatigue. Subjectively, fatigue is experienced as a state of weariness, tiredness, or lack of energy that reduces the ability to work safely and effectively. Objective: In this theoretical paper, we pinpoint the physical origin of brain fatigue in the gradual deterioration of biochemical reaction quotients and transmembrane ion concentration gradients, which increase neuronal excitability and decrease the signal-to-noise ratio in the brain cortex. Methods: Brain performance in a rested state versus fatigue is examined by well-established, data-driven computer models for energy transport inside protein $α$-helices in the presence of thermal noise for different ATP energy states or for pyramidal neuron firing of action potentials under electric stimulation in a rested membrane state versus fatigue. Results: We found that reduced Gibbs free energy supply from ATP hydrolysis impairs the cooperative effect between amide I excitons propagating inside protein $α$-helices, with resulting decreased thermal stability of molecular solitons. Concurrent changes in Nernst reversal potentials for Na+ or K+ ions further led to neuronal hyperexcitability and a higher risk of neuronal depolarization block during mental fatigue. Conclusions: Detailed computational modeling showed that inefficient protein function due to diminished ATP energy status, alters the electrophysiological properties of individual neurons, thereby impairing their information processing capacity for the proper execution of cognitive tasks. Scheduling practices aimed at intermittent recovery of the rested brain state during intellectually challenging work could protect physical and mental wellbeing, prevent burnout, and enhance long-term productivity.