Brain fatigue linked to depleted ATP energy in new computational model

A new theoretical paper from physicists Danko D. Georgiev, Oskan B. Tasinov, Danail V. Pavlov, and Deyan S. Hrusafov, published on arXiv (2608.10211), pinpoints the physical origin of mental fatigue to a diminished supply of Gibbs free energy from ATP hydrolysis. Using data-driven computer models, the team simulated energy transport inside protein alpha-helices under thermal noise and modeled pyramidal neuron firing in rested versus fatigued states. They found that reduced ATP energy weakens the cooperative interaction between amide I excitons—vibrationally excited states that propagate along protein backbones—resulting in decreased thermal stability of molecular solitons, which are critical for efficient energy transduction in neurons.

Concurrently, the models show that fatigue alters Nernst reversal potentials for sodium and potassium ions, making neurons hyperexcitable and increasing the risk of depolarization block, where neurons fail to fire action potentials entirely. This combination of inefficient protein function and disrupted electrophysiology impairs the signal-to-noise ratio in the brain cortex, degrading information processing during cognitive tasks. The authors conclude that the brain's performance decline during fatigue is not a subjective illusion but a measurable thermodynamic and electrochemical phenomenon. They recommend scheduling intermittent recovery periods during intellectually demanding work to restore the rested brain state, which could protect mental wellbeing, prevent burnout, and enhance long-term productivity. The study was also published in the journal Fatigue: Biomedicine, Health & Behavior (2026; 14(3): 216-233).