Non-equilibrium dynamics and entropy production in the human brain

It has long been suspected that living systems operate out of thermodynamic equilibrium1, consuming energy and producing entropy in the environment in order to perform biological functions. Recent efforts at the microscale have established that non-equilibrium processes are critical for molecular and cellular operations2–8. However, it remains unclear whether non-equilibrium dynamics manifest at macroscopic scales, and if so, how such dynamics support higher-order biological functions. Here we present a framework to probe for non- equilibrium processes by quantifying entropy production in macroscopic systems. We apply our method to the human brain, an organ whose immense metabolic consumption drives a diverse range of cognitive functions9,10. Using whole-brain imaging data, we demonstrate that the brain fundamentally operates out of equilibrium at large scales. Moreover, we find that the brain produces more entropy – operating further from equilibrium – when per- forming physically and cognitively demanding tasks. To understand how the brain operates at different distances from equilibrium, we use simulations to show that the non-equilibrium nature of macroscopic systems is modulated by the strength of interactions at the microscale. Together, these results suggest that non-equilibrium dynamics are vital for cognition, and provide a general tool for quantifying the non-equilibrium nature of macroscopic systems.