Fluctuation-dissipation theorem and the discovery of distinctive off-equilibrium signatures of brain states

Abstract

The brain is able to sustain many different states as shown by the daily natural transitions between wakefulness and sleep. Yet, the underlying complex dynamics of these brain states are essentially in nonequilibrium. Here, we develop a thermodynamical formalism based on the off-equilibrium extension of the fluctuation-dissipation theorem (FDT) together with a whole-brain model. This allows us to investigate the nonequilibrium dynamics of different brain states and more specifically to apply this formalism to wakefulness and deep sleep brain states. We show that the off-equilibrium thermodynamical signatures of brain states are significantly different in terms of the overall level of differential and integral violation of FDT. Furthermore, the framework allows for a detailed understanding of how different brain regions and networks are contributing to the off-equilibrium signatures in different brain states. Overall, this framework shows great promise for characterizing and differentiating brain states in health and disease.

J.M.M. acknowledges financial support from CONICET through external scholarship for researchers. G.D. was supported by several sources: NEMESIS project (Ref. 101071900) funded by the EU ERC Synergy Horizon Europe; AGAUR research support Grant (Ref. 2021 SGR 00917) funded by the Department of Research and Universities of the Generalitat of Catalunya; and Project PID2022-136216NB-I00 financed by the MCIN /AEI /10.13039/501100011033 / FEDER, UE., the Ministry of Science and Innovation, the State Research Agency and the European Regional Development Fund. M.L.K. is supported by the Centre for Eudaimonia and Human Flourishing (funded by the Pettit and Carlsberg Foundations) and Center for Music in the Brain (funded by the Danish National Research Foundation, DNRF117). Y.S.P. is supported by European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant 896354.