Non-equilibrium whole-brain dynamics arise from pairwise interactions

The human brain is a complex system of multiple neural elements that interact at different orders (pairwise, triplets, etc.), displaying non-equilibrium processes from the neuronal scale to the whole-brain scale. Here, we study how non-equilibrium dynamics of large-scale brain activity is driven by the interaction of its constituent elements at different orders. We hypothesize that the interactions generating non-equilibrium dynamics at the macroscopic brain scale are typically pairwise, with higher-order dependences playing a diminishing role. By expanding the entropy production into a sequence of orders of interactions, we find that pairwise interactions contribute dominantly. In light of this finding, we demonstrate that it is possible to characterize non-equilibrium brain dynamics using the interactions of pairs of macroscopic brain regions rather than complex interactions involving three or more regions. Furthermore, we propose that the entropy production of pairs of brain regions is a sensitive indicator for characterizing task-induced brain states.