Disrupted hierarchical organization in disorders of consciousness revealed by fluctuation-dissipation deviations

Evaluating consciousness levels after coma remains clinically challenging, and probing the brain's functional hierarchy offers model-based biomarkers of brain states. We characterize the hierarchy loss in disorders of consciousness (DoC) via departures from non-equilibrium dynamics. Irreversible, directed interactions are indexed by deviation from the fluctuation-dissipation theorem (FDT), computed from individualized whole-brain models fit to fMRI from controls and patients in minimally conscious state (MCS) or unresponsive wakefulness syndrome (UWS). Global and resting-state network dynamics in DoC were closer to equilibrium than in controls, decreasing stepwise with decreasing levels of consciousness. Mapping site-specific hierarchical drive over the system revealed disruptions within default-mode network components (e.g., medial and dorsolateral superior frontal gyrus) and subcortical hubs (e.g., thalamus, pallidum and putamen) differentiating between all groups. Recovery of near-control hierarchy in the visual network differentiated MCS from UWS, whereas multiple limbic areas showed similar abnormalities across both DoC groups. Together, these results identify non-equilibrium dynamics as a signature of conscious capacity and stablish FDT deviation as a principled, model-based hierarchy measure that can be operationalised for clinical stratification and monitoring, opening avenues for targeted in silico intervention planing.