Brain dynamics of classical psychedelics show paradoxical hierarchical flattening with increased complexity

Both psychedelic states and reduced states of consciousness flatten the brain's functional hierarchy, yet their behavioral and phenomenological profiles differ. To resolve this paradox, researchers defined hierarchy by the brain's proximity to thermodynamic equilibrium and examined changes induced by three serotonergic psychedelics: psilocybin, LSD, and DMT. All three consistently reduced the functional hierarchy globally. Unlike loss of consciousness, psychedelics moved the brain toward equilibrium while increasing neural activity complexity, indicating a distinct mechanism involving altered configuration and differentiation of resting-state networks. This work demonstrates how statistical mechanics metrics can characterize different global brain states, advancing understanding of consciousness as an emergent collective process.

Study at a glance

Abstract

Despite divergent behavioral and phenomenological profiles, both psychedelic states and reduced states of consciousness have been associated with a flattening of the brain's functional hierarchy. To address this apparent paradox, we developed a more specific definition of hierarchy based on the proximity of the brain to thermodynamic equilibrium and then applied it to investigate the changes to the functional hierarchy elicited by three classical serotonergic psychedelics: psilocybin, lysergic acid diethylamide, and dimethyltryptamine. We found that all three psychedelics consistently induced a global reduction in the functional hierarchy. In contrast to the flattening of the functional hierarchy observed during loss of consciousness, psychedelics displaced the brain towards equilibrium while simultaneously increasing the complexity of neural activity, indicating a unique mechanism linked to specific changes in the configuration and differentiation of resting-state networks. This work showcases how metrics based on statistical mechanics can be used for the specific characterization of different global brain states, contributing to the understanding of consciousness as a collective process emerging from complex neural interactions.