The transition into a psychedelic brain state is often overlooked in favor of static descriptions of acute effects. Using a time-dependent whole-brain model and fMRI data from 15 volunteers given intravenous DMT, the work shows that a transient of heightened reactivity in fronto-parietal regions and visual cortices correlates with serotonin 5HT2a receptor density. Simulated perturbations suggest that minimal disturbances can achieve maximal effects during this brief period, and the temporal evolution of these features aligns with pharmacokinetics. These findings indicate a mechanism for how short psychedelic episodes may exert a lasting influence over time.
The brain state induced by psychedelic drugs is often studied as a static snapshot, but this work focuses on the transition itself. Using a time-dependent whole-brain model and fMRI data from 15 volunteers given intravenous DMT, the authors show that the drug briefly pushes the brain near a critical point where it becomes maximally responsive to perturbations. This heightened reactivity is concentrated in fronto-parietal regions and visual cortices and correlates with serotonin 5HT2a receptor density. The findings suggest that even a short psychedelic episode can have a lasting influence because minimal perturbations during this transient achieve maximal effect, with the temporal evolution aligning with the drug's pharmacokinetics.