Transient destabilization of whole brain dynamics induced by DMT

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.

Study at a glance

Abstract

Abstract The transition towards the brain state induced by psychedelic drugs is frequently neglected in favor of a static description of their acute effects. We used a time-dependent whole-brain model to reproduce large-scale brain dynamics measured with fMRI from 15 volunteers under 20 mg intravenous N,N-Dimethyltryptamine (DMT), a short-acting psychedelic. To capture its transient effects, we parametrized the proximity to a global bifurcation using a pharmacokinetic equation. Simulated perturbations revealed a transient of heightened reactivity concentrated in fronto-parietal regions and visual cortices, correlated with serotonin 5HT2a receptor density, the primary target of psychedelics. These advances suggest a mechanism to explain key features of the psychedelic state and also predicts that the temporal evolution of these features aligns with pharmacokinetics. Our results contribute to understanding how psychedelics introduce a transient where minimal perturbations can achieve a maximal effect, shedding light on how short psychedelic episodes may extend an overarching influence over time.