Transient destabilization of whole brain dynamics induced by N,N-Dimethyltryptamine (DMT)

Abstract

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