Transient destabilization of whole brain dynamics induced by N,N-Dimethyltryptamine (DMT)
Carhart-Harris, R. L., Deco, G., Kringelbach, M. L., Nutt, D. J., Pallavicini, C., Perl, Y. S., Piccinini, J. I., Tagliazucchi, E., Timmermann, C.
This computational fMRI study (n=15) examines brain dynamics after DMT (iv; 20mg) administration, focusing on the onset of the psychedelic state. It reveals a peak destabilization of brain dynamics around 5 minutes post-administration and identifies a heightened reactivity phase, primarily affecting fronto-parietal and visual regions. The study links these changes to serotonin 5HT2a receptor density, suggesting these dynamics underpin the psychedelic state's complexity and flexibility.
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 use 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 parametrize the proximity to a global bifurcation using a pharmacokinetic equation. Simulated perturbations reveal 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.