DMT induces a transient destabilization of whole-brain dynamics

Piccinini, J.; Sanz Perl, Y.; Pallavicini, C.; Deco, G.; Kringelbach, M. L.; Nutt, D.; Carhart-Harris, R.; Timmermann, C.; Tagliazucchi, E.

doi:10.1101/2024.01.26.577435

bioRxiv · 10.1101/2024.01.26.577435

DMT induces a transient destabilization of whole-brain dynamics

Piccinini, J.·Sanz Perl, Y.·Pallavicini, C.·Deco, G.·Kringelbach, M. L.·Nutt, D.·Carhart-Harris, R.·Timmermann, C.·Tagliazucchi, E.

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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.

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Piccinini, J., Sanz Perl, Y., Pallavicini, C., Deco, G., Kringelbach, M. L., Nutt, D., Carhart-Harris, R., Timmermann, C., Tagliazucchi, E.. 2024-01-29. DMT induces a transient destabilization of whole-brain dynamics. https://doi.org/10.1101/2024.01.26.577435

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