DMT induces a transient destabilization of whole-brain dynamics

This pre-print computational fMRI study (n=15; re-analysis of earlier data) 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 of DMT induces a transient destabilization of whole-brain dynamics

“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 of bolus intravenous N,N-Dimethyltryptamine (DMT), a short-lasting psychedelic. To capture the transient effects of DMT, we parametrized the proximity to a global bifurcation using a pharmacokinetic equation and adopted the empirical functional connectivity dynamics (FCD) as optimization target. Post-administration, DMT rapidly destabilized brain dynamics, peaking after ≈5 minutes, followed by a recovery to baseline. Simulated perturbations revealed a transient of heightened reactivity, where stimulation maximally impacted the FCD. Local reactivity concentrated in fronto-parietal regions and visual cortices, and correlated with serotonin 5HT2a receptor density, the primary target of psychedelics. These advances suggest a mechanism to explain key features of the psychedelic state, such as increased brain complexity, diversity, and flexibility. Our model also predicts that the temporal evolution of these features aligns with pharmacokinetics. These 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.”

Authors: Juan I. Piccinini, Yonatan S. Perl, Carla Pallavicini, Gustavo Deco, Morten Kringelbach, David J. Nutt, Robin L. Carhart-Harris, Christopher Timmermann, & Enzo Tagliazucchi

Summary of DMT induces a transient destabilization of whole-brain dynamics

Psychedelic drugs increase global network integration measured with functional magnetic resonance imaging (fMRI), and evidence from multiple modalities links their effects to increased entropy and complexity of spontaneous brain activity fluctuations. Integrative understanding of psychedelic action requires identification of causal mechanisms behind empirical observations.

Generative whole-brain activity models have been increasingly adopted to test potential mechanisms underlying neuroimaging data, including successful applications to the specific case of psychedelic compounds psilocybin and LSD. The use of simpler models fitted to the empirical measurements can help shift the focus from the neurobiological details of drug action to the qualitative aspects of brain dynamics that characterize the acute effects of psychedelics.

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Find this paper

DMT induces a transient destabilization of whole-brain dynamics

https://doi.org/10.1101/2024.01.26.577435

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Cite this paper (APA)

Piccinini, J., Sanz Perl, Y., Pallavicini, C., Deco, G., Kringelbach, M. L., Nutt, D., ... & Tagliazucchi, E. (2024). DMT induces a transient destabilization of whole-brain dynamics. bioRxiv, 2024-01.

Study details

Compounds studied
DMT

Topics studied
Neuroscience

Study characteristics
Original Open-Label

Participants
15 Humans

Compound Details

The psychedelics given at which dose and how many times

DMT 20 mg | 1x

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Human brain effects of DMT assessed via EEG-fMRI
This neuroimaging study (n=20) aimed to understand the effects of DMT (20mg) on the human brain. The researchers used EEG-fMRI (electroencephalography-functional MRI) to measure brain activity before, during, and after administering DMT to healthy volunteers. They found that DMT increased global functional connectivity (GFC), network disintegration and desegregation, and a compression of the principal cortical gradient.

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