Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience.

Publication Type Academic Article
Authors Singleton S, Timmermann C, Luppi A, Eckernäs E, Roseman L, Carhart-Harris R, Kuceyeski A
Journal Commun Biol
Volume 8
Issue 1
Pagination 631
Date Published 04/18/2025
ISSN 2399-3642
Keywords Brain, Hallucinogens, N, N-Dimethyltryptamine, Receptors, Serotonin
Abstract Psychedelics offer a profound window into the human brain through their robust effects on perception, subjective experience, and brain activity patterns. The serotonergic psychedelic N,N-dimethyltryptamine (DMT) induces a profoundly immersive altered state of consciousness lasting under 20 min, allowing the entire experience to be captured during a single functional magnetic resonance imaging (fMRI) scan. Using network control theory, we map energy trajectories of 14 individuals undergoing fMRI during DMT and placebo. We find that global control energy is reduced after DMT injection compared to placebo. Longitudinal trajectories of global control energy correlate with longitudinal trajectories of electroencephalography (EEG) signal diversity (a measure of entropy) and subjective drug intensity ratings. At the regional level, spatial patterns of DMT's effects on these metrics correlate with serotonin 2a receptor density from positron emission tomography (PET) data. Using receptor distribution and pharmacokinetic information, we recapitulate DMT's effects on global control energy trajectories, demonstrating control models can predict pharmacological effects on brain dynamics.
DOI 10.1038/s42003-025-08078-9
PubMed ID 40251353
PubMed Central ID PMC12008288
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