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Time-resolved network control analysis links reduced control energy under DMT with the serotonin 2a receptor, signal diversity, and subjective experience.
Singleton, S Parker; Timmermann, Christopher; Luppi, Andrea I; Eckernäs, Emma; Roseman, Leor; Carhart-Harris, Robin L; Kuceyeski, Amy.
Afiliación
  • Singleton SP; Department of Computational Biology, Cornell University, Ithaca, USA.
  • Timmermann C; Center for Psychedelic Research, Department of Brain Science, Imperial College London, London, United Kingdom.
  • Luppi AI; Montreal Neurological Institute, Montreal, Canada.
  • Eckernäs E; Unit for Pharmacokinetics and Drug Metabolism, Department of Pharmacology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
  • Roseman L; Center for Psychedelic Research, Department of Brain Science, Imperial College London, London, United Kingdom.
  • Carhart-Harris RL; Center for Psychedelic Research, Department of Brain Science, Imperial College London, London, United Kingdom.
  • Kuceyeski A; Psychedelics Division, Neuroscape, University of California San Francisco, USA.
bioRxiv ; 2023 May 12.
Article en En | MEDLINE | ID: mdl-37214949
Psychedelics offer a profound window into the functioning of the human brain and mind through their robust acute effects on perception, subjective experience, and brain activity patterns. In recent work using a receptor-informed network control theory framework, we demonstrated that the serotonergic psychedelics lysergic acid diethylamide (LSD) and psilocybin flatten the brain's control energy landscape in a manner that covaries with more dynamic and entropic brain activity. Contrary to LSD and psilocybin, whose effects last for hours, the serotonergic psychedelic N,N-dimethyltryptamine (DMT) rapidly induces a profoundly immersive altered state of consciousness lasting less than 20 minutes, allowing for the entirety of the drug experience to be captured during a single resting-state fMRI scan. Using network control theory, which quantifies the amount of input necessary to drive transitions between functional brain states, we integrate brain structure and function to map the energy trajectories of 14 individuals undergoing fMRI during DMT and placebo. Consistent with previous work, we find that global control energy is reduced following injection with DMT compared to placebo. We additionally show longitudinal trajectories of global control energy correlate with longitudinal trajectories of EEG signal diversity (a measure of entropy) and subjective ratings of drug intensity. We interrogate these same relationships on a regional level and find that the spatial patterns of DMT's effects on these metrics are correlated with serotonin 2a receptor density (obtained from separately acquired PET data). Using receptor distribution and pharmacokinetic information, we were able to successfully recapitulate the effects of DMT on global control energy trajectories, demonstrating a proof-of-concept for the use of control models in predicting pharmacological intervention effects on brain dynamics.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Clinical_trials / Prognostic_studies Idioma: En Revista: BioRxiv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Clinical_trials / Prognostic_studies Idioma: En Revista: BioRxiv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos