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Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain’s control energy landscape
Psychedelics including lysergic acid diethylamide (LSD) and psilocybin temporarily alter subjective experience through their neurochemical effects. Serotonin 2a (5-HT2a) receptor agonism by these compounds is associated with more diverse (entropic) brain activity. We postulate that this increase in...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530221/ https://www.ncbi.nlm.nih.gov/pubmed/36192411 http://dx.doi.org/10.1038/s41467-022-33578-1 |
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author | Singleton, S. Parker Luppi, Andrea I. Carhart-Harris, Robin L. Cruzat, Josephine Roseman, Leor Nutt, David J. Deco, Gustavo Kringelbach, Morten L. Stamatakis, Emmanuel A. Kuceyeski, Amy |
author_facet | Singleton, S. Parker Luppi, Andrea I. Carhart-Harris, Robin L. Cruzat, Josephine Roseman, Leor Nutt, David J. Deco, Gustavo Kringelbach, Morten L. Stamatakis, Emmanuel A. Kuceyeski, Amy |
author_sort | Singleton, S. Parker |
collection | PubMed |
description | Psychedelics including lysergic acid diethylamide (LSD) and psilocybin temporarily alter subjective experience through their neurochemical effects. Serotonin 2a (5-HT2a) receptor agonism by these compounds is associated with more diverse (entropic) brain activity. We postulate that this increase in entropy may arise in part from a flattening of the brain’s control energy landscape, which can be observed using network control theory to quantify the energy required to transition between recurrent brain states. Using brain states derived from existing functional magnetic resonance imaging (fMRI) datasets, we show that LSD and psilocybin reduce control energy required for brain state transitions compared to placebo. Furthermore, across individuals, reduction in control energy correlates with more frequent state transitions and increased entropy of brain state dynamics. Through network control analysis that incorporates the spatial distribution of 5-HT2a receptors (obtained from publicly available positron emission tomography (PET) data under non-drug conditions), we demonstrate an association between the 5-HT2a receptor and reduced control energy. Our findings provide evidence that 5-HT2a receptor agonist compounds allow for more facile state transitions and more temporally diverse brain activity. More broadly, we demonstrate that receptor-informed network control theory can model the impact of neuropharmacological manipulation on brain activity dynamics. |
format | Online Article Text |
id | pubmed-9530221 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95302212022-10-05 Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain’s control energy landscape Singleton, S. Parker Luppi, Andrea I. Carhart-Harris, Robin L. Cruzat, Josephine Roseman, Leor Nutt, David J. Deco, Gustavo Kringelbach, Morten L. Stamatakis, Emmanuel A. Kuceyeski, Amy Nat Commun Article Psychedelics including lysergic acid diethylamide (LSD) and psilocybin temporarily alter subjective experience through their neurochemical effects. Serotonin 2a (5-HT2a) receptor agonism by these compounds is associated with more diverse (entropic) brain activity. We postulate that this increase in entropy may arise in part from a flattening of the brain’s control energy landscape, which can be observed using network control theory to quantify the energy required to transition between recurrent brain states. Using brain states derived from existing functional magnetic resonance imaging (fMRI) datasets, we show that LSD and psilocybin reduce control energy required for brain state transitions compared to placebo. Furthermore, across individuals, reduction in control energy correlates with more frequent state transitions and increased entropy of brain state dynamics. Through network control analysis that incorporates the spatial distribution of 5-HT2a receptors (obtained from publicly available positron emission tomography (PET) data under non-drug conditions), we demonstrate an association between the 5-HT2a receptor and reduced control energy. Our findings provide evidence that 5-HT2a receptor agonist compounds allow for more facile state transitions and more temporally diverse brain activity. More broadly, we demonstrate that receptor-informed network control theory can model the impact of neuropharmacological manipulation on brain activity dynamics. Nature Publishing Group UK 2022-10-03 /pmc/articles/PMC9530221/ /pubmed/36192411 http://dx.doi.org/10.1038/s41467-022-33578-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Singleton, S. Parker Luppi, Andrea I. Carhart-Harris, Robin L. Cruzat, Josephine Roseman, Leor Nutt, David J. Deco, Gustavo Kringelbach, Morten L. Stamatakis, Emmanuel A. Kuceyeski, Amy Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain’s control energy landscape |
title | Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain’s control energy landscape |
title_full | Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain’s control energy landscape |
title_fullStr | Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain’s control energy landscape |
title_full_unstemmed | Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain’s control energy landscape |
title_short | Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain’s control energy landscape |
title_sort | receptor-informed network control theory links lsd and psilocybin to a flattening of the brain’s control energy landscape |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530221/ https://www.ncbi.nlm.nih.gov/pubmed/36192411 http://dx.doi.org/10.1038/s41467-022-33578-1 |
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