Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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
_version_ 1784801630856675328
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
work_keys_str_mv AT singletonsparker receptorinformednetworkcontroltheorylinkslsdandpsilocybintoaflatteningofthebrainscontrolenergylandscape
AT luppiandreai receptorinformednetworkcontroltheorylinkslsdandpsilocybintoaflatteningofthebrainscontrolenergylandscape
AT carhartharrisrobinl receptorinformednetworkcontroltheorylinkslsdandpsilocybintoaflatteningofthebrainscontrolenergylandscape
AT cruzatjosephine receptorinformednetworkcontroltheorylinkslsdandpsilocybintoaflatteningofthebrainscontrolenergylandscape
AT rosemanleor receptorinformednetworkcontroltheorylinkslsdandpsilocybintoaflatteningofthebrainscontrolenergylandscape
AT nuttdavidj receptorinformednetworkcontroltheorylinkslsdandpsilocybintoaflatteningofthebrainscontrolenergylandscape
AT decogustavo receptorinformednetworkcontroltheorylinkslsdandpsilocybintoaflatteningofthebrainscontrolenergylandscape
AT kringelbachmortenl receptorinformednetworkcontroltheorylinkslsdandpsilocybintoaflatteningofthebrainscontrolenergylandscape
AT stamatakisemmanuela receptorinformednetworkcontroltheorylinkslsdandpsilocybintoaflatteningofthebrainscontrolenergylandscape
AT kuceyeskiamy receptorinformednetworkcontroltheorylinkslsdandpsilocybintoaflatteningofthebrainscontrolenergylandscape