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Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain's control energy landscape.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Singleton, S Parker  ORCID logo  https://orcid.org/0000-0002-7102-7820
Carhart-Harris, Robin L 
Roseman, Leor 

Abstract

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.

Description

Keywords

Brain, Hallucinogens, Humans, Lysergic Acid Diethylamide, Psilocybin, Receptor, Serotonin, 5-HT2A, Serotonin, Serotonin 5-HT2 Receptor Agonists

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

13

Publisher

Springer Science and Business Media LLC
Sponsorship
National Science Foundation (NSF) (DGE-1650441)
Canadian Institute for Advanced Research (L'Institut Canadien de Recherches Avancées) (RCZB/072 RG93193)
U.S. Department of Health & Human Services | National Institutes of Health (NIH) (R21NS104634, RF1MH123232, R01NS102646)
Danmarks Grundforskningsfond (Danish National Research Foundation) (DNRF117)