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RETRACTED ARTICLE: A mechanistic model of the neural entropy increase elicited by psychedelic drugs

Rubén Herzog, Pedro A. M. Mediano, Fernando E. Rosas, Robin Carhart-Harris, Yonatan Sanz Perl, Enzo Tagliazucchi, Rodrigo Cofré

Scientific Reports October 20, 2020 Retracted DOI: 10.1038/s41598-020-74060-6 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Computational modeling study Peer reviewed
Topics Default mode network LSD Serotonin
Keywords Consciousness 5-HT Receptor
Citations 60
Key points Activation of the serotonin 2A receptor increases neural entropy in a topographically non-uniform manner, with the reconfiguration linked to anatomical connectivity rather than receptor density.

Abstract

Abstract Psychedelic drugs, including lysergic acid diethylamide and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, mediating both acute alterations in consciousness and long-term effects. However, no clear mechanistic explanation for this entropy increase has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experiments in vivo, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in some regions and decreased in others, suggesting a topographical reconfiguration mediated by 5HT2A-R activation. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain’s anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.

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