RETRACTED ARTICLE: A mechanistic model of the neural entropy increase elicited by psychedelic drugs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 DOI: 10.1038/s41598-020-74060-6 via OpenAlex
Summary
AI-generated from the abstractPsychedelic drugs such as lysergic acid diethylamide, which activate the serotonin 2A receptor, produce profound changes in consciousness and increase entropy in spontaneous neural activity. This study provides the first model-based explanation for that entropy increase by extending a whole-brain model of serotonergic neuromodulation. The model reproduced the overall entropy rise seen in previous experiments. Entropy changes were not uniform: some brain regions showed increased entropy while others showed decreases, indicating a topographical reconfiguration driven by receptor activation. At the whole-brain level, this reconfiguration was not well explained by receptor density but was closely related to the brain's anatomical connectivity topology.
Study at a glance
| Characteristics | Computational modeling study Peer reviewed |
|---|---|
| Topics | Default mode network LSD Serotonin |
| Keywords | Neuroscience Consciousness |
| Citations | 60 |
| Key finding | 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.