A whole-brain model of the neural entropy increase elicited by psychedelic drugs.
Rubén Herzog, Pedro A. M. Mediano, Fernando E. Rosas, Paul Lodder, Robin Carhart-Harris, Yonatan Sanz Perl, Enzo Tagliazucchi, Rodrigo Cofré
Scientific Reports April 17, 2023 DOI: 10.1038/s41598-023-32649-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Computational modeling study Peer reviewed |
|---|---|
| Topics | Serotonin |
| Keywords | Psychedelics Brain connectivity Neural entropy |
| Citations | 51 |
| Key points | Activation of serotonin 2A receptors increases neural entropy across the brain, especially in visuo-occipital regions, and this effect is linked to the brain's anatomical connectivity rather than receptor density. |
Abstract
Psychedelic drugs, including lysergic acid diethylamide (LSD) 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 all regions, but the larger effect were localised in visuo-occipital regions. 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.