A mechanistic 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
Research Square October 26, 2022 DOI: 10.21203/rs.3.rs-2187775/v1
Summary
AI-generated from the abstractPsychedelic drugs like LSD, which activate serotonin 2A receptors, dramatically alter subjective experience and offer a window into the neurobiology of consciousness. A key signature of these drugs is increased entropy—or randomness—in spontaneous brain activity, but why this occurs was unclear. Using a computational model of serotonin's effects on the whole brain, researchers reproduced the entropy increase seen in living brains, providing the first model-based explanation. Entropy rose across all brain regions but was most pronounced in visual and occipital areas. Surprisingly, this pattern was not tied to the density of serotonin receptors but instead linked to the brain's structural connectivity network. The findings clarify how psychedelics reconfigure brain activity.
Study at a glance
| Characteristics | Computational modeling study Peer reviewed |
|---|---|
| Topics | Serotonin |
| Keywords | Psychedelics: hallucinogens Entheogens Psychotropic drugs Mind-altering substances Neuroscience: neurobiology |
| Citations | 6 |
| Key finding | Activation of serotonin 2A receptors increases neural entropy across the brain, with the largest effects in visual-occipital regions, and this reconfiguration is explained by the brain's anatomical connectivity rather than receptor density. |
Abstract
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.