TY - JOUR T1 - A mechanistic model of the neural entropy increase elicited by psychedelic drugs JF - bioRxiv DO - 10.1101/2020.05.13.093732 SP - 2020.05.13.093732 AU - Rubén Herzog AU - Pedro A.M. Mediano AU - Fernando E. Rosas AU - Robin Carhart-Harris AU - Yonatan Sanz Perl AU - Enzo Tagliazucchi AU - Rodrigo Cofre Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/05/15/2020.05.13.093732.abstract N2 - 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, encoding both acute alterations in consciousness and mediating long-term effects. However, no clear mechanistic explanation for this ‘entropic’ phenomenon 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.Competing Interest StatementThe authors have declared no competing interest. ER -