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

This whole-brain simulation study (DMF model) reproduced increased entropy under psychedelics, but also found this to be different (higher/lower) in various parts of the brain, this was correlated with the connections between brain regions, not serotonin (5-HT2a) receptor density.


“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.”

Authors: Ruben Herzog, Pedro A. M. Mediano, Fernando E. Rosas, Robin L. Carhart-Harris, Yonatan Sanz Perl, Enzo Tagliazucchi & Rodrigo Cofre


This paper builds on earlier (fMRI, brain imaging) work by Carhart-Harris et al. (2016) (and many other papers) which mapped the brain under the influence of LSD.

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