A whole-brain model of the neural entropy increase elicited by psychedelic drugs

Introduction

Psychedelic drugs acting at the serotonin 2A receptor (5HT2A-R), such as LSD, DMT and psilocybin, produce profound alterations of perception, cognition and selfhood. Earlier empirical work has identified two prominent neurophysiological signatures of the acute psychedelic state: suppression of alpha-band spectral power and an increase in the information-theoretic diversity of neural signals, commonly expressed as an increase in entropy. These entropy increases have been proposed to relate to both the acute alterations of consciousness and some longer-term psychological effects, and lie at the heart of the Entropic Brain Hypothesis (EBH), which links richness of subjective experience to the diversity of ongoing neural activity. Despite converging experimental evidence for elevated neural entropy under psychedelics, a clear mechanistic, whole-brain explanation for how 5HT2A-R activation produces these entropy changes has been lacking. Herzog and colleagues set out to provide a mechanistic account by extending a Dynamic Mean-Field (DMF) whole-brain model that incorporates neuromodulation by 5HT2A-R. The study aimed to test whether modulating neuronal response gain according to the empirical topography of 5HT2A-R could reproduce the experimentally observed increase in neural entropy, to map the regional patterning of entropy change, and to identify the roles of receptor density and structural connectivity (and their topological properties) in explaining those changes. By simulating resting-state population firing rates with and without 5HT2A-R activation and analysing regional differential entropy, the investigators sought a model-based explanation for the entropic effects attributed to serotonergic psychedelics.