Psilocybin Induces Aberrant Prediction Error Processing of Tactile Mismatch Responses-A Simultaneous EEG-FMRI Study

Introduction

The skin provides the primary interface between the body and environment and plays a central role in boundary processing and self/non-self discrimination. Disruption of multisensory integration that supports bodily self-awareness is implicated in several psychiatric disorders. Within a predictive coding framework, the brain minimises surprise by comparing incoming sensory input with top-down priors; prediction error (PE) signals arising from mismatches drive updating of internal models. The mismatch negativity (MMN) event-related potential is an index of early PE and perceptual learning and has been linked to altered sensory processing in conditions such as schizophrenia. Serotonergic psychedelics, including psilocybin (Psi), act primarily at 5-HT2A receptors and produce dose-dependent, reversible alterations in self- and body-perception, making them useful probes of the neurobiology of bodily awareness. Duerler and colleagues set out to test whether psilocybin alters the neural processing of tactile surprising stimuli and whether such changes relate to subjective alterations in body and self-experience. Using a simultaneous EEG–fMRI design and a roving somatosensory oddball task, the investigators hypothesised that Psi (versus placebo) 1) changes blood-oxygen-level-dependent (BOLD) responses in regions implicated in tactile deviancy processing, 2) reduces the EEG MMN amplitude to tactile deviants, and 3) that these neural changes correlate with self-reported alterations in body and self-experience. The study aimed to link spatial (fMRI) and temporal (EEG) markers of tactile PE processing under 5-HT2A stimulation.