Abstract
Background: Psilocybin is a serotonergic psychedelic that provides a pharmacological tool for examining neural activity associated with altered states of consciousness. Existing studies report reduced power (4-30 Hz) in posterior regions and altered functional connectivity (FC) at rest, but have typically involved small samples and coarse anatomical parcellations. Additionally, perceptual engagement has been shown to attenuate psilocybin-related whole-brain FC changes. However, how naturalistic context modifies psilocybin's frequency-specific electrophysiological effects remains incompletely characterised.
Methods: We analysed the largest psilocybin electroencephalography (EEG) dataset to date (n = 56), with matched baseline recordings acquired before psilocybin administration. EEG was recorded during movie viewing, eyes-closed rest, guided meditation, and music listening. Cortical source activity was estimated using minimum-norm estimation and analysed across six canonical frequency bands (1-80 Hz). Spectral power, alpha peak frequency (APF), and magnitude-squared coherence within and between seven functional networks were quantified. Psilocybin effects were assessed using permutation testing with FDR correction, and linear mixed-effects models separated the contributions of drug, context, and their interaction to alpha-band connectivity.
Results: At rest, psilocybin decreased alpha (8-13 Hz) power, increased gamma-range power, and elevated APF. Alpha-band FC decreased within and between higher-order networks implicated in top-down control. Relative to eyes-closed rest, psilocybin-context interactions showed that structured sensory environments attenuated or reversed psilocybin-related alpha-band connectivity changes.
Conclusions: These findings identify alpha-band activity as a key electrophysiological correlate of psilocybin-related changes in cortical communication. Structured sensory input reshapes psilocybin-related cortical dynamics, particularly alpha-band connectivity across large-scale cortical networks, with the strength and direction of this modulation differing by context.