Healthy VolunteersNeuroimaging & Brain MeasuresPsilocybin

Dynamic Functional Hyperconnectivity after Psilocybin Intake is Primarily Associated with Oceanic Boundlessness

In healthy volunteers given psilocybin, ultra-high field fMRI revealed a recurrent hyperconnected, low‑BOLD‑amplitude brain state reflecting increased cortical arousal and overall functional connectivity. Transition probabilities into this hyperconnected pattern were linked primarily to feelings of oceanic boundlessness (and secondarily to visionary restructuralization), providing a first direct neurophenomenological association between dynamic brain states and psychedelic experience.

Authors

  • Johannes Ramaekers
  • Nathalie Mason
  • Paolo Mallaroni

Published

Biological Psychiatry
individual Study

Abstract

To provide insights into neurophenomenological richness after psilocybin intake, we investigated the link between dynamical brain patterns and the ensuing phenomenological pattern after psilocybin intake. Healthy participants received either psilocybin (n=22) or placebo (n=27) while in ultra-high field 7T MRI scanning. Changes in the phenomenological patterns were quantified using the 5-Dimensional Altered States of Consciousness (5D-ASC) Rating Scale, revealing alterations across all dimensions under psilocybin. Changes in the neurobiological patterns displayed that psilocybin induced widespread increases in averaged functional connectivity. Time-varying connectivity analysis unveiled a recurrent hyperconnected pattern characterized by low BOLD signal amplitude, suggesting heightened cortical arousal. In terms of neurophenomenology, canonical correlation analysis primarily linked the transition probabilities of the hyperconnected pattern with feelings of oceanic boundlessness (OBN), and secondly with visionary restructuralization. We suggest that the brain’s tendency to enter a hyperconnected-hyperarousal pattern under psilocybin represents the potential to entertain variant mental associations. For the first time, these findings link brain dynamics with phenomenological alterations, providing new insights into the neurophenomenology and neurophysiology of the psychedelic state.

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Research Summary of 'Dynamic Functional Hyperconnectivity after Psilocybin Intake is Primarily Associated with Oceanic Boundlessness'

Introduction

Classical serotonergic hallucinogens such as psilocybin produce a characteristic altered state of consciousness that combines marked subjective changes (for example ego dissolution, altered perception, hyper-associative cognition and changes in time and selfhood) with measurable shifts in brain activity and connectivity. Previous neuroimaging work has reported both averaged effects — including increased global connectivity and reduced modularity, and region-specific alterations (for example in the posterior cingulate cortex and default mode network) — and dynamic effects, with the brain visiting transient, less-stable connectivity patterns more frequently under psychedelics. However, the relationship between these time-varying neural patterns and the rich, multi-dimensional phenomenology of the psychedelic state has generally been treated separately and remains incompletely characterised. Mortaheb and colleagues set out to bridge that gap by adopting a neurophenomenological approach: they administered a single moderate dose of psilocybin or placebo to healthy adults and used ultra-high-field 7T resting-state fMRI acquired at the peak subjective effect together with the 5‑Dimensional Altered States of Consciousness (5D-ASC) questionnaire to link dynamic whole-brain functional connectivity patterns to detailed self-reported experiential dimensions. The analysis combined phase-based, time-resolved connectivity, clustering into recurrent connectivity patterns, Markov modelling of state transitions, and canonical correlation analysis to relate transition dynamics to phenomenological measures.

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