Neuroimaging & Brain MeasuresPsilocybin

Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin

This experiment measured brain states (fMRI) under psilocybin infusion, and found more general coherence (communication) and lower frontoparietal network activity.

Authors

  • Robin Carhart-Harris
  • David Nutt
  • Leor Roseman

Published

NeuroImage
individual Study

Abstract

Growing evidence from the dynamical analysis of functional neuroimaging data suggests that brain function can be understood as the exploration of a repertoire of metastable connectivity patterns (‘functional brain networks’), which potentially underlie different mental processes. The present study characterizes how the brain's dynamical exploration of resting-state networks is rapidly modulated by intravenous infusion of psilocybin, a tryptamine psychedelic found in “magic mushrooms”. We employed a data-driven approach to characterize recurrent functional connectivity patterns by focusing on the leading eigenvector of BOLD phase coherence at single-TR resolution. Recurrent BOLD phase-locking patterns (PL states) were assessed and statistically compared pre- and post-infusion of psilocybin in terms of their probability of occurrence and transition profiles. Results were validated using a placebo session. Recurrent BOLD PL states revealed high spatial overlap with canonical resting-state networks. Notably, a PL state forming a frontoparietal subsystem was strongly destabilized after psilocybin injection, with a concomitant increase in the probability of occurrence of another PL state characterized by global BOLD phase coherence. These findings provide evidence of network-specific neuromodulation by psilocybin and represent one of the first attempts at bridging molecular pharmacodynamics and whole-brain network dynamics.

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Research Summary of 'Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin'

Introduction

Lord and colleagues frame brain function as the exploration of a repertoire of metastable, large-scale functional networks that reconfigure over time. Previous work has suggested that transitions between recurrent network states can relate to cognition and that psychoactive compounds may alter these dynamical explorations; however, how a serotonergic psychedelic modulates the relative occupancy and transitions of specific whole-brain network states has not been fully characterised. The authors situate psilocybin—an agonist at serotonin 2A (5-HT2A) receptors with well‑documented subjective effects such as hyper‑associative cognition and altered selfhood—as a useful probe to link molecular pharmacodynamics to changes in large‑scale network dynamics. This study therefore aims to characterise how intravenous psilocybin rapidly modulates the brain's dynamical repertoire at rest. Using a data‑driven approach (Leading Eigenvector Dynamics Analysis, LEiDA) applied to single‑TR BOLD phase coherence, the investigators identify recurrent phase‑locking (PL) patterns, quantify their probabilities of occurrence and their state‑to‑state transition profiles before and after psilocybin infusion, and validate findings against a placebo session. They also compare recovered PL states to canonical resting‑state networks (RSNs) to assess functional correspondence.

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Dynamical exploration of the repertoire of brain... — Research Summary & Context | Blossom