Neuroimaging & Brain MeasuresHealthy VolunteersPsilocybin

Psilocybin-induced changes in brain network integrity and segregation correlate with plasma psilocin level and psychedelic experience

This fMRI study (n=15) investigated the effects of psilocybin (14-21mg/70kg) on the brain and found that the higher the psilocin (active metabolite of psilocybin) and subjective drug experience (SDI) correlated with lower network integrity and segregation (less top-down, more bottom-up).

Authors

  • Gitte Knudsen
  • Patrick Fisher
  • Dea Stenbæk

Published

European Neuropsychopharmacology
individual Study

Abstract

The emerging novel therapeutic psilocybin produces psychedelic effects via engagement of cerebral serotonergic targets by psilocin (active metabolite). The serotonin 2A receptor critically mediates these effects by altering distributed neural processes that manifest as increased entropy, reduced functional connectivity (FC) within discrete brain networks (i.e., reduced integrity) and increased FC between networks (i.e., reduced segregation). Reduced integrity of the default mode network (DMN) is proposed to play a particularly prominent role in psychedelic phenomenology, including perceived ego-dissolution. Here, we investigate the effects of a psychoactive oral dose of psilocybin (0.2-0.3 mg/kg) on plasma psilocin level (PPL), subjective drug intensity (SDI) and their association in fifteen healthy individuals. We further evaluate associations between these measures and resting-state FC, measured with functional magnetic resonance imaging, acquired over the course of five hours after psilocybin administration. We show that PPL and SDI correlate negatively with measures of network integrity (including DMN) and segregation, both spatially constrained and unconstrained. We also find that the executive control network and dorsal attention network desegregate, increasing connectivity with other networks and throughout the brain as a function of PPL and SDI. These findings provide direct evidence that psilocin critically shapes the time course and magnitude of changes in the cerebral functional architecture and subjective experience following psilocybin administration. Our findings provide novel insight into the neurobiological mechanisms underlying profound perceptual experiences evoked by this emerging transnosological therapeutic and implicate the expression of network integrity and segregation in the psychedelic experience and consciousness.

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Research Summary of 'Psilocybin-induced changes in brain network integrity and segregation correlate with plasma psilocin level and psychedelic experience'

Introduction

Contemporary neuroimaging frameworks propose that behaviour and conscious experience emerge from coordinated activity among large-scale functional brain networks. These networks are identified with resting-state BOLD fMRI and are characterised by strong functional connectivity (FC) within a network (network integrity) and weak FC between networks (network segregation). Earlier work has suggested that psychedelics, including psilocybin, reduce within-network FC and increase between-network FC, producing a more desegregated and entropic functional architecture; however, neuroimaging studies to date have not directly related these network changes to plasma levels of psilocin (the active metabolite) or tracked them across the full acute oral psilocybin time course (ascent, peak, descent). Madsen and colleagues set out to map how plasma psilocin level (PPL) and moment-to-moment subjective drug intensity (SDI) relate to changes in network integrity and segregation after a clinically relevant oral psilocybin dose. The study tests the hypotheses that PPL and SDI would correlate negatively with default mode network (DMN) and overall within-network RSFC (reflecting reduced integrity) and positively with between-network RSFC (reflecting reduced segregation). To probe spatial specificity, the investigators also examined RSFC within and between individual networks and performed voxel-level, spatially unconstrained analyses using local correlation (LCOR) and global correlation (GCOR), measures of local integrity and whole-brain connectivity respectively.

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Study Details

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