Anxiety DisordersNeuroimaging & Brain MeasuresPsilocybin

The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity

This study further analyzed fMRI data (BOLD signals) using dynamic causal modeling and found that psilocybin decreased top-down connectivity from the amygdala to visual cortex.

Authors

  • Erich Seifritz
  • Franz Vollenweider
  • Katrin Preller

Published

NeuroImage
individual Study

Abstract

Stimulation of serotonergic neurotransmission by psilocybin has been shown to shift emotional biases away from negative towards positive stimuli. We have recently shown that reduced amygdala activity during threat processing might underlie psilocybin's effect on emotional processing. However, it is still not known whether psilocybin modulates bottom-up or top-down connectivity within the visual-limbic-prefrontal network underlying threat processing. We therefore analyzed our previous fMRI data using dynamic causal modeling and used Bayesian model selection to infer how psilocybin modulated effective connectivity within the visual-limbic-prefrontal network during threat processing. First, both placebo and psilocybin data were best explained by a model in which threat affect modulated bidirectional connections between the primary visual cortex, amygdala, and lateral prefrontal cortex. Second, psilocybin decreased the threat-induced modulation of top-down connectivity from the amygdala to primary visual cortex, speaking to a neural mechanism that might underlie putative shifts towards positive affect states after psilocybin administration. These findings may have important implications for the treatment of mood and anxiety disorders.

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Research Summary of 'The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity'

Introduction

Serotonin (5-HT) signalling is central to neural circuits involved in emotion processing, and Kraehenmann and colleagues have previously reported that psilocybin (a 5-HT2A receptor agonist) attenuates amygdala blood oxygen level-dependent (BOLD) responses to threat-related visual stimuli and is linked to acute mood enhancement. The authors motivate the present work by noting uncertainty about whether psilocybin alters bottom-up (visual→amygdala→prefrontal) or top-down (prefrontal/amygdala→visual) effective connectivity within the visual–limbic–prefrontal network that underlies threat processing. To address this gap the study re-analysed earlier fMRI data with dynamic causal modelling (DCM) and Bayesian model selection (BMS). The investigators set out to test three alternative mechanisms for threat-induced modulation of connectivity (bottom-up only, top-down only, or both), and to determine which connectivity changes account for the previously observed psilocybin-related reductions in amygdala and primary visual cortex (V1) activation during threat processing.

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References (5)

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