Neural Mechanisms of Resting-State Networks and the Amygdala underlying the Cognitive and Emotional Effects of Psilocybin
This follow-up fMRI analysis of an RCT of healthy subjects (n=24) finds that psilocybin (15mg/70kg) led to a pattern of decreased top-down effectivity between the default mode network (DMN), salience network (SN), and central executive network (CEN) to the amygdala.
Authors
- Franz Vollenweider
- Katrin Preller
- Adeel Razi
Published
Abstract
Classic psychedelics alter sense of self and patterns of self-related thought. These changes are hypothesised to underlie their therapeutic efficacy across internalising pathologies such as addiction, anxiety, and depression. Using resting-state functional MRI images from a randomised, double blinded, placebo-controlled clinical trial of 24 healthy adults under 0.215mg/kg psilocybin, we investigated the effective connectivity changes between the amygdala and the default mode network (DMN), salience network (SN) and central executive network (CEN). This connectivity underpins the appraisal and regulation of emotion and is associated with clinical symptomatology. We observed a general pattern of decreased top-down effective connectivity from the resting state networks of interest to the amygdala and directed connectivity changes associated with altered emotion and meaning under psilocybin. Our findings identify cognitive-emotional connectivity associated with the subjective effects of psilocybin and the attenuation of the amygdala as a potential biomarker of psilocybin's therapeutic efficacy.
Research Summary of 'Neural Mechanisms of Resting-State Networks and the Amygdala underlying the Cognitive and Emotional Effects of Psilocybin'
Introduction
Psilocybin is a serotonergic psychedelic whose primary action at 5-HT2A receptors produces marked alterations of perception, self-experience and emotion, including phenomena described as mystical experiences and ego dissolution. Previous research links such subjective experiences to improvements in depression and anxiety, and several imaging studies report altered amygdala responsivity under psychedelics—most commonly reduced amygdala responses to negative stimuli during the acute drug state, and variable amygdala changes in the post-acute period. Cortical regions, notably prefrontal areas, are known to modulate amygdala activity and are implicated in emotional regulation and disorders of mood and anxiety; however, how psychedelics alter directed (effective) connectivity between large-scale resting-state networks (RSNs) involved in cognition and the amygdala remains incompletely characterised. Stoliker and colleagues set out to examine acute psilocybin-induced changes in directed connectivity between the amygdala and three canonical RSNs: the default mode network (DMN), the salience network (SN) and the central executive network (CEN). Using resting-state fMRI collected during a randomised, double-blind, placebo-controlled crossover trial in healthy adults, the investigators applied spectral dynamic causal modelling (DCM) to estimate effective connectivity and tested whether network–amygdala modulation related to subjective alterations measured after dosing. The authors hypothesised that increased top-down inhibition of the amygdala would contribute to the subjective effects of psilocybin and be relevant to mechanisms underlying therapeutic change.
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Study Details
- Study Typeindividual
- Journal
- Compound
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- APA Citation
Stoliker, D., Novelli, L., Vollenweider, F. X., Egan, G. F., Preller, K. H., & Razi, A. (2024). Neural Mechanisms of Resting-State Networks and the Amygdala underlying the Cognitive and Emotional Effects of Psilocybin. Biological Psychiatry, 96(1), 57-66. https://doi.org/10.1016/j.biopsych.2024.01.002
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