Neural Mechanisms of Resting-State Networks and the Amygdala Underlying the Cognitive and Emotional Effects of Psilocybin

Devon Stoliker; Leonardo Novelli; Franz X Vollenweider; Gary F Egan; Katrin H Preller; Adeel Razi

doi:10.1016/j.biopsych.2024.01.002

Neural Mechanisms of Resting-State Networks and the Amygdala Underlying the Cognitive and Emotional Effects of Psilocybin

Biol Psychiatry. 2024 Jan 6:S0006-3223(24)00004-0. doi: 10.1016/j.biopsych.2024.01.002. Online ahead of print.

Authors

Devon Stoliker¹, Leonardo Novelli¹, Franz X Vollenweider², Gary F Egan¹, Katrin H Preller², Adeel Razi³

Affiliations

¹ Turner Institute for Brain and Mental Health, Monash University, Clayton, Victoria, Australia; Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia.
² Department of Psychiatry, Psychotherapy & Psychosomatics, Psychiatric University Hospital Zurich, Zurich, Switzerland.
³ Turner Institute for Brain and Mental Health, Monash University, Clayton, Victoria, Australia; Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia; Wellcome Centre for Human Neuroimaging, University College London, London, United Kingdom; CIFAR Azrieli Global Scholars Program, CIFAR, Toronto, Ontario, Canada. Electronic address: adeel.razi@monash.edu.

PMID: 38185235
DOI: 10.1016/j.biopsych.2024.01.002

Abstract

Background: Serotonergic psychedelics, such as psilocybin, alter perceptual and cognitive systems that are functionally integrated with the amygdala. These changes can alter cognition and emotions that are hypothesized to contribute to their therapeutic utility. However, the neural mechanisms of cognitive and subcortical systems altered by psychedelics are not well understood.

Methods: We used resting-state functional magnetic resonance images collected during a randomized, double-blind, placebo-controlled clinical trial of 24 healthy adults under 0.2 mg/kg psilocybin to estimate the directed (i.e., effective) changes between the amygdala and 3 large-scale resting-state networks involved in cognition. These networks are the default mode network, the salience network, and the central executive network.

Results: We found a pattern of decreased top-down effective connectivity from these resting-state networks to the amygdala. Effective connectivity decreased within the default mode network and salience network but increased within the central executive network. These changes in effective connectivity were statistically associated with behavioral measures of altered cognition and emotion under the influence of psilocybin.

Conclusions: Our findings suggest that temporary amygdala signal attenuation is associated with mechanistic changes to resting-state network connectivity. These changes are significant for altered cognition and perception and suggest targets for research investigating the efficacy of psychedelic therapy for internalizing psychiatric disorders. More broadly, our study suggests the value of quantifying the brain's hierarchical organization using effective connectivity to identify important mechanisms for basic cognitive function and how they are integrated to give rise to subjective experiences.

Keywords: Amygdala; Cognition; Effective connectivity; Emotion; Psilocybin; Psychedelics.