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

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 hypothesised 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 functional MRI resting state images collected during a randomised, double-blinded, placebo-controlled clinical trial of 24 healthy adults under 0.2mg/kg psilocybin to estimate the directed (i.e., effective) changes between the amygdala and three large-scale resting-state networks involved in cognition. These networks are the default mode network (DMN), the salience network (SN), and the central executive network (CEN). RESULTS:We found a pattern of decreased top-down effective connectivity from these resting-state networks to the amygdala. Effective connectivity decreased within the DMN and SN however increased within the CEN. These changes in effective connectivity were statistically associated with behavioural 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 RSN network connectivity. These changes are significant for altered cognition and perception and suggests targets for research investigating the efficacy of psychedelic therapy for internalising psychiatric disorders. More broadly, our study suggests the value of quantifying the brain's hierarchical organisation using effective using effective connectivity to identify important mechanisms for basic cognitive function and how they are integrated to give rise to subjective experiences.