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

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.