Effective connectivity of emotion and cognition under 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 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 how psilocybin modulates the effective connectivity between resting state networks and the amygdala that are involved in the appraisal and regulation of emotion and association with clinical symptoms. The networks included the default mode network (DMN), salience network (SN) and central executive network (CEN). Psilocybin decreased top-down effective connectivity from the resting state networks to the amygdala and decreased effective connectivity within the DMN and SN, while the within CEN effective connectivity increased. Effective connectivity changes were also associated with altered emotion and meaning under psilocybin. Our findings identify changes to cognitive-emotional connectivity associated with the subjective effects of psilocybin and the attenuation of the amygdala signal as a potential biomarker of psilocybin’s therapeutic efficacy.