Effective connectivity of functionally anticorrelated networks under LSD

Introduction

Psilocybin is a serotonergic psychedelic whose agonism at 5-HT2A receptors produces profound alterations of perception, emotion and self-experience, including graded experiences of ego dissolution. Previous work has implicated the amygdala and large-scale resting-state networks (RSNs) — notably the default mode network (DMN), central executive network (CEN) and salience network (SN) — in emotional appraisal, self-related cognition and psychopathology. However, the directional (effective) connectivity that links cortical RSNs with the amygdala during the acute psychedelic state, and how such directed interactions relate to subjective reports, remain poorly characterised. Stoliker and colleagues set out to test whether psilocybin alters top-down effective connectivity from RSNs to the amygdala and whether these directed changes associate with aspects of the acute subjective experience. Using spectral dynamic causal modelling (spDCM) to infer directional influences among predefined cortical ROIs and the amygdala, the study specifically examined changes in DMN–amygdala, CEN–amygdala and SN–amygdala interactions and related those changes to two dimensions of the 5D-ASC (changed meaning of percepts and blissful state). The primary hypothesis was reduced top-down effective connectivity from RSNs to the amygdala under psilocybin, with such changes linked to altered meaning and positive affective experiences.