Altered insula connectivity under MDMA

Introduction

MDMA (3,4-methylenedioxymethamphetamine) is described as an entactogen with stimulant- and psychedelic-like properties, notable for pronounced serotonin release and subjective effects that include elevated mood, pro-social feelings and unusual bodily sensations. Previous neuroimaging work using PET, EEG and fMRI has reported MDMA-related decreases in regional cerebral blood flow and changes in connectivity in medial temporal and limbic structures; converging evidence has also implicated the insula in interoception and anxiety, and prior PET work reported insular blood-flow decreases after MDMA. However, earlier resting-state functional connectivity (RSFC) studies of MDMA have not specifically examined salience-network membership or insula-centred network integrity, partly because of methodological choices such as seed selection or independent component approaches that did not target the salience network directly. Walpola and colleagues therefore re-analysed an existing within-subjects, double-blind, placebo-controlled resting-state fMRI data set to test the hypothesis that MDMA acutely alters insula connectivity and salience-network integrity. The primary aim was to use a data‑driven voxelwise metric, the Intrinsic Connectivity Contrast (ICC), to identify regions with altered whole-brain connectivity under MDMA and then interrogate those regions with conventional seed-to-voxel and ROI-to-ROI analyses. The authors also examined whether MDMA-induced changes in insula connectivity related to baseline trait anxiety and reports of unusual bodily sensations as a proxy for altered interoception.