title: Altered Insula Connectivity under MDMA.
abstract: Recent work with noninvasive human brain imaging has started to investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA) on large-scale patterns of brain activity. MDMA, a potent monoamine-releaser with particularly pronounced serotonin- releasing properties, has unique subjective effects that include: marked positive mood, pleasant/unusual bodily sensations and pro-social, empathic feelings. However, the neurobiological basis for these effects is not properly understood, and the present analysis sought to address this knowledge gap. To do this, we administered MDMA-HCl (100 mg p.o.) and, separately, placebo (ascorbic acid) in a randomized, double-blind, repeated-measures design with twenty-five healthy volunteers undergoing fMRI scanning. We then employed a measure of global resting-state functional brain connectivity and follow-up seed-to-voxel analysis to the fMRI data we acquired. Results revealed decreased right insula/salience network functional connectivity under MDMA. Furthermore, these decreases in right insula/salience network connectivity correlated with baseline trait anxiety and acute experiences of altered bodily sensations under MDMA. The present findings highlight insular disintegration (ie, compromised salience network membership) as a neurobiological signature of the MDMA experience, and relate this brain effect to trait anxiety and acutely altered bodily sensations-both of which are known to be associated with insular functioning.
authors.affiliation: Department of Psychiatry, McGill University Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Ishan C
authors.initials: IC
authors.lastname: Walpola
authors.affiliation: Department of Psychiatry, McGill University Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Timothy
authors.initials: T
authors.lastname: Nest
authors.affiliation: Division of Brain Sciences, Faculty of Medicine, Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: Leor
authors.initials: L
authors.lastname: Roseman
authors.affiliation: Division of Brain Sciences, Faculty of Medicine, Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Erritzoe
authors.affiliation: The Beckley Foundation, Oxford, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Feilding
authors.affiliation: Division of Brain Sciences, Faculty of Medicine, Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.affiliation: Division of Brain Sciences, Faculty of Medicine, Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Carhart-Harris
mesh_terms: D000328:Adult; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000187:drug effects*; D012146:Rest; D055815:Young Adult
chemical_list: D006213:Hallucinogens; D018817:N-Methyl-3,4-methylenedioxyamphetamine