title: Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution.
abstract: Lysergic acid diethylamide (LSD) is a non-selective serotonin-receptor agonist that was first synthesized in 1938 and identified as (potently) psychoactive in 1943. Psychedelics have been used by indigenous cultures for millennia [1]; however, because of LSD's unique potency and the timing of its discovery (coinciding with a period of major discovery in psychopharmacology), it is generally regarded as the quintessential contemporary psychedelic [2]. LSD has profound modulatory effects on consciousness and was used extensively in psychological research and psychiatric practice in the 1950s and 1960s [3]. In spite of this, however, there have been no modern human imaging studies of its acute effects on the brain. Here we studied the effects of LSD on intrinsic functional connectivity within the human brain using fMRI. High-level association cortices (partially overlapping with the default-mode, salience, and frontoparietal attention networks) and the thalamus showed increased global connectivity under the drug. The cortical areas showing increased global connectivity overlapped significantly with a map of serotonin 2A (5-HT2A) receptor densities (the key site of action of psychedelic drugs [4]). LSD also increased global integration by inflating the level of communication between normally distinct brain networks. The increase in global connectivity observed under LSD correlated with subjective reports of "ego dissolution." The present results provide the first evidence that LSD selectively expands global connectivity in the brain, compromising the brain's modular and "rich-club" organization and, simultaneously, the perceptual boundaries between the self and the environment.
authors.affiliation: Department of Sleep and Cognition, Netherlands Institute for Neuroscience (NIN), an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam 1105 BA, the Netherlands; Institute for Medical Psychology, University of Kiel, Kiel 24113, Germany. Electronic address: tagliazucchi.enzo@googlemail.com.
authors.forename: Enzo
authors.initials: E
authors.lastname: Tagliazucchi
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, London W12 0NN, UK; Computational, Cognitive and Clinical Neuroscience Laboratory (C3NL), Department of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: Leor
authors.initials: L
authors.lastname: Roseman
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: Mendel
authors.initials: M
authors.lastname: Kaelen
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: Csaba
authors.initials: C
authors.lastname: Orban
authors.affiliation: Cardiff University Brain Research Imaging Centre (CUBRIC), Department of Psychology, Cardiff CF10 3AT, UK; Schools of Pharmacy and Psychology, University of Auckland, Auckland 1010, New Zealand.
authors.forename: Suresh D
authors.initials: SD
authors.lastname: Muthukumaraswamy
authors.affiliation: Cardiff University Brain Research Imaging Centre (CUBRIC), Department of Psychology, Cardiff CF10 3AT, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Murphy
authors.affiliation: Neurology Department, Schleswig-Holstein University Hospital, University of Kiel, Kiel 24113, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Laufs
authors.affiliation: Computational, Cognitive and Clinical Neuroscience Laboratory (C3NL), Department of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Leech
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: John
authors.initials: J
authors.lastname: McGonigle
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neurosciences, King's College London, London WC2R 2LS, UK.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Crossley
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge CB2 2QQ, UK; Cambridgeshire & Peterborough NHS Foundation Trust, Cambridge CB21 5EF, UK; Alternative Discovery & Development, GlaxoSmithKline, Brentford TW8 9GS, UK.
authors.forename: Edward
authors.initials: E
authors.lastname: Bullmore
authors.affiliation: AWP Mental Health NHS Trust, Blackberry Centre, Manor Road, Bristol BS16 2EW, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Williams
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Bolstridge
authors.affiliation: The Beckley Foundation, Oxford OX3 9SY, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Feilding
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, London W12 0NN, UK. Electronic address: r.carhart-harris@imperial.ac.uk.
authors.forename: Robin
authors.initials: R
authors.lastname: Carhart-Harris
mesh_terms: D001921:Brain / Q000187:drug effects*; D003243:Consciousness / Q000187:drug effects*; D004532:Ego; D059907:Functional Neuroimaging; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects*; D012649:Self Concept
chemical_list: D006213:Hallucinogens; D008238:Lysergic Acid Diethylamide