title: LSD modulates music-induced imagery via changes in parahippocampal connectivity.
abstract: Psychedelic drugs such as lysergic acid diethylamide (LSD) were used extensively in psychiatry in the past and their therapeutic potential is beginning to be re-examined today. Psychedelic psychotherapy typically involves a patient lying with their eyes-closed during peak drug effects, while listening to music and being supervised by trained psychotherapists. In this context, music is considered to be a key element in the therapeutic model; working in synergy with the drug to evoke therapeutically meaningful thoughts, emotions and imagery. The underlying mechanisms involved in this process have, however, never been formally investigated. Here we studied the interaction between LSD and music-listening on eyes-closed imagery by means of a placebo-controlled, functional magnetic resonance imaging (fMRI) study. Twelve healthy volunteers received intravenously administered LSD (75µg) and, on a separate occasion, placebo, before being scanned under eyes-closed resting conditions with and without music-listening. The parahippocampal cortex (PHC) has previously been linked with (1) music-evoked emotion, (2) the action of psychedelics, and (3) mental imagery. Imaging analyses therefore focused on changes in the connectivity profile of this particular structure. Results revealed increased PHC-visual cortex (VC) functional connectivity and PHC to VC information flow in the interaction between music and LSD. This latter result correlated positively with ratings of enhanced eyes-closed visual imagery, including imagery of an autobiographical nature. These findings suggest a plausible mechanism by which LSD works in combination with music listening to enhance certain subjective experiences that may be useful in a therapeutic context.
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London W12, UK. Electronic address: m.kaelen@imperial.ac.uk.
authors.forename: Mendel
authors.initials: M
authors.lastname: Kaelen
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London W12, UK; The Computational, Cognitive and Clinical Neuroimaging Laboratory, The Centre for Neuroscience, Division of Brain Sciences, Imperial College London, London W12, UK.
authors.forename: Leor
authors.initials: L
authors.lastname: Roseman
authors.affiliation: Sobell Department of Motor Neuroscience & Movement Disorders, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Joshua
authors.initials: J
authors.lastname: Kahan
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London W12, UK.
authors.forename: Andre
authors.initials: A
authors.lastname: Santos-Ribeiro
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London W12, UK.
authors.forename: Csaba
authors.initials: C
authors.lastname: Orban
authors.affiliation: The Computational, Cognitive and Clinical Neuroimaging Laboratory, The Centre for Neuroscience, Division of Brain Sciences, Imperial College London, London W12, UK.
authors.forename: Romy
authors.initials: R
authors.lastname: Lorenz
authors.affiliation: Behavioral Pharmacology Research Unit, Johns Hopkins School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Barrett
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London W12, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Bolstridge
authors.affiliation: Academic Unit of Psychiatry, University of Bristol, Bristol BS8 2BN, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Williams
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London W12, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: Williams
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London W12, UK; Imanova Centre for Imaging Sciences, Hammersmith Hospital, London W12, UK; Clinical Psychopharmacology Unit, University College London, London UK.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Wall
authors.affiliation: The Beckley Foundation, Beckley Park, Oxford OX3 9SY, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Feilding
authors.affiliation: Schools of Pharmacy and Psychology, University of Auckland, Auckland 1142, New Zealand.
authors.forename: Suresh
authors.initials: S
authors.lastname: Muthukumaraswamy
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London W12, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London W12, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Carhart-Harris
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D001307:Auditory Perception / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping; D005260:Female; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D007092:Imagination / Q000187:drug effects* / Q000502:physiology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009146:Music; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D020534:Parahippocampal Gyrus / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D012146:Rest; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: D006213:Hallucinogens; D008238:Lysergic Acid Diethylamide
keywords: Effective connectivity; LSD; Mental imagery; Music; Parahippocampus; Psychedelic