title: Perceptual distortions and delusional thinking following ketamine administration are related to increased pharmacological MRI signal changes in the parietal lobe.
abstract: Ketamine produces effects in healthy humans that resemble the positive, negative and cognitive symptoms of schizophrenia. We investigated the effect of ketamine administration on brain activity as indexed by blood-oxygen-level-dependent (BOLD) signal change response, and its relationship to ketamine-induced subjective changes, including perceptual distortion. Thirteen healthy participants volunteered for the study. All underwent a 15-min functional MRI acquisition with a ketamine infusion commencing after 5 min (approx 0.26 mg/kg over 20s followed by an infusion of approx. 0.42 mg/kg/h). Following the scan, participants self-rated ketamine-induced effects using the Psychotomimetic States Inventory. Ketamine led to widespread cortical and subcortical increases in BOLD response (FWE-corrected p < 0.01). Self-rated perceptual distortions and delusional thoughts correlated with increased BOLD response in the paracentral lobule (FWE-corrected p < 0.01). The findings suggest that BOLD increases in parietal cortices reflect ketamine effects on circuits that contribute to its capacity to produce perceptual alterations and delusional interpretations.
authors.affiliation: Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK james.m.stone@kcl.ac.uk.
authors.forename: James
authors.initials: J
authors.lastname: Stone
authors.affiliation: Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: Vasileia
authors.initials: V
authors.lastname: Kotoula
authors.affiliation: Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: Craige
authors.initials: C
authors.lastname: Dietrich
authors.affiliation: Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: De Simoni
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA Psychiatry Services, Yale-New Haven Hospital, New Haven, CT, USA Clinical Neuroscience Division, VA National Center for PTSD, VA, USA Connecticut Healthcare System, West Haven, CT, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.affiliation: Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: Mitul A
authors.initials: MA
authors.lastname: Mehta
mesh_terms: D000293:Adolescent; D000328:Adult; D000778:Anesthetics, Dissociative / Q000008:administration & dosage*; D003702:Delusions / Q000097:blood / Q000139:chemically induced*; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010296:Parietal Lobe / Q000187:drug effects*; D010469:Perceptual Distortion / Q000187:drug effects*; D011605:Psychoses, Substance-Induced / Q000097:blood; D012559:Schizophrenia / Q000097:blood / Q000139:chemically induced; D055815:Young Adult
chemical_list: D000778:Anesthetics, Dissociative; D007649:Ketamine; D010100:Oxygen
keywords: BOLD; Ketamine; fMRI; psychosis