title: Effects of Ketamine on Resting-State EEG Activity and Their Relationship to Perceptual/Dissociative Symptoms in Healthy Humans.
abstract: N-methyl-D-aspartate (NMDA) receptor antagonists administered to healthy humans results in schizophrenia-like symptoms, which preclinical research suggests are due to glutamatergically altered brain oscillations. Here, we examined resting-state electroencephalographic activity in 21 healthy volunteers assessed in a placebo-controlled, double-blind, randomized study involving administration of either a saline infusion or a sub-anesthetic dose of ketamine, an NMDA receptor antagonist. Frequency-specific current source density (CSD) was assessed at sensor-level and source-level using eLORETA within regions of interest of a triple network model of schizophrenia (this model posits a dysfunctional switching between large-scale Default Mode and Central Executive networks by the monitor-controlling Salience Network). These CSDs were measured in each session along with subjective symptoms as indexed with the Clinician Administered Dissociative States Scale. Ketamine-induced CSD reductions in slow (delta/theta and alpha) and increases in fast (gamma) frequencies at scalp electrode sites were paralleled by frequency-specific CSD changes in the Default Mode, Central Executive, and Salience networks. Subjective symptoms scores were increased with ketamine and ratings of depersonalization in particular were associated with alpha CSD reductions in general and in specific regions of interest in each of the three networks. These results tentatively support the hypothesis that pathological brain oscillations associated with hypofunctional NMDA receptor activity may contribute to the emergence of the perceptual/dissociate symptoms of schizophrenia.
authors.affiliation: School of Psychology, University of Ottawa Ottawa, ON, Canada.
authors.forename: Sara
authors.initials: S
authors.lastname: de la Salle
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa Ottawa, ON, Canada.
authors.forename: Joelle
authors.initials: J
authors.lastname: Choueiry
authors.affiliation: School of Psychology, University of Ottawa Ottawa, ON, Canada.
authors.forename: Dhrasti
authors.initials: D
authors.lastname: Shah
authors.affiliation: Department of Psychology, University of Guelph Guelph, ON, Canada.
authors.forename: Hayley
authors.initials: H
authors.lastname: Bowers
authors.affiliation: University of Ottawa Institute of Mental Health Research Ottawa, ON, Canada.
authors.forename: Judy
authors.initials: J
authors.lastname: McIntosh
authors.affiliation: Department of Psychiatry, University of OttawaOttawa, ON, Canada; Royal Ottawa Mental Health CentreOttawa, ON, Canada.
authors.forename: Vadim
authors.initials: V
authors.lastname: Ilivitsky
authors.affiliation: School of Psychology, University of OttawaOttawa, ON, Canada; Department of Cellular and Molecular Medicine, University of OttawaOttawa, ON, Canada; University of Ottawa Institute of Mental Health ResearchOttawa, ON, Canada; Department of Psychiatry, University of OttawaOttawa, ON, Canada.
authors.forename: Verner
authors.initials: V
authors.lastname: Knott
keywords: N-methyl-D-aspartate; brain oscillations; electroencephalography; ketamine; psychosis; schizophrenia