title: General and emotion-specific neural effects of ketamine during emotional memory formation.
abstract: Animal studies suggest that N-methyl-D-aspartate receptor (NMDAR) dependent signalling in limbic and prefrontal regions is critically involved in both cognitive and emotional functions. In humans, ketamine-induced transient, and disorder associated chronic NMDAR hypofunction (i.e. in schizophrenia) has been associated with deficient performance in the domains of memory and higher-order emotional functioning, as well as altered neural activity in the underlying limbic-prefrontal circuits. To model the effects of NMDAR hypofunction on the integration of emotion and cognition the present pharmacological fMRI study applied the NMDAR antagonist ketamine (target plasma level=100ng/ml) to 21 healthy volunteers in a within-subject placebo-controlled crossover design during encoding of neutral, positive and negative pictures. Our results show that irrespective of emotion, ketamine suppressed parahippocampal and medial prefrontal activity. In contrast, ketamine selectively increased amygdala and orbitofrontal activity during successful encoding of negative stimuli. On the network level ketamine generally increased medial prefrontal-parahippocampal coupling while specifically decreasing amygdala-orbitofrontal interplay during encoding of negative stimuli. On the behavioural level, ketamine produced generally decreased memory performance and abolished the emotional enhancement of memory after a wash-out period of 5 days. The present findings suggest that ketamine produces general as well as valence-specific effects during emotional memory formation. The pattern partly overlaps with alterations previously observed in patients with schizophrenia.
authors.affiliation: Key Laboratory for NeuroInformation, School of Life Science, Center for Information in Medicine, University of Electronic Science and Technology of China, Chengdu, China; Department of Psychiatry and Division of Medical Psychology, University of Bonn, Bonn, Germany. Electronic address: ben_becker@gmx.de.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Becker
authors.affiliation: Department of Psychology, University of Bonn, Bonn, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Steffens
authors.affiliation: Key Laboratory for NeuroInformation, School of Life Science, Center for Information in Medicine, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Key Laboratory for NeuroInformation, School of Life Science, Center for Information in Medicine, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Kendrick
authors.affiliation: Department of Anesthesiology, University of Bonn, Bonn, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Neumann
authors.affiliation: Center for Economics and Neuroscience and Department of Epileptology, University of Bonn, Bonn, Germany; Department of NeuroCognition/Imaging, Life&Brain Research Center, Bonn, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Weber
authors.affiliation: Department of Psychiatry and Division of Medical Psychology, University of Bonn, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schultz
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Mitul A
authors.initials: MA
authors.lastname: Mehta
authors.affiliation: Department of Psychology, University of Bonn, Bonn, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ettinger
authors.affiliation: Department of Psychiatry and Division of Medical Psychology, University of Bonn, Bonn, Germany. Electronic address: renehurlemann@me.com.
authors.forename: Rene
authors.initials: R
authors.lastname: Hurlemann
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007649:Ketamine / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine
keywords: Emotion regulation; Limbic cortex; NMDAR; Orbitofrontal cortex; Schizophrenia