title: Differential effects of rumination and distraction on ketamine induced modulation of resting state functional connectivity and reactivity of regions within the default-mode network.
abstract: Distraction and rumination are distinct response styles that determine how an individual deals with negative thoughts and feelings. Rumination is accompanied by an elevated self-focus, which is associated with increased resting state functional connectivity and decreased reactivity within the default mode network. Interestingly, the NMDA receptor antagonist ketamine reduces functional connectivity in this network, while its effects on blood oxygenation level-dependent (BOLD) responses during stimulus perception are not known. Ketamine might lead to a more variable processing of the external world with an attenuated self-focus by reducing the resting state connectivity. Here, we used an emotional picture-viewing task in combination with functional magnetic resonance imaging to test the hypothesis that a single ketamine administration to healthy subjects increases BOLD reactivity to negative stimuli. We found a region specific increase in BOLD reactivity in the pregenual anterior cingulate cortex and not in a posterior control region after ketamine compared with placebo administration. Moreover, a linear regression revealed that the increase in BOLD reactivity was more pronounced for subjects with a low ability to apply distraction during negative experiences. Our results implicate that ketamine attenuates a potentially pathological increased self-focus during negative experiences.
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, 8032, Switzerland Department of Biopsychology, University of Zurich, Zurich, 8050, Switzerland ETH Zurich, Neuroscience Center, Zurich, 8057, Switzerland mick.lehmann@uzh.ch.
authors.forename: Mick
authors.initials: M
authors.lastname: Lehmann
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, 8032, Switzerland ETH Zurich, Neuroscience Center, Zurich, 8057, Switzerland.
authors.forename: Erich
authors.initials: E
authors.lastname: Seifritz
authors.affiliation: Institute for Biomedical Engineering, ETH Zurich, Switzerland.
authors.forename: Anke
authors.initials: A
authors.lastname: Henning
authors.affiliation: Department of Psychiatry, Otto-von-Guericke University, Magdeburg, Germany Department of Behavioral Neurology, Leibniz Institute for Neurobiology, Magdeburg, 39106, Germany Clinical Affective Neuroimaging Laboratory (CANLAB), Center for Behavioral and Brain Sciences, CBBS, 39120 Magdeburg, Germany Department of Psychiatry University Tuebingen, 72076 Tuebingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Walter
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, 8032, Switzerland.
authors.forename: Heinz
authors.initials: H
authors.lastname: Böker
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, 8032, Switzerland Institute for Biomedical Engineering, ETH Zurich, Switzerland.
authors.forename: Milan
authors.initials: M
authors.lastname: Scheidegger
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, 8032, Switzerland Department of Psychiatry, Charité, CBF, 12203 Berlin, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Grimm
mesh_terms: D000328:Adult; D001288:Attention / Q000187:drug effects*; D063132:Connectome / Q000379:methods*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006179:Gyrus Cinguli / Q000187:drug effects*; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D013850:Thinking / Q000187:drug effects*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine
keywords: DMN; fMRI; ketamine; response styles; resting state connectivity