title: Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence.
abstract: In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n = 31 detoxified patients diagnosed with alcohol dependence and n = 24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Mitte, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Garbusow
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Mitte, Germany.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Schad
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Mitte, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Sebold
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Mitte, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Friedel
authors.affiliation: Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Germany.|Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Bernhardt
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Mitte, Germany.
authors.forename: Stefan P
authors.initials: SP
authors.lastname: Koch
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatic Geriatric Psychiatry, Vivantes Wenckebach-Klinikum, Germany.
authors.forename: Bruno
authors.initials: B
authors.lastname: Steinacher
authors.affiliation: Department of Psychology, Humboldt-Universität zu Berlin, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Kathmann
authors.affiliation: Radboud University, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands.|Radboud University Medical Center, Department of Psychiatry, Nijmegen, The Netherlands.
authors.forename: Dirk E M
authors.initials: DE
authors.lastname: Geurts
authors.affiliation: Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sommer
authors.affiliation: Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Germany.|Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Dirk K
authors.initials: DK
authors.lastname: Müller
authors.affiliation: Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Germany.|Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Nebe
authors.affiliation: Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Paul
authors.affiliation: Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Wittchen
authors.affiliation: Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Germany.
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Zimmermann
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Mitte, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Walter
authors.affiliation: Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Germany.|Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Michael N
authors.identifier: http://orcid.org/0000-0001-5398-5569
authors.initials: MN
authors.lastname: Smolka
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Mitte, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Sterzer
authors.affiliation: Social and Preventive Medicine, Area of Excellence Cognitive Sciences, University of Potsdam, Germany.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rapp
authors.affiliation: Centre for Addiction Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zürich, Switzerland.|Translational Neuromodeling Unit, Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Switzerland.
authors.forename: Quentin J M
authors.initials: QJ
authors.lastname: Huys
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Mitte, Germany.|Max Planck Fellow Group 'Cognitive and Affective Control of Behavioral Adaptation', Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schlagenhauf
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Mitte, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000523:psychology; D016022:Case-Control Studies; D003214:Conditioning, Classical; D003216:Conditioning, Operant; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009042:Motivation; D009714:Nucleus Accumbens / Q000000981:diagnostic imaging* / Q000503:physiopathology; D012008:Recurrence; D014163:Transfer, Psychology
keywords: human Pavlovian-to-instrumental transfer; nucleus accumbens; relapse in alcohol use disorder