title: Hyperresponsivity and impaired prefrontal control of the mesolimbic reward system in schizophrenia.
abstract: Schizophrenia is characterized by substantial dysfunctions of reward processing, leading to detrimental consequences for decision-making. The neurotransmitter dopamine is responsible for the transmission of reward signals and also known to be involved in the mechanism of psychosis. Using functional magnetic resonance imaging (fMRI), sixteen medicated patients with schizophrenia and sixteen healthy controls performed the 'desire-reason dilemma' (DRD) paradigm. This paradigm allowed us to directly investigate reward-related brain activations depending on the interaction of bottom-up and top-down mechanisms, when a previously conditioned reward stimulus had to be rejected to achieve a superordinate long-term goal. Both patients and controls showed significant activations in the mesolimbic reward system. In patients with schizophrenia, however, we found a significant hyperactivation of the left ventral striatum (vStr) when they were allowed to accept the conditioned reward stimuli, and a reduced top-down regulation of activation in the ventral striatum (vStr) and ventral tegmental area (VTA) while having to reject the immediate reward to pursue the superordinate task-goal. Moreover, while healthy subjects exhibited a negative functional coupling of the vStr with both the anteroventral prefrontal cortex (avPFC) and the ventromedial prefrontal cortex (VMPFC) in the dilemma situation, this functional coupling was significantly impaired in the patient group. These findings provide evidence for an increased ventral striatal activation to reward stimuli and an impaired top-down control of reward signals by prefrontal brain regions in schizophrenia.
authors.affiliation: Center for Translational Research in Systems Neuroscience and Psychiatry, University Medical Center Göttingen, 37075, Germany. Electronic address: anja.richter@med.uni-goettingen.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Richter
authors.affiliation: Center for Translational Research in Systems Neuroscience and Psychiatry, University Medical Center Göttingen, 37075, Germany.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Petrovic
authors.affiliation: Center for Translational Research in Systems Neuroscience and Psychiatry, University Medical Center Göttingen, 37075, Germany; Biocenter Grindel and Zoological Museum, University of Hamburg, 20146, Germany.
authors.forename: Esther K
authors.initials: EK
authors.lastname: Diekhof
authors.affiliation: Center for Translational Research in Systems Neuroscience and Psychiatry, University Medical Center Göttingen, 37075, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Trost
authors.affiliation: Center for Translational Research in Systems Neuroscience and Psychiatry, University Medical Center Göttingen, 37075, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wolter
authors.affiliation: Center for Translational Research in Systems Neuroscience and Psychiatry, University Medical Center Göttingen, 37075, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gruber
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001931:Brain Mapping; D003342:Corpus Striatum / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011601:Psychophysics; D012201:Reward; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents
keywords: Biomarker; Functional connectivity; Functional neuroimaging; Nucleus accumbens; Schizophrenic disorder; Subcortical