title: Negative symptoms in schizophrenia are associated with aberrant striato-cortical connectivity in a rewarded perceptual decision-making task.
abstract: BACKGROUND
  Negative symptoms in schizophrenia have been associated with structural and functional changes in the prefrontal cortex. They often persist after treatment with antipsychotic medication which targets, in particular, the ventral striatum (VS). As schizophrenia has been suggested to arise from dysfunctional connectivity between neural networks, it is possible that residual aberrant striato-cortical connectivity in medicated patients plays a role in enduring negative symptomology. The present study examined the relationship between striato-cortical connectivity and negative symptoms in medicated schizophrenia patients.
  
  
  METHODS
  We manipulated motivation in a perceptual decision-making task during functional magnetic resonance imaging. Comparing healthy controls (n = 21) and medicated patients with schizophrenia (n = 18) we investigated how motivation-mediated changes in VS activation affected functional connectivity with the frontal cortex, and how changes in connectivity strength from the neutral to motivated condition related to negative symptom severity.
  
  
  RESULTS
  A pattern of aberrant striato-cortical connectivity was observed in the presence of intact VS, but altered left inferior frontal gyrus (IFG) motivation-mediated activation in patients. The more severe the patient's negative symptoms, the less the connectivity strength between the right VS and left IFG changed from the neutral to the motivated condition. Despite aberrant striato-cortical connectivity and altered recruitment of the left IFG among patients, both patients and healthy controls adopted a more liberal response strategy in the motivated compared to the neutral condition.
  
  
  CONCLUSIONS
  The present findings suggest that there is a link between dysfunctional striato-cortical connectivity and negative symptom severity, and offer a possible explanation as to why negative symptoms persist after treatment with antipsychotics.
authors.affiliation: NORMENT - KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway ; Department of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Greg E
authors.initials: GE
authors.lastname: Reckless
authors.affiliation: NORMENT - KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway ; Department of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.affiliation: Department of Neuroradiology, Oslo University Hospital, Oslo, Norway.
authors.forename: Andres
authors.initials: A
authors.lastname: Server
authors.affiliation: NORMENT - KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Tiril
authors.initials: T
authors.lastname: Østefjells
authors.affiliation: NORMENT - KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway ; Department of Clinical Medicine, University of Oslo, Oslo, Norway ; Centre for Psychology, Kristianstad University, Kristianstad, Sweden.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Jensen
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003657:Decision Making / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009042:Motivation / Q000502:physiology; D009434:Neural Pathways / Q000503:physiopathology; D010465:Perception / Q000502:physiology; D012201:Reward; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D012720:Severity of Illness Index; D066328:Ventral Striatum / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents
keywords: Connectivity; Motivation; Negative symptoms; Perceptual decision-making; Schizophrenia; fMRI