title: Functional magnetic resonance imaging of a parametric working memory task in schizophrenia: relationship with performance and effects of antipsychotic treatment.
abstract: BACKGROUND
  Working memory dysfunction is frequently observed in schizophrenia. The neural mechanisms underlying this dysfunction remain unclear, with functional neuroimaging studies reporting increased, decreased or unchanged activation compared to controls.
  
  
  OBJECTIVE
  We investigated the neural correlates of spatial working memory in schizophrenia with particular consideration of effects of antipsychotic treatment and relation to performance levels in the patient group.
  
  
  METHODS
  We used functional magnetic resonance imaging and studied the blood-oxygen-level-dependent (BOLD) response of 45 schizophrenia outpatients and 19 healthy controls during a parametric spatial n-back task.
  
  
  RESULTS
  Performance in both groups deteriorated with increasing memory load (0-back, 1-back, 2-back), but the two groups did not significantly differ in performance overall or as a function of load. Patients produced stronger BOLD signal in occipital and lateral prefrontal cortex during task performance than controls. This difference increased with increasing working memory load in the prefrontal areas. We also found that in patients with good task performance, the BOLD response in left prefrontal cortex showed a stronger parametric increase with working memory load than in patients with poor performance. Second-generation antipsychotics were independently associated with left prefrontal BOLD increase in response to working memory load, whereas first-generation antipsychotics were associated with BOLD decrease with increasing load in this area.
  
  
  CONCLUSIONS
  Together, these findings suggest that in schizophrenia patients, normal working memory task performance may be achieved through compensatory neural activity, especially in well-performing patients and in those treated with second-generation antipsychotics.
authors.affiliation: Department of Psychiatry, University of Munich, Nussbaumstr. 7, 80336, Munich, Germany. ulrich.ettinger@med.uni-muenchen.de
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ettinger
authors.forename: Steven C R
authors.initials: SC
authors.lastname: Williams
authors.forename: Dominic
authors.initials: D
authors.lastname: Fannon
authors.forename: Preethi
authors.initials: P
authors.lastname: Premkumar
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kuipers
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Möller
authors.forename: Veena
authors.initials: V
authors.lastname: Kumari
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D013647:Task Performance and Analysis
chemical_list: D014150:Antipsychotic Agents; D010100:Oxygen