title: Impairment of working memory maintenance and response in schizophrenia: functional magnetic resonance imaging evidence.
abstract: BACKGROUND
  Comparing prefrontal cortical activity during particular phases of working memory in healthy subjects and individuals diagnosed with schizophrenia might help to define the phase-specific deficits in cortical function that contribute to cognitive impairments associated with schizophrenia. This study featured a spatial working memory task, similar to that used in nonhuman primates, that was designed to facilitate separating brain activation into encoding, maintenance, and response phases.
  
  
  METHODS
  Fourteen patients with schizophrenia (4 medication-free) and 12 healthy comparison participants completed functional magnetic resonance imaging while performing a spatial working memory task with two levels of memory load.
  
  
  RESULTS
  Task accuracy was similar in patients and healthy participants. However, patients showed reductions in brain activation during maintenance and response phases but not during the encoding phase. The reduced prefrontal activity during the maintenance phase of working memory was attributed to a greater rate of decay of prefrontal activity over time in patients. Cortical deficits in patients did not appear to be related to antipsychotic treatment. In patients and in healthy subjects, the time-dependent reduction in prefrontal activity during working memory maintenance correlated with poorer performance on the memory task.
  
  
  CONCLUSIONS
  Overall, these data highlight that basic research insights into the distinct neurobiologies of the maintenance and response phases of working memory are of potential importance for understanding the neurobiology of cognitive impairment in schizophrenia and advancing its treatment.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519, USA. naomi.driesen@yale.edu
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Driesen
authors.forename: Hoi-Chung
authors.initials: HC
authors.lastname: Leung
authors.forename: Vincent D
authors.initials: VD
authors.lastname: Calhoun
authors.forename: R Todd
authors.initials: RT
authors.lastname: Constable
authors.forename: Ralitza
authors.initials: R
authors.lastname: Gueorguieva
authors.forename: Ralph
authors.initials: R
authors.lastname: Hoffman
authors.forename: Pawel
authors.initials: P
authors.lastname: Skudlarski
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Goldman-Rakic
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
mesh_terms: D000328:Adult; D001921:Brain / Q000098:blood supply* / Q000503:physiopathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008569:Memory Disorders / Q000209:etiology* / Q000473:pathology*; D008570:Memory, Short-Term / Q000502:physiology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011930:Reaction Time / Q000502:physiology; D012559:Schizophrenia / Q000150:complications* / Q000473:pathology; D013997:Time Factors
chemical_list: D010100:Oxygen