title: Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance.
abstract: BACKGROUND
  Working memory (WM) deficits in schizophrenia have been associated with dorsolateral prefrontal cortex (DLPFC) dysfunction in neuroimaging studies. We previously found increased DLPFC activation in schizophrenic versus normal subjects during WM performance (Manoach et al 1999b). We now have investigated whether schizophrenic subjects recruit different brain regions, particularly the basal ganglia and thalamus, components of frontostriatal circuitry thought to mediate WM.
  
  
  METHODS
  We examined regional brain activation in nine normal and nine schizophrenic subjects during WM performance using functional magnetic resonance imaging. Subjects performed a modified version of the Sternberg Item Recognition Paradigm that included a monetary reward for correct responses. We compared high and low WM load conditions to each other and to a non-WM baseline condition. We examined activation in both individual subjects and averaged group data.
  
  
  RESULTS
  Relative to normal subjects, schizophrenic subjects exhibited deficient WM performance, at least an equal magnitude of right DLPFC activation, significantly greater left DLPFC activation, and increased spatial heterogeneity of DLPFC activation. Furthermore, only the schizophrenic group activated the basal ganglia and thalamus, even when matched for task performance with the normal group.
  
  
  CONCLUSIONS
  Aberrant WM performance and brain activation in schizophrenia may reflect dysfunction of frontostriatal circuitry that subserves WM. Future studies will elucidate the contribution of the anatomical components of this circuitry to WM deficits.
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Manoach
authors.forename: R L
authors.initials: RL
authors.lastname: Gollub
authors.forename: E S
authors.initials: ES
authors.lastname: Benson
authors.forename: M M
authors.initials: MM
authors.lastname: Searl
authors.forename: D C
authors.initials: DC
authors.lastname: Goff
authors.forename: E
authors.initials: E
authors.lastname: Halpern
authors.forename: C B
authors.initials: CB
authors.lastname: Saper
authors.forename: S L
authors.initials: SL
authors.lastname: Rauch
mesh_terms: D000328:Adult; D001479:Basal Ganglia / Q000002:abnormalities* / Q000503:physiopathology*; D010054:Brief Psychiatric Rating Scale; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis*; D017397:Prefrontal Cortex / Q000002:abnormalities* / Q000503:physiopathology*; D011930:Reaction Time; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology*; D013788:Thalamus / Q000503:physiopathology