title: Working memory and DLPFC inefficiency in schizophrenia: the FBIRN study.
abstract: BACKGROUND
  The Functional Imaging Biomedical Informatics Network is a consortium developing methods for multisite functional imaging studies. Both prefrontal hyper- or hypoactivity in chronic schizophrenia have been found in previous studies of working memory.
  
  
  METHODS
  In this functional magnetic resonance imaging (fMRI) study of working memory, 128 subjects with chronic schizophrenia and 128 age- and gender-matched controls were recruited from 10 universities around the United States. Subjects performed the Sternberg Item Recognition Paradigm1,2 with memory loads of 1, 3, or 5 items. A region of interest analysis examined the mean BOLD signal change in an atlas-based demarcation of the dorsolateral prefrontal cortex (DLPFC), in both groups, during both the encoding and retrieval phases of the experiment over the various memory loads.
  
  
  RESULTS
  Subjects with schizophrenia performed slightly but significantly worse than the healthy volunteers and showed a greater decrease in accuracy and increase in reaction time with increasing memory load. The mean BOLD signal in the DLPFC was significantly greater in the schizophrenic group than the healthy group, particularly in the intermediate load condition. A secondary analysis matched subjects for mean accuracy and found the same BOLD signal hyperresponse in schizophrenics.
  
  
  CONCLUSIONS
  The increase in BOLD signal change from minimal to moderate memory loads was greater in the schizophrenic subjects than in controls. This effect remained when age, gender, run, hemisphere, and performance were considered, consistent with inefficient DLPFC function during working memory. These findings from a large multisite sample support the concept not of hyper- or hypofrontality in schizophrenia, but rather DLPFC inefficiency that may be manifested in either direction depending on task demands. This redirects the focus of research from direction of difference to neural mechanisms of inefficiency.
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA 92617, USA. sgpotkin@uci.edu
authors.forename: S G
authors.initials: SG
authors.lastname: Potkin
authors.forename: J A
authors.initials: JA
authors.lastname: Turner
authors.forename: G G
authors.initials: GG
authors.lastname: Brown
authors.forename: G
authors.initials: G
authors.lastname: McCarthy
authors.forename: D N
authors.initials: DN
authors.lastname: Greve
authors.forename: G H
authors.initials: GH
authors.lastname: Glover
authors.forename: D S
authors.initials: DS
authors.lastname: Manoach
authors.forename: A
authors.initials: A
authors.lastname: Belger
authors.forename: M
authors.initials: M
authors.lastname: Diaz
authors.forename: C G
authors.initials: CG
authors.lastname: Wible
authors.forename: J M
authors.initials: JM
authors.lastname: Ford
authors.forename: D H
authors.initials: DH
authors.lastname: Mathalon
authors.forename: R
authors.initials: R
authors.lastname: Gollub
authors.forename: J
authors.initials: J
authors.lastname: Lauriello
authors.forename: D
authors.initials: D
authors.lastname: O'Leary
authors.forename: T G M
authors.initials: TG
authors.lastname: van Erp
authors.forename: A W
authors.initials: AW
authors.lastname: Toga
authors.forename: A
authors.initials: A
authors.lastname: Preda
authors.forename: K O
authors.initials: KO
authors.lastname: Lim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis / Q000209:etiology; D008570:Memory, Short-Term; D008875:Middle Aged; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012559:Schizophrenia / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology*; D012720:Severity of Illness Index; D055815:Young Adult