title: Working memory circuitry in schizophrenia shows widespread cortical inefficiency and compensation.
abstract: BACKGROUND
  Working memory studies in schizophrenia (SZ), using functional magnetic resonance imaging (fMRI) and univariate analyses, have led to observations of hypo- or hyperactivation of discrete cortical regions and subsequent interpretations (e.g. neural inefficiencies). We employed a data-driven, multivariate analysis to identify the patterns of brain-behavior relationships in SZ during working memory.
  
  
  METHODS
  fMRI scans were collected from 13 SZ and 18 healthy control (HC) participants performing a modified Sternberg item recognition paradigm with three memory loads. We applied partial least squares analysis (PLS) to assess brain activation during the task both alone and with behavioral measures (accuracy and response time, RT) as covariates.
  
  
  RESULTS
  While the HC primary pattern was not affected by increasing load demands, SZ participants showed an exaggerated change in the Blood Oxygenation Level Dependent (BOLD) signal from the low to moderate memory load conditions and subsequent decrease in the greatest memory load, in frontal, motor, parietal and subcortical areas. With behavioral covariates, the separate groups identified distinct brain-behavior relationships and circuits. Increased activation of the middle temporal gyrus was associated with greater accuracy and faster RT only in SZ.
  
  
  CONCLUSIONS
  The inverted U-shaped curves in the SZ BOLD signal in the same areas that show flat activation in the HC data indicate widespread neural inefficiency in working memory in SZ. While both groups performed the task with similar levels of accuracy, participants with schizophrenia show a compensatory network of different sub-regions of the prefrontal cortex, parietal lobule, and the temporal gyri in this working memory task.
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92617, USA.
authors.forename: Miyoung A
authors.initials: MA
authors.lastname: Kim
authors.forename: Emanuela
authors.initials: E
authors.lastname: Tura
authors.forename: Steven G
authors.initials: SG
authors.lastname: Potkin
authors.forename: James H
authors.initials: JH
authors.lastname: Fallon
authors.forename: Dara S
authors.initials: DS
authors.lastname: Manoach
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Turner
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis* / Q000209:etiology*; D008570:Memory, Short-Term / Q000502:physiology*; D009415:Nerve Net / Q000503:physiopathology*; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000503:physiopathology; D011930:Reaction Time; D021641:Recognition, Psychology / Q000502:physiology; D012559:Schizophrenia / Q000150:complications* / Q000503:physiopathology*; D013702:Temporal Lobe / Q000503:physiopathology