title: Functional magnetic resonance imaging reveals neuroanatomical dissociations during semantic integration in schizophrenia.
abstract: BACKGROUND
  Schizophrenia symptoms can be conceptualized in terms of a breakdown of a balance between 1) activating, retrieving, and matching stored representations to incoming information (semantic memory-based processing) and 2) fully integrating activated semantic representations with one another and with other types of representations to form a gestalt representation of meaning (semantic integration). Semantic memory-based processes are relatively more dependent on inferior frontal and temporal cortices, whereas particularly demanding integrative processes additionally recruit the dorsolateral prefrontal cortex (DLPFC) and sometimes parietal cortices. We used functional magnetic resonance imaging (fMRI) to determine whether the modulation of temporal/inferior frontal cortices and the DLPFC can be neuroanatomically dissociated in schizophrenia, as semantic integration demands increase. Integration demands were manipulated by varying the nature (concrete vs. abstract) and the congruity (incongruous vs. congruous) of words within sentences.
  
  
  METHODS
  Sixteen right-handed schizophrenia patients and 16 healthy volunteers, matched on age and parental socioeconomic status, underwent event-related fMRI scanning while they read sentences. Blood oxygen level dependent (BOLD) effects were contrasted to words within sentences that were 1) concrete versus abstract and 2) semantically incongruous versus congruous with their preceding contexts.
  
  
  RESULTS
  In both contrasts, large networks mediating the activation and retrieval of verbal and imagistic representations were normally modulated in patients. However, unlike control subjects, patients failed to recruit the DLPFC, medial frontal and parietal cortices to incongruous (relative to congruous) sentences, and failed to recruit the DLPFC to concrete (relative to abstract) sentences.
  
  
  CONCLUSIONS
  As meaning is built from language, schizophrenia patients demonstrate a neuroanatomical dissociation in the modulation of temporal/inferior frontal cortices and the DLPFC.
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. kuperber@nmr.mgh.harvard.edu
authors.forename: Gina R
authors.initials: GR
authors.lastname: Kuperberg
authors.forename: W Caroline
authors.initials: WC
authors.lastname: West
authors.forename: Balaji M
authors.initials: BM
authors.lastname: Lakshmanan
authors.forename: Don
authors.initials: D
authors.lastname: Goff
mesh_terms: D000328:Adult; D001931:Brain Mapping; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation / Q000379:methods; D017397:Prefrontal Cortex / Q000098:blood supply*; D011930:Reaction Time / Q000502:physiology; D012559:Schizophrenia / Q000473:pathology* / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D012660:Semantics; D013997:Time Factors
chemical_list: D010100:Oxygen