Functional Magnetic Resonance Imaging Reveals Neuroanatomical Dissociations During Semantic Integration in Schizophrenia

  • Gina R. Kuperberg
    Address reprint requests to Gina R. Kuperberg, M.D., Ph.D., Department of Psychology, Tufts University, 490 Boston Avenue, Medford, MA 02155, or Department of Psychiatry, Massachusetts General Hospital, Bldg. 149, 13th Street, Charlestown, MA 02129
    MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts

    Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts

    Department of Psychology, Tufts University, Medford, Massachusetts
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  • W. Caroline West
    MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts

    Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.
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  • Balaji M. Lakshmanan
    MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts
    Search for articles by this author
  • Don Goff
    Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts
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      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.


      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.


      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.


      As meaning is built from language, schizophrenia patients demonstrate a neuroanatomical dissociation in the modulation of temporal/inferior frontal cortices and the DLPFC.

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