Schizophrenia Bulletin Advance Access published online on November 27, 2008
Schizophrenia Bulletin, doi:10.1093/schbul/sbn162
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Working memory and DLPFC inefficiency in schizophrenia: The FBIRN study
2 Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA 92697
3 Department of Psychiatry, University of California San Diego, San Diego, CA 92161
4 Department of Psychiatry, Yale University, New Haven, CT 06520
5 Neuroimaging Division, Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA 02129
6 Lucas Imaging Center, Stanford University, Palo Alto, CA
7 University of North Carolina, Chapel Hill, NC
8 Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC 27710
9 Department of Psychiatry, Harvard Medical School and Brockton VAMC, Radiology, Brigham Woman's Hospital, Boston, MA 02115
10 University of California, San Francisco, CA
11 Department of Psychiatry, University of New Mexico, Albuquerque, NM 87131
12 The Mind Research Network, Albuquerque, NM 87131
13 Department of Psychiatry, University of Iowa, Iowa City, IA 52242
14 Department of Psychology, University of California Los Angeles, CA 90095
15 Department of Neurology, University of California Los Angeles, CA 90095
16 Department of Psychiatry, University of Minnesota, Minneapolis, MN
1 To whom correspondence should be addressed; Department of Psychiatry and Human Behavior, University of California, Irvine, 5251 California Avenue, Suite 240, Irvine, CA 92617; tel: 949-824-8040, fax: 949-824-3324, e-mail: sgpotkin{at}uci.edu.
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.
Keywords: fMRI / schizophrenia / working memory / dorsolateral prefrontal cortex / cortical inefficiency