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Schizophrenia Bulletin Advance Access originally published online on November 20, 2008
Schizophrenia Bulletin 2009 35(1):32-46; doi:10.1093/schbul/sbn149
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© The Author 2008. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Brain-Performance Correlates of Working Memory Retrieval in Schizophrenia: A Cognitive Modeling Approach

Gregory G. Brown2, Gregory McCarthy3, Amanda Bischoff-Grethe4, Burak Ozyurt4, Doug Greve5, Steven G. Potkin6, Jessica A. Turner6, Randy Notestine4, Vince D. Calhoun7, Judy M. Ford8, Daniel Mathalon8, Dara S. Manoach5, Syam Gadde9, Gary H. Glover10, Cynthia G. Wible11, Aysenil Belger12, Randy L. Gollub5, John Lauriello13, Daniel O'Leary14 and Kelvin O. Lim
2 Department of Psychiatry, University of California San Diego; Psychology Service, VA San Diego Healthcare System
3 Department of Psychiatry, Yale University
4 Department of Psychiatry, University of California San Diego
5 Department of Psychiatry, Massachusetts General Hospital
6 Department of Psychiatry, University of California Irvine
7 Electrical and Computer Engineering; The Mind Research Network, University of New Mexico, Albuquerque, NM 87131
8 Department of Psychiatry, University of California San Francisco
9 Department of Psychiatry, Duke University
10 Radiological Sciences Laboratory, Stanford University
11 Department of Psychiatry, Harward Medical School and Brockton VAMC
12 Department of Psychiatry, University of North Carolina—Chapel Hill
13 Department of Psychiatry, University of New Mexico
14 Department of Psychiatry, University of Iowa
15 Department of Psychiatry; Minneapolis VA Medical Center, University of Minnesota

1 To whom correspondence should be addressed; tel: 858-246-06-7, fax: 858-552-7414, e-mail: gbrown{at}ucsd.edu.

Correlations of cognitive functioning with brain activation during a sternberg item recognition paradigm (SIRP) were investigated in patients with schizophrenia and in healthy controls studied at 8 sites. To measure memory scanning times, 4 response time models were fit to SIRP data. The best fitting model assumed exhaustive serial memory scanning followed by self-terminating memory search and involved one intercept parameter to represent SIRP processes not contributing directly to memory scanning. Patients displayed significantly longer response times with increasing memory load and differed on the memory scanning, memory search, and intercept parameters of the best fitting probability model. Groups differed in the correlation between the memory scanning parameter and linear brain response to increasing memory load within left inferior and left middle frontal gyrus, bilateral caudate, and right precuneus. The pattern of findings in these regions indicated that high scanning capacity was associated with high neural capacity among healthy subjects but that scanning speed was uncoupled from brain response to increasing memory load among schizophrenia patients. Group differences in correlation of the best fitting model's scanning parameter with a quadratic trend in brain response to increasing memory load suggested inefficient or disordered patterns of neural inhibition among individuals with schizophrenia, especially in the left perirhinal and entorhinal cortices. The results show at both cognitive and neural levels that disordered memory scanning contributes to deficient SIRP performance among schizophrenia patients.

Keywords: schizophrenia / item recognition / functional magnetic resonance imaging / stochastic models


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