Working memory circuitry in schizophrenia shows widespread cortical inefficiency and compensation

Kim, Miyoung A.; Tura, Emanuela; Potkin, Steven G.; Fallon, James H.; Manoach, Dara S.; Calhoun, Vince D.; FBIRN,; Turner, Jessica A.

doi:10.1016/j.schres.2009.12.014

« Previous Next »Schizophrenia Research
Volume 117, Issue 1 , Pages 42-51, March 2010

Working memory circuitry in schizophrenia shows widespread cortical inefficiency and compensation

Miyoung A. Kim
- Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92617, USA
Emanuela Tura
- Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
Steven G. Potkin
- Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92617, USA
James H. Fallon
- Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92617, USA
Dara S. Manoach
- Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School, Boston MA, USA
Vince D. Calhoun
- The Mind Research Network, Albuquerque, NM 87131, USA
- Department of ECE, University of New Mexico, Albuquerque, NM 87131, USA
FBIRN
- www.fbirn.org
Jessica A. Turner
- Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92617, USA
- Corresponding author. 5251 California Avenue, Suite 240, Irvine, California, 92617, USA. Tel.: +1 949 824 3331; fax: +1 949 824 3324.

Received 2 September 2009; received in revised form 9 December 2009; accepted 14 December 2009. published online 22 January 2010.

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.

Keywords: Schizophrenia, Working memory, Functional magnetic resonance imaging, Partial least squares, Multivariate analysis, Neurocircuitry