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Tyrone D. Cannon, PhD; David C. Glahn, PhD; Junghoon Kim, PhD; Theo G. M. Van Erp, MA; Katherine Karlsgodt, MA; Mark S. Cohen, PhD; Keith H. Nuechterlein, PhD; Sunita Bava; David Shirinyan, MA

Arch Gen Psychiatry. 2005;62:1071-1080.

Context  It remains unclear whether altered regional brain physiological activity in patients with schizophrenia during working memory tasks relates to maintenance-related processes, manipulation-related (ie, executive) processes, or both.

Objective  To examine regional functional activations of the brain during maintenance- and manipulation-related working memory processing in patients with schizophrenia and in healthy comparison subjects.

Design  Functional images of the brain were acquired in 11 schizophrenic patients and 12 healthy control subjects (matched for age, sex, handedness, and parental education) during 2 spatial working memory paradigms, one contrasting maintenance-only processing with maintenance and manipulation processing and the other contrasting parametrically varying maintenance demands.

Results  Patients and controls showed activation of a large, spatially distributed network of cortical and subcortical regions during spatial working memory processing. When task demands required explicit manipulation of information held in memory, controls recruited right dorsolateral prefrontal cortex (Brodmann areas 45 and 46) to a significantly greater extent than patients. A similar effect was observed for the larger memory set sizes of the memory set size task. No other brain regions showed activation differences between groups for either task. These differences persisted when comparing activation maps for memory set sizes in which the 2 groups were equivalent in behavioral accuracy and when comparing subgroups of patients and controls matched for behavioral accuracy on either task.

Conclusions  Physiological disturbances in the dorsolateral prefrontal cortex contribute differentially to patients’ difficulties with maintaining spatial information across a brief delay, as well as with manipulating the maintained representation. These differences persisted when comparing conditions in which the 2 groups were equivalent in behavioral accuracy.

Author Affiliations: Departments of Psychology (Drs Cannon, Kim, and Nuechterlein, Messrs Van Erp and Shirinyan, and Mss Karlsgodt and Bava) and Psychiatry and Biobehavioral Sciences (Drs Cannon, Cohen, and Nuechterlein), University of California, Los Angeles; and Department of Psychiatry, University of Texas Health Science Center at San Antonio (Dr Glahn).

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