Dorsolateral prefrontal cortex activity during maintenance and manipulation of information in working memory in patients with schizophrenia.
BACKGROUND
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.


METHODS
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.
Cannon
Tyrone D
TD
Department of Psychology, University of California, Los Angeles 90095-1563, USA. cannon@psych.ucla.edu
Glahn
David C
DC
Kim
Junghoon
J
Van Erp
Theo G M
TG
Karlsgodt
Katherine
K
Cohen
Mark S
MS
Nuechterlein
Keith H
KH
Bava
Sunita
S
Shirinyan
David
D
D000293:Adolescent; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000502:physiology / Q000503:physiopathology; D004192:Discrimination, Psychological / Q000502:physiology; D005260:Female; D005556:Form Perception / Q000502:physiology; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000175:diagnosis / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000502:physiology / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000502:physiology; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D013028:Space Perception / Q000502:physiology