Relation of Prefrontal Cortex Dysfunction to Working Memory and Symptoms in Schizophrenia

doi:10.1176/appi.ajp.158.7.1105



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	Neurophysiology
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	Schizophrenia Spectrum Disorders

Am J Psychiatry 158:1105-1113, July 2001
© 2001 American Psychiatric Association

Article

Relation of Prefrontal Cortex Dysfunction to Working Memory and Symptoms in Schizophrenia

William M. Perlstein, Ph.D., Cameron S. Carter, M.D., Douglas C. Noll, Ph.D., and Jonathan D. Cohen, M.D., Ph.D.

OBJECTIVE: The dorsolateral prefrontal cortex has been implicatedin both working memory and the pathophysiology of schizophrenia.A relationship among dorsolateral prefrontal cortex activity,working memory dysfunction, and symptoms in schizophrenia hasnot been firmly established, partly because of generalized cognitiveimpairments in patients and task complexity. Using tasks thatparametrically manipulated working memory load, the authorstested three hypotheses: 1) patients with schizophrenia differin prefrontal activity only when behavioral performance differentiatesthem from healthy comparison subjects, 2) dorsolateral prefrontalcortex dysfunction is associated with poorer task performance,and 3) dorsolateral prefrontal cortex dysfunction is associatedwith cognitive disorganization but not negative or positivesymptoms. METHOD: Seventeen conventionally medicated patientswith schizophrenia and 16 healthy comparison subjects underwentfunctional magnetic resonance imaging while performing multiplelevels of the "n-back" sequential-letter working memory task.RESULTS: Patients with schizophrenia showed a deficit in physiologicalactivation of the right dorsolateral prefrontal cortex (Brodmann’sarea 46/9) in the context of normal task-dependent activityin other regions, but only under the condition that distinguishedthem from comparison subjects on task performance. Patientswith greater dorsolateral prefrontal cortex dysfunction performedmore poorly. Dorsolateral prefrontal cortex dysfunction wasselectively associated with disorganization symptoms. CONCLUSIONS:These results are consistent with the hypotheses that workingmemory dysfunction in patients with schizophrenia is causedby a disturbance of the dorsolateral prefrontal cortex and thatthis disturbance is selectively associated with cognitive disorganization.Further, the pattern of behavioral performance suggests thatdorsolateral prefrontal cortex dysfunction does not reflecta deficit in the maintenance of stimulus representations perse but points to deficits in more associative components ofworking memory.

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