Prefrontal cortex dysfunction mediates deficits in working memory and prepotent responding in schizophrenia.
BACKGROUND
Schizophrenic patients show deficits in working memory (WM) and inhibition of prepotent responses. We examined brain activity while subjects performed tasks that placed demands on WM and overriding prepotent response tendencies, testing predictions that both processes engage overlapping prefrontal cortical (PFC) regions and that schizophrenic patients show reduced PFC activity and performance deficits reflecting both processes.


METHODS
Functional magnetic resonance imaging data were acquired while 16 schizophrenic and 15 healthy subjects performed the N-Back task that varied WM load and a version of the AX-CPT that required overriding a prepotent response tendency.


RESULTS
Both tasks engaged overlapping cortical networks (e.g., bilateral dorsolateral PFC, Broca's area, parietal cortex). Increased WM load monotonically increased activity; preparation to override a prepotent response produced greater and more enduring activity. Group differences on each task emerged in a right dorsolateral PFC region: schizophrenic subjects showed lesser magnitude increases under conditions of high WM and prepotent response override demands, with concomitant performance impairments.


CONCLUSIONS
Schizophrenic patients exhibit PFC-mediated deficits in WM and preparation to override prepotent responses. Findings are consistent with the operation of a single underlying PFC-mediated cognitive control mechanism and with physiologic dysfunction of the dorsolateral PFC in schizophrenic patients reflecting impairments in this mechanism.
Perlstein
William M
WM
Department of Clinical and Health Psychology and the McKnight Brain Institute, University of Florida, Gainesville, 32610, USA.
Dixit
Neha K
NK
Carter
Cameron S
CS
Noll
Douglas C
DC
Cohen
Jonathan D
JD
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002746:Chlorpromazine / Q000627:therapeutic use; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology; D017397:Prefrontal Cortex / Q000033:anatomy & histology / Q000503:physiopathology*; D011930:Reaction Time; D012559:Schizophrenia / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology*
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D002746:Chlorpromazine