Impact of modafinil on prefrontal executive function in schizophrenia.
OBJECTIVE
The purpose of this study was to investigate the acute effects of modafinil on prefrontal activation and cognitive control of motor activity in people with schizophrenia and prominent negative symptoms.


METHODS
In a crossover design, 12 subjects with schizophrenia were studied twice, receiving either modafinil or placebo prior to functional magnetic resonance imaging (fMRI). Inside the scanner, they performed a task probing cognitive control that required deliberate variation of motor activity in time.


RESULTS
Modafinil administration was associated with significantly greater activation of the dorsolateral prefrontal cortex during fMRI. Its physiological and behavioral effects were correlated. This was most evident in individuals with worse baseline executive function. Focal response to modafinil in the left dorsolateral prefrontal cortex and baseline letter fluency scores predicted most of the variance in the drug's effect on cognitive control.


CONCLUSIONS
Modafinil did not improve cognitive control in all schizophrenia patients. Increased activation in the dorsolateral prefrontal cortex and in neuropsychological performance were observed in patients with suboptimal baseline function.
Hunter
Michael D
MD
Academic Units of Clinical Psychiatry and Radiology, University of Sheffield, Sheffield, UK. m.d.hunter@shef.ac.uk
Ganesan
Venkatasubramanian
V
Wilkinson
Iain D
ID
Spence
Sean A
SA
D000328:Adult; D001559:Benzhydryl Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000494:pharmacology* / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008297:Male; D000077408:Modafinil; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D012044:Regression Analysis; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil