Michael D. Hunter, M.R.C.Psych., Venkatasubramanian Ganesan, M.D., Iain
D. Wilkinson, Ph.D. and Sean A. Spence, M.D., F.R.C.Psych.
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.
METHOD: 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.