Functional magnetic resonance imaging neuroactivation studies in normal subjects and subjects with the narcoleptic syndrome. Actions of modafinil

Functional magnetic resonance imaging (RMRI) can be used to detect regional brain responses to changes in sensory stimuli. We have used fMRI to determ ine the amount of visual and auditory cortical activation in 12 normal subj ects and 12 subjects with the narcoleptic syndrome, using a multiplexed vis ual and auditory stimulation paradigm. In both normal and narcoleptic subje cts, mean cortical activation levels during the presentation of periodic vi sual and auditory stimulation showed no appreciable differences with either age or sex. Normal subjects showed higher levels of visual activation at 1 0:00 hours than 15:00 hours, with a reverse pattern in narcoleptic subjects (P=0.007). The group differences in spatial extent of cortical activation between control and narcoleptic subjects were small and statistically insig nificant. The alerting action, and imaging response, to a single oral dose of the sleep-preventing drug modafinil 400 mg were then determined and comp ared with placebo in both the 12 normal (8 given modafinil, 4 placebo) and 12 narcoleptic subjects (8 modafinil, 4 placebo). Modafinil caused an incre ase in self-reported levels of alertness in 7 of 8 narcoleptic subjects, bu t there was no significant difference between mean pretreatment and post-tr eatment activation levels as determined by fMRI for either normal or narcol eptic syndrome subjects given modafnnil. However, in the modafinil-treated group of 8 normal and 8 narcoleptic subjects, there was a clock time indepe ndent correlation between the initial level of activation as determined by the pretreatment scan and the post-treatment change in activation (visual, P=0.002; and auditory, P=0.001). No correlation was observed in placebo-tre ated subjects (P=0.99 and 0.77, respectively). Although limited by the small number of subjects, and the lack of an object ive measure of alertness, the findings of this study suggest that low corti cal activation levels in both normal and narcoleptic subjects are increased following the administration of modafinil. Functional magnetic resonance i maging may be a valuable addition to established studies of attention.