Using 24 h of total sleep deprivation to perturb normal cognitive function, we conducted a double-blind, placebo-controlled crossover study to evaluate the effect of the acetylcholinesterase inhibitor, donepezil, on behavioral performance and task-related brain activation in 28 healthy, young, adult volunteers. The behavioral tasks involved the parametric manipulation of visual short-term memory load and perceptual load in separate experiments indirectly evaluating attention. Sleep deprivation significantly reduced posterior cortical activation (intraparietal sulcus and extrastriate cortex) at all levels of visual memory as well as perceptual load. Donepezil modulated an individual's performance in both tasks in accordance to whether accuracy declined after sleep deprivation without treatment. Critically, there were significant correlations between donepezil-induced increases in neural activation in the posterior cortical areas and improvement in accuracy. Reduced visual short-term memory after sleep deprivation may thus originate from a decline in visual attention and/or visual processing. Cholinergic augmentation can alleviate these deficits in individuals vulnerable to the effects of sleep deprivation, but it may have neutral or negative effects on those resistant to sleep deprivation.
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