Cholinergic Augmentation Modulates Visual Task Performance in Sleep-Deprived Young Adults

Abstract

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.

Lapsing when sleep deprived: Neural activation characteristics of resistant and vulnerable individuals

“…However, as pointed out earlier, there was no significant relationship between state-related change in activation and task difficulty. Similar findings have been reported in experiments evaluating SD-related decline in visual short term memory capacity (Chee and Chuah, 2007), visual tracking (Tomasi et al, 2009) and the effect of cholinergic augmentation on performance (Chuah and Chee, 2008).…”

Drug Therapy of Post-Stroke Aphasia: A Review of Current Evidence

“…It also has a vascular action by dilating cerebral parenchymal arterioles via the activation of neuronal nitric oxide enzymes (Nakahata et al 2008). In normal subjects, cholinergic augmentation with donepezil improves cognitive functions linked with language, such as learning and memory encoding (Yesavage et al 2002;Grön et al 2005;FitzGerald et al 2008), perceptual and attentional processing during visual encoding (Chuah and Chee 2008), and speed of information processing (Hutchison et al 2001). The theoretical justification for using donepezil in PSA comes for studies demonstrating involvement of the cholinergic system in patients with vascular brain lesions (Mesulam et al 2003;Swartz et al 2003;Sharp et al 2009).…”

Reduced visual processing capacity in sleep deprived persons

“…Across several studies, SD-vulnerable individuals have been found to show greater decline in task-related activation when sleep deprived Chuah and Chee, 2008;Lim et al, 2007). As only correct responses were analyzed in these experiments, trials in which reduced activation could be attributed to volunteers falling asleep were excluded.…”

“…Interestingly, attenuation of brain activation at different task loads (Chuah and Chee, 2008) or levels of perceptual difficulty has been observed even with correct trials, suggesting that a portion of the higher task-related activation observed after a normal night of sleep might correspond to spare information processing capacity. Supporting this hypothesis, maintained or increased task-related activation during SD often corresponds with less compromised or maintained task performance Chee and Choo, 2004a;Drummond et al, 2005).…”