Effects of COMT genotype and tolcapone on lapses of sustained attention after sleep deprivation in healthy young men

Tolcapone, a brain penetrant selective inhibitor of catechol-O-methyltransferase (COMT) devoid of psychostimulant properties, improves cognition and cortical information processing in rested volunteers, depending on the genotype of the functional Val158Met polymorphism of COMT. The impact of this common genetic variant on behavioral and neurophysiological markers of increased sleep need after sleep loss is controversial. Here we investigated the potential usefulness of tolcapone to mitigate consequences of sleep deprivation on lapses of sustained attention, and tested the hypothesis that dopamine signaling in the prefrontal cortex (PFC) causally contributes to neurobehavioral and neurophysiological markers of sleep homeostasis in humans. We first quantified in 73 young male volunteers the impact of COMT genotype on the evolution of attentional lapses during 40 h of extended wakefulness. Subsequently, we tested in an independent group of 30 young men whether selective inhibition of COMT activity with tolcapone counteracts attentional and neurophysiological markers of elevated sleep need in a genotype-dependent manner. Neither COMT genotype nor tolcapone affected brain electrical activity in wakefulness and sleep. By contrast, COMT genotype and tolcapone modulated the sleep loss-induced impairment of vigilant attention. More specifically, Val/Met heterozygotes produced twice as many lapses after a night without sleep than Met/Met homozygotes. Unexpectedly, tolcapone further deteriorated the sleep loss-induced performance deficits when compared to placebo, particularly in Val/Met and Met/Met genotypes. The findings suggest that PFC dopaminergic tone regulates sustained attention after sleep loss according to an inverse U-shaped relationship, independently of neurophysiological markers of elevated sleep need

Sleep and the processing of emotions

How emotions interact with cognitive processes has been a topic of growing interest in the last decades, as well as studies investigating the role of sleep in cognition. We review here evidence showing that sleep and emotions entertain privileged relationships. The literature indicates that exposure to stressful and emotional experiences can induce changes in the post-exposure sleep architecture, whereas emotional disturbances are likely to develop following sleep alterations. In addition, post-training sleep appears particularly beneficial for the consolidation of intrinsically emotional memories, suggesting that emotions modulate the off-line brain activity patterns subtending memory consolidation processes. Conversely, sleep contributes unbinding core memories from their affective blanket and removing the latter, eventually participating to habituation processes and reducing aversive reactions to stressful stimuli. Taken together, these data suggest that sleep plays an important role in the regulation and processing of emotions, which highlight its crucial influence on human's abilities to manage and respond to emotional information.JOURNAL ARTICLESCOPUS: re.jinfo:eu-repo/semantics/publishe