Genes predict how brain responds to fatigue, human study shows

Tuesday 23 June 2009

Imaging study shows why some are resilient and others vulnerable to sleep deprivation

New imaging research in the June 24th issue of The Journal of Neuroscience explains why sleep deprivation affects some people more than others. After staying awake all night, those who are genetically vulnerable to sleep loss showed reduced brain activity, while those who are genetically resilient showed expanded brain activity, the study found. The findings help explain individual differences in the ability to compensate for lack of sleep.

“The extent to which individuals are affected by sleep deprivation varies, with some crashing out and others holding up well after a night without sleep,” said Michael Chee, MBBS, at the Duke–National University of Singapore Graduate Medical School, an expert on sleep deprivation who was not affiliated with the study. However, studying how the brain produces these behavioural differences is difficult: researchers usually do not know whether their study participants will be vulnerable to sleep deprivation until after a study is complete.

In the current study, the researchers, led by Pierre Maquet, MD, at the University of Lìege in Belgium and Derk Jan Dijk at the University of Surrey in the UK, avoided this problem by selecting study participants based on their genes. Previous research showed that the PERIOD3 (PER3) gene predicts how people will respond to sleep deprivation. People carry either long or short variants of the gene. Those with the short PER3 variant are resilient to sleep loss — they perform well on cognitive tasks after sleep deprivation. However, those with the long PER3 variant are vulnerable — they show deficits in cognitive performance after sleep deprivation. Now the new study explains why.

The authors imaged study participants while they did a working memory task that requires attention and cognitive control — also called executive function. The researchers imaged each participant four times: the night before and the morning after a good night’s sleep, and the night before and morning after a sleepless night.

They found that the resilient, short gene variant group compensated for sleep loss by “recruiting” extra brain structures. In addition to brain structures normally activated by the cognitive task, these participants showed increased activity in other frontal, temporal, and subcortical brain structures after a sleepless night.

In contrast, after a sleepless night, vulnerable participants, the long PER3 group, showed reduced activity in brain structures normally activated by the task. These participants also showed reduced brain activity in one brain structure — the right posterior inferior frontal gyrus — after a normal waking day. These data are consistent with previous research suggesting that people with the long gene variant perform better on executive tasks earlier, but not later, in the day.

“Our study uncovers some of the networks underlying individual differences in sleep loss vulnerability and shows for the first time how genetic differences in brain activity associate with cognitive performance and fatigue,” said study author Maquet. “The data also provide a basis for the development of measures to counteract individual cognitive deficits associated with sleep loss,” he said.

“This study and others like it will help in choosing better candidates for extremely demanding jobs, like shift work, that make challenges on sleep biology and will help develop countermeasures for at-risk people,” said Chee, the expert unaffiliated with the study.

The Belgian Fonds de la Recherche Scientifique, Queen Elizabeth Medical Foundation, University of Lìege, Interuniversity Attraction Pole – Phase V, Wellcome Trust, and Biotechnology and Biological Sciences Research Council supported the research.

The Journal of Neuroscience is published by the Society for Neuroscience, an organization of more than 38,000 basic scientists and clinicians who study the brain and nervous system. Maquet can be reached at pmaquet@ulg.ac.be and Dijk can be contacted at d.j.dijk@surrey.ac.uk

Media Enquiries

Peter La, Press Office at the University of Surrey, Tel: +44 (0)1483 689191, or Email mediarelations@surrey.ac.uk

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