Imaging Sheds Light on Sleep Loss, Circadian Rhythm

Nancy A. Melville

August 24, 2016

Sleep deprivation and circadian rhythms each influence brain regions distinctively, underscoring the complex and sometimes separate effect of disrupted circadian rhythms on cognitive performance.

"We found that cognitive performance does not only depend on sleep debt but is also nonlinearly regulated by the oscillating circadian clock," senior author Pierre Maquet, MD, of the University of Liege, in Belgium, told Medscape Medical News.

"It seems that we do not have one but multiple clocks in the brain," he said.

The findings were published this month in Science.

Although it is well known that circadian rhythms and sleep deficits affect human performance, research on the interactions between the two at the neural level is lacking.

To evaluate the issue, Dr Maquet and colleagues enrolled 33 healthy participants, including 17 men and 16 women (mean age, 21 years), who were subjected to 2 days (42 hours) of wakefulness, with no sleep beginning in the morning of day 1, followed by a 12-hour recovery night of sleep.

The participants' brain activity during the study period was assessed in 13 functional MRI (fMRI) sessions, including 12 conducted in the mornings and evenings, when changes in the circadian modulation and cognitive performance are known to be most rapid, and one conducted after recovery sleep.

During the fMRI sessions, participants performed psychomotor vigilance tasks that assess reaction times to pseudo–randomly occurring, low-frequency stimuli.

The cognitive assessments showed stability in the reaction time performances during the first day, as expected. Significant declines were observed with the first and second melatonin onsets, considered markers of brain circadian rhythms. Notably, a partial recovery was observed during the second day. The responses returned to baseline after the recovery sleep.

Although the fMRI data on the brain regions showed cortical responses that correlated significantly with accrued sleep deprivation as well as with the rhythmic levels of melatonin, subcortical changes corresponded more with the fluctuations in melatonin.

"Subcortical areas exhibited primarily a circadian modulation that closely followed the melatonin profile," the authors write.

Other regions, especially frontal brain areas, had a reduction in activity corresponding more to the amount of time awake, or sleep deprivation. The activity returned to presleep deprivation levels after recovery sleep.

"A significant negative effect of sleep debt was observed in a large set of cortical areas that spanned high-order association cortices of the frontal, parietal, insular, and cingulate cortices, as well as visual and sensorimotor cortices," the authors write.

"Their response pattern showed a decrease in response to elapsed time awake, with a return to baseline levels after recovery sleep."

Other brain regions showed responses that reflected a combination of a circadian rhythm and sleep deficit.

The findings underscore the fact that circadian rhythm appears to have more of an effect on brain regions than realized, Dr Marquet says.

"A major emphasis has been put on sleep debt during the last years, and the community forgot about the circadian rhythm," he says.

"This paper reminds us of the powerful influence of the circadian clocks on cognitive performance and the underlying brain activity."

The results indicate that disrupted circadian rhythms cannot be easily compensated for, Dr Marquet added.

"It is very likely that you cannot get enough sleep if you do not sleep at the right circadian phase, usually during the night, as we are a diurnal species.

"That is exactly what happens during shift work and jet lag. The circadian rhythm is something you cannot escape, and changing the phase of your main circadian rhythm takes time, about 1 day per hour change."

Coauthor Derk-Jan Dijk, PhD, professor of sleep and physiology and director of the Surrey Sleep Research Center at the University of Surrey, Guildford, United Kingdom, emphasized that the study offers valuable insights in understanding sleep cycles at the level of brain responses.

"It is very gratifying to see directly at the level of fMRI-detected brain responses that circadian rhythmicity and lack of sleep both have such a profound influence on brain function," he said in a press statement.

"Our data may ultimately help us to better understand how the brain maintains performance during the day, why many symptoms in psychiatric and neurodegenerative conditions wax and wane, and why in the early morning after a night without sleep we struggle to maintain attention, whereas in the evening it is not an issue."

The authors have disclosed no relevant financial relationships.

Science. Published online August 12, 2016. Abstract

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