Unveiling Sleep Secrets – How a Tiny Brain Nucleus Impacts REM Sleep and Aging

Deep Sleep Brain Waves

Researchers at the University of Liège used a 7 Tesla MRI to discover the locus coeruleus’s role in regulating sleep, particularly REM sleep. They found that activity in this small brain nucleus is linked to the quality of REM sleep and its function diminishes to initiate and allow REM sleep, a pattern especially notable in individuals aged between 50 and 70.

New research using ultra-high field 7 Tesla MRI are enhancing understanding of sleep regulation mechanisms.

A study carried out by a research team at the University of Liège (BE) Institute, utilizing ultra-high field 7 Tesla MRI, is offering enhanced insights into sleep regulation mechanisms.

We’ve known for a long time that sleep is good for the brain. We also know that light is not just for seeing, but also plays an important role in other aspects such as mood. What we don’t know is how all this happens in our brains. Two separate studies, carried out by researchers at the University of Liège using the 7 Tesla MRI on the GIGA-Centre de Recherche du Cyclotron platform, offer the premises of an explanation.

A scientific team from the ULiège Cyclotron Research Centre /In Vivo Imaging (GIGA-CRC-IVI) has just demonstrated that the quality of our REM sleep (the part of sleep during which we dream the most) is linked to the activity of the locus coeruleus. This small brain nucleus, the size of a 2cm-long spaghetti, is located at the base of the brain (in the brainstem).

The locus coeruleus – Latin for “blue spot” – owes its name to its color when observed in autopsy. It projects to just about every area of the brain (and to the spinal cord) to secrete a neuromodulator called noradrenaline. Noradrenaline is not only important for stimulating neurons and keeping them awake, but also for a whole series of cognitive processes such as memory, emotional processing, stress and anxiety. Its stimulating activity must diminish to initiate sleep and stop to allow REM sleep.

“This allows REM sleep to work without noradrenaline, sorting out the synapses that need to be retained or eliminated during sleep and enabling a new day, full of new experiences,” explains Gilles Vandewalle, co-director of the GIGA CRC-IVI.

Animal research has already shown that the functioning of this small nucleus is essential for sleep and wakefulness.

“In humans, little has been verified because the small size of the nucleus and its deep position make it difficult to observe it in vivo with conventional MRI,” explains Ekaterina Koshmanova, a researcher in the laboratory and first author of the article published in JCI Insight. “Thanks to the higher resolution of 7 Tesla MRI, we were able to isolate the nucleus and extract its activity during a simple cognitive task during wakefulness, and thus show that the more reactive our locus coeruleus is during the day, the poorer the perceived quality of our sleep and the less intense our REM sleep.”

This seems to be particularly true with advancing age, as this effect was only detected in the individuals aged between 50 and 70 included in the study and not in young adults aged between 18 and 30. This finding could explain why some people become progressively insomniac with age. These initial results also lay the foundations for future studies on the activity of this small nucleus during sleep and the role it could play in insomnia and in the link between sleep and Alzheimer’s disease.

A network that spreads light in our brain

At the same time, the same research team tried to understand better how light stimulates our cognition. Light acts like a cup of coffee and helps keep us awake. That’s why we recommend not using too much light on our smartphones and tablets in the evening. This can disrupt our sleep. On the other hand, the same light can help us during the day.

Many studies have shown that good lighting can help students in schools, hospital staff and patients, and company employees. It’s the blue part of light that’s most effective for this, as we have blue light detectors in our eyes that tell our brains about the quality and quantity of light around us.

Once again, the brain regions responsible for this stimulating impact of light (also known as the ‘non-visual’ impact of light) are not well known.

Activation and Eigenvariate Extraction From the Two Regions of Interest

Parietal (A) and thalamic (B) regions involved in the more complex auditory cognitive task while participants were illuminated in 7T MRI. On the right, reconstruction of the time course of the activity during the 25 min of the recording.(C) Location of different nuclei of the thalamus and area of the thalamus used for the analysis. It is this latter area that receives the light information and modifies the activity of the parietal region. Credit: Université de Liège / GIGA CRC IVI

“They are small and located in the subcortical part of the brain,” explains Ilenia Paparella, FNRS doctoral student in the laboratory and first author of the article published in Communications Biology. The team of researchers from the GIGA-CRC-IVI was once again able to take advantage of the higher resolution of 7 Tesla MRI to show that the thalamus, a subcortical region located just below the corpus callosum (that connects our two hemispheres), plays a role in relaying non-visual light information to the parietal cortex in an area known to control attention levels.

“We knew of its important role in vision, but its role in non-visual aspects was not yet certain. With this study, we have demonstrated that the thalamus stimulates the parietal regions and not the other way around, as we might have thought.”

These new advances in our knowledge of the role of the thalamus will ultimately enable us to propose lighting solutions that will help cognition when we need to be fully awake and focused, or that will contribute to better sleep through relaxing light.

References: “Locus coeruleus activity while awake is associated with REM sleep quality in older individuals” by  Ekaterina Koshmanova, Alexandre Berger, Elise Beckers, Islay Campbell, Nasrin Mortazavi, Roya Sharifpour, Ilenia Paparella, Fermin Balda, Christian Berthomier, Christian Degueldre, Eric Salmon, Laurent Lamalle, Christine Bastin, Maxime Van Egroo, Christophe Phillips, Pierre Maquet, Fabienne Collette, Vincenzo Muto, Daphne Chylinski, Heidi I.L. Jacobs, Puneet Talwar, Siya Sherif and Gilles Vandewalle, 12 September 2023, JCI Insight.
DOI: 10.1172/jci.insight.172008

“Light modulates task-dependent thalamo-cortical connectivity during an auditory attentional task” by Ilenia Paparella, Islay Campbell, Roya Sharifpour, Elise Beckers, Alexandre Berger, Jose Fermin Balda Aizpurua, Ekaterina Koshmanova, Nasrin Mortazavi, Puneet Talwar, Christian Degueldre, Laurent Lamalle, Siya Sherif, Christophe Phillips, Pierre Maquet and Gilles Vandewalle, 16 September 2023, Communications Biology.
DOI: 10.1038/s42003-023-05337-5

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