Locus coeruleus activity while awake is associated with REM sleep quality in older individuals.

BACKGROUNDThe locus coeruleus (LC) is the primary source of norepinephrine in the brain and regulates arousal and sleep. Animal research shows that it plays important roles in the transition between sleep and wakefulness, and between slow wave sleep and rapid eye movement sleep (REMS). It is unclear, however, whether the activity of the LC predicts sleep variability in humans.METHODSWe used 7-Tesla functional MRI, sleep electroencephalography (EEG), and a sleep questionnaire to test whether the LC activity during wakefulness was associated with sleep quality in 33 healthy younger (~22 years old; 28 women, 5 men) and 19 older (~61 years old; 14 women, 5 men) individuals.RESULTSWe found that, in older but not in younger participants, higher LC activity, as probed during an auditory attentional task, was associated with worse subjective sleep quality and with lower power over the EEG theta band during REMS. The results remained robust even when accounting for the age-related changes in the integrity of the LC.CONCLUSIONThese findings suggest that LC activity correlates with the perception of the sleep quality and an essential oscillatory mode of REMS, and we found that the LC may be an important target in the treatment of sleep- and age-related diseases.FUNDINGThis work was supported by Fonds National de la Recherche Scientifique (FRS-FNRS, T.0242.19 & J. 0222.20), Action de Recherche Concertée - Fédération Wallonie-Bruxelles (ARC SLEEPDEM 17/27-09), Fondation Recherche Alzheimer (SAO-FRA 2019/0025), ULiège, and European Regional Development Fund (Radiomed & Biomed-Hub).

Structural and functional characterization of the locus coeruleus in young and late middle-aged individuals.

Introduction: The brainstem locus coeruleus (LC) influences a broad range of brain processes, including cognition. The so-called LC contrast is an accepted marker of the integrity of the LC that consists of a local hyperintensity on specific Magnetic Resonance Imaging (MRI) structural images. The small size of the LC has, however, rendered its functional characterization difficult in humans, including in aging. A full characterization of the structural and functional characteristics of the LC in healthy young and late middle-aged individuals is needed to determine the potential roles of the LC in different medical conditions. Here, we wanted to determine whether the activation of the LC in a mismatch negativity task changes in aging and whether the LC functional response was associated to the LC contrast. Methods: We used Ultra-High Field (UHF) 7-Tesla functional MRI (fMRI) to record brain response during an auditory oddball task in 53 healthy volunteers, including 34 younger (age: 22.15y ± 3.27; 29 women) and 19 late middle-aged (age: 61.05y ± 5.3; 14 women) individuals. Results: Whole-brain analyses confirmed brain responses in the typical cortical and subcortical regions previously associated with mismatch negativity. When focusing on the brainstem, we found a significant response in the rostral part of the LC probability mask generated based on individual LC images. Although bilateral, the activation was more extensive in the left LC. Individual LC activity was not significantly different between young and late middle-aged individuals. Importantly, while the LC contrast was higher in older individuals, the functional response of the LC was not significantly associated with its contrast. Discussion: These findings may suggest that the age-related alterations of the LC structural integrity may not be related to changes in its functional response. The results further suggest that LC responses may remain stable in healthy individuals aged 20 to 70.

In vivo Locus Coeruleus activity while awake is associated with REM sleep quality in healthy older individuals.

The locus coeruleus (LC) is the primary source of norepinephrine (NE) in the brain, and the LC-NE system is involved in regulating arousal and sleep. It plays key roles in the transition between sleep and wakefulness, and between slow wave sleep (SWS) and rapid eye movement sleep (REMS). However, it is not clear whether the LC activity during the day predicts sleep quality and sleep properties during the night, and how this varies as a function of age. Here, we used 7 Tesla functional Magnetic Resonance Imaging (7T fMRI), sleep electroencephalography (EEG) and a sleep questionnaire to test whether the LC activity during wakefulness was associated with sleep quality in 52 healthy younger (N=33; ~22y; 28 women) and older (N=19; ~61y; 14 women) individuals. We find that, in older, but not in younger participants, higher LC activity, as probed during an auditory mismatch negativity task, is associated with worse subjective sleep quality and with lower power over the EEG theta band during REMS (4-8Hz), which are two sleep parameters significantly correlated in our sample of older individuals. The results remain robust even when accounting for the age-related changes in the integrity of the LC. These findings suggest that the activity of the LC may contribute to the perception of the sleep quality and to an essential oscillatory mode of REMS, and that the LC may be an important target in the treatment of sleep disorders and age-related diseases.