BACKGROUND: The 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. METHODS: We 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. RESULTS: We 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. CONCLUSION: These 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. FUNDING: This 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).

Animal studies show that sleep regulation depends on subcortical networks, but whether the connectivity between subcortical areas contributes to human sleep variability remains unclear. We investigated whether the effective connectivity between the LC and hypothalamic subparts during wakefulness relates to sleep electrophysiology. Thirty-three younger (~22 y, 27 women) and 18 late middle-aged (~61 y, 14 women) healthy individuals underwent 7-Tesla functional MRI during wakefulness to assess LC–hypothalamus effective connectivity. Additionally, sleep EEG was recorded at night in the lab to examine the relationships between effective connectivity measures and REM sleep theta energy as well as sigma power prior to REM. Connectivity analyses revealed strong mutual positive influences between the LC and both the anterior–superior and posterior hypothalamus, consistent with animal studies. Aging was negatively associated with the connectivity from the anterior–superior hypothalamus (including the preoptic area) to the LC. In late middle-aged adults, but not younger adults, stronger effective connectivity from the anterior–superior hypothalamus to the LC was associated with lower REM theta energy. This association extended to other low-frequency bands during REM and NREM sleep. These findings highlight the age-dependent modulation of LC–hypothalamus interactions and their potential roles in sleep regulation, providing new insights into neural mechanisms underlying age-related sleep changes.