Locus coeruleus activity while awake is associated with REM sleep quality in older individuals
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, Gilles Vandewalle
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, Gilles Vandewalle
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Clinical Research and Public Health Aging Neuroscience

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

Abstract

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).

Authors

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, Gilles Vandewalle

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Figure 2

Associations between the LC and sleep metrics.

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Associations between the LC and sleep metrics. (A) Association between h...
(A) Association between habitual subjective sleep quality, as indexed by PSQI, and the activity of the LC. The GLMM yielded a significant age group by LC activity interaction, and post hoc analyses led to a significant association for the older but not the young group (Table 2). (B) Association between habitual subjective sleep quality, as indexed by PSQI, and the LC contrast. The GLMM yielded a significant main effect of LC activity (Table 3). (C) Association between the REMS theta power (cumulated overnight 4–8 Hz EEG power) and the LC activity with age-group interaction. The GLMM yielded a significant age group by LC activity interaction, and post hoc tests led to a significant association for the older but not the young group (Table 2). The 2 circled dots correspond to 2 putative outliers (≥ 3 SD for LC activity and REMS theta), and we note that the P value of the LC activity by age group interaction went down to P = 0.012 when removed from the analyses. LC activity, LC contrast, and subjective sleep quality are measured in arbitrary units [a.u.]. Orange dots represent younger individuals (18–30 y, n = 33), while the blue dots represent older individuals (50–70 y, n = 19). Simple regression lines are used for a visual display and do not substitute the GLMM outputs. The black line represents the regression irrespective of age groups (young + old, n = 52). Solid and dashed regression lines are used for significant and nonsignificant outputs of the GLMM, respectively. The LC activity was computed as a mean of the activity estimates (betas) associated with the appearance of the target sounds in the bilateral LC mask of each participant, within the participant brain space. Displays are similar when using the left and right LC separately. Subjective sleep quality was estimated using the Pittsburgh Sleep Quality Index (PSQI) (27) where a higher score is indicative of some sleep difficulties.