The crosstalk between the anterior hypothalamus and the locus coeruleus during wakefulness is associated with low frequency oscillations power during sleep

Mortazavi, N.; Talwar, P.; Koshmanova, E.; Sharifpour, R.; Beckers, E.; Paparella, I.; Balda, F.; Bastin, C.; Collette, F.; Lamalle, L.; Phillips, C.; Zubkov, M.; Vandewalle, G.

doi:10.1101/2025.04.15.647930

bioRxiv · 10.1101/2025.04.15.647930

The crosstalk between the anterior hypothalamus and the locus coeruleus during wakefulness is associated with low frequency oscillations power during sleep

Mortazavi, N.·Talwar, P.·Koshmanova, E.·Sharifpour, R.·Beckers, E.·Paparella, I.·Balda, F.·Bastin, C.·Collette, F.·Lamalle, L.·Phillips, C.·Zubkov, M.·Vandewalle, G.

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Abstract

Study ObjectivesAnimal research has demonstrated that sleep regulation heavily depends on a network of subcortical nuclei. In particular, whether the crosstalk between the Locus Coeruleus (LC) and hypothalamic nuclei influences sleep variability and age-related changes in humans remains unexplored. This study investigated whether the effective connectivity between the LC and subparts of the hypothalamus is associated with the electrophysiology of rapid eye movement sleep (REMS). MethodsThirty-three healthy younger ([~]22y, 27 women) and 18 older ([~]61y, 14 women) individuals underwent 7-Tesla functional magnetic resonance imaging during wakefulness to investigate the effective connectivity between LC and distinct hypothalamus subparts encompassing several nuclei. Additionally, we recorded their sleep electroencephalogram (EEG) to explore relationships between effective connectivity measures and REMS theta energy and sigma power prior to REMS episodes. ResultsThe effective connectivity analysis revealed robust evidence of a mutual positive influence between the LC and the anterior-superior and posterior hypothalamus, supporting the idea that the connectivity patterns observed in animal models are also present in humans. Furthermore, our results suggest that in older adults, stronger effective connectivity from the anterior-superior hypothalamus, including the preoptic area, to the LC is associated with reduced REM theta energy. Specificity analysis showed that this association was not limited to REM theta energy but also extended to specific lower-frequency bands during REMS and NREMS. ConclusionsThese findings highlight the complex age-dependent modulation of the LC circuitry and its role in sleep regulation. Understanding these neural interactions offers valuable insight into the mechanisms driving age-related sleep changes.

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Mortazavi, N., Talwar, P., Koshmanova, E., Sharifpour, R., Beckers, E., Paparella, I., Balda, F., Bastin, C., Collette, F., Lamalle, L., Phillips, C., Zubkov, M., Vandewalle, G.. 2025-04-20. The crosstalk between the anterior hypothalamus and the locus coeruleus during wakefulness is associated with low frequency oscillations power during sleep. https://doi.org/10.1101/2025.04.15.647930

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