Investigating the link between locus coeruleus activity during wakefulness and sleep electrophysiology using ultra‐high‐field MRI ‐ implications for AD

Abstract

AbstractBackgroundA bidirectional link between sleep regulation and Alzheimer’s disease neuropathology emerges in the literature. The locus coeruleus (LC) is the main source of norepinephrine (NE) of the brain, it is the first brain site show signs of tau pathology and is central to the regulation of arousal and sleep. It may therefore contribute to the link between sleep and AD. However, the precise role of the LC in shaping healthy sleep variability is not established in humans.MethodHere, we used 7 Tesla functional Magnetic Resonance Imaging (7T fMRI) and sleep questionnaires and electroencephalography (EEG) in 53 younger (N = 34; 18‐30y) and older (N = 19; 50‐70y) healthy individuals to test whether the address this first question and assess whether activity of the LC during wakefulness was associated with sleep metrics in healthy younger and older individuals.ResultWe found that higher LC activity during wakefulness probed in an auditory attentional task is associated with worse subjective sleep quality (P = 0.007) and with lower EEG theta (4‐8 Hz) power during REM sleep in late midlife (50‐70 y) (P = 0.037), but not in young (18‐30 y) individuals. Further preliminary results suggest that LC activity probed with a visual perceptual rivalry task confirm the associations. These preliminary results may indicate, however, that higher LC activity during wakefulness may be association with better sleep quality.ConclusionThese results suggest that the inverted U‐shape between LC activity during wakefulness and brain functioning reported for cognition also pertains to some aspects of nighttime sleep. They contribute to the understanding of the role of the LC in sleep physiology and pave the to investigate its contribution to AD through sleep.