Heart rate variability during slow wave sleep is linked to functional connectivity in the central autonomic network.

ABSTRACT

Reduced heart rate variability can be an early sign of autonomic dysfunction in neurodegenerative diseases and may be related to brain dysfunction in the central autonomic network. As yet, such autonomic dysfunction has not been examined during sleep-which is an ideal physiological state to study brain-heart interaction as both the central and peripheral nervous systems behave differently compared to during wakefulness. Therefore, the primary aim of the current study was to examine whether heart rate variability during nocturnal sleep, specifically slow wave (deep) sleep, is associated with central autonomic network functional connectivity in older adults 'at-risk' of dementia. Older adults (n = 78; age range = 50-88 years; 64% female) attending a memory clinic for cognitive concerns underwent resting-state functional magnetic resonance imaging and an overnight polysomnography. From these, central autonomic network functional connectivity strength and heart rate variability data during sleep were derived, respectively. High-frequency heart rate variability was extracted to index parasympathetic activity during distinct periods of sleep, including slow wave sleep as well as secondary outcomes of non-rapid eye movement sleep, wake after sleep onset, and rapid eye movement sleep. General linear models were used to examine associations between central autonomic network functional connectivity and high-frequency heart rate variability. Analyses revealed that increased high-frequency heart rate variability during slow wave sleep was associated with stronger functional connectivity (F = 3.98, P = 0.022) in two core brain regions within the central autonomic network, the right anterior insular and posterior midcingulate cortex, as well as stronger functional connectivity (F = 6.21, P = 0.005) between broader central autonomic network brain regions-the right amygdala with three sub-nuclei of the thalamus. There were no significant associations between high-frequency heart rate variability and central autonomic network connectivity during wake after sleep onset or rapid eye movement sleep. These findings show that in older adults 'at-risk' of dementia, parasympathetic regulation during slow wave sleep is uniquely linked to differential functional connectivity within both core and broader central autonomic network brain regions. It is possible that dysfunctional brain-heart interactions manifest primarily during this specific period of sleep known for its role in memory and metabolic clearance. Further studies elucidating the pathophysiology and directionality of this relationship should be conducted to determine if heart rate variability drives neurodegeneration, or if brain degeneration within the central autonomic network promotes aberrant heart rate variability.