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Berthomier, C.

Publications and source records attributed to Berthomier, C..

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Age-related differences in the association between REM sleep and the polygenic risk for Parkinson's disease

ObjectiveParkinsons disease (PD) is one of the rare diseases for which sleep alteration is a true marker of disease outcome. Yet, how the association between sleep and PD emerges over the healthy lifetime is not established. We examined association between the polygenic risk score (PRS) for PD and the variability in the electrophysiology of Rapid Eye Movement (REM) sleep in 433 younger (18-31y) and 85 late-midlife (50-69y) healthy individuals. MethodsIn this prospective cross-sectional study, in-lab EEG recordings of sleep were recorded to extract REM sleep metrics. PRS was computed using SBayesR approach. ResultsGeneralized Additive Model for Location, Scale and Shape (GAMLSS) analysis showed significant association of REM duration (pcorr=0.03) and theta energy in REM (pcorr=0.004) with PRS for PD in interaction with age group. In the younger sub-sample, REM duration and theta energy were positively associated with PD PRS. In contrast, in the late-midlife sub-sample, the same associations were negative (though only qualitatively for REM theta energy) and may differ between men and women. InterpretationREM sleep is associated with the PRS for PD in early adulthood, 2 to 5 decades prior to typical symptoms onset. The association changes from positive in younger individuals, presumably free of alpha-synuclein, to negative in late-midlife individuals, possibly because of the progressive presence of alpha-synuclein aggregates or of the repeated increased oxidative metabolism imposed by REM sleep. Our findings may unravel core associations between PD and sleep and may contribute to novel intervention targets to prevent or delay PD.

neuroscience↗

REM sleep quality is associated with balanced tonic activity of the locus coeruleus during wakefulness

BackgroundAnimal studies established that the locus coeruleus (LC) plays important roles in sleep and wakefulness regulation. Whether it contributes to sleep variability in humans is not yet established. Here, we investigated if the in vivo activity of the LC is related to the variability in the quality of Rapid Eye Movement (REM) sleep. MethodsWe assessed the LC activity of 34 healthy younger ([~]22y) and 18 older ([~]61y) individuals engaged in bottom-up and top-down cognitive tasks using 7-Tesla functional Magnetic Resonance Imaging (fMRI). We further recorded their sleep electroencephalogram (EEG) to evaluate associations between LC fMRI measures and REM sleep EEG metrics. ResultsTheta oscillation energy during REM sleep was positively associated with LC response in the top-down task. In contrast, REM sleep theta energy was negatively associated with LC activity in older individuals during the bottom-up task. Importantly, sigma oscillations power immediately preceding a REM sleep episode was positively associated with LC activity in the top-down task. ConclusionsLC activity during wakefulness was related to REM sleep intensity and to a transient EEG change preceding REM sleep, a feature causally related to LC activity in animal studies. The associations depend on the cognitive task, suggesting that a balanced level of LC tonic activity during wakefulness is required for optimal expression of REM sleep. The findings may have implications for the high prevalence of sleep complaints reported in aging and for disorders such as insomnia, Alzheimers, and Parkinsons disease, for which the LC may play pivotal roles through sleep.

neuroscience↗

Napping and circadian sleep-wake regulation during healthy aging.

Study objectivesDaytime napping is frequently reported among the older population and has attracted increasing attention due to its association with multiple health conditions. Here, we tested whether napping in the aged is associated with altered circadian regulation of sleep, sleepiness and vigilance performance. MethodsSixty healthy older individuals (mean age: 69y., 39 women) were recruited with respect to their napping habits (30 nappers, 30 non-nappers). All participants underwent an in-lab 40-h multiple nap protocol (10 cycles of 80 mins of sleep opportunity alternating with 160 mins of wakefulness), preceded and followed by a baseline and recovery sleep period. Saliva samples for melatonin assessment, sleepiness and vigilance performance were collected during wakefulness and electrophysiological data were recorded to derive sleep parameters during scheduled sleep opportunities. ResultsThe circadian amplitude of melatonin secretion was reduced in nappers, compared to non-nappers. Furthermore, nappers were characterized by higher sleep efficiencies and REM sleep proportion during day-compared to night-time naps. The nap group also presented altered modulation in sleepiness and vigilance performance at specific circadian phases. DiscussionOur data indicate that napping is associated with an altered circadian sleep-wake propensity rhythm and thereby contribute to the understanding of the biological correlates underlying napping and/or sleep-wake cycle fragmentation during healthy aging. Altered circadian sleep-wake promotion can lead to a less distinct allocation of sleep into night-time and/or a reduced wakefulness drive during the day, thereby potentially triggering the need to sleep at adverse circadian phase. SIGNIFICANCE STATEMENTWhile napping has raised increasing interest as a health risk factor in epidemiological studies, its underlying regulation processes in the aged remain largely elusive. Here we assessed whether napping in the older population is associated with physiological and behavioral changes in circadian sleep-wake characteristics. Our data indicate that, concomitant to a reduced circadian amplitude in melatonin secretion, healthy older nappers are characterized by reduced day-night differences in sleep efficiency and more particularly in REM sleep, compared to their non-napping counterparts. These results suggest altered circadian response as a cause or consequence of chronic napping in the aged and thereby contribute to the understanding of nap regulation during healthy aging.

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In vivo marker of brainstem myelin is associated to quantitative sleep parameters in healthy young men

Brain structural integrity has been suggested to contribute to the variability in human sleep quality and composition. The associations between sleep parameters and the regional integrity of subcortical structures implicated in sleep-wake regulation remain, however, largely unexplored. The present study aimed at assessing association between quantitative Magnetic Resonance Imaging (qMRI)-derived marker of the myelin content of the brainstem with the variability in the sleep electrophysiology in a large sample of healthy young men (N=321;[~]22y). Generalized Additive Model for Location, Scale and Shape (GAMLSS) was used to seek associations between sleep metrics and Magnetisation Transfer saturation (MTsat) qMRI values, proxy for myelin content. Separate GAMLSS revealed that sleep onset latency and slow wave sleep intensity were significantly associated with MTsat-derived myelin estimates in the brainstem (pcorrected[≤].03), with overall higher MTsat value associated with values reflecting better sleep quality. The association changed with age, however (MTsat-by-age interaction - pcorrected[≤].03), with higher MTsat value linked to better values in the two sleep metrics in the individuals of our sample aged [~]18 to 20y. Similar associations were detected across different parts of the brainstem (pcorrected[≤].03), suggesting that the overall maturation and integrity of the brainstem was associated with both sleep metrics. Our results suggest that myelination of the many reticular nuclei of the brainstem essential to regulation of sleep is associated with inter-individual differences in sleep characteristics during early adulthood. They may have implications for sleep disorders or neurological diseases related to myelin.

neuroscience↗

In vivo Locus Coeruleus activity while awake is associated with REM sleep quality in healthy older individuals

The locus coeruleus (LC) is the primary source of norepinephrine (NE) in the brain, and the LC-NE system is involved in regulating arousal and sleep. It plays key roles in the transition between sleep and wakefulness, and between slow wave sleep (SWS) and rapid eye movement sleep (REMS). However, it is not clear whether the LC activity during the day predicts sleep quality and sleep properties during the night, and how this varies as a function of age. Here, we used 7 Tesla functional Magnetic Resonance Imaging (7T fMRI), sleep electroencephalography (EEG) and a sleep questionnaire to test whether the LC activity during wakefulness was associated with sleep quality in 52 healthy younger (N=33; ~22y; 28 women) and older (N=19; ~61y; 14 women) individuals. We find that, in older, but not in younger participants, higher LC activity, as probed during an auditory mismatch negativity task, is associated with worse subjective sleep quality and with lower power over the EEG theta band during REMS (4-8Hz), which are two sleep parameters significantly correlated in our sample of older individuals. The results remain robust even when accounting for the age-related changes in the integrity of the LC. These findings suggest that the activity of the LC may contribute to the perception of the sleep quality and to an essential oscillatory mode of REMS, and that the LC may be an important target in the treatment of sleep disorders and age-related diseases.

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Timely sleep coupling: spindle-slow wave synchrony is linked to early amyloid-β burden and predicts memory decline

Sleep alteration is a hallmark of ageing and emerges as a risk factor for Alzheimers disease (AD). While the fine-tuned coalescence of sleep microstructure elements may influence age-related cognitive trajectories, its association with AD processes is not fully established. Here, we investigated whether the coupling of spindles and slow waves is associated with early amyloid-beta (A{beta}) brain burden, a hallmark of AD neuropathology, and cognitive change over 2 years in 100 healthy individuals in late-midlife (50-70y; 68 women). We found that, in contrast to other sleep metrics, earlier occurrence of spindles on slow-depolarisation slow waves is associated with higher medial prefrontal cortex A{beta} burden (p=0.014, r2{beta}*=0.06), and is predictive of greater longitudinal memory decline (p=0.032, r2{beta}*=0.07). These findings unravel early links between sleep, AD-related processes and cognition and suggest that altered coupling of sleep microstructure elements, key to its mnesic function, contributes to poorer brain and cognitive trajectories in ageing.

neuroscience↗

Regular caffeine intake attenuates REM sleep promotion and sleep quality in healthy men

Acute caffeine intake can attenuate homeostatic sleep pressure and worsen sleep quality. Besides, caffeine intake - particularly in high doses and close to bedtime - may also affect circadian-regulated REM sleep promotion, an important determinant of subjective sleep quality. However, it is not known whether such changes persist under chronic caffeine consumption during daytime. Twenty male caffeine consumers (26.4 {+/-} 4 years old, habitual caffeine intake 478.1 {+/-} 102.8 mg/day) participated in a double-blind crossover study. Each volunteer completed a caffeine (3 x 150 mg caffeine daily), a withdrawal (3 x 150 mg caffeine for eight days then placebo), and a placebo condition. After ten days of controlled intake and a fixed sleep-wake cycle, we recorded 8 h of electroencephalography starting 5 h after habitual bedtime (i.e., start on average at 04:22 am which is around the peak of circadian REM sleep promotion). A 60 min evening nap preceded each sleep episode and reduced high sleep pressure levels. While total sleep time and sleep architecture did not significantly differ between the three conditions, REM latency was longer after daily caffeine intake compared to both placebo and withdrawal. Moreover, the accumulation of REM sleep proportion was slower, and volunteers reported more difficulties at awakening after sleep and feeling more tired upon wake-up in the caffeine condition compared to placebo. Our data indicate that besides acute also regular daytime caffeine intake affects REM sleep regulation in men. We have evidence that regular caffeine intake during daytime weakens circadian sleep promotion when compared to placebo. Moreover, the observed caffeine-induced deterioration in the quality of awakening may suggest a potential motive to reinstate caffeine intake after sleep.

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Looking for a reference for large datasets: relative reliability of visual and automatic sleep scoring

Study ObjectivesNew challenges in sleep science require to describe fine grain phenomena or to deal with large datasets. Beside the human resource challenge of scoring huge datasets, the inter- and intra-expert variability may also reduce the sensitivity of such studies. Searching for a way to disentangle the variability induced by the scoring method from the actual variability in the data, visual and automatic sleep scorings of healthy individuals were examined.\n\nMethodsA first dataset (DS1, 4 recordings) scored by 6 experts plus an autoscoring algorithm was used to characterize inter-scoring variability. A second dataset (DS2, 88 recordings) scored a few weeks later was used to investigate intra-expert variability. Percentage agreements and Congers kappa were derived from epoch-by-epoch comparisons on pairwise, consensus and majority scorings.\n\nResultsOn DS1 the number of epochs of agreement decreased when the number of expert increased, in both majority and consensus scoring, where agreement ranged from 86% (pairwise) to 69% (all experts). Adding autoscoring to visual scorings changed the kappa value from 0.81 to 0.79. Agreement between expert consensus and autoscoring was 93%. On DS2 intra-expert variability was evidenced by the kappa systematic decrease between autoscoring and each single expert between datasets (0.75 to 0.70).\n\nConclusionsVisual scoring induces inter- and intra-expert variability, which is difficult to address especially in big data studies. When proven to be reliable and if perfectly reproducible, autoscoring methods can cope with intra-scorer variability making them a sensible option when dealing with large datasets.\n\nStatement of SignificanceWe confirmed and extended previous findings highlighting the intra- and inter-expert variability in visual sleep scoring. On large datasets those variability issues cannot be completely addressed by neither practical nor statistical solutions such as group training, majority or consensus scoring.\n\nWhen an automated scoring method can be proven to be as reasonably imperfect as visual scoring but perfectly reproducible, it can serve as a reliable scoring reference for sleep studies.

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