Biology subjects

Vandewalle, G.

Publications and source records attributed to Vandewalle, G..

30 records · Page 2Linked to original sources

bioRxiv2023

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.

neuroscience↗

bioRxiv2023

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.

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bioRxiv2023

Light modulates task-dependent thalamo-cortical connectivity during an auditory attentional task

Exposure to blue wavelength light stimulates alertness and performance by modulating a widespread set of task-dependent cortical and subcortical areas. How light affects the crosstalk between brain areas to trigger this stimulating effect is not established. We recorded the brain activity of 19 healthy young participants (24.05{+/-}2.63; 12 women) while they completed an auditory attentional task in darkness or under an active (blue-enriched) or a control (orange) light, in an ultra-high-field 7 Tesla MRI scanner. We tested if light modulated the effective connectivity between an area of the posterior associative thalamus, encompassing the pulvinar, and the intraparietal sulcus (IPS), key areas in the regulation of attention. We found that only the blue-enriched light strengthened the connection from the posterior thalamus to the IPS. Our results provide the first empirical data supporting that blue wavelength light affects ongoing non-visual cognitive activity by modulating task-dependent information flow from subcortical to cortical areas.

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bioRxiv2023

Impact of light on task-evoked pupil responses during cognitive tasks.

Light has many non-image-forming functions including modulation of pupil size and stimulation of alertness and cognition. Part of these non-image-forming effects may be mediated by the brainstem locus coeruleus. The processing of sensory inputs can be associated with a transient pupil dilation that is likely driven in part by the phasic activity of the locus coeruleus. Here, we aimed to characterise the task-evoked pupil response associated with auditory inputs under different light levels and across two cognitive tasks. We continuously monitored the pupil of 20 young healthy participants (24.05y {+/-}4.0; 14 women) while they completed an attentional and an emotional auditory task whilst exposed to repeated 30-to-40s-blocks of light interleaved with darkness periods. Blocks could either consist of monochromatic orange light [0.16 melanopic Equivalent Daylight Illuminance (EDI) lux] or blue-enriched white light of three different levels [37, 92, 190 melanopic EDI lux; 6500K]. For the analysis 15 and then 14 participants were included in the attentional and emotional tasks respectively. Generalized Linear Mixed Models showed a significant main effect of light level on the task-evoked pupil responses triggered by the attentional and emotional tasks (p[≤].0001). The impact of light was different for the target vs. non-target stimulus of the attentional task but was not different for the emotional and neutral stimulus of the emotional task. Despite a smaller sustained pupil size during brighter light blocks, a higher light level triggers a stronger task-evoked pupil response to auditory stimulation, presumably through the recruitment of the locus coeruleus.

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bioRxiv2023

Impact of repeated short light exposures on sustained pupil responses in an fMRI environment

Light triggers numerous non-image forming (NIF), or non-visual, biological effects. The brain correlates of these NIF effects have been investigated, notably using Magnetic Resonance Imaging (MRI) and short light exposures varying in irradiance and spectral quality. However, it is not clear whether having light in subsequent blocks may induce carry over effects of one light block onto the next, thus biasing the study. We reasoned that pupil light reflex (PLR) was an easy readout of one of the NIF effects of light that could be used to address this issue. We characterized the sustained PLR in 13 to 16 healthy young individuals under short light exposures during three distinct cognitive processes (executive, emotional and attentional). Light conditions pseudo-randomly alternated between monochromatic orange light [0.16 melanopic Equivalent Daylight Illuminance (mel EDI) lux] and polychromatic blue-enriched white light of three different levels [37, 92, 190 mel EDI lux]. As expected, higher melanopic irradiance was associated with larger sustained PLR in each cognitive domain. This result was stable over the light block sequence under higher melanopic irradiance levels as compared to lower ones. Exploratory frequency-domain analyses further revealed that PLR was more variable within a light block under lower melanopic irradiance levels. Importantly, PLR varied across tasks independently of the light condition pointing to a potential impact of the light history and/or cognitive context on PLR. Together, our results emphasize that the distinct contribution and adaptation of the different retinal photoreceptors influence the NIF effects of light and therefore potentially their brain correlates.

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bioRxiv2023

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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bioRxiv2023

MRI-assessed locus coeruleus contrast and functional response are not associated in young and late middle-aged individuals

The brainstem locus coeruleus (LC) influences a broad range of brain processes, including cognition. The so-called LC contrast is an accepted marker of the integrity of the LC that consists of a local hyperintensity on specific Magnetic Resonance Imaging (MRI) structural images. The small size of the LC has, however, rendered its functional characterization difficult in humans, including in aging. A full characterization of the structural and functional characteristics of the LC in healthy young and late middle-aged individuals is needed to determine to potential roles of the LC in different medical conditions. Here, we wanted to determine whether the activation of the LC in a mismatch negativity task changes in aging and whether the LC functional response was associated to the LC contrast. We used Ultra-High Field (UHF) 7-Tesla functional MRI (fMRI) to record brain response during an auditory oddball task in 53 healthy volunteers, including 34 younger (age: 22.15y {+/-} 3.27; 29 women) and 19 late middle-aged (age: 61.05y {+/-} 5.3; 14 women) individuals. Whole-brain analyses confirmed brain responses in the typical cortical and subcortical regions previously associated with mismatch negativity. When focusing on the brainstem, we found a significant response in the rostral part of the LC probability mask generated based on individual LC images. Although bilateral, the activation was more extensive in the left LC. Individual LC activity was not significantly different between young and late middle-aged individuals. Critically, while the LC contrast was higher in older individuals, the functional response of the LC was not associated with its contrast. These findings show that the age-related alterations of the LC structural integrity may not necessarily be related to changes in its functional response. The results further indicate that LC responses could remain stable in healthy individuals aged 20 to 70.

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bioRxiv2022

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.

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bioRxiv2020

Melanopsin retinal ganglion cell-driven contribution to visual and cognitive brain responses in LHON

Melanopsin retinal ganglion cells (mRGCs) are intrinsically photosensitive photoreceptors contributing to visual and non-image-forming functions of the eye. Isolating mRGC roles in humans is challenging, therefore mRGCs functions remains to be fully characterized. We explored mRGCs contribution to light-driven visual and cognitive brain responses in Lebers Hereditary Optic Neuropathy (LHON), given mRGC relative sparing in LHON. Twelve patients and twelve matched healthy controls (HC) participated in an fMRI protocol including visual and visual-cognitive paradigms under blue (480nm) and red light (620nm). Higher occipital activation was found in response to sustained blue vs. red stimulation in LHON vs. HC. Similarly, brain responses to the executive task were larger under blue vs. red light in LHON over lateral prefrontal cortex. These findings are in line with LHON mRGCs relative sparing and support mRGCs contribution to non-visual and visual functions in humans, with potential implication for visual rehabilitation in optic neuropathy patients.

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bioRxiv2019

Preserved wake-dependent cortical excitability dynamics predict cognitive fitness beyond age-related brain alterations

Age-related cognitive decline arises from alterations in brain integrity as well as in sleep-wake regulation. Here, we investigated whether preserved sleep-wake regulation of cortical function during wakefulness could represent a positive factor for cognitive fitness in aging, independently of early age-related changes in brain structure. We quantified cortical excitability dynamics during prolonged wakefulness as a sensitive marker of age-related alteration in sleep-wake regulation in 60 healthy older individuals (50-69y; 42 women). Brain structural integrity was assessed with amyloid-beta- and tau-PET, and with MRI. Participants cognition was extensively investigated. We show that individuals with preserved cortical excitability dynamics exhibit better cognitive performance, particularly in the executive domain, which is essential to successful cognitive aging. Critically, this association remained significant after accounting for brain integrity measures. Preserved dynamics of basic brain function during wakefulness could be essential to cognitive fitness in aging, independently from age-related brain structural modifications that can ultimately lead to dementia.

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bioRxiv2019

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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bioRxiv2017

A (blue) light in the dark: Blue light modulates oscillatory alpha activity in the occipital cortex of totally visually blind individuals with intact non-visual photoreception

The discovery of intrinsically photosensitive retinal ganglion cells (ipRGCs) marked a major shift in our understanding of how light is processed by the mammalian brain. These ipRGCs influence multiple functions not directly related to vision such as the synchronization of circadian rhythmicity, pupil constriction, the regulation of alertness and sleep, as well as the modulation of cognition. More recently, it was demonstrated that ipRGCs may also contribute to basic visual functions. The impact of ipRGCs on visual functions, independently of image forming photoreceptors, remains however difficult to isolate, particularly in humans. We previously showed that exposure to intense monochromatic blue light (465nm) induced awareness of light in a forced choice task in three rare totally visually blind individuals without detectable rod and cone function, but who retained non-visual responses to light, very likely via ipRGCs. The neural foundation of such light awareness in the absence of conscious vision is unknown, however. In this study, we characterized the brain activity of these three rare participants using electroencephalography (EEG), and demonstrate that unconsciously perceived light triggers an early and reliable transient desynchronization (i.e. decreased power) of the alpha EEG rhythm (8-14 Hz) over the occipital cortex. These results provide compelling insight into how ipRGC may contribute to transient changes in ongoing brain activity. They suggest that occipital alpha rhythm synchrony, which is typically linked to the visual system, is modulated by ipRGCs photoreception; a process that may contribute to the awareness of light in those blind individuals.

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