Biology subjects

Maquet, P.

Publications and source records attributed to Maquet, P..

13 recordsLinked to original sources

bioRxiv2026

Pooling quantitative MRI data: A multi-protocol study of healthy subcortical ageing

Quantitative MRI (qMRI) measures relaxation rates, exchange rates and proton densities that reflect biophysical properties of tissue and are ideally free from protocol- and scanner-dependence. In practice, qMRI has not yet achieved this level of independence from sequence and hardware choice, and quantitative estimates often differ across sites and acquisition schemes. At the same time pooling data across different sources can be beneficial to statistical power of longitudinal, cross-sectional or case-control studies. Here we investigate how protocol and hardware differences can affect pooling data from different sources in large ultra high field (UHF) qMRI studies in the context of healthy aging. We combine the openly available ageing UHF qMRI MP2RAGEME-based dataset with two different MPM-based sets of qMRI data. We evaluate how pooling affects age dependence of qMRI parameters and investigate protocol-related biases, with a particular focus on subcortical structures. We focus the analysis, first, on replication and expansion of the reference qMRI dataset on normative aging, second, the examination of the protocol influence on the estimated qMRI values, and third, on detecting the protocol effect on the age dependence inferred from the data. We find that the age-related changes for R1 measure around 4-17% of the lifespan mean in different structures. Similarly, age-related R2* variation in different structures constitutes around 6-30%. Subcortical structure volume change is on the order of 5-27%. We further observe larger relative difference between protocols for R1 and volume, while R2* remains more consistent for most regions. We show how pooling the UHF qMRI data from different sites and collected with different quantitative protocols can be both detrimental and beneficial for the analysis outcomes.

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bioRxiv2025

Sleep arousals are associated with the polygenic risk for developing Alzheimer's disease and with cognitive decline in healthy late middle-aged individuals

ObjectiveSleep disturbances are increasingly recognized as early features of Alzheimers disease (AD) neuropathology. In that context, spontaneous arousals during sleep have been associated with the burden of Amyloid beta in the brain of healthy late middle-aged individuals. Whether the heterogeneity of arousals during sleep may be related to the genetic risk of developing AD in young adults is not established. Likewise, whether arousals may be associated with cognitive decline is not known. Here, we evaluated the association between arousals, the genetic risk for developing AD and cognitive performance and cognitive decline in healthy young and late-middle-aged individuals. MethodsWe classified spontaneous arousals using in-lab EEG recordings of sleep in 453 younger individuals (22+/-2.7y; 49 women) and 87 late middle-aged individuals (59.3+/-5.3y; 59 women) based on their association with sleep stage transitions and changes in muscle tone. We examined the associations between arousal types and the polygenic risk scores (PRS) for AD, cognitive performance at baseline and, in late middle-aged individuals, cognitive decline over 2 and 7 years. ResultsThe prevalence of arousals associated with sleep stage transition was higher in late middle-aged vs. younger individuals. Among these arousals, those with and without muscle tone increases were, respectively, associated with lower and higher PRS for AD in late middle-aged but not in younger individuals. In the late middle-aged individuals, transition arousals associated with and without muscle tone increases were, respectively, correlated with better and worse attentional performance at baseline, and lower and larger memory decline over 2 or 7 years. ConclusionThe heterogeneity in spontaneous arousals during sleep may reflect their physiological intensity or underlying neural activation, and may indicate vulnerability to AD in late middle-aged individuals. The findings may contribute to identifying early markers of neurodegenerative risk. Statement of SignificanceSleep arousals are typically regarded as disruptive events, yet their physiological diversity may reveal important insights into brain health. In this study, we report that distinct subtypes of spontaneous sleep arousals are differentially associated with genetic vulnerability to Alzheimers disease (AD) and with future cognitive decline in healthy late middle-aged adults. Specifically, sleep arousals linked to sleep stage transitions but lacking muscle activation were related to higher polygenic risk for AD and greater memory decline, while those accompanied by muscle tone increases showed the opposite pattern. These findings indicate that subtle variations in sleep microstructure can reflect neurobiological vulnerability to AD before clinical symptoms emerge. By identifying electrophysiological markers associated with genetic risk and cognitive trajectories, this work advances the potential for using sleep-based biomarkers to detect and monitor preclinical neurodegenerative processes.

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bioRxiv2025

The specificity of fatigue cerebral substrates in early Multiple Sclerosis - An fMRI study

ContextThe cerebral substrates of fatigue in patients with Multiple Sclerosis (pwMS) are not elucidated yet. This study aims at exploring the disease-specific functional brain substrates of fatigue in pwMS with a recent disease history MethodsSixteen pwMS (disease history < 5 years) and 17 matched Healthy Controls (HC) performed a N-Back task with three difficulty levels during fMRI acquisitions following high vs. low fatigue induction. Measures of subjective trait and state fatigue were also recorded. Behavioral performance at n-back task and evolution of subjective fatigue states were analyzed by means of Bayesian repeated measures analyses of variance. Functional MRI data were analyzed to determine between-group differences (1) in task-related brain activity, independently of trait fatigue score; (2) in the association between trait fatigue and brain activity ResultsA similar trajectory was observed in the two groups for subjective and task-related measures following fatigue induction. No between-group difference was observed in brain activity unrelated to fatigue score. However, negative associations between trait fatigue score and brain activity were observed in pwMS, while the associations are positive in HC. Specifically, interactions between group and task difficulty were observed in regions belonging to the Striato-Thalamo-Cortical (STC) network and the fronto-parietal cortex ConclusionGroup-specific patterns of brain activity related to fatigue were identified in pwMS and HC in the STC circuitry, despite similar behavioral performance and subjective fatigue level. This confirms the implication of the STC loops in fatigue pathophysiology, occurring from the early stages of the disease.

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bioRxiv2025

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.

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bioRxiv2024

7 Tesla MRS estimates of GABA concentration relate to physiological measures of tonic inhibition in the human motor cortex

GABAergic neurotransmission within the cortex plays a key role in learning and is altered in several brain diseases. Quantification of bulk GABA in the human brain is typically obtained by Magnetic Resonance Spectroscopy (MRS). However, the interpretation of MRS-GABA is still debated. A recent mathematical simulation contends that MRS detects extrasynaptic GABA, mediating tonic inhibition. Nevertheless, no empirical data have yet confirmed this hypothesis. Here we collected ultra-high field 7 Tesla MRS and Transcranial Magnetic Stimulation coupled with high-density Electroencephalography (TMS-hdEEG) from the motor cortex of twenty healthy participants (age 23.95{+/-}6.4), while they were at rest. We first applied a Neural Mass Model to TMS-evoked potentials to disentangle the contribution of different GABAergic pools. We then assessed to which of these different pools MRS-GABA was related to by means of Parametric Empirical Bayesian (PEB) analysis. We found that MRS-GABA was mostly positively related to the NMM-derived measures of tonic inhibition and overall functionality of the GABAergic synapse. This relationship was reliable enough to predict MRS-GABA from NMM-GABA. These findings clarify the mesoscopic underpinnings of GABA levels measured by MRS and will contribute to the concretization of MRS-GABA promises to improve our understanding of human behaviour, brain physiology and pathophysiology. Key pointsO_LIGABA neurotransmission is essential for synaptic plasticity and learning (especially motor learning) and is altered in several brain disorders, such as epilepsy and stroke. C_LIO_LIQuantification of GABA in the human brain is typically obtained by Magnetic Resonance Spectroscopy (MRS). However, the interpretation of MRS-GABA is still debated. C_LIO_LIBy using a biophysical Neural Mass Model, here we show that MRS-GABA relates to physiological measures of tonic inhibition in the human cortex. C_LI

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bioRxiv2024

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.

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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.

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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

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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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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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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