Biology subjects

Bastin, C.

Publications and source records attributed to Bastin, C..

10 recordsLinked to original sources

bioRxiv2026

Cognitive Fitness in Ageing (COFITAGE): A Multimodal and Longitudinal Neuroimaging Dataset

Purpose: Brain aging involves interrelated changes in molecular processes, neuroinflammatory mechanisms, brain macro- and microstructure, sleep physiology, and cognition. The 50 to 70 years age range represents a critical transition period, in which these subtle alterations may precede measurable cognitive decline and the onset of clinical neurodegenerative disease. To allow systematic investigation of these early alterations and the subsequent progression in brain aging, we provide an open-access data resource from a multidisciplinary longitudinal study integrating neuroimaging, genetics, sleep, and neuropsychological phenotyping with assessments at baseline and at 2-year follow-up. Acquisition and Validation Methods: The baseline cohort comprises 101 community-dwelling participants (50-69 years old) who underwent magnetic resonance imaging (MRI) using a 3T protocol that included high-resolution structural imaging (T1- and T2-weighted), quantitative multi-parametric acquisitions with B1 mapping, and multi-shell diffusion-weighted imaging. Moreover, positron emission tomography (PET) imaging was performed using [18F]Flutemetamol or [18F]Florbetapir (amyloid-beta tracers) in all participants, with a subset also undergoing [18F]THK-5351 PET (tau-related/neuroinflammation). The dataset was complemented by extensive phenotypic data, including sleep and neuropsychological assessments, and by genotype data through genetic analysis. 66 participants underwent a 2-year cognitive follow-up, enabling longitudinal analyses of cognitive trajectories. Data acquisition and curation were performed using standardized procedures, with systematic quality control to support reliable cross-sectional and longitudinal analyses. Data Format and Usage Notes: All data are distributed in a BIDS-compliant format, and released in open-access (EBRAINS). Potential Applications: This dataset supports multimodal analyses, allowing the identification of interpretable patterns characterizing brain aging from multiple perspectives. It enables the comparison of different models to derive (semi)quantitative MRI parameters, the discovery of imaging biomarkers associated with early cognitive decline, and the monitoring or prediction of brain aging progression. In addition, it offers focused coverage of adults aged 50-70 years, which is often underrepresented in existing healthy subjects public datasets.

neuroscience↗

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.

neuroscience↗

bioRxiv2025

The crosstalk between the anterior hypothalamus and the locus coeruleus during wakefulness is associated with low frequency oscillations power during sleep

Study ObjectivesAnimal research has demonstrated that sleep regulation heavily depends on a network of subcortical nuclei. In particular, whether the crosstalk between the Locus Coeruleus (LC) and hypothalamic nuclei influences sleep variability and age-related changes in humans remains unexplored. This study investigated whether the effective connectivity between the LC and subparts of the hypothalamus is associated with the electrophysiology of rapid eye movement sleep (REMS). MethodsThirty-three healthy younger ([~]22y, 27 women) and 18 older ([~]61y, 14 women) individuals underwent 7-Tesla functional magnetic resonance imaging during wakefulness to investigate the effective connectivity between LC and distinct hypothalamus subparts encompassing several nuclei. Additionally, we recorded their sleep electroencephalogram (EEG) to explore relationships between effective connectivity measures and REMS theta energy and sigma power prior to REMS episodes. ResultsThe effective connectivity analysis revealed robust evidence of a mutual positive influence between the LC and the anterior-superior and posterior hypothalamus, supporting the idea that the connectivity patterns observed in animal models are also present in humans. Furthermore, our results suggest that in older adults, stronger effective connectivity from the anterior-superior hypothalamus, including the preoptic area, to the LC is associated with reduced REM theta energy. Specificity analysis showed that this association was not limited to REM theta energy but also extended to specific lower-frequency bands during REMS and NREMS. ConclusionsThese findings highlight the complex age-dependent modulation of the LC circuitry and its role in sleep regulation. Understanding these neural interactions offers valuable insight into the mechanisms driving age-related sleep changes.

neuroscience↗

bioRxiv2025

Diurnal dynamics of multilayer brain networks predict cognitive trajectories in aging

ObjectivesResting-state functional connectivity (rsFC) is a highly dynamic process that varies across different times of the day within each individual. Although this variability was long considered to be noise, recent evidence suggests it may allow for an optimal adaptation to changes in the environment. However, the way rsFC is shaped on a circadian scale and its association with cognition are still unclear. MethodsWe analyzed data from 90 late-middle-age participants from the Cognitive Fitness in Aging study (61 women; 50-69y). Participants completed five electroencephalographic (EEG) recordings of spontaneous resting-state activity spread over 20h of prolonged wakefulness. Using a temporal multilayer network approach, we characterized the diurnal variations of the dynamic recruitment and integration of resting-state brain networks. We focused on the theta and gamma frequency bands within the default mode network (DMN), central executive network (CEN), and salience network (SN). Additionally, we investigated the relationship recruitment and integration of these network with baseline cognitive performance and at 7-year longitudinal follow-up, as well as with positron emission tomography (PET) early neuropathological markers of Alzheimers disease such as {beta}-amyloid and tau/neuroinflammation. ResultsDiurnal changes in theta and gamma dynamics were associated with distinct cognitive aspects. Specifically, higher baseline memory performance was associated with higher theta dynamic integration of the SN and the CEN, as well as higher theta dynamic recruitment of the DMN. Moreover, lower longitudinal memory decline at 7-year was associated with higher theta dynamic integration of the SN, CEN, and DMN. In contrast, higher gamma diurnal dynamic integration of the SN and the CEN was associated with lower executive and attentional performance, as well as higher early {beta}-amyloid accumulation, at baseline. DiscussionThese findings suggest that maintaining a balance between network flexibility and stability throughout the diurnal phase of the circadian cycle may play a crucial role in cognitive aging, with stable theta-band connectivity supporting memory, whereas excessive gamma-band stability in the SN and CEN may contribute to executive decline and early amyloid accumulation. These insights highlight the importance of considering time-of-day in brain rsFC studies, calling for a temporal multilayer approach to capture these dynamic patterns more effectively.

neuroscience↗

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.

neuroscience↗

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.

neuroscience↗

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.

neuroscience↗

bioRxiv2022

Age-dependent attentional style and pupil-linked arousal regulate the reportability of spontaneous mental states

Spontaneous thinking significantly relies on attention and arousal. As these cognitive faculties change with age, we aimed at providing a comprehensive account to ongoing mental states in seniors, testing how these are influenced by attentional control and arousal. Using experience sampling at rest, 20 senior (65-75yrs) and 20 young participants (20-30yrs) were prompted to report mind-wandering (MW), sensory-related thoughts (S), and the newly introduced state of mind blanking (MB). Attentional control was assessed with the Attentional Style Questionnaire, and arousal with continuous monitoring of pupil diameter. Both age groups showed equally high occurrences of MW compared to MB or S. For young responders, we replicated that MW was more prevalent in easily-distracted participants and that it associated with higher arousal. In seniors, though, MB was more prevalent in easily-distracted participants, and it was associated with higher arousal, reversing the pattern found in young adults and focused seniors. Overall, our results show that attentional control and arousal jointly regulate ongoing mental states in an age-dependent manner and uncover the presence a specific profile of ongoing mental state regulation in healthy aging, being a potentially critical marker of age-associated diseases.

neuroscience↗

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.

neuroscience↗

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.

neuroscience↗