Biology subjects

Carrier, J.

Publications and source records attributed to Carrier, J..

14 recordsLinked to original sources

bioRxiv2026

Sleep Spindle-Locked Targeted Memory Reactivation Enhances Declarative Memory Consolidation

Study ObjectivesSleep spindles are implicated in memory consolidation. Yet direct evidence linking spindle dynamics to declarative memory outcomes remains limited. We thus tested whether targeted memory reactivation (TMR) time-locked to sleep spindles enhances declarative memory, and whether the temporal organization of stimulated spindles-trains versus isolated events-is selectively associated with distinct memory outcomes. MethodsTwenty-eight healthy young adults learned image locations from two categories (animals, clothing) in a grid, each paired with a distinct auditory cue. During overnight NREM sleep, one cue was replayed time-locked to spindles detected in real-time using a closed-loop system (TMR condition); the other served as the non-reactivated control (No-TMR condition). Category-cue assignment was counterbalanced. Post-sleep recall, recognition accuracy, and movement time were assessed. ResultsRecall accuracy was significantly higher in the TMR than the No-TMR condition (93.96% vs. 90.61%, p = .024), whereas recognition accuracy (p = .139) and movement time (p = .651) did not differ. Stimulation intensity within spindle trains correlated with the TMR effect on recall (Spearman {rho} = .531, p = .004), whereas the proportion of isolated spindle stimulations correlated with the TMR effect on recognition ({rho} = .563, p = .002). Cross-associations were not significant. ConclusionsSpindle-locked TMR enhances recall-based declarative memory retention. The selective association between spindle temporal clustering and memory outcomes suggests that train-embedded and isolated spindles support different aspects of memory consolidation, highlighting spindle temporal context as a functionally relevant dimension of sleep-dependent memory processing.

neuroscience↗

bioRxiv2025

Slow Spindle Trains During Daytime Naps are Associated with Improved Declarative Memory Consolidation

Memory consolidation refers to the process by which newly encoded memories are strengthened and retained over time, and ample evidence indicates that sleep supports this process for both procedural and declarative memories. Although sleep spindles during non-rapid eye movement (NREM) sleep have been associated to consolidation, it remains unclear whether all spindle types contribute equally. Spindles vary in frequency and topography-slow spindles ([≤]12.5Hz) predominating over frontal regions, whereas fast spindles (>12.5Hz) peak parietally - and recent work suggests that procedural memory consolidation during overnight sleep is related to the temporal organization of spindles in trains (i.e., events occurring <6s apart). Here we investigated whether a similar mechanism operates for declarative memory during daytime naps. Participants were assigned to a Nap (N=23) or No-Nap (N=15) group, and completed an object-spatial location task involving 36 item-location associations. Memory was assessed immediately after learning and again following a 90-minute nap or an equivalent wake period. Results showed that the Nap group exhibited significantly better delayed memory, as measured by combined recall-recognition score, and a greater proportion of participants maintained or improved their performance. In the Nap group, memory performance correlated with local spindle density at frontal and parietal sites, and, critically, with the proportion of slow spindles clustered in trains during NREM2. These findings suggest the temporal organization of slow spindles into clusters support declarative memory consolidation, pointing to a shared spindle-based mechanism across domains.

neuroscience↗

bioRxiv2025

Telomerase mRNA Reduces Radiation-induced DNA Damage of human skin

Over four million people undergo radiation therapy annually in the United States. Among these, more than 90% experience varying degrees of radiation-induced skin injury. Despite the enormity of the problem, there is currently no FDA-approved agent to prevent or treat skin damage caused by ionizing radiation. In the current study, ionizing radiation induced dose-dependent genomic and mitochondrial DNA damage, leading to apoptosis in primary cutaneous cells. Prior treatment with mRNA encoding telomerase reverse transcriptase (TERT) substantially reduced radiation-induced DNA damage in human primary skin cells and tissues. Mechanistically, TERT mRNA pretreatment enhances DNA repair, reduces mitochondrial ROS, and decreases apoptosis without extending telomere length during the experimental period, suggesting a non-canonical function of TERT to accelerate the cellular recovery from radiation. These findings highlight a potential therapeutic approach for preventing radiation-induced skin injury. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=197 HEIGHT=200 SRC="FIGDIR/small/636031v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@5bcee4org.highwire.dtl.DTLVardef@16c0c28org.highwire.dtl.DTLVardef@922c5dorg.highwire.dtl.DTLVardef@9eafd0_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

Rhythms and Background (RnB): The Spectroscopy of Sleep Recordings

Non-rapid eye movement (NREM) sleep is characterized by the interaction of multiple coupled oscillations essential for various functions such as memory consolidation, alongside a pervasive and dynamic arrhythmic 1/f scale-free background that may also contribute to these functions. Although recent spectral parametrization methods such as FOOOF (Fitting-One-and-Over-f) allowed to dissociate rhythmic and arrhythmic components in the spectral domain, they fail to resolve these processes in the time domain, where instantaneous measures of frequency, amplitude, and phase-amplitude coupling are still confounded by arrhythmic activity. This limitation represents a significant pitfall for studies of NREM sleep, which often rely on phase-based analyses of specific oscillations. To address this limitation, we introduce Rhythms & Background (RnB), a novel wavelet-based methodology designed to dynamically denoise time-series data by correcting for arrhythmic interference. This enables the extraction of a purely rhythmic time-series suitable for enhanced time-domain analyses of sleep rhythms. We first validate RnB through simulations, demonstrating its robust performance in accurately estimating spectral profiles of individual and multiple oscillations across a range of arrhythmic conditions. We then apply RnB to publicly available intracranial EEG sleep recordings, showing that it provides an improved spectral and time-domain representation of hallmark NREM rhythms. Finally, we demonstrate that RnB significantly enhances the assessment of phase-amplitude coupling between cardinal NREM oscillations, outperforming traditional methods that conflate rhythmic and arrhythmic components. This methodological advance offers a substantial improvement in the analysis of sleep oscillations, providing greater precision in the study of rhythmic activity critical to NREM sleep functions. SIGNIFICANCE STATEMENTThe Rhythms and Background (RnB) algorithm introduces a novel approach to signal processing in electrophysiology by isolating rhythmic activity from the arrhythmic background at the time-series level. Unlike existing spectral decomposition methods, RnB enables more precise analysis of brain rhythms in both the time and spectral domains, providing clearer insights into cerebral oscillatory processes. This breakthrough has direct applications in studying brain connectivity and oscillation dynamics during sleep. Additionally, its application in clinical populations where pathological changes in arrhythmic activity are common, such as neurodevelopmental and neurodegenerative disorders, will help to better understand abnormal oscillatory processes. By improving the accuracy of rhythmic signal analysis, RnB opens new avenues for understanding brain function and dysfunction in research and clinical settings.

neuroscience↗

bioRxiv2024

Caffeine induces age-dependent increases in brain complexity and criticality during sleep

Caffeine is the most widely consumed psychoactive stimulant worldwide. Yet important gaps persist in understanding its effects on the brain, especially during sleep. We analyzed sleep electroen-cephalography (EEG) in 40 subjects, contrasting 200mg of caffeine against a placebo condition, utilizing inferential statistics and machine learning. We found that caffeine ingestion led to an increase in brain complexity, a widespread flattening of the power spectrums 1/f-like slope, and a reduction in long-range temporal correlations. Being most prominent during non-rapid eye movement (NREM) sleep, these results suggest that caffeine shifts the brain towards a critical regime and more diverse neural dynamics. Interestingly, this was more pronounced in younger adults (20-27 years) compared to middle-aged participants (41-58 years) during rapid eye movement (REM) sleep, while no significant age effects were observed during NREM. Interpreting these data in the light of modeling and empirical work on EEG-derived measures of excitation-inhibition balance suggests that caffeine promotes a shift in brain dynamics towards increased neural excitation and closer proximity to a critical regime, particularly during NREM sleep.

neuroscience↗

bioRxiv2024

Neurophysiological Correlates of Phase-Specific Enhancement of Motor Memory Consolidation via Slow-Wave Closed-Loop Targeted Memory Reactivation

Memory consolidation can be enhanced during sleep using targeted memory reactivation (TMR) and closed-loop (CL) acoustic stimulation on the up-phase of slow oscillations (SOs). Here, we tested whether applying TMR at specific phases of the SOs (up vs. down vs. no reactivation) could influence the behavioral and neural correlates of motor memory consolidation in healthy young adults. Results showed that up- (as compared to down-) state cueing resulted in greater performance improvement. Sleep electrophysiological data indicated that up-stimulated SOs exhibited higher amplitude and greater peak-nested sigma power. Task-related functional magnetic resonance images revealed that up-state cueing strengthened activity in - and segregation of - striato-motor and hippocampal networks; and that these modulations were related to the beneficial effect of TMR on sleep features and performance. Overall, these findings highlight the potential of CL-TMR to induce phase-specific modulations of motor performance, sleep oscillations and brain responses during motor memory consolidation.

neuroscience↗

bioRxiv2023

Sleep spindle density and temporal clustering are associated with sleep-dependent memory consolidation in Parkinson's disease

Sleep is required for successful memory consolidation. Sleep spindles, bursts of oscillatory activity occurring during non-REM sleep, are known to be crucial for this process and, recently, it has been proposed that the temporal organization of spindles into clusters might additionally play a role in memory consolidation. In Parkinsons disease, spindle activity is reduced, and this reduction has been found to be predictive of cognitive decline. However, it remains unknown whether alterations in sleep spindles in Parkinsons disease are predictive of sleep-dependent cognitive processes like memory consolidation, leaving open questions about the possible mechanisms linking sleep and more general cognitive state in Parkinsons patients. The current study sought to fill this gap by recording overnight polysomnography and measuring overnight declarative memory consolidation in a sample of thirty-five Parkinsons patients. Memory consolidation was measured using a verbal paired-associates task administered before and after the night of recorded sleep. We found that lower sleep spindle density at frontal leads during non-REM stage 3 was associated with worse overnight declarative memory consolidation. We also found that patients who showed less temporal clustering of spindles exhibited worse declarative memory consolidation. These results suggest alterations to sleep spindles, which are known to be a consequence of Parkinsons disease, might represent a mechanism by which poor sleep leads to worse cognitive function in Parkinsons patients. Statement of significanceSleep -- particularly spindle activity -- is critical for memory consolidation, a core cognitive process. Changes to the architecture and oscillations of sleep are well documented in Parkinsons disease (PD) and have been associated with worse overall cognition. However, whether altered sleep plays a causal role in this relationship, by directly interfering with sleep-dependent cognitive processes, or whether it represents a mere epiphenomenon of advancing disease, remains unknown. Our study is the first to investigate a possible direct relationship between sleep and cognition in PD. We show that sleep spindles and their temporal clustering into trains relate to impairments in overnight declarative memory consolidation in patients. These findings are an important first step towards identifying modifiable sources of cognitive impairment in PD.

neuroscience↗

bioRxiv2022

Clustering and temporal organization of sleep spindles underlie motor memory consolidation

Sleep benefits motor memory consolidation, which is mediated by sleep spindle activity and associated memory reactivations during non-rapid eye movement (NREM) sleep. However, the particular role of NREM2 and NREM3 sleep spindles and the mechanisms triggering this memory consolidation process remain controversial. Here, simultaneous electroencephalographic and functional magnetic resonance imaging (EEG-fMRI) recordings were collected during night-time sleep following the learning of a motor sequence task. Adopting a time-based clustering approach, we provide evidence that spindles iteratively occur within clustered and temporally organized patterns during both NREM2 and NREM3 sleep. However, the clustering of spindles in trains is related to motor memory consolidation during NREM2 sleep only. Altogether, our findings suggest that spindles clustering and rhythmic occurrence during NREM2 sleep may serve as an intrinsic rhythmic sleep mechanism for the timed reactivation and subsequent consolidation of motor memories, through synchronized oscillatory activity within a subcortical-cortical network involved during learning.

neuroscience↗

bioRxiv2022

Electrophysiological signatures of targeted memory reactivation during sleep are not accompanied by motor performance improvements in older adults

Targeted memory reactivation (TMR) during sleep enhances memory consolidation in young adults by modulating electrophysiological markers of neuroplasticity. Interestingly, older adults exhibit deficits in motor memory consolidation, an impairment that has been linked to age-related degradations in the same sleep features sensitive to TMR. We hypothesized that TMR would enhance consolidation in older adults via the modulation of these markers. Seventeen older participants were trained on a motor task involving two auditory-cued sequences. During a post-learning nap, two auditory cues were played: one associated to a learned (i.e., reactivated) sequence and one control. Performance during two delayed retests did not differ between reactivated and non-reactivated sequences. Moreover, both associated and control sounds modulated brain responses, yet there were no consistent differences between the auditory cue types. Our results collectively demonstrate that older adults do not benefit from specific reactivation of a motor memory trace by an associated auditory cue during post-learning sleep. It is possible, however, that auditory stimulation during post-learning sleep boosts motor memory consolidation in a non-specific manner.

neuroscience↗

bioRxiv2022

The length of the thalamo-cortical white matter fibers brings insight into sex differences in sleep spindle frequency

Sleep spindles (SS) are crucial to brain functions like memory and learning. SS characteristics result from the propagation of nerve impulses along white matter (WM) projections underlying an intricate loop between the thalamus and the cortex. SS amplitude and density have been associated with WM diffusion microarchitecture but physiological mechanisms underlying individual and sex-related variations in SS frequency are unknown. Here, we tested a model of traveling signals along the thalamo-cortico-thalamic projections to explain individual differences in spindle frequency. We predicted the presence of a relationship between the length of the thalamo-cortical WM bundles and a specific characteristic of this functional network, SS frequency. Thirty young participants underwent a polysomnographic recording and a 3T MRI including a diffusion sequence. The length of WM fiber bundles between the thalamus and the frontal cortex was derived from probabilistic tractography computed through constrained spherical deconvolution. Longer WM fiber bundles between the thalamus and specific regions of the frontal cortex (rostral middle frontal gyrus and anterior and middle part of the superior frontal gyrus) were associated with slower SS frequency. Moreover, the length of these WM fiber bundles statistically mediated the sex-related differences in SS frequency. By providing a neuroanatomical marker of individual and sex-related differences in SS frequency, this study is the first to highlight the association between the anatomy of a specific brain network and a specific functional characteristic of this network, the frequency of oscillations produced during sleep.

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↗

bioRxiv2021

Sigma Oscillations Protect or Reinstate Motor Memory Depending on their Temporal Coordination with Slow Waves

Targeted memory reactivation (TMR) during post-learning sleep is known to enhance motor memory consolidation but the underlying neurophysiological processes remain unclear. Here, we confirm the beneficial effect of auditory TMR on motor performance. At the neural level, TMR enhanced slow wave (SW) characteristics. Additionally, greater TMR-related phase-amplitude coupling between slow (0.5-2 Hz) and sigma (12-16 Hz) oscillations after the SW peak was related to higher TMR effect on performance. Importantly, sounds that were not associated to learning strengthened SW-sigma coupling at the SW trough and the increase in sigma power nested in the trough of the potential evoked by these unassociated sounds was related to the TMR benefit. Altogether, our data suggest that, depending on their precise temporal coordination during post learning sleep, slow and sigma oscillations play a crucial role in either memory reinstatement or protection against irrelevant information; two processes that critically contribute to motor memory consolidation.

neuroscience↗

bioRxiv2021

Sleeping at the Switch

Sleep slow waves are studied for their role in brain plasticity, homeostatic regulation and their changes during aging. Here, we address the possibility that two types of slow waves co-exist in humans. Thirty young and 29 older adults underwent a night of polysomnographic recordings. Using the Transition frequency, slow waves with a slow transition (slow switchers) and with a fast transition (fast switchers) were discovered. Slow switchers had a high EEG connectivity along their depolarization transition while fast switchers had a lower connectivity dynamic and dissipated faster during the night. Aging was associated with lower temporal dissipation of sleep pressure in slow and fast switchers and lower EEG connectivity at the microscale of the oscillations, suggesting a decreased flexibility in the connectivity network of older individuals. Our findings show that two different types of slow waves with possible distinct underlying functions, coexist in the slow wave spectrum.

neuroscience↗

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.

neuroscience↗