Sleep and memory consolidation in aging: A neuroimaging perspective

Hamel, A.; Mary, A.; Rauchs, G.

doi:10.1016/j.neurol.2023.08.003

Cited by 2 publications

(1 citation statement)

References 80 publications

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“…Sleep is a fundamental physiological process that plays a pivotal role in various aspects of neurodevelopment and overall well-being [ 2 , 39 – 41 ]. It is during sleep that critical functions such as memory consolidation [ 42 – 44 ], neural plasticity [ 45 – 47 ], and emotional regulation [ 40 , 48 – 51 ] take place. Individuals with Dup15q syndrome experience disrupted sleep, characterized by abnormal NREM sleep [ 10 ] and elevated beta oscillations [ 10 , 12 , 13 ].…”

Section: Discussionmentioning

confidence: 99%

Sleep EEG signatures in mouse models of 15q11.2-13.1 duplication (Dup15q) syndrome

Saravanapandian,

Madani,

Nichols

et al. 2024

J Neurodevelop Disord

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Background Sleep disturbances are a prevalent and complex comorbidity in neurodevelopmental disorders (NDDs). Dup15q syndrome (duplications of 15q11.2-13.1) is a genetic disorder highly penetrant for NDDs such as autism and intellectual disability and it is frequently accompanied by significant disruptions in sleep patterns. The 15q critical region harbors genes crucial for brain development, notably UBE3A and a cluster of gamma-aminobutyric acid type A receptor (GABAAR) genes. We previously described an electrophysiological biomarker of the syndrome, marked by heightened beta oscillations (12-30 Hz) in individuals with Dup15q syndrome, akin to electroencephalogram (EEG) alterations induced by allosteric modulation of GABAARs. Those with Dup15q syndrome exhibited increased beta oscillations during the awake resting state and during sleep, and they showed profoundly abnormal NREM sleep. This study aims to assess the translational validity of these EEG signatures and to delve into their neurobiological underpinnings by quantifying sleep physiology in chromosome-engineered mice with maternal (matDp/ + mice) or paternal (patDp/ + mice) inheritance of the full 15q11.2-13.1-equivalent duplication, and mice with duplication of just the UBE3A gene (Ube3a overexpression mice; Ube3a OE mice) and comparing the sleep metrics with their respective wildtype (WT) littermate controls. Methods We collected 48-h EEG/EMG recordings from 35 (23 male, 12 female) 12–24-week-old matDp/ + , patDp/ + , Ube3a OE mice, and their WT littermate controls. We quantified baseline sleep, sleep fragmentation, spectral power dynamics during sleep states, and recovery following sleep deprivation. Within each group, distinctions between Dup15q mutant mice and WT littermate controls were evaluated using analysis of variance (ANOVA) and student’s t-test. The impact of genotype and time was discerned through repeated measures ANOVA, and significance was established at p < 0.05. Results Our study revealed that across brain states, matDp/ + mice mirrored the elevated beta oscillation phenotype observed in clinical EEGs from individuals with Dup15q syndrome. Time to sleep onset after light onset was significantly reduced in matDp/ + and Ube3a OE mice. However, NREM sleep between Dup15q mutant and WT littermate mice remained unaltered, suggesting a divergence from the clinical presentation in humans. Additionally, while increased beta oscillations persisted in matDp/ + mice after 6-h of sleep deprivation, recovery NREM sleep remained unaltered in all groups, thus suggesting that these mice exhibit resilience in the fundamental processes governing sleep-wake regulation. Conclusions Quantification of mechanistic and translatable EEG biomarkers is essential for advancing our understanding of NDDs and their underlying pathophysiology. Our study of sleep physiology in the Dup15q mice underscores that the beta EEG biomarker has strong translational validity, thus opening the door for pre-clinical studies of putative drug targets, using the biomarker as a translational measure of drug-target engagement. The unaltered NREM sleep may be due to inherent differences in neurobiology between mice and humans. These nuanced distinctions highlight the complexity of sleep disruptions in Dup15q syndrome and emphasize the need for a comprehensive understanding that encompasses both shared and distinct features between murine models and clinical populations.

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Section: Discussionmentioning

confidence: 99%

Sleep EEG signatures in mouse models of 15q11.2-13.1 duplication (Dup15q) syndrome

Saravanapandian,

Madani,

Nichols

et al. 2024

J Neurodevelop Disord

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Resting-state functional connectivity and fast spindle temporal organization contribute to episodic memory consolidation in healthy aging

Hamel,

Champetier,

Rehel

et al. 2024

Preprint

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Episodic memory consolidation relies on the functional specialization of brain networks and sleep quality, both of which are affected by aging. Functional connectivity during wakefulness is crucial to support the integration of newly acquired information into memory networks. Additionally, the temporal dynamics of sleep spindles facilitates overnight memory consolidation by promoting hippocampal replay and integration of memories within neocortical structures. This study aimed at exploring how resting-state functional connectivity during wakefulness contributes to sleep-dependent memory consolidation in aging, and whether spindles clustered in trains modulates this relationship.Forty-two healthy older adults (68.82 ± 3.03 years), enrolled in the Age-Well clinical trial, were included. Sleep-dependent memory consolidation was assessed using a visuo-spatial memory task performed before and after a polysomnography night. Resting-state functional connectivity data were analyzed using graph theory applied to the whole brain, specific brain networks and the hippocampus.Lower limbic network integration and higher centrality of the anterior hippocampus were associated with better memory consolidation. Spindle trains modulated these effects, such that older participants with longer spindle trains exhibited a stronger negative association between limbic network integration and memory consolidation.These results indicate that lower functional specialization at rest is associated with weaker memory consolidation during sleep. This aligns with the dedifferentiation hypothesis, which posits that aging is associated with reduced brain specificity, leading to less efficient cognitive functioning. These findings reveal a novel mechanism linking daytime brain network organization and sleep-dependent memory consolidation, and suggest that targeting spindle dynamics could help preserve cognitive functioning in aging.

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Sleep and memory consolidation in aging: A neuroimaging perspective

Cited by 2 publications

References 80 publications

Sleep EEG signatures in mouse models of 15q11.2-13.1 duplication (Dup15q) syndrome

Sleep EEG signatures in mouse models of 15q11.2-13.1 duplication (Dup15q) syndrome

Resting-state functional connectivity and fast spindle temporal organization contribute to episodic memory consolidation in healthy aging

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