Marjolaine Lafortune

Fast and slow spindle involvement in the consolidation of a new motor sequence

This study aimed to determine the distinct contribution of slow (11-13 Hz) and fast (13-15 Hz) spindles in the consolidation process of a motor sequence learning task (MSL). Young subjects (n = 12) were trained on both a finger MSL task and a control (CTRL) condition, which were administered one week apart in a counterbalanced order. Subjects were asked to practice the MSL or CTRL task in the evening (approximately 9:00 p.m.) and their performance was retested on the same task 12h later (approximately 9:00 a.m.). Polysomnographic (PSG) recordings were performed during the night following training on either task, and an automatic algorithm was used to detect fast and slow spindles and to quantify their characteristics (i.e., density, amplitude, and duration). Statistical analyses revealed higher fast (but not slow) spindle density after training on the MSL than after practice of the CTRL task. The increase in fast spindle density on the MSL task correlated positively with overnight performance gains on the MSL task and with difference in performance gain between the MSL and CTRL tasks. Together, these results suggest that fast sleep spindles help activate the cerebral network involved in overnight MSL consolidation, while slow spindles do not appear to play a role in this mnemonic process.

Topography of age-related changes in sleep spindles.

Aging induces multiple changes to sleep spindles, which may hinder their alleged functional role in memory and sleep protection mechanisms. Brain aging in specific cortical regions could affect the neural networks underlying spindle generation, yet the topography of these age-related changes is currently unknown. In the present study, we analyzed spindle characteristics in 114 healthy volunteers aged between 20 and 73 years over 5 anteroposterior electroencephalography scalp derivations. Spindle density, amplitude, and duration were higher in young subjects than in middle-aged and elderly subjects in all derivations, but the topography of age effects differed drastically. Age-related decline in density and amplitude was more prominent in anterior derivations, whereas duration showed a posterior prominence. Age groups did not differ in all-night spindle frequency for any derivation. These results show that age-related changes in sleep spindles follow distinct topographical patterns that are specific to each spindle characteristic. This topographical specificity may provide a useful biomarker to localize age-sensitive changes in underlying neural systems during normal and pathological aging.

Sleep slow wave changes during the middle years of life

Slow waves (SW; < 4 Hz and > 75 μV) during non‐rapid eye movement (NREM) sleep in humans are characterized by hyperpolarization [surface electroencephalogram (EEG) SW negative phase], during which cortical neurons are silent, and depolarization (surface EEG positive phase), during which the cortical neurons fire intensively. We assessed the effects of age, sex and topography on the dynamics of SW characteristics in a large population (n = 87) of healthy young (23.3 ± 2.4 years) and middle‐aged (51.9 ± 4.6 years) volunteers. Older subjects showed lower SW density and amplitude than young subjects. Age‐related lower SW density in men was especially marked in prefrontal/frontal brain areas, where they originate more frequently. Older subjects also showed longer SW positive and negative phase durations. These last results indicate that, in young subjects, cortical neurons would synchronously enter the SW hyperpolarization and depolarization phases, whereas this process would take longer in older subjects, leading to lower slope and longer SW positive and negative phases. Importantly, after controlling for SW amplitude, middle‐aged subjects still showed lower slope than young subjects in prefrontal, frontal, parietal and occipital derivations. Age‐related effects on SW density, frequency and positive phase duration were more prominent at the beginning of the night, when homeostatic sleep pressure is at its highest. Age‐related SW changes may be associated with changes in synaptic density and white matter integrity and may underlie greater sleep fragmentation and difficulty in recuperating and maintaining sleep under challenges in older subjects.

NREM Sleep Oscillations and Brain Plasticity in Aging.

The human electroencephalogram (EEG) during non-rapid eye movement sleep (NREM) is characterized mainly by high-amplitude (>75 μV), slow-frequency (<4 Hz) waves (slow waves), and sleep spindles (∼11–15 Hz; >0.25 s). These NREM oscillations play a crucial role in brain plasticity, and importantly, NREM sleep oscillations change considerably with aging. This review discusses the association between NREM sleep oscillations and cerebral plasticity as well as the functional impact of age-related changes on NREM sleep oscillations. We propose that age-related reduction in sleep-dependent memory consolidation may be due in part to changes in NREM sleep oscillations.

Sleep spindles and rapid eye movement sleep as predictors of next morning cognitive performance in healthy middle-aged and older participants.

Spindles and slow waves are hallmarks of non‐rapid eye movement sleep. Both these oscillations are markers of neuronal plasticity, and play a role in memory and cognition. Normal ageing is associated with spindle and slow wave decline and cognitive changes. The present study aimed to assess whether spindle and slow wave characteristics during a baseline night predict cognitive performance in healthy older adults the next morning. Specifically, we examined performance on tasks measuring selective and sustained visual attention, declarative verbal memory, working memory and verbal fluency. Fifty‐eight healthy middle‐aged and older adults (aged 50–91 years) without sleep disorders underwent baseline polysomnographic sleep recording followed by neuropsychological assessment the next morning. Spindles and slow waves were detected automatically on artefact‐free non‐rapid eye movement sleep electroencephalogram. All‐night stage N2 spindle density (no./min) and mean frequency (Hz) and all‐night non‐rapid eye movement sleep slow wave density (no./min) and mean slope (μV/s) were analysed. Pearsons correlations were performed between spindles, slow waves, polysomnography and cognitive performance. Higher spindle density predicted better performance on verbal learning, visual attention and verbal fluency, whereas spindle frequency and slow wave density or slope predicted fewer cognitive performance variables. In addition, rapid eye movement sleep duration was associated with better verbal learning potential. These results suggest that spindle density is a marker of cognitive functioning in older adults and may reflect neuroanatomic integrity. Rapid eye movement sleep may be a marker of age‐related changes in acetylcholine transmission, which plays a role in new information encoding.

Sleep spindles in Parkinson's disease may predict the development of dementia

Sleep disturbances and cognitive impairment are common non-motor manifestations of Parkinsons disease (PD). Recent studies suggest that sleep spindles and slow waves play a role in brain plasticity mechanisms and are associated with cognitive performance. However, it remains unknown whether these sleep parameters could serve as markers of cognitive decline in PD. Therefore, we examined whether alterations in sleep spindles and slow waves at baseline visit were associated with increased likelihood of developing dementia at follow-up in PD. Sixty-eight nondemented PD patients (64.9 ± 8.8 years old; 46 men) participated in the study, along with 47 healthy individuals (65.0 ± 10.6 years old; 30 men). All participants underwent baseline polysomnographic recording and a comprehensive neuropsychological assessment. Sleep spindles (12-15 Hz) and slow waves (>75 μV and <4 Hz) were automatically detected on all-night non-rapid eye movement sleep electroencephalography. At follow-up (mean: 4.5 years later), 18 PD patients developed dementia (70.2 ± 7.6 years old; 13 men) and 50 remained dementia-free (63.0 ± 8.5 years old; 33 men). Sleep spindle density and amplitude were lower in PD patients who converted to dementia compared with both patients who remained dementia-free and controls, mostly in posterior cortical regions (p < 0.05). Dementia-free PD patients were intermediate between dementia patients and controls, with lower baseline sleep spindle density in all cortical areas compared with controls (p < 0.01). In demented PD patients, lower sleep spindle amplitude in parietal and occipital areas was associated with poorer visuospatial abilities. Although slow wave amplitude was lower in PD patients compared with controls (p < 0.0001), no difference was observed between those who developed or did not develop dementia. Results demonstrate non-rapid eye movement sleep electroencephalographic abnormalities in PD patients. Sleep spindle activity was particularly impaired in PD patients who developed dementia, with a more posterior topographic pattern. Sleep spindle alterations are associated with later development of dementia in PD, and thus may serve as an additional marker of cognitive decline in these patients.

Cortical Thinning Explains Changes in Sleep Slow Waves during Adulthood

Sleep slow waves (SWs) change considerably throughout normal aging. In humans, SWs are generated and propagate on a structural backbone of highly interconnected cortical regions that form most of the default mode network, such as the insula, cingulate cortices, temporal lobe, parietal lobe, and medial frontal lobe. Regions in this network undergo cortical thinning and breakdown in structural and functional connectivity over the course of normal aging. In this study, we investigated how changes in cortical thickness (CT), a measure of gray matter integrity, are involved in modifications of sleep SWs during adulthood in humans. Thirty young (mean age = 23.49 years; SD = 2.79) and 33 older (mean age = 60.35 years; SD = 5.71) healthy subjects underwent a nocturnal polysomnography and T1 MRI. We show that, when controlling for age, higher SW density (nb/min of nonrapid eye movement sleep) was associated with higher CT in cortical regions involved in SW generation surrounding the lateral fissure (insula, superior temporal, parietal, middle frontal), whereas higher SW amplitude was associated with higher CT in middle frontal, medial prefrontal, and medial posterior regions. Mediation analyses demonstrated that thinning in a network of cortical regions involved in SW generation and propagation, but also in cognitive functions, explained the age-related decrease in SW density and amplitude. Altogether, our results suggest that microstructural degradation of specific cortical regions compromise SW generation and propagation in older subjects, critically contributing to age-related changes in SW oscillations.

Reduced Slow-Wave Rebound during Daytime Recovery Sleep in Middle-Aged Subjects

Cortical synchronization during NREM sleep, characterized by electroencephalographic slow waves (SW <4Hz and >75 µV), is strongly related to the number of hours of wakefulness prior to sleep and to the quality of the waking experience. Whether a similar increase in wakefulness length leads to a comparable enhancement in NREM sleep cortical synchronization in young and older subjects is still a matter of debate in the literature. Here we evaluated the impact of 25-hours of wakefulness on SW during a daytime recovery sleep episode in 29 young (27y ±5), and 34 middle-aged (51y ±5) subjects. We also assessed whether age-related changes in NREM sleep cortical synchronization predicts the ability to maintain sleep during daytime recovery sleep. Compared to baseline sleep, sleep efficiency was lower during daytime recovery sleep in both age-groups but the effect was more prominent in the middle-aged than in the young subjects. In both age groups, SW density, amplitude, and slope increased whereas SW positive and negative phase duration decreased during daytime recovery sleep compared to baseline sleep, particularly in anterior brain areas. Importantly, compared to young subjects, middle-aged participants showed lower SW density rebound and SW positive phase duration enhancement after sleep deprivation during daytime recovery sleep. Furthermore, middle-aged subjects showed lower SW amplitude and slope enhancements after sleep deprivation than young subjects in frontal and prefrontal derivations only. None of the SW characteristics at baseline were associated with daytime recovery sleep efficiency. Our results support the notion that anterior brain areas elicit and may necessitate more intense recovery and that aging reduces enhancement of cortical synchronization after sleep loss, particularly in these areas. Age-related changes in the quality of wake experience may underlie age-related reduction in markers of cortical synchronization enhancement after sustained wakefulness.

Non-rapid eye movement sleep characteristics in idiopathic REM sleep behavior disorder

This study investigated slow waves (SW; >75μV and <4Hz) characteristics in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). Thirty patients with iRBD and 30 age- and sex-matched healthy subjects underwent one polysomnographic (PSG) nocturnal sleep recording. SW automatic detection was performed on F3, C3, P3, and O1 leads and SW characteristics were derived (SW density, amplitude, frequency, slope, and duration of negative and positive phases). We also compared iRBD patients and control subjects on PSG variables and delta (0.25-4.0Hz) spectral power. No between-group differences were found on PSG variables, delta spectral power, or SW characteristics. Results show no SW abnormalities in iRBD patients compared to healthy participants, which suggests similar level of synchronization of thalamo-cortical neurons during N-REM sleep.

Age-related changes in sleep spindles characteristics during daytime recovery following a 25-hour sleep deprivation.

Objectives: The mechanisms underlying sleep spindles (~11–15 Hz; >0.5 s) help to protect sleep. With age, it becomes increasingly difficult to maintain sleep at a challenging time (e.g., daytime), even after sleep loss. This study compared spindle characteristics during daytime recovery and nocturnal sleep in young and middle-aged adults. In addition, we explored whether spindles characteristics in baseline nocturnal sleep were associated with the ability to maintain sleep during daytime recovery periods in both age groups. Methods: Twenty-nine young (15 women and 14 men; 27.3 y ± 5.0) and 31 middle-aged (19 women and 13 men; 51.6 y ± 5.1) healthy subjects participated in a baseline nocturnal sleep and a daytime recovery sleep after 25 hours of sleep deprivation. Spindles were detected on artifact-free Non-rapid eye movement (NREM) sleep epochs. Spindle density (nb/min), amplitude (μV), frequency (Hz), and duration (s) were analyzed on parasagittal (linked-ears) derivations. Results: In young subjects, spindle frequency increased during daytime recovery sleep as compared to baseline nocturnal sleep in all derivations, whereas middle-aged subjects showed spindle frequency enhancement only in the prefrontal derivation. No other significant interaction between age group and sleep condition was observed. Spindle density for all derivations and centro-occipital spindle amplitude decreased whereas prefrontal spindle amplitude increased from baseline to daytime recovery sleep in both age groups. Finally, no significant correlation was found between spindle characteristics during baseline nocturnal sleep and the marked reduction in sleep efficiency during daytime recovery sleep in both young and middle-aged subjects. Conclusion: These results suggest that the interaction between homeostatic and circadian pressure modulates spindle frequency differently in aging. Spindle characteristics do not seem to be linked with the ability to maintain daytime recovery sleep.