Topographic distribution of sleep spindles in young healthy subjects

The application of an automatic sleep spindle detection procedure allowed the documentation of the topographic distribution of spindle characteristics, such as number, amplitude, frequency and duration, as a function of sleep depth and of recording time. Multichannel all-night EEG recordings were performed in 10 normal healthy subjects aged 20–35 years. Although the interindividual variability in the number of sleep spindles was very high (2.7±2.1 spindles per minute stage 2 sleep), all but two subjects showed maximal spindle activity in centro-parietal midline leads. Moreover, this topography was seen in all sleep stages and changed only slightly – to a more central distribution – towards the end of the night. On the other hand, slow (11.5–14 Hz) and fast (14–16 Hz) spindles showed a completely different topography, with slow spindles distributed anteriorly and fast spindles centro-parietally. The number of sleep spindles per min was significant depending on sleep stages, with the expected highest occurrence in stage 2, and on recording time, with a decrease in spindle density from the beginning towards the end of the night. However, spindle amplitude, frequency and individual duration was not influenced by sleep depth or time of the night.     

Cortical activation patterns herald successful dream recall after NREM and REM sleep

Dreaming pertains to both REM and NREM sleep. However, frequency and regional specific differences in EEG activity remains controversial. We investigated NREM and REM sleep EEG power density associated with and without dream recall in 17 young subjects during a 40-h multiple nap protocol under constant routine conditions. NREM sleep was associated with lower EEG power density for dream recall in the delta range, particularly in frontal derivations, and in the spindle range in centro-parietal derivations. REM sleep was associated with low frontal alpha activity and with high alpha and beta activity in occipital derivations. Our data indicate that specific EEG frequency- and topography changes underlie differences between dream recall and no recall after both NREM and REM sleep awakening. This dual NREM-REM sleep modulation holds strong implications for the mechanistic understanding of this complex ongoing cognitive process.     

REM sleep behaviour disorder is associated with lower fast and higher slow sleep spindle densities

To investigate differences in sleep spindle properties and scalp topography between patients with rapid eye movement sleep behaviour disorder (RBD) and healthy controls, whole‐night polysomnograms of 35 patients diagnosed with RBD and 35 healthy control subjects matched for age and sex were compared. Recordings included a 19‐lead 10–20 electroencephalogram montage and standard electromyogram, electrooculogram, electrocardiogram and respiratory leads. Sleep spindles were automatically detected using a standard algorithm, and their characteristics (amplitude, duration, density, frequency and frequency slope) compared between groups. Topological analyses of group‐discriminative features were conducted. Sleep spindles occurred at a significantly (e.g. t₃₄ = ?4.49; P = 0.00008 for C3) lower density (spindles?min^?1) for RBD (mean ± SD: 1.61 ± 0.56 for C3) than for control (2.19 ± 0.61 for C3) participants. However, when distinguishing slow and fast spindles using thresholds individually adapted to the electroencephalogram spectrum of each participant, densities smaller (31–96%) for fast but larger (20–120%) for slow spindles were observed in RBD in all derivations. Maximal differences were in more posterior regions for slow spindles, but over the entire scalp for fast spindles. Results suggest that the density of sleep spindles is altered in patients with RBD and should therefore be investigated as a potential marker of future neurodegeneration in these patients.     

The space-time profiles of sleep spindles and their coordination with slow oscillations on the electrode manifold

Sleep spindles are important for sleep quality and cognitive functions, with their coordination with slow oscillations (SOs) potentially organizing cross-region reactivation of memory traces. Here, we describe the organization of spindles on the electrode manifold and their relation to SOs. We analyzed the sleep night EEG of 34 subjects and detected spindles and SOs separately at each electrode. We compared spindle properties (frequency, duration, and amplitude) in slow wave sleep (SWS) and Stage 2 sleep (S2); and in spindles that coordinate with SOs or are uncoupled. We identified different topographical spindle types using clustering analysis that grouped together spindles co-detected across electrodes within a short delay (±300 ms). We then analyzed the properties of spindles of each type, and coordination to SOs. We found that SWS spindles are shorter than S2 spindles, and spindles at frontal electrodes have higher frequencies in S2 compared to SWS. Furthermore, S2 spindles closely following an SO (about 10% of all spindles) show faster frequency, shorter duration, and larger amplitude than uncoupled ones. Clustering identified Global, Local, Posterior, Frontal-Right and Left spindle types. At centro-parietal locations, Posterior spindles show faster frequencies compared to other types. Furthermore, the infrequent SO-spindle complexes are preferentially recruiting Global SO waves coupled with fast Posterior spindles. Our results suggest a non-uniform participation of spindles to complexes, especially evident in S2. This suggests the possibility that different mechanisms could initiate an SO-spindle complex compared to SOs and spindles separately. This has implications for understanding the role of SOs-spindle complexes in memory reactivation.     

Genetic risk factors for schizophrenia associate with sleep spindle activity in healthy adolescents

Schizophrenia has been associated with disturbed sleep, even before the onset of the disorder, and also in non‐schizophrenic first‐order relatives. This may point to an underlying genetic influence. Here we examine whether weighted polygenic risk scores (PRS) for schizophrenia are associated with sleep spindle activity in healthy adolescents. Our sample comes from a community‐based cohort of 157 non‐schizophrenic adolescents (57% girls) having both genetic data and an overnight sleep EEG measurement available. Based on a recent genome‐wide association study, we calculated PRS for schizophrenia across the whole genome. We also calculated PRS for the CACNA1l gene region, which has been associated with both schizophrenia and sleep spindle formation. We performed an overnight sleep EEG at the homes of the participants. Stage two sleep spindles were detected using an automated algorithm. Sleep spindle amplitude, duration, intensity and density were measured separately for central and frontal derivations and for fast (13–16 Hz) and slow (10–13 Hz) spindles. PRS for schizophrenia was associated with higher fast spindle amplitude (p = 0.04), density (p = 0.006) and intensity (p = 0.04) at the central derivation, and PRS in the CACNA1l region associated with higher slow spindle amplitude (p = 0.01), duration (p = 0.03) and intensity (p = 0.002) at the central derivation. A positive association between genetic variants for schizophrenia and sleep spindle activity among healthy adolescents supports a view that sleep spindles and schizophrenia share similar genetic pathways. This study suggests that altered sleep spindle activity might serve as an endophenotype of schizophrenia.     

Effect of infant sleeping position on sleep spindles

Sleep spindles play an active role in inducing and maintaining sleep and may affect arousal by blocking the transmission of external stimuli through the thalamus to the cortex. Previously we have demonstrated that sleeping in the prone position impairs arousal in infants at 2-3 months of age, but not at 5-6 months. We aimed to examine if sleeping position and postnatal age affected duration and/or density of sleep spindles. Twenty-one healthy term infants were studied using daytime polysomnography at 2-3 months and 16 were again studied at 5-6 months. Infants slept both prone and supine at each study. The mean duration of non-rapid eye movement (NREM) sleep was not different between the two studies in either position. At 2-3 months both spindle density (P < 0.001) and proportion of NREM sleep (P < 0.025) with spindles were significantly greater in the supine than in the prone position. At 5-6 months spindle duration was longer in the supine than in the prone position (P < 0.03). Spindle density in the supine position was not different between the two studies, however, when infants slept prone, it was significantly increased at 5-6 months compared with 2-3 months (P < 0.001). Arousal threshold was not correlated with either spindle density or percentage of NREM sleep with spindles in either position at either study. In this study spindle density and the percentage time spent with spindles were not well correlated with infant arousability, and hence may not be able to be used as markers of depressed arousal responses in infants.     

Sleep spindle activity changes in patients with affective disorders

Various polysomnographic sleep patterns are associated with affective disorders, but very little is known about sleep spindle characteristics in adult depression. In primary endogenous depressive male patients (unipolar, UP, and bipolar, BP) with comparable depression scores and in normal control subjects recorded during 3 consecutive nights, no night effect was observed on the sleep variables investigated except for REM latencies of stages 1 and 2. Stage 2 duration and variables related to sleep spindle characteristics (the number and the density of spindles of 1/2 s; the number and the density of full spindles of stage 2 over the 3 nights) were significantly lower in depressed patients than in control subjects, the mean number of spindles being lower in UP than in BP patients. Sleep spindle measures were clearly negatively correlated with age in the overall group (i.e., depressed plus control subjects). They were also negatively correlated with the REM latencies of stages 1 and 2 in BP depressed patients, whereas this relation was not observed in UP patients.     

The association between sleep spindles and IQ in healthy school-age children

Recent studies have suggested that sleep is associated with IQ measures in children, but the underlying mechanism remains unknown. An association between sleep spindles and IQ has been found in adults, but only two previous studies have explored this topic in children. The goal of this study was to examine whether sleep spindle frequency, amplitude, duration and/or density were associated with performance on the perceptual reasoning, verbal comprehension, working memory, and processing speed subscales of the Wechsler Intelligence Scale for Children-IV (WISC-IV). We recruited 29 typically developing children 7–11 years of age. We used portable polysomnography to document sleep architecture in the natural home environment and evaluated IQ. We found that lower sleep spindle frequency was associated with better performance on the perceptual reasoning and working memory WISC-IV scales, but that sleep spindle amplitude, duration and density were not associated with performance on the IQ test.     

Sensory stimulation triggers spindles during sleep stage 2

STUDY OBJECTIVES: Toward understanding the function of sleep spindle, we examined whether sensory stimulation triggers sleep spindles. PARTICIPANTS: Eleven normal subjects participated in the experiments. INTERVENTION: The subjects had a nap in the afternoon, and sensory stimulation was applied during sleep stage 2. MEASUREMENTS: 21-channel EEG was recorded during the 2-3 hour experiment carried out between 13:00 and 16:00. Somatosensory, auditory, or visual stimulation was performed over a 5-minute period during stage 2. The frequency and duration of spindles were compared in 2 different segments of 5 minutes, with and without sensory stimulation. The latency from the onset of a sensory stimulus to the succeeding spindle was also analyzed. To estimate the active brain regions during a spindle, the EEG recordings were modeled with a single equivalent moving dipole (SEMD) model. RESULTS: In the period with stimulation, spindle frequency and duration increased compared with the period without stimulation. Statistical tests revealed that with stimulation, the interval between 2 consecutive spindles was significantly shorter (p < 0.05, regardless of the modality) and that the duration of the spindles was significantly longer with stimulation (p < 0.05, regardless of the modality). The latency was approximately 2 s. During a spindle after somatosensory stimulation brain activities were observed near the somatosensory area, while with auditory stimulation active regions were observed near the auditory cortex. CONCLUSIONS: A sensory stimulus appeared to trigger a sleep spindle during sleep stage 2. SEMD trajectories suggest that active brain regions during spindle are different according to the modality of the preceding stimulus.     

Age effects on spectral electroencephalogram activity prior to dream recall

Ageing is associated with marked changes in sleep timing, structure and electroencephalographic (EEG) activity. Older people exhibit less slow-wave and spindle activity during non-rapid eye movement (NREM) sleep, together with attenuated levels of rapid eye movement (REM) sleep as compared to young individuals. However, the extent to which these age-related changes in sleep impact on dream processing remains largely unknown. Here we investigated NREM and REM sleep EEG activity prior to dream recall and no recall in 17 young (20-31 years) and 15 older volunteers (57-74 years) during a 40 h multiple nap protocol. Dream recall was assessed immediately after each nap. During NREM sleep prior to dream recall, older participants displayed higher frontal EEG delta activity (1-3 Hz) and higher centro-parietal sigma activity (12-15 Hz) than the young volunteers. Conversely, before no recall, older participants had less frontal-central delta activity and less sigma activity in frontal, central and parietal derivations than the young participants. REM sleep was associated to age-related changes, such that older participants had less frontal-central alpha (10-12 Hz) and beta (16-19 Hz) activity, irrespective of dream recall and no recall. Our data indicate that age-related differences in dream recall seem to be directly coupled to specific frequency and topography EEG patterns, particularly during NREM sleep. Thus, the spectral correlates of dreaming can help to understand the cortical pathways of dreaming.     

Nicotine increases sleep spindle activity

Studies have shown that both nicotine and sleep spindles are associated with enhanced memorisation. Further, a few recent studies have shown how cholinergic input through nicotinic and muscarinic receptors can trigger or modulate sleep processes in general, and sleep spindles in particular. To better understand the interaction between nicotine and sleep spindles, we compared in a single blind randomised study the characteristics of sleep spindles in 10 healthy participants recorded for 2 nights, one with a nicotine patch and one with a sham patch. We investigated differences in sleep spindle duration, amplitude, intra‐spindle oscillation frequency and density (i.e. spindles per min). We found that under nicotine, spindles are more numerous (average increase: 0.057 spindles per min; 95% confidence interval: [0.025–0.089]; p = .0004), have higher amplitude (average amplification: 0.260 μV; confidence interval: [0.119–0.402]; p = .0032) and last longer (average lengthening: 0.025 s; confidence interval: [0.017–0.032]; p = 2.7e‐11). These results suggest that nicotine can increase spindle activity by acting on nicotinic acetylcholine receptors, and offer an attractive hypothesis for common mechanisms that may support memorisation improvements previously reported to be associated with nicotine and sleep spindles.     

Learning-dependent changes in sleep spindles and Stage 2 sleep

It has become increasingly clear that sleep is necessary for efficient memory consolidation. Recently, it has been found that Stage 2 sleep disruption impairs procedural memory performance, and that memory performance is correlated with the duration of Stage 2 sleep; but the mechanisms involved in synaptic plasticity for procedural memory during sleep have not been identified. The present study examined the learning-dependent changes in sleep, including Stage 2 sleep spindles. Following an intense period of simple motor procedural learning, the duration of Stage 2 sleep and spindle density increased. There were no changes observed in the duration of any other stage of sleep or in the density of rapid eye movements. These findings support the hypothesis that sleep spindles are involved in the off-line reprocessing of simple motor procedural memory during Stage 2 sleep.     

Age-related changes in the circadian modulation of sleep-spindle frequency during nap sleep

STUDY OBJECTIVES: Sleep spindles exhibit a clear circadian modulation in healthy younger people. During the biological night (when melatonin is secreted), spindle density and spindle amplitude are high and spindle frequency and its variability are low, as compared with the biological day. We investigated whether this circadian modulation of spindle characteristics changes with age. DESIGN: A 40-hour multiple-nap paradigm under constant-routine conditions SETTING: Chronobiology Laboratory, University Psychiatric Hospitals, Basel, Switzerland PARTICIPANTS: Seventeen younger (20-31 years) and 15 older (57-74 years) volunteers. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Whereas the circadian modulation of spindle density, amplitude, duration, and intraspindle frequency variability was not greatly affected by age, we found significant changes in the circadian modulation of spindle frequency. The pronounced circadian modulation of spindle frequency in younger, but not older, subjects was phase locked with the circadian rhythm in melatonin secretion. In the latter, circadian modulation was attenuated and tended to be advanced with respect to the timing of melatonin secretion. There was no difference between age groups in the phase of the sleep-wake cycle or that of melatonin, nor did the phase angle between them differ. Although changes in the circadian modulation of spindle frequency in older subjects were accompanied by reduced amplitude in the sleep consolidation profile, there was no significant correlation between spindle frequency and sleep consolidation. CONCLUSION: This multiple-nap protocol under constant-routine conditions revealed an age-dependent weaker coupling of the circadian rhythms of spindle frequency and sleep propensity to the circadian rhythm of melatonin secretion.     

The adolescent pattern of sleep spindle development revealed by HD-EEG

Sleep spindles are developmentally relevant cortical oscillatory patterns; however, they have mostly been studied by considering the entire spindle frequency range (11–15 Hz) without a distinction between the functionally and topographically different slow and fast spindles, using relatively few electrodes and analysing wide age-ranges. Here, we employ high-density night sleep electroencephalography in three age-groups between 12 and 20 years of age (30 females and 30 males) and analyse the adolescent developmental pattern of the four major parameters of slow and fast sleep spindles. Most of our findings corroborate those very few previous studies that also make a distinction between slow and fast spindles in their developmental analysis. We find spindle frequency increasing with age. A spindle density change is not obvious in our study. We confirm the declining tendencies for amplitude and duration, although within narrower, more specific age-windows than previously determined. Spindle frequency seems to be higher in females in the oldest age-group. Based on the pattern of our findings, we suggest that high-density electroencephalography, specifically targeting slow and fast spindle ranges and relatively narrow age-ranges would advance the understanding of both adolescent cortical maturation and development and the functional relevance of sleep spindles in general.     

Validating an automated sleep spindle detection algorithm using an individualized approach

The goal of the current investigation was to develop a systematic method to validate the accuracy of an automated method of sleep spindle detection that takes into consideration individual differences in spindle amplitude. The benchmarking approach used here could be employed more generally to validate automated spindle scoring from other detection algorithms. In a sample of Stage 2 sleep from 10 healthy young subjects, spindles were identified both manually and automatically. The minimum amplitude threshold used by the prana ^® (PhiTools, Strasbourg, France) software spindle detection algorithm to identify a spindle was subject‐specific and determined based upon each subject’s mean peak spindle amplitude. Overall sensitivity and specificity values were 98.96 and 88.49%, respectively, when compared to manual scoring. Selecting individual amplitude thresholds for spindle detection based on systematic benchmarking data may validate automated spindle detection methods and improve reproducibility of experimental results. Given that interindividual differences are accounted for, we feel that automatic spindle detection provides an accurate and efficient alternative approach for detecting sleep spindles.     

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. Pearson's 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.     

Investigation of sleep spindle activity and morphology as predictors of neurocognitive functioning in medicated patients with schizophrenia

Neurocognitive impairment is a trait marker of schizophrenia, but no effective treatment has yet been identified. Sleep spindle deficits have been associated with diminished sleep‐dependent memory learning. We examined whether this link could be extended into various cognitive domains by investigating the association of a neurocognitive test battery (the Brief Assessment of Cognition in Schizophrenia) with sleep spindle activity and morphology. We examined 37 outpatients diagnosed with schizophrenia and medicated with both antipsychotics and benzodiazepines. Participants underwent 1 night polysomnography and test of neurocognitive functioning. We identified and analysed sleep spindles in all non‐rapid eye movement sleep and in non‐rapid eye movement sleep stage 2 in a central electroencephalography channel using an automatic sleep spindle detector previously validated. Slow sleep spindle density was computed from a frontal electroencephalography channel as well. We found no association between cognitive functioning and sleep spindle density or sleep spindle morphology for spindles in non‐rapid eye movement sleep when controlling for gender, age, symptom severity, and daily dose of antipsychotics and benzodiazepines. For spindles in non‐rapid eye movement sleep stage 2, we found that motor speed was associated with frontal slow sleep spindle density. We conclude that frontal slow spindle density might predict motor speed in medicated patients with schizophrenia, but that no other sleep spindle activity or sleep spindle morphology measures were predictors of neurocognitive functioning.     

Automated measurement of alpha, beta, sigma, and theta burst characteristics.

An automatic system was used for the selection and analysis of alpha, beta, and theta waveforms occurring in the awake and REM sleep states and sleep spindles occurring in stage 2 sleep. Two nights of sleep were analyzed for each of five normal subjects in each of five age groups: 3--5; 13; 25--34; 43--53; and 67--79 years of age. The waveform frequencies, length, and rate of occurrence were measured. No age-related changes were found in the alpha frequency (except for the younger group). No significant age differences were found in the beta and theta frequencies in the awake state. During REM sleep, the average beta and theta frequencies of the two youngest groups were significantly different from those of the three older groups. The average frequency of stage 2 sleep spindles of the two youngest groups was less than that in the middle group; the average spindle frequency of this group was significantly less than that of the two older groups. The number of spindles per minute was significantly less for the younger group and significantly more for the 25- to 34-year-olds.     

Naps reliably estimate nocturnal sleep spindle density in health and schizophrenia

Sleep spindles, defining oscillations of non‐rapid eye movement stage 2 sleep (N2), mediate memory consolidation. Spindle density (spindles/minute) is a stable, heritable feature of the sleep electroencephalogram. In schizophrenia, reduced spindle density correlates with impaired sleep‐dependent memory consolidation and is a promising treatment target. Measuring sleep spindles is also important for basic studies of memory. However, overnight sleep studies are expensive, time consuming and require considerable infrastructure. Here we investigated whether afternoon naps can reliably and accurately estimate nocturnal spindle density in health and schizophrenia. Fourteen schizophrenia patients and eight healthy controls had polysomnography during two overnights and three afternoon naps. Although spindle density was lower during naps than nights, the two measures were highly correlated. For both groups, naps and nights provided highly reliable estimates of spindle density. We conclude that naps provide an accurate, reliable and more scalable alternative to measuring spindle density overnight.     

Spindles are highly heritable as identified by different spindle detectors

Study ObjectivesSleep spindles, a defining feature of stage N2 sleep, are maximal at central electrodes and are found in the frequency range of the electroencephalogram (EEG) (sigma 11–16 Hz) that is known to be heritable. However, relatively little is known about the heritability of spindles. Two recent studies investigating the heritability of spindles reported moderate heritability, but with conflicting results depending on scalp location and spindle type. The present study aimed to definitively assess the heritability of sleep spindle characteristics.MethodsWe utilized the polysomnography data of 58 monozygotic and 40 dizygotic same-sex twin pairs to identify heritable characteristics of spindles at C3/C4 in stage N2 sleep including density, duration, peak-to-peak amplitude, and oscillation frequency. We implemented and tested a variety of spindle detection algorithms and used two complementary methods of estimating trait heritability.ResultsWe found robust evidence to support strong heritability of spindles regardless of detector method (h² > 0.8). However not all spindle characteristics were equally heritable, and each spindle detection method produced a different pattern of results.ConclusionsThe sleep spindle in stage N2 sleep is highly heritable, but the heritability differs for individual spindle characteristics and depends on the spindle detector used for analysis.