Sleep and neurocognitive functioning in children with eczema

Sleep disruption in childhood is associated with clearly defined deficits in neurocognition and behaviour. Childhood eczema is also a potent cause of sleep disruption though it is unknown whether it too results in neurocognitive deficits. To test this hypothesis, neurocognitive (WISC-IV), parental-reported sleep quality (Sleep Disturbance Scale of Children (SDSC)) and overnight polysomnographic (PSG) data were collected in 21 children with eczema and 20 healthy controls (age range 6–16 years). Children with eczema had worse sleep quality on both PSG (notably increased nocturnal wakefulness, a higher number of stage shifts and a longer latency to REM onset) and parental report. In addition, they demonstrated significant neurocognitive deficits (especially verbal comprehension, perceptual reasoning and to a lesser extent working memory) with a composite Full Scale IQ 16 points lower than controls. Parental reported sleep problems but not PSG parameters were correlated with reduced neurocognitive performance. However, hierarchical regression analyses revealed that eczema status was predictive while sleep fragmentation (parental or PSG) was not predictive of neurocognitive performance. As this is the first study to systematically examine neurocognitive functioning in children with eczema and given the finding of significant deficits it merits replication especially given the prevalence of the condition. The unanswered question is whether these cognitive deficits normalise with effective eczema treatment and if this is mediated by improvements in sleep architecture.     

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 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.     

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.     

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.     

Automatic analysis of electro-encephalogram sleep spindle frequency throughout the night

A fully automatic method to analyse electro-encephalogram (EEG) sleep spindle frequency evolution during the night was developed and tested. Twenty allnight recordings were studied from ten healthy control subjects and ten sleep apnoea patients. A total of 22 868 spindles were detected. The overall mean spindle frequency was significantly higher in the control subjects than in the apnoea patients (12.5Hz against 11.7Hz, respectively; p<0.004). The proposed method further identified the sleep depth cycles, and the mean spindle frequency was automatically determined inside each sleep depth cycle. In control subjects, the mean spindle frequency increased from 12.0Hz in the first sleep depth cycle to 12.6Hz in the fifth cycle. No such increase was observed in the sleep apnoea patients. This difference in the spindle frequency evolution was statistically significant (p<0.004). The advantage of the method is that no EEG amplitude thresholds are needed.     

Reliability of sleep spindle measurements in adolescents: How many nights are necessary?

Evidence of night‐to‐night variation in adolescent sleep spindle characteristics is lacking. Twelve adolescents (M = 15.8 ± 0.8 years, eight males) participated in a laboratory study involving 9 nights with 10 hr sleep opportunity. Sleep electroencephalograph was analysed and intra‐class coefficients calculated to determine the reliability of sleep spindles across multiple nights of recording. Slow spindle amplitude and fast spindle density, duration and amplitude characteristics all had acceptable reliability within a single night of sleep recording. Slow spindle density and duration measurements needed a minimum of 4 and 2 nights, respectively, for reliable estimation. Theoretical and methodological implications are discussed.     

Fast sleep spindle (13-15 hz) activity correlates with sleep-dependent improvement in visuomotor performance

STUDY OBJECTIVES: The relationship between memory enhancement and fast (13-16 Hz) versus slow (10-13 Hz) spindle activity during sleep was investigated. DESIGN: Standard polysomnographic recordings were conducted during an adaptation, control nonlearning, and learning night. Automatic spindle detection and measurement was utilized with visual confirmation. SETTING: Participants slept in individual, temperature-controlled bedrooms in a sleep laboratory. PARTICIPANTS: Twelve healthy student volunteers (9 women and 3 men, mean age: 22.3 years) participated. INTERVENTIONS: On the learning night, participants completed a presleep learning session on a modified version of mirror-tracing task followed by a postsleep test session. No learning or test sessions were performed on the adaptation and nonlearning nights. MEASUREMENTS AND RESULTS: Tracing time was reduced by 6.4 seconds (20.6% +/- 2.07%) from the presleep to the postsleep session. Mean amplitude and duration of fast spindles was greater on the learning night than on the nonlearning night (both P values < 0.05). Skill improvement and fast-spindle activity were positively correlated (density [r = 0.76, P < 0.01], amplitude [r = 0.69, P < 0.05], and duration [r = 0.67, P <0.05]). Significant correlations between fast-spindle activity and mirror-tracing performance were also evident for the nonlearning night. There was no significant relationship between mirror-tracing performance and slow-spindle activity on any night. CONCLUSIONS: The thalamocortical network underlying fast-spindle generation may contribute to or reflect plasticity during sleep.     

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.     

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.     

Consolidation of temporal order in episodic memories

Even though it is known that sleep benefits declarative memory consolidation, the role of sleep in the storage of temporal sequences has rarely been examined. Thus we explored the influence of sleep on temporal order in an episodic memory task followed by sleep or sleep deprivation. Thirty-four healthy subjects (17 men) aged between 19 and 28 years participated in the randomized, counterbalanced, between-subject design. Parameters of interests were NREM/REM cycles, spindle activity and spindle-related EEG power spectra. Participants of both groups (sleep group/sleep deprivation group) performed retrieval in the evening, morning and three days after the learning night. Results revealed that performance in temporal order memory significantly deteriorated over three days only in sleep deprived participants. Furthermore our data showed a positive relationship between the ratios of the (i) first NREM/REM cycle with more REM being associated with delayed temporal order recall. Most interestingly, data additionally indicated that (ii) memory enhancers in the sleep group show more fast spindle related alpha power at frontal electrode sites possibly indicating access to a yet to be consolidated memory trace. We suggest that distinct sleep mechanisms subserve different aspects of episodic memory and are jointly involved in sleep-dependent memory consolidation.     

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.     

Genetic Covariance Structure of Reading,Intelligence and Memory in Children

This study investigates the genetic relationship among reading performance, IQ, verbal and visuospatial working memory (WM) and short-term memory (STM) in a sample of 112, 9-year-old twin pairs and their older siblings. The relationship between reading performance and the other traits was explained by a common genetic factor for reading performance, IQ, WM and STM and a genetic factor that only influenced reading performance and verbal memory. Genetic variation explained 83% of the variation in reading performance; most of this genetic variance was explained by variation in IQ and memory performance. We hypothesize, based on these results, that children with reading problems possibly can be divided into three groups: (1) children low in IQ and with reading problems; (2) children with average IQ but a STM deficit and with reading problems; (3) children with low IQ and STM deficits; this group may experience more reading problems than the other two. Edited by Chandra Reynolds.     

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.     

Development and comparison of four sleep spindle detection methods

OBJECTIVE: The objective of the present work was to develop and compare methods for automatic detection of bilateral sleep spindles. METHODS AND MATERIALS: All-night sleep electroencephalographic (EEG) recordings of 12 healthy subjects with a median age of 40 years were studied. The data contained 6043 visually scored bilateral spindles occurring in frontopolar or central brain location. In the present work a new sigma index for spindle detection was developed, based on the fast Fourier transform (FFT) spectrum, aiming at approximating our previous fuzzy spindle detector. The sigma index was complemented with spindle amplitude analysis, based on finite impulse response (FIR) filtering, to form of a combination detector of bilateral spindles. In this combination detector, the spindle amplitude distribution of each recording was estimated and used to tune two different amplitude thresholds. This combination detector was compared to bilaterally extracted sigma indexes and fuzzy detections, which aim to be independent of absolute spindle amplitudes. As a fourth method a fixed spindle amplitude detector was included. RESULTS: The combination detector provided the best overall performance; in S2 sleep a 70% true positive rate was reached with a specificity of 98.6%, and a false-positive rate of 32%. The bilateral sigma indexes provided the second best results, followed by fuzzy detector, while the fixed amplitude detector provided the poorest results so that in S2 sleep a 70% true positive rate was reached with a specificity of 97.7% and false-positive rate of 46%. The spindle amplitude distributions automatically determined for each recording by the combination detector were compared to amplitudes of visually scored spindles and they proved to correspond well. Inter-hemispheric amplitude variation of visually scored bilateral spindles is also presented. CONCLUSION: Flexibility is beneficial in the detection of bilateral spindles. The present work advances automated spindle detection and increases the knowledge of bilateral sleep spindle characteristics.     

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.     

Impaired memory consolidation during sleep in patients with functional memory disorder

Functional memory disorder (FMD) is characterized by mnestic and attentional deficits without symptoms of mild cognitive impairment or dementia. FMD usually develops in subjects with high psychosocial stress level and is classified to the somatoform disorders. We assessed memory performance (procedural mirror tracing task, declarative visual and verbal memory task) and other cognitive functions before and after one night of sleep in 12 FMD patients (mean age: 51.7 yrs, 7 females) and 12 healthy subjects matched for age, gender and IQ. Memory performance and other neurocognitive tasks did not differ between the groups at baseline. After one night of sleep, FMD patients showed an impairment of declarative memory consolidation compared to healthy subjects (visual task: p = 0.004; verbal task: p = 0.039). Spectral analysis of sleep-EEG indicated an increased cortical excitation in FMD. We hypothesize that a hyperarousal state in FMD might contribute to sleep disturbance implicating negative effects on declarative memory consolidation.     

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.     

Effects of insomnia symptoms and objective short sleep duration on memory performance in youths

Sleep quantity and quality are both important for optimal development and functioning during youth. Yet few studies have examined the effects of insomnia symptoms and objective short sleep duration on memory performance among adolescents and young adults. One‐hundred and ninety participants (female: 61.6%) aged from 12 to 24 years completed this study. All participants underwent a clinical interview, a 7‐day actigraphic assessment, a battery of self‐report questionnaires and cognitive tests to assess working memory and episodic memory. Insomnia symptoms were defined as a score ≥ 9 on the Insomnia Severity Index, and objective short sleep duration was defined as average total sleep time less than 7 hr for those aged 12–17 years, and 6 hr for those aged 18 years and above as assessed by actigraphy. Insomnia symptoms were significantly associated with worse self‐perceived memory (p < .05) and poorer performance on the digit span task (p < .01), but not the dual N‐back task and verbal learning task. There was no significant difference in any of the memory measures between participants with objective short sleep duration and their counterparts. No interaction effect was found between insomnia and short sleep duration on any of the objective memory outcomes. Insomnia symptoms, but not objective short sleep duration, were associated with poorer subjective memory and objective working memory performance in youths. Further studies are needed to investigate the underlying mechanisms linking insomnia and memory impairments, and to delineate the long‐term impacts of insomnia on other aspects of neurocognitive functioning in youth.     

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.