[Recent studies about the underlying cerebral mechanism of the fearfull arousals from slow wave sleep].

We consider the disorders of arousal and sleep-related hypermotor epilepsy as genetic twin-conditions, one without, one with epilepsy. They share an augmented arousal-activity during NREM sleep with sleep-wake dissociations, culminating in sleep terrors and sleep-related hypermotor seizures with similar symptoms. The known mutations underlying the two spectra are different, but there are multifold population-genetic-, family- and even individual (the two conditions occurring in the same person) overlaps supporting common genetic roots. In the episodes of disorders of arousal, the anterior cingulate, anterior insular and pre-frontal cortices (shown to be involved in fear- and emotion processing) are activated within a sleeping brain. These regions overlap with the seizure-onset zones of successfully operated sleep-related hypermotor seizures, and notably, belong to the salience network being consistent with its hubs. The arousal-relatedness and the similar fearful disorientation occurring in sleep terrors and hypermotor seizures, make them alike the acute stress-responses emerging from sleep; triggered by false alarms. An acute stress-response can easily mobilize the hypothalamo-pituitary-adrenal axis (preparing fight-flight responses in wakefulness); through its direct pathways to and from the salience network. This hypothesis has never been studied.

Study protocol of the Hungarian Longitudinal Study of Healthy Brain Aging (HuBA).

Background and purpose:

Neuro­cog­nitive aging and the associated brain diseases impose a major social and economic burden. Therefore, substantial efforts have been put into revealing the lifestyle, the neurobiological and the genetic underpinnings of healthy neurocognitive aging. However, these studies take place almost exclusively in a limited number of highly-developed countries. Thus, it is an important open question to what extent their findings may generalize to neurocognitive aging in other, not yet investigated regions. The purpose of the Hungarian Longitudinal Study of Healthy Brain Aging (HuBA) is to collect multi-modal longitudinal data on healthy neurocognitive aging to address the data gap in this field in Central and Eastern Europe.

We adapted the Australian Ima­ging, Biomarkers and Lifestyle (AIBL) study of aging study protocol to local circumstances and collected demographic, lifestyle, men­tal and physical health, medication and medical history related information as well as re­cor­ded a series of magnetic resonance imaging (MRI) data. In addition, participants were al­so offered to participate in the collection of blood samples to assess circulating in­flam­matory biomarkers as well as a sleep study aimed at evaluating the general sleep quality based on multi-day collection of subjective sleep questionnaires and whole-night elec­troencephalographic (EEG) data.

Baseline data collection has al­ready been accomplished for more than a hundred participants and data collection in the se­cond
session is on the way. The collected data might reveal specific local trends or could also indicate the generalizability of previous findings. Moreover, as the HuBA protocol al­so offers a sleep study designed for tho­rough characterization of participants’ sleep quality and related factors, our extended multi-modal dataset might provide a base for incorporating these measures into healthy and clinical aging research. 

Besides its straightforward na­tional benefits in terms of health ex­pen­di­ture, we hope that this Hungarian initiative could provide results valid for the whole Cent­ral and Eastern European region and could also promote aging and Alzheimer’s disease research in these countries.

A daytime nap with REM sleep is linked to enhanced generalization of emotional stimuli.

How memory representations are shaped during and after their encoding is a central question in the study of human memory. Recognition responses to stimuli that are similar to those observed previously can hint at the fidelity of the memories or point to processes of generalization at the expense of precise memory representations. Experimental studies utilizing this approach showed that emotions and sleep both influence these responses. Sleep, and more specifically rapid eye movement sleep, is assumed to facilitate the generalization of emotional memories. We studied mnemonic discrimination by the emotional variant of the Mnemonic Separation Task in participants (N = 113) who spent a daytime nap between learning and testing compared with another group that spent an equivalent time awake between the two sessions. Our findings indicate that the discrimination of similar but previously not seen items from previously seen ones is enhanced in case of negative compared with neutral and positive stimuli. Moreover, whereas the sleep and the wake groups did not differ in memory performance, participants entering rapid eye movement sleep exhibited increased generalization of emotional memories. Our findings indicate that entering into rapid eye movement sleep during a daytime nap shapes emotional memories in a way that enhances recognition at the expense of detailed memory representations.

Fearful arousals in sleep terrors and sleep-related hypermotor epileptic seizures may involve the salience network and the acute stress response of Cannon and Selye.

We consider the disorders of arousal and sleep-related hypermotor epilepsy as genetic twin-conditions, one without, one with epilepsy. They share an augmented arousal-activity during NREM sleep with sleep-wake dissociations, culminating in sleep terrors and sleep-related hypermotor seizures with similar symptoms. The known mutations underlying the two spectra are different, but there are multifold population-genetic-, family- and even individual (the two conditions occurring in the same person) overlaps supporting common genetic roots. In the episodes of disorders of arousal, the anterior cingulate, anterior insular and pre-frontal cortices (shown to be involved in fear- and emotion processing) are activated within a sleeping brain. These regions overlap with the seizure-onset zones of successfully operated sleep-related hypermotor seizures, and notably, belong to the salience network being consistent with its hubs. The arousal-relatedness and the similar fearful confusion occurring in sleep terrors and hypermotor seizures, make them alike acute stress-responses emerging from sleep; triggered by false alarms. The activation of the anterior cingulate, prefrontal and insular regions in the episodes of both conditions, can easily mobilize the hypothalamo-pituitary-adrenal axis (preparing fight-flight responses in wakefulness); through its direct pathways to and from the salience network. This hypothesis has never been studied.

Temporal association between sleep spindles and ripples in the human anterior and mediodorsal thalamus.

Sleep spindles are major oscillatory components of Non-Rapid Eye Movement (NREM) sleep, reflecting hyperpolarization-rebound sequences of thalamocortical neurons. Reports suggest a link between sleep spindles and several forms of high-frequency oscillations which are considered as expressions of pathological off-line neural plasticity in the central nervous system. Here we investigated the relationship between thalamic sleep spindles and ripples in the anterior and mediodorsal nuclei (ANT and MD) of epilepsy patients. Whole-night LFP from the ANT and MD were co-registered with scalp EEG/polysomnography by using externalized leads in 15 epilepsy patients undergoing a Deep Brain Stimulation protocol. Slow (~12 Hz) and fast (~14 Hz) sleep spindles were present in the human ANT and MD and roughly, 20% of them were associated with ripples. Ripple-associated thalamic sleep spindles were characterized by longer duration and exceeded pure spindles in terms of spindle power as indicated by time-frequency analysis. Furthermore, ripple amplitude was modulated by the phase of sleep spindles within both thalamic nuclei. No signs of pathological processes were correlated with measures of ripple and spindle association, furthermore, the density of ripple-associated sleep spindles in the ANT showed a positive correlation with verbal comprehension. Our findings indicate the involvement of the human thalamus in coalescent spindle-ripple oscillations of NREM sleep.

Altered parasympathetic activity during sleep and emotionally arousing wakefulness in frequent nightmare recallers.

Nightmare disorder is characterized by dysfunctional emotion regulation and poor subjective sleep quality reflected in pathophysiological features such as abnormal arousal processes and sympathetic influences. Dysfunctional parasympathetic regulation, especially before and during rapid eye movement (REM) phases, is assumed to alter heart rate (HR) and its variability (HRV) of frequent nightmare recallers (NM). We hypothesized that cardiac variability is attenuated in NMs as opposed to healthy controls (CTL) during sleep, pre-sleep wakefulness and under an emotion-evoking picture-rating task. Based on the polysomnographic recordings of 24 NM and 30 CTL participants, we examined HRV during pre-REM, REM, post-REM and slow wave sleep, separately. Additionally, electrocardiographic recordings of resting state before sleep onset and under an emotionally challenging picture-rating task were also analyzed. Applying repeated measures analysis of variance (rmANOVA), a significant difference was found in the HR of NMs and CTLs during nocturnal segments but not during resting wakefulness, suggesting autonomic dysregulation, specifically during sleep in NMs. As opposed to the HR, the HRV values were not significantly different in the rmANOVA in the two groups, implying that the extent of parasympathetic dysregulation on a trait level might depend on the severeness of dysphoric dreaming. Nonetheless, in the group comparisons, the NM group showed increased HR and reduced HRV during the emotion-evoking picture-rating task, which aimed to model the nightmare experience in the daytime, indicating disrupted emotion regulation in NMs under acute distress. In conclusion, trait-like autonomic changes during sleep and state-like autonomic responses to emotion-evoking pictures indicate parasympathetic dysregulation in NMs.

Reduced REM and N2 sleep, and lower dream intensity predict increased mind-wandering.

Mind-wandering is a mental state in which attention shifts from the present environment or current task to internally driven, self-referent mental content. Homeostatic sleep pressure seems to facilitate mind-wandering as indicated by studies observing links between increased mind-wandering and impaired sleep. Nevertheless, previous studies mostly relied on cross-sectional measurements and self-reports. We aimed to combine the accuracy of objective sleep measures with the use of self-reports in a naturalistic setting in order to examine if objective sleep parameters predict the tendency for increased mind-wandering on the following day. We used mobile sleep electroencephalographic (EEG) headbands and self-report scales over 7 consecutive nights in a group of 67 healthy participants yielding ~400 analyzable nights. Nights with more wakefulness and shorter REM and slow wave sleep were associated with poorer subjective sleep quality at the intraindividual level. Reduced REM and N2 sleep, as well as less intense dream experiences, predicted more mind-wandering the following day. Our micro-longitudinal study indicates that intraindividual fluctuations in the duration of specific sleep stages predict the perception of sleep quality as assessed in the morning, as well as the intensity of daytime mind-wandering the following hours. The combined application of sleep EEG assessments and self-reports over repeated assessments provides new insights into the subtle intraindividual, night-to-day associations between nighttime sleep and the next day's subjective experiences.

The utility of wearable headband electroencephalography and pulse photoplethysmography to assess cortical and physiological arousal in individuals with stress-related mental disorders.

Several stress-related mental disorders are characterised by disturbed sleep, but objective sleep biomarkers are not routinely examined in psychiatric patients. We examined the use of wearable-based sleep biomarkers in a psychiatric sample with headband electroencephalography (EEG) including pulse photoplethysmography (PPG), with an additional focus on microstructural elements as especially the shift from low to high frequencies appears relevant for several stress-related mental disorders. We analysed 371 nights of sufficient quality from 83 healthy participants and those with a confirmed stress-related mental disorder (anxiety-affective spectrum). The median value of macrostructural, microstructural (spectral slope fitting), and heart rate variables was calculated across nights and analysed at the individual level (N = 83). The headbands were accepted well by patients and the data quality was sufficient for most nights. The macrostructural analyses revealed trends for significance regarding sleep continuity but not sleep depth variables. The spectral analyses yielded no between-group differences except for a group × age interaction, with the normal age-related decline in the low versus high frequency power ratio flattening in the patient group. The PPG analyses showed that the mean heart rate was higher in the patient group in pre-sleep epochs, a difference that reduced during sleep and dissipated at wakefulness. Wearable devices that record EEG and/or PPG could be used over multiple nights to assess sleep fragmentation, spectral balance, and sympathetic drive throughout the sleep-wake cycle in patients with stress-related mental disorders and healthy controls, although macrostructural and spectral markers did not differ between the two groups.

Multivariate prediction of cognitive performance from the sleep electroencephalogram.

Human cognitive performance is a key function whose biological foundations have been partially revealed by genetic and brain imaging studies. The sleep electroencephalogram (EEG) is tightly linked to structural and functional features of the central nervous system and serves as another promising biomarker. We used data from MrOS, a large cohort of older men and cross-validated regularized regression to link sleep EEG features to cognitive performance in cross-sectional analyses. In independent validation samples 2.5-10% of variance in cognitive performance can be accounted for by sleep EEG features, depending on the covariates used. Demographic characteristics account for more covariance between sleep EEG and cognition than health variables, and consequently reduce this association by a greater degree, but even with the strictest covariate sets a statistically significant association is present. Sigma power in NREM and beta power in REM sleep were associated with better cognitive performance, while theta power in REM sleep was associated with worse performance, with no substantial effect of coherence and other sleep EEG metrics. Our findings show that cognitive performance is associated with the sleep EEG (r = 0.283), with the strongest effect ascribed to spindle-frequency activity. This association becomes weaker after adjusting for demographic (r = 0.186) and health variables (r = 0.155), but its resilience to covariate inclusion suggest that it also partially reflects trait-like differences in cognitive ability.

Sleep and dreaming in the light of reactive and predictive homeostasis.

Dreams are often viewed as fascinating but irrelevant mental epihenomena of the sleeping mind with questionable functional relevance. Despite long hours of oneiric activity, and high individual differences in dream recall, dreams are lost into oblivion. Here, we conceptualize dreaming and dream amnesia as inherent aspects of the reactive and predictive homeostatic functions of sleep. Mental activity during sleep conforms to the interplay of restorative processes and future anticipation, and particularly during the second half of the night, it unfolds as a special form of non-constrained, self-referent, and future-oriented cognitive process. Awakening facilitates constrained, goal-directed prospection that competes for shared neural resources with dream production and dream recall, and contributes to dream amnesia. We present the neurophysiological aspects of reactive and predictive homeostasis during sleep, highlighting the putative role of cortisol in predictive homeostasis and forgetting dreams. The theoretical and methodological aspects of our proposal are discussed in relation to the study of dreaming, dream recall, and sleep-related cognitive processes.

The graded novelty encoding task: Novelty gradually improves recognition of visual stimuli under incidental learning conditions.

It has been argued that novel compared to familiar stimuli are preferentially encoded into memory. Nevertheless, treating novelty as a categorical variable in experimental research is considered simplistic. We highlight the dimensional aspect of novelty and propose an experimental design that manipulates novelty continuously. We created the Graded Novelty Encoding Task (GNET), in which the difference between stimuli (i.e. novelty) is parametrically manipulated, paving the way for quantitative models of novelty processing. We designed an algorithm which generates visual stimuli by placing colored shapes in a grid. During the familiarization phase of the task, we repeatedly presented five pictures to the participants. In a subsequent incidental learning phase, participants were asked to differentiate between the "familiars" and novel images that varied in the degree of difference to the familiarized pictures (i.e. novelty). Finally, participants completed a surprise recognition memory test, where the novel stimuli from the previous phase were interspersed with distractors with similar difference characteristics. We numerically expressed the differences between the stimuli to compute a dimensional indicator of novelty and assessed whether it predicted recognition memory performance. Based on previous studies showing the beneficial effect of novelty on memory formation, we hypothesized that the more novel a given picture was, the better subsequent recognition performance participants would demonstrate. Our hypothesis was confirmed: recognition performance was higher for more novel stimuli. The GNET captures the continuous nature of novelty, and it may be useful in future studies that examine the behavioral and neurocognitive aspects of novelty processing.

Lateralized tactile stimulation during NREM sleep globally increases both slow and fast frequency activities.

Slow frequency activity during non-rapid eye movement (NREM) sleep emerges from synchronized activity of widely distributed thalamo-cortical and cortico-cortical networks, reflecting homeostatic and restorative properties of sleep. Slow frequency activity exhibits a reactive nature, and can be increased by acoustic stimulation. Although non-invasive brain stimulation is a promising technique in basic and clinical sleep research, sensory stimulation studies focusing on modalities other than the acoustic are scarce. We explored here the potential of lateralized vibro-tactile stimulation (VTS) of the finger to locally modify electroencephalographic activity during nocturnal NREM sleep. Eight seconds-long sequences of vibro-tactile pulses were delivered at a rate of 1 Hz either to the left or to the right index finger, in addition to a sham condition, in fourteen healthy participants. VTS markedly increased slow frequency activity that peaked between 1-4 Hz but extended to higher (~13 Hz) frequencies, with fronto-central dominance. Enhanced slow frequency activity was accompanied by increased (14-22 Hz) fast frequency power peaking over central and posterior locations. VTS increased the amplitude of slow waves, especially during the first 3-4 s of stimulation. Noticeably, we did not observe local-hemispheric effects, that is, VTS resulted in a global cortical response regardless of stimulation laterality. VTS moderately increased slow and fast frequency activities in resting wakefulness, to a much lower extent compared to NREM sleep. The concomitant increase in slow and fast frequency activities in response to VTS indicates an instant homeostatic response coupled with wake-like, high-frequency activity potentially reflecting transient periods of increased environmental processing.

The sleep EEG envelope is a novel, neuronal firing-based human biomarker.

Sleep EEG reflects voltage differences relative to a reference, while its spectrum reflects its composition of various frequencies. In contrast, the envelope of the sleep EEG reflects the instantaneous amplitude of oscillations, while its spectrum reflects the rhythmicity of the occurrence of these oscillations. The sleep EEG spectrum is known to relate to demographic, psychological and clinical characteristics, but the envelope spectrum has been rarely studied. In study 1, we demonstrate in human invasive data from cortex-penetrating microelectrodes and subdural grids that the sleep EEG envelope spectrum reflects neuronal firing. In study 2, we demonstrate that the scalp EEG envelope spectrum is stable within individuals. A multivariate learning algorithm could predict age (r = 0.6) and sex (r = 0.5) from the EEG envelope spectrum. With age, oscillations shifted from a 4-5 s rhythm to faster rhythms. Our results demonstrate that the sleep envelope spectrum is a promising biomarker of demographic and disease-related phenotypes.

Overnight dynamics in scale-free and oscillatory spectral parameters of NREM sleep EEG.

Unfolding the overnight dynamics in human sleep features plays a pivotal role in understanding sleep regulation. Studies revealed the complex reorganization of the frequency composition of sleep electroencephalogram (EEG) during the course of sleep, however the scale-free and the oscillatory measures remained undistinguished and improperly characterized before. By focusing on the first four non-rapid eye movement (NREM) periods of night sleep records of 251 healthy human subjects (4-69 years), here we reveal the flattening of spectral slopes and decrease in several measures of the spectral intercepts during consecutive sleep cycles. Slopes and intercepts are significant predictors of slow wave activity (SWA), the gold standard measure of sleep intensity. The overnight increase in spectral peak sizes (amplitudes relative to scale-free spectra) in the broad sigma range is paralleled by a U-shaped time course of peak frequencies in frontopolar regions. Although, the set of spectral indices analyzed herein reproduce known age- and sex-effects, the interindividual variability in spectral slope steepness is lower as compared to the variability in SWA. Findings indicate that distinct scale-free and oscillatory measures of sleep EEG could provide composite measures of sleep dynamics with low redundancy, potentially affording new insights into sleep regulatory processes in future studies.

Predictive coding, multisensory integration, and attentional control: A multicomponent framework for lucid dreaming.

Lucid dreaming (LD) is a mental state in which we realize not being awake but are dreaming while asleep. It often involves vivid, perceptually intense dream images as well as peculiar kinesthetic sensations, such as flying, levitating, or out-of-body experiences. LD is in the cross-spotlight of cognitive neuroscience and sleep research as a particular case to study consciousness, cognition, and the neural background of dream experiences. Here, we present a multicomponent framework for the study and understanding of neurocognitive mechanisms and phenomenological aspects of LD. We propose that LD is associated with prediction error signals arising during sleep and occurring at higher or lower levels of the processing hierarchy. Prediction errors are resolved by generating a superordinate self-model able to integrate ambiguous stimuli arriving from sensory periphery and higher-order cortical regions. While multisensory integration enables lucidity maintenance and contributes to peculiar kinesthetic experiences, attentional control facilitates multisensory integration by dynamically regulating the balance between the influence of top-down mental models and the precision weighting of bottom-up sensory inputs. Our novel framework aims to link neural correlates of LD with current concepts of sleep and arousal regulation and provide testable predictions on interindividual differences in LD as well as neurocognitive mechanisms inducing lucid dreams.

Scale-free and oscillatory spectral measures of sleep stages in humans.

Power spectra of sleep electroencephalograms (EEG) comprise two main components: a decaying power-law corresponding to the aperiodic neural background activity, and spectral peaks present due to neural oscillations. "Traditional" band-based spectral methods ignore this fundamental structure of the EEG spectra and thus are susceptible to misrepresenting the underlying phenomena. A fitting method that attempts to separate and parameterize the aperiodic and periodic spectral components called "fitting oscillations and one over f" (FOOOF) was applied to a set of annotated whole-night sleep EEG recordings of 251 subjects from a wide age range (4-69 years). Most of the extracted parameters exhibited sleep stage sensitivity; significant main effects and interactions of sleep stage, age, sex, and brain region were found. The spectral slope (describing the steepness of the aperiodic component) showed especially large and consistent variability between sleep stages (and low variability between subjects), making it a candidate indicator of sleep states. The limitations and arisen problems of the FOOOF method are also discussed, possible solutions for some of them are suggested.

Schizotypy unfolding into the night? Schizotypal traits and daytime psychotic-like experiences predict negative and salient dreams.

Symptoms of insomnia and frequent nightmares are prevalent in psychotic disorders, and are associated with psychotic-like experiences (PLEs) in the non-clinical population. Whereas the role of impaired sleep in psychosis was extensively examined by longitudinal and interventional approaches, studies on the association between psychosis and dream quality are scarce, and mainly cross-sectional. We conducted a three-week long prospective study in a group of healthy adults (N = 55), assessed schizotypal traits, daily PLEs, and the emotional quality of dreams recalled in the morning (N = 490). We extracted the latent factors of schizotypal traits and dream emotions, and examined the predictive value of trait-and state-like variables on day-to-day reports of PLEs and dream quality. PLEs reported in the evening predicted emotionally more negative and salient dream reports the following morning. On the other hand, the quality of dreams were not predictive of PLEs reported later during the day. Schizotypal personality traits were differentially associated with dream quality: Introvertive Anhedonia, Cognitive Disorganization, and General-Disorganized schizotypy were linked to more negative dream valence, whereas Unusual Experiences were associated with more salient dreams. Our findings highlight the relevance of the multidimensional nature of schizotypal traits, the role of different facets of schizotypy in daytime and nocturnal mental experiences, and the day-to-day associations between PLEs and dream affect. GENERAL SCIENTIFIC SUMMARIES (GSS): The aim of the study was to examine the temporal associations between psychotic-like experiences and dream emotions, taking into account the trait factors of schizotypy. Psychotic-like experiences during the evening hours predicted reporting more negative and salient dreams the following morning, and schizotypal personality traits were differentially associated with the dimensions of dream emotions.

Expectation of irrelevant novel stimuli has no consistent effect on recognition memory.

Novelty is defined as the part of an experience that is not yet represented by memory systems. Novelty has been claimed to exert various memory-enhancing effects. A pioneering study by Wittmann et al. (2007) has shown that memory formation may even benefit from the expectation of novelty. We aimed to replicate this assumed memory effect in four behavioral studies. However, our results do not support the idea that anticipated novel stimuli are more memorable than unexpected novelty. In our experiments, we systematically manipulated the novelty predicting cues to ensure that the expectations were correctly formed by the participants, however, the results showed that there was no memory enhancement for expected novel pictures in any of the examined indices, thus we could not replicate the main behavioral finding of Wittmann et al. (2007). These results call into question the original effect, and we argue that this fits more into current thinking on memory formation and brain function in general. Our results are more consistent with the view that unexpected stimuli are more likely to be retained by memory systems. Predictive coding theory suggests that unexpected stimuli are prioritized by the nervous system and this may also benefit memory processes. Novel stimuli may be unexpected and thus recognized better in some experimental setups, yet novelty and unexpectedness do not always coincide. We hope that our work can bring more consistency in the literature on novelty, as educational methods in general could also benefit from this clarification.

The heartbeat evoked potential is a questionable biomarker in nightmare disorder: A replication study.

Frequent nightmares are highly prevalent and constitute a risk factor for a wide range of psychopathological conditions. Despite its prevalence and clinical relevance however, the pathophysiological mechanisms of nightmares are poorly understood. A recent study (Perogamvros et, al 2019) examined the heart beat evoked potential (HEP) in a small group of nightmare sufferers (N = 11) and matched healthy controls (N = 11) and observed markedly different (Hedges' g = 1.42 [0.62-2.22]) HEP response across the groups during Rapid Eye Movement (REM) sleep. Moreover, the HEP correlated with depression scores in the nightmare group only. The authors concluded that the HEP in REM sleep could be used as a trait-like biomarker reflecting pathological emotional-and sleep regulation in nightmare disorder. To replicate the above study, we performed the same analyses of HEPs in two separate, and larger databases comprising the polysomnographic recordings of nightmare sufferers and matched controls (NStudy 1 = 39 ; NStudy 2 = 41). In contrast to the original findings, we did not observe significant differences in HEP across the two groups in either of the two databases. Moreover, we found no associations between depression scores and HEP amplitudes in the relevant spatiotemporal cluster. Our data cast doubts on the utility of HEP as a biomarker in the diagnostic and treatment procedures of nightmare disorder and suggests that the interpretation of HEP as a marker of impaired arousal and emotional processing during REM sleep is premature and requires further validation.

Sleep-spindle frequency: Overnight dynamics, afternoon nap effects, and possible circadian modulation.

Homeostatic and circadian processes play a pivotal role in determining sleep structure, timing, and quality. In sharp contrast with the wide accessibility of the electroencephalogram (EEG) index of sleep homeostasis, an electrophysiological measure of the circadian modulation of sleep is still unavailable. Evidence suggests that sleep-spindle frequencies decelerate during biological night. In order to test the feasibility of measuring this marker in common polysomnographic protocols, the Budapest-Munich database of sleep records (N = 251 healthy subjects, 122 females, age range: 4-69 years), as well as an afternoon nap sleep record database (N = 112 healthy subjects, 30 females, age range: 18-30 years) were analysed by the individual adjustment method of sleep-spindle analysis. Slow and fast sleep-spindle frequencies were characterised by U-shaped overnight dynamics, with highest values in the first and the fourth-to-fifth sleep cycle and the lowest values in the middle of the sleeping period (cycles two to three). Age-related attenuation of sleep-spindle deceleration was evident. Estimated phases of the nadirs in sleep-spindle frequencies were advanced in children as compared to other age groups. Additionally, nap sleep spindles were faster than night sleep spindles (0.57 and 0.39 Hz difference for slow and fast types, respectively). The fine frequency resolution analysis of sleep spindles is a feasible method of measuring the assumed circadian modulation of sleep. Moreover, age-related attenuation of circadian sleep modulation might be measurable by assessing the overnight dynamics in sleep-spindle frequency. Phase of the minimal sleep-spindle frequency is a putative biomarker of chronotype.