Slow Sleep Spindles Research Articles

Sleep endophenotypes of schizophrenia: slow waves and sleep spindles in unaffected first-degree relatives

Sleep spindles and slow waves are the main brain oscillations occurring in non-REM sleep. Several lines of evidence suggest that spindles are initiated within the thalamus, whereas slow waves are generated and modulated in the cortex. A decrease in sleep spindle activity has been described in Schizophrenia (SCZ), including chronic, early course, and early onset patients. In contrast, slow waves have been inconsistently found to be reduced in SCZ, possibly due to confounds like duration of illness and antipsychotic medication exposure. Nontheless, the implication of sleep spindles and slow waves in the neurobiology of SCZ and related disorders, including their heritability, remains largely unknown. Unaffected first-degree relatives (FDRs) share a similar genetic background and several neurophysiological and cognitive deficits with SCZ patients, and allow testing whether some of these measures are candidate endophenotypes. In this study, we performed sleep high-density EEG recordings to characterise the spatiotemporal features of sleep spindles and slow waves in FDRs of SCZ probands and healthy subjects (HS) with no family history of SCZ. We found a significant reduction of integrated spindle activity (ISAs) in FDRs relative to HS, whereas spindle density and spindle duration were not different between groups. FDRs also had decreased slow wave amplitude and slopes. Altogether, our results suggest that ISAs deficits might represent a candidate endophenotype for SCZ. Furthermore, given the slow wave deficits observed in FDRs, we propose that disrupted cortical synchronisation increases the risk for SCZ, but thalamic dysfunction is necessary for the disorder to fully develop.

The Effect of a Slowly Rocking Bed on Sleep

Rocking movements appear to affect human sleep. Recent research suggested a facilitated transition from wake to sleep and a boosting of slow oscillations and sleep spindles due to lateral rocking movements during an afternoon nap. This study aimed at investigating the effect of vestibular stimulation on sleep onset, nocturnal sleep and its potential to increase sleep spindles and slow waves, which could influence memory performance. Polysomnography was recorded in 18 males (age: 20–28 years) during three nights: movement until sleep onset (C1), movement for 2 hours (C2), and one baseline (B) without motion. Sleep dependent changes in memory performance were assessed with a word-pair learning task. Although subjects preferred nights with vestibular stimulation, a facilitated sleep onset or a boost in slow oscillations was not observed. N2 sleep and the total number of sleep spindles increased during the 2 h with vestibular stimulation (C2) but not over the entire night. Memory performance increased over night but did not differ between conditions. The lack of an effect might be due to the already high sleep efficiency (96%) and sleep quality of our subjects during baseline. Nocturnal sleep in good sleepers might not benefit from the potential facilitating effects of vestibular stimulation.

Different maturational changes of fast and slow sleep spindles in the first four years of life

Objective/BackgroundMassive changes in brain morphology and function in the first years of life reveal a postero-anterior trajectory of cortical maturation accompanied by regional modifications of NREM sleep. One of the most sensible marker of this maturation process is represented by electroencephalographic (EEG) activity within the frequency range of sleep spindles. However, direct evidence that these changes actually reflect maturational modifications of fast and slow spindles still lacks.Our study aimed at answering the following questions:1. Do cortical changes at 11.50 Hz frequency correspond to slow spindles?2. Do fast and slow spindles show different age trajectories and different topographical distributions?3. Do changes in peak frequency explain age changes of slow and fast spindles? Patients/MethodsWe measured the antero-posterior changes of slow and fast spindles in the first 60 min of nightly sleep of 39 infants and children (0–48 mo.). ResultsWe found that (A) changes of slow spindles from birth to childhood mostly affect frontal areas (B) variations of fast and slow spindles across age groups go in opposite direction, the latter progressively increasing across ages; (C) this process is not merely reducible to changes of spindle frequency. ConclusionsAs a main finding, our cross-sectional study shows that the first form of mature spindle (i.e., corresponding to the adult phasic event of NREM sleep) is marked by the emergence of slow spindles on anterior regions around the age of 12 months.

High-density EEG characterization of brain responses to auditory rhythmic stimuli during wakefulness and NREM sleep

Auditory rhythmic sensory stimulation modulates brain oscillations by increasing phase-locking to the temporal structure of the stimuli and by increasing the power of specific frequency bands, resulting in Auditory Steady State Responses (ASSR). The ASSR is altered in different diseases of the central nervous system such as schizophrenia. However, in order to use the ASSR as biological markers for disease states, it needs to be understood how different vigilance states and underlying brain activity affect the ASSR. Here, we compared the effects of auditory rhythmic stimuli on EEG brain activity during wake and NREM sleep, investigated the influence of the presence of dominant sleep rhythms on the ASSR, and delineated the topographical distribution of these modulations. Participants (14 healthy males, 20-33 years) completed on the same day a 60 min nap session and two 30 min wakefulness sessions (before and after the nap). During these sessions, amplitude modulated (AM) white noise auditory stimuli at different frequencies were applied. High-density EEG was continuously recorded and time-frequency analyses were performed to assess ASSR during wakefulness and NREM periods. Our analysis revealed that depending on the electrode location, stimulation frequency applied and window/frequencies analysed the ASSR was significantly modulated by sleep pressure (before and after sleep), vigilance state (wake vs. NREM sleep), and the presence of slow wave activity and sleep spindles. Furthermore, AM stimuli increased spindle activity during NREM sleep but not during wakefulness. Thus, (1) electrode location, sleep history, vigilance state and ongoing brain activity needs to be carefully considered when investigating ASSR and (2) auditory rhythmic stimuli during sleep might represent a powerful tool to boost sleep spindles.

Sleep and cortical maturation: slow and fast sleep spindles in the first 4 years of life

Sleep and cortical maturation: slow and fast sleep spindles in the first 4 years of life

Dynamic coupling between slow waves and sleep spindles during slow wave sleep in humans is modulated by functional pre-sleep activation

Co-existent sleep spindles and slow waves have been viewed as a mechanism for offline information processing. Here we explored if the temporal synchronization between slow waves and spindle activity during slow wave sleep (SWS) in humans was modulated by preceding functional activations during pre-sleep learning. We activated differentially the left and right hemisphere before sleep by using a lateralized variant of serial response time task (SRTT) and verified these inter-hemispheric differences by analysing alpha and beta electroencephalographic (EEG) activities during learning. The stability and timing of coupling between positive and negative phases of slow waves and sleep spindle activity during SWS were quantified. Spindle activity was temporally synchronized with both positive (up-state) and negative (down-state) slow half waves. Synchronization of only the fast spindle activity was laterally asymmetric after learning, corresponding to hemisphere-specific activations before sleep. However, the down state was associated with decoupling, whereas the up-state was associated with increased coupling of fast spindle activity over the pre-activated hemisphere. These observations provide original evidence that (1) the temporal grouping of fast spindles by slow waves is a dynamic property of human SWS modulated by functional pre-sleep activation patterns, and (2) fast spindles synchronized by slow waves are functionally distinct.

Circadian preference towards morningness is associated with lower slow sleep spindle amplitude and intensity in adolescents

Individual circadian preference types and sleep EEG patterns related to spindle characteristics, have both been associated with similar cognitive and mental health phenotypes. However, no previous study has examined whether sleep spindles would differ by circadian preference. Here, we explore if spindle amplitude, density, duration or intensity differ by circadian preference and whether these associations are moderated by spindle location, frequency, and time distribution across the night. The participants (N = 170, 59% girls; mean age = 16.9, SD = 0.1 years) filled in the shortened 6-item Horne-Östberg Morningness-Eveningness Questionnaire. We performed an overnight sleep EEG at the homes of the participants. In linear mixed model analyses, we found statistically significant lower spindle amplitude and intensity in the morning as compared to intermediate (P < 0.001) and evening preference groups (P < 0.01; P > 0.06 for spindle duration and density). Spindle frequency moderated the associations (P < 0.003 for slow (<13 Hz); P > 0.2 for fast (>13 Hz)). Growth curve analyses revealed a distinct time distribution of spindles across the night by the circadian preference: both spindle amplitude and intensity decreased more towards morning in the morning preference group than in other groups. Our results indicate that circadian preference is not only affecting the sleep timing, but also associates with sleep microstructure regarding sleep spindle phenotypes.

Sleep Spindles in the Right Hemisphere Support Awareness of Regularities and Reflect Pre-Sleep Activations.

Study ObjectivesThe present study explored the sleep mechanisms which may support awareness of hidden regularities.MethodsBefore sleep, 53 participants learned implicitly a lateralized variant of the serial response-time task in order to localize sensorimotor encoding either in the left or right hemisphere and induce implicit regularity representations. Electroencephalographic (EEG) activity was recorded at multiple electrodes during both task performance and sleep, searching for lateralized traces of the preceding activity during learning. Sleep EEG analysis focused on region-specific slow (9–12 Hz) and fast (13–16 Hz) sleep spindles during nonrapid eye movement sleep.ResultsFast spindle activity at those motor regions that were activated during learning increased with the amount of postsleep awareness. Independently of side of learning, spindle activity at right frontal and fronto-central regions was involved: there, fast spindles increased with the transformation of sequence knowledge from implicit before sleep to explicit after sleep, and slow spindles correlated with individual abilities of gaining awareness. These local modulations of sleep spindles corresponded to regions with greater presleep activation in participants with postsleep explicit knowledge.ConclusionsSleep spindle mechanisms are related to explicit awareness (1) by tracing the activation of motor cortical and right-hemisphere regions which had stronger involvement already during learning and (2) by recruitment of individually consolidated processing modules in the right hemisphere. The integration of different sleep spindle mechanisms with functional states during wake collectively supports the gain of awareness of previously experienced regularities, with a special role for the right hemisphere.

Individual Differences in Frequency and Topography of Slow and Fast Sleep Spindles.

Sleep spindles are transient oscillatory waveforms that occur during non-rapid eye movement (NREM) sleep across widespread cortical areas. In humans, spindles can be classified as either slow or fast, but large individual differences in spindle frequency as well as methodological difficulties have hindered progress towards understanding their function. Using two nights of high-density electroencephalography recordings from 28 healthy individuals, we first characterize the individual variability of NREM spectra and demonstrate the difficulty of determining subject-specific spindle frequencies. We then introduce a novel spatial filtering approach that can reliably separate subject-specific spindle activity into slow and fast components that are stable across nights and across N2 and N3 sleep. We then proceed to provide detailed analyses of the topographical expression of individualized slow and fast spindle activity. Group-level analyses conform to known spatial properties of spindles, but also uncover novel differences between sleep stages and spindle classes. Moreover, subject-specific examinations reveal that individual topographies show considerable variability that is stable across nights. Finally, we demonstrate that topographical maps depend nontrivially on the spindle metric employed. In sum, our findings indicate that group-level approaches mask substantial individual variability of spindle dynamics, in both the spectral and spatial domains. We suggest that leveraging, rather than ignoring, such differences may prove useful to further our understanding of the physiology and functional role of sleep spindles.

P384 The role of sleep spindles in overnight verbal memory consolidation in temporal lobe epilepsy patients

Introduction Declarative memory performance and hippocampal functioning are highly associated. Learning induced memory consolidation results in an increased coupling between mesial temporal lobe, thalamus and frontal areas during sleep, resulting in the increase of sleep spindles and slow wave sleep. Our aim was to investigate the modulatory effect of learning on sleep spindles in temporal lobe epilepsy (TLE) patients and to see whether the association between declarative memory consolidation and sleep parameters are altered. Materials and methods We administered three modified versions of the Rey Auditory Verbal Learning Task to TLE patients (n = 22) on three consecutive nights undergoing video-EEG monitoring. Delayed recall was measured 30 min after learning, memory retention was measured in the following morning. Sleep stages were detected manually, sleep spindles were detected with an automated threshold-cutting method based on individually adjusted slow and fast sleep spindle frequency values. Fast and slow sleep spindle density, duration and amplitude were correlated with both online and offline learning. Results Online learning scores showed positive correlation with slow spindle duration, density and amplitude, and a negative correlation with fast spindle density and duration. On the contrary, memory retention scores showed a negative relationship with slow spindle density, duration and amplitude. Conclusion Our results indicate that learning and overnight memory consolidation related sleep spindles are compromised by the pathological process.

S75 Sleep spindles in humans: From invasive recordings to sexual dimorphism

Sleep spindles are episodic bursts of mid-frequency (alpha Bodizs et al., 2009 ). Evidences for prevailing slow spindles and frontofugal modulation of the human anterior thalamic local field potentials, as well as for predominant fast sleep spindling in the parahippocampal gyrus are derived from invasive recordings of epilepsy patients. These new evidences are completed with findings on sleep spindles of healthy subjects indicating sex differences in spindle density (female male), frequency (female > male), hemispheric lateralization (region-specific sex differences), local-global nature (females more global), as well as inter- and intra-hemispheric synchronization (females > males). Some of the sex differences revealed in our studies are depending on age (density, amplitude, and frequency), menstrual cycle phase (oestrogen and progesterone levels → frequency) and contraceptive use (hemispheric laterality). We conclude that slow and fast sleep spindles travel different routes. Moreover, the sexual dimorphism of sleep spindles might reflect the sex differences in neurocognitive architectures. Future studies distinguishing slow-frontal from fast-parietal sleep spindles and considering the sex differences in spindle activity could increase the reproducibility of the findings in the field of sleep-state dependent neural oscillations.

S113 The thalamo-cortical system as central actor of NREM sleep

Neuronal activity in several brain regions is state dependent. This is best exemplified by the dramatic changes that occur in the electroencephalogram as states of vigilance transition from waking to sleep leading to brain waves of various frequencies. The main generator of these state dependent rhythmic activities is the thalamocortical system, a reciprocally interconnected network consisting of thalamocortical relay neurons, two types of thalamic inhibitory neurons including thalamic reticular neurons and local circuit interneurons and various neocortical principal cells and inhibitory interneurons. In the absence of sensory inputs, as happens during sleep and relaxed wakefulness neurons in the thalamus and neocortex engage in stereotyped rhythmic activity patterns spanning a wide range of frequencies, including slow waves, d-waves and sleep spindles. The generation of these rhythms is governed by an interplay between spatially and temporally coordinated synaptic interactions and intrinsic membrane properties of various thalamic and cortical neurons. Thalamic involvement in NREM sleep rhythms relies on a peculiar intrinsic cellular substrate of thalamic burst firing, the low-threshold Ca2+ spike. Cortico-thalamo-cortical synaptic interactions fine tune these intrinsic activity patterns to generate the plethora of state-dependent rhythmic activities.

Electrophysiological and microstructural features of sleep in children at high risk for depression: a preliminary study

ObjectiveThis preliminary study investigated electrophysiological and microstructural features of sleep in children and adolescents 4–18 years of age who were born to depressed mothers. MethodsA total of 31 healthy subjects (15 male and 16 female) participated in the study. In this sample, 20 children born to mothers diagnosed with Major Depressive Disorder (MDD) were designated as “high-risk”; 11 children born to mothers without a personal history of depression were designated as “low-risk.” Polysomnography including three-channel electroencephalography (EEG) was recorded for one night at the Pediatric Sleep Unit of the University Hospital of Lyon, France. Clinical and demographic data were collected. Sleep architectural parameters were analyzed. Sleep microstructure was assessed with the scoring of cyclic alternating pattern (CAP) and CAP measures were calculated. Spectral analysis was performed, and mean EEG band power was computed for each sleep stage. Sleep electrophysiological features (slow waves and sleep spindles) were detected, and related parameters were analyzed. Data were compared between high- and low-risk groups using Student t tests. ResultsA reduction in low-frequency spindle activity and slow spindles spatio-temporal characteristics over frontal and central derivations, and an altered distribution of CAP phase A subtypes (reduction of A1 over A2–3 ratio) were observed in the high-risk group relative to the low-risk group. ConclusionLimited spindles generation and increased non-rapid eye movement sleep instability, observed in children born to depressed mothers, might reflect functional anomalies in cortical plasticity that could represent a pathogenic factor or an epiphenomenon for MDD.

Sleep-dependent consolidation of face recognition and its relationship to REM sleep duration, REM density and Stage 2 sleep spindles.

Face recognition is a highly specialized capability that has implicit and explicit memory components. Studies show that learning tasks with facial components are dependent on rapid eye movement and non-rapid eye movement sleep features, including rapid eye movement sleep density and fast sleep spindles. This study aimed to investigate the relationship between sleep-dependent consolidation of memory for faces and partial rapid eye movement sleep deprivation, rapid eye movement density, and fast and slow non-rapid eye movement sleep spindles. Fourteen healthy participants spent 1night each in the laboratory. Prior to bed they completed a virtual reality task in which they interacted with computer-generated characters. Half of the participants (REMD group) underwent a partial rapid eye movement sleep deprivation protocol and half (CTL group) had a normal amount of rapid eye movement sleep. Upon awakening, they completed a face recognition task that contained a mixture of previously encountered faces from the task and new faces. Rapid eye movement density and fast and slow sleep spindles were detected using in-house software. The REMD group performed worse than the CTL group on the face recognition task; however, rapid eye movement duration and rapid eye movement density were not related to task performance. Fast and slow sleep spindles showed differential relationships to task performance, with fast spindles being positively and slow spindles negatively correlated with face recognition. The results support the notion that rapid eye movement and non-rapid eye movement sleep characteristics play complementary roles in face memory consolidation. This study also raises the possibility that fast and slow spindles contribute in opposite ways to sleep-dependent memory consolidation.

Enhanced Memory Consolidation Via Automatic Sound Stimulation During Non-REM Sleep.

Introduction:Slow-wave sleep (SWS) slow waves and sleep spindle activity have been shown to be crucial for memory consolidation. Recently, memory consolidation has been causally facilitated in human participants via auditory stimuli phase-locked to SWS slow waves.Aims:Here, we aimed to develop a new acoustic stimulus protocol to facilitate learning and to validate it using different memory tasks. Most importantly, the stimulation setup was automated to be applicable for ambulatory home use.Methods:Fifteen healthy participants slept 3 nights in the laboratory. Learning was tested with 4 memory tasks (word pairs, serial finger tapping, picture recognition, and face-name association). Additional questionnaires addressed subjective sleep quality and overnight changes in mood. During the stimulus night, auditory stimuli were adjusted and targeted by an unsupervised algorithm to be phase-locked to the negative peak of slow waves in SWS. During the control night no sounds were presented.Results:Results showed that the sound stimulation increased both slow wave (p = .002) and sleep spindle activity (p < .001). When overnight improvement of memory performance was compared between stimulus and control nights, we found a significant effect in word pair task but not in other memory tasks. The stimulation did not affect sleep structure or subjective sleep quality.Conclusions:We showed that the memory effect of the SWS-targeted individually triggered single-sound stimulation is specific to verbal associative memory. Moreover, the ambulatory and automated sound stimulus setup was promising and allows for a broad range of potential follow-up studies in the future.

Widespread reduction in sleep spindle activity in socially anxious children and adolescents

Social anxiety disorder (SAD) is one of the most prevalent psychiatric diseases typically emerging during childhood and adolescence. Biological vulnerabilities such as a protracted maturation of prefrontal cortex functioning together with heightened reactivity of the limbic system leading to increased emotional reactivity are discussed as factors contributing to the emergence and maintenance of SAD. Sleep slow wave activity (SWA, 0.75–4.5 Hz) and sleep spindle activity (9–16 Hz) reflect processes of brain maturation and emotion regulation. We used high-density electroencephalography to characterize sleep SWA and spindle activity and their relationship to emotional reactivity in children and adolescents suffering from SAD and healthy controls (HC). Subjectively rated arousal was assessed using an emotional picture-word association task. SWA did not differ between socially anxious and healthy participants. We found a widespread reduction in fast spindle activity (13–16 Hz) in SAD patients compared to HC. SAD patients rated negative stimuli to be more arousing and these arousal ratings were negatively correlated with fast spindle activity. These results suggest electrophysiological alterations that are evident at an early stage of psychopathology and that are closely linked to one core symptom of anxiety disorders such as increased emotional reactivity. The role of disturbed GABAergic neurotransmission is discussed as an underlying factor.

Tactile stimulation during sleep alters slow oscillation and spindle densities but not motor skill

Studies using targeted memory reactivation have shown that presentation of auditory or olfactory contextual cues during sleep can bias hippocampal reactivations towards the preferential replay of the cue-associated material, thereby resulting in enhanced consolidation of that information. If the same cortical ensembles are indeed used for encoding and storage of a given piece of information, forcing the sleeping brain to re-engage in task-intrinsic information processing should disturb the natural ongoing consolidation processes and therefore impair possible sleep benefits. Here we aimed at recreating an integral part of the sensory experience of a motor skill in a daytime nap, by means of a tactile stimulation. We hypothesized that tampering with the tactile component of a motor skill during sleep would result in hindered performance at retest, due to interference between the highly congruent incoming stimuli and the core skill trace. Contrary to our predictions, the tactile stimulation did not influence neither speed nor accuracy, when compared to natural sleep. However, an exploratory sleep EEG analysis revealed stimulation-induced alterations in the abundance and cortical topography of slow oscillations and spindles. These findings suggest that despite the lack of a significant effect on motor behavior, tactile stimulation induced changes in EEG features suggestive of a possible uncoupling between the sleep oscillations thought to underlie consolidation processes, i.e. slow oscillations and sleep spindles.

Fast sleep spindle reduction in schizophrenia and healthy first-degree relatives: association with impaired cognitive function and potential intermediate phenotype.

Several studies in patients with schizophrenia reported a marked reduction in sleep spindle activity. To investigate whether the reduction may be linked to genetic risk of the illness, we analysed sleep spindle activity in healthy volunteers, patients with schizophrenia and first-degree relatives, who share an enriched set of schizophrenia susceptibility genes. We further investigated the correlation of spindle activity with cognitive function in first-degree relatives and whether spindle abnormalities affect both fast (12-15Hz) and slow (9-12Hz) sleep spindles. We investigated fast and slow sleep spindle activity during non-rapid eye movement sleep in a total of 47 subjects comprising 17 patients with schizophrenia, 13 healthy first-degree relatives and 17 healthy volunteers. Groups were balanced for age, gender, years of education and estimated verbal IQ. A subsample of relatives received additional testing for memory performance. Compared to healthy volunteers, fast spindle density was reduced in patients with schizophrenia and healthy first-degree relatives following a pattern consistent with an assumed genetic load for schizophrenia. The deficit in spindle density was specific to fast spindles and was associated with decreased memory performance. Our findings indicate familial occurrence of this phenotype and thus support the hypothesis that deficient spindle activity relates to genetic liability for schizophrenia. Furthermore, spindle reductions predict impaired cognitive function and are specific to fast spindles. This physiological marker should be further investigated as an intermediate phenotype of schizophrenia. It could also constitute a target for drug development, especially with regard to cognitive dysfunction.

Slow rhythms and sleep spindles in early infancy

ObjectiveTo investigate the slow rhythm and its relationship to spindling in early infancy. MethodsWe analyzed sleep MEG recordings containing sleep spindles, taken from 7 normal, healthy subjects at conceptional age 46–63 weeks in 21 sessions. ResultsWe show that the sleep MEG in early infancy contains a slow rhythm, centered at approximately 0.2Hz, which showed a striking association with spindling. The slow rhythm grouped sleep spindles, which were clock-like with a recurrence rate of approximately 0.1Hz. ConclusionsThe association of the 0.2Hz oscillation and low delta rhythms with spindling was so strong as to suggest that they may play a critical role during brain development in the genesis of sleep spindles. SignificanceInfant brain rhythms exhibit relatively simple, regular behavior, allowing the relationships between them to be more easily discerned.

Stage 2 Sleep EEG Sigma Activity and Motor Learning in Childhood ADHD: A Pilot Study

Attention deficit hyperactivity disorder (ADHD) is associated with deficits in motor learning and sleep. In healthy adults, overnight improvements in motor skills are associated with sleep spindle activity in the sleep electroencephalogram (EEG). This association is poorly characterized in children, particularly in pediatric ADHD. Polysomnographic sleep was monitored in 7 children with ADHD and 14 typically developing controls. All children were trained on a validated motor sequence task (MST) in the evening with retesting the following morning. Analyses focused on MST precision (speed–accuracy trade-off). NREM Stage 2 sleep EEG power spectral analyses focused on spindle-frequency EEG activity in the sigma (12–15 Hz) band. The ADHD group demonstrated a selective decrease in power within the sigma band. Evening MST precision was lower in ADHD, yet no difference in performance was observed following sleep. Moreover, ADHD status moderated the association between slow sleep spindle activity (12–13.5 Hz) and overnight improvement; spindle-frequency EEG activity was positively associated with performance improvements in children with ADHD but not in controls. These data highlight the importance of sleep in supporting next-day behavior in ADHD while indicating that differences in sleep neurophysiology may contribute to deficits in this population.