Characteristics Of Sleep Spindles Research Articles

Spindles in WAG/Rij Rats with Absence Epilepsy and Comorbid Depression

WAG/Rij rats are a valid model of absence epilepsy and comorbid depression. We have previously shown that WAG/Rij rats have disturbances in the sleep-wake cycle and changes in the characteristics of sleep spindles. A negative correlation was also found between the number of spike-wave discharges (SWD) and the duration of rapid eye movement (REM) sleep. Clinical evidence suggests that the traditional antidepressants imipramine and fluoxetine are effective in suppressing symptoms of depression, but may have a negative impact on the sleep-wake cycle and comorbid epilepsy in patients. Our previous studies in WAG/Rij rats showed that imipramine, when administered chronically, increases the number of SWDs, while fluoxetine at the same dose reduces their number, although both antidepressants have a pronounced antidepressant effect. Comparison of the effects of the antidepressants imipramine and fluoxetine on the sleep-wake cycle and sleep spindles in WAG/Rij rats remains unstudied. The purpose of this work is to find out: 1) what effects do imipramine and fluoxetine have on the sleep-wake cycle and the characteristics of sleep spindles in WAG/Rij rats and 2) whether there are differences in their effects. To achieve this goal, the characteristics of the sleep-wake cycle and sleep spindles were compared in WAG/Rij rats after chronic administration of antidepressants and saline and in non-epileptic Wistar rats. Administration of imipramine led to a significant decrease in the duration of REM sleep. The administration of imipramine, compared with fluoxetine, also increased the latency of the transition to sleep and the transition to REM sleep. Sleep spindle amplitude was significantly increased by both antidepressants. However, the spectral power density of “slow” and “medium” spindles, which predominate in WAG/Rij rats compared to Wistar rats, was significantly higher after administration of imipramine than fluoxetine. The results suggest that imipramine causes greater negative changes in the sleep-wake cycle and sleep spindles than fluoxetine. Studies in the WAG/Rij rat model indicate that fluoxetine is more preferable antidepressant for the treatment of depressive disorders comorbid with absence epilepsy, since it does not cause a significant deterioration in sleep quality. These results are consistent with clinical data.

Comparison of the Effect of the Antidepressants Imipramine and Fluoxetine on the Sleep–Wake Cycle and Characteristics of Sleep Spindles in Wag/Rij Rats with Absence Epilepsy and Comorbid Depression

Comparison of the Effect of the Antidepressants Imipramine and Fluoxetine on the Sleep–Wake Cycle and Characteristics of Sleep Spindles in Wag/Rij Rats with Absence Epilepsy and Comorbid Depression

Maternal Methyl-Enriched Diet Normalizes Characteristics of the Sleep–Wake Cycle and Sleep Spindles in Adult Offspring of WAG/Rij Rats with Genetic Absence Epilepsy

It has been previously shown that the perinatal maternal methyl-enriched diet (MED) reduces the number of spike-wave discharges (SWDs) and behavioral symptoms of depression in the adult offspring of WAG/Rij rats. Epilepsy and depression are usually accompanied by disturbances in the sleep-wake cycle. SWDs and sleep spindles are different manifestations of thalamocortical activity It is assumed that pathological alterations in the thalamocortical system that lead to SWD also change the sleep spindles. It is possible that the maternal MED has a positive effect not only on the SWD, but also on the sleep spindles. The purpose of this work is to find out whether maternal MED affects the sleep-wake cycle and whether it changes the characteristics of sleep spindles in adult offspring of WAG/Rij rats. It has been shown that in the offspring of WAG/Rij rats born to mothers who consumed MED during the perinatal period compared to the offspring whose mothers consumed control diet (CD), the relative duration of REM sleep significantly increases. In the offspring of WAG/Rij rats whose mothers consumed MED, the relative duration of REM sleep and the number of its episodes become indistinguishable from those in non-epileptic Wistar rats. Maternal MED also increases the number of transitions from slow-wave to REM sleep. There is a significant negative correlation between the number of SWDs and the duration of REM sleep. Maternal MED compare to CD decreased the amplitude and spectral power density of sleep spindles. They became much closer to the amplitude and spectral power of density of sleep spindles in Wistar rats. Thus, maternal MED normalizes characteristics of the sleep-wake cycle and sleep spindles in adult offspring of WAG/Rij rats. We hypothesize that this positive effect is associated with a reduction in the symptoms of absence epilepsy and comorbid depression, as well as with the correction of the activity of the thalamocortical system.

More than just immaturity: evidence supporting the hypothesis that sleep spindle characteristics reflect GABAergic depolarization in infancy.

Sleep spindles are thalamocortical oscillations with waxing-waning morphology, which comprise the key electroencephalographic (EEG) hallmark of stage 2 non-rapid eye movement sleep. The functional role of sleep spindles is not sufficiently clear, but there is a large body of literature that indicates the relationship between spindle activity and neural plasticity. Many of the spindle parameters (frequency, configuration, duration, density, and topography) vary significantly throughout life. However, the long duration, asynchrony and sharp morphology are the most distinctive characteristics of sleep spindles in infants. This unique infantile phenotype of sleep spindles typically changes after approximately one year of postnatal life in humans. Considering that EEG reflects brain electrochemical activity, there is evidence to suggest that substantial neurochemical events underlie these changes. In this paper, we hypothesize that the GABA (gamma-aminobutyric acid) shift is a key event influencing the sleep spindle phenotype during infancy. We briefly review evidence for the relation between infantile sleep spindles and depolarizing GABA transmission occurring in the developing brain.

0191 Characteristics of sleep spindles across development in males with Duchenne/Becker Muscular Dystrophy Disorder

Abstract Introduction Sleep supports cognition, in particular, the consolidation of memories. Sleeping brain rhythms, such as slow oscillations (1hz) and spindles (9-15 Hz), play a key role in facilitating this consolidation. Our prior research reported age-associated declines in slow oscillations in Duchenne and Becker Muscular Dystrophy (DMD/BMD) (Simon et al., 2020). Here, we characterize age-associated changes in sleep spindle characteristics across development in this group. Methods Following our 2020 analysis, we retrospectively analyzed the clinical sleep studies of 28 DMD/BMD males (Age span: 4 to 20 years). We applied our spindle detection algorithm to six electrodes (F3, F4, C3, C4, 01, O2). We assessed spindle density, frequency, and amplitude based on age (child, early adolescent, and late adolescent). Results We conducted rmANOVAs to evaluate each spindle characteristics using within-factors (Stage and Electrode) and between-factor (Age). We found significantly more spindles with longer durations in N2 than N3; greater spindle density at frontal compared to occipital regions; and higher amplitudes at central compared to frontal sites. We found no age-associated changes in these spindle metrics. We did find an age-associated change in the frequency of spindles, with significantly greater average spindle amplitude increasing significantly with age. Conclusion In line with prior research, we found more spindles in N2 than N3 and greater spindle density at frontal compared to posterior electrodes. In contrast to our previous research demonstrating age-associated declines in slow oscillations, our current analyses show minimal age-associated changes in spindle characteristics from 4 to 20 years. Further analysis is required to assess for age-associated changes in spindle-slow oscillation coupling occur across development. Our findings have implications for functional changes in sleep-dependent cognition mechanisms across development in BMD/DMD. Support (If Any)

Altered sleep spindles and slow waves during space shuttle missions

Sleep deficiencies and associated performance decrements are common among astronauts during spaceflight missions. Previously, sleep in space was analyzed with a focus on global measures while the intricate structure of sleep oscillations remains largely unexplored. This study extends previous findings by analyzing how spaceflight affects characteristics of sleep spindles and slow waves, two sleep oscillations associated with sleep quality and quantity, in four astronauts before, during and after two Space Shuttle missions. Analysis of these oscillations revealed significantly increased fast spindle density, elevated slow spindle frequency, and decreased slow wave amplitude in space compared to on Earth. These results reflect sleep characteristics during spaceflight on a finer electrophysiological scale and provide an opportunity for further research on sleep in space.

Characteristics of sleep spindles in school-aged children with attention-deficit/hyperactivity disorder

ObjectiveAttention deficit/hyperactivity disorder (ADHD) is a complex disorder, characterized by different presentations with distinct cognitive and neurobiological characterizations. Here we aimed to investigate whether sleep spindle activity, which has been associated with brain maturation, may be a potential biomarker able to differentiate ADHD presentations in school-aged children (7–11 years). MethodSpindle characteristics were extracted from overnight polysomnography in 74 children (27 ADHD-Inattentive [IQ = 96.04], 25 ADHD-hyperactive/impulsive [IQ = 98.9], and 22 ADHD-combined [IQ = 96.1]). We obtained data of the frontal (Fz) and parietal (Pz) derivations using a validated spindle detection algorithm. ResultsChildren with ADHD showed a higher number and density of slow compared to fast spindles which were more frequent in frontal area. No differences were observed among ADHD presentations for any spindle characteristics. Spindle frequency and density increased with age, indicating an age-dependent maturation of different sleep spindles. However, no associations between IQ and spindle characteristics were observed. ConclusionsIn children with ADHD the spindle characteristics evolve with age but sleep spindle activity does not seem to be a valid biomarker of ADHD phenotypes or general cognitive ability.

Analysis of sleep spindles in children with Asperger's syndrome.

Sleep spindles are an element of the sleep microstructure observed on the EEG during the NREM sleep phase. Sleep spindles are associated to sleep stability functions as well as memory consolidation and optimization of different cognitive processes. On the other hand, Asperger’s syndrome (AS) is a generalized developmental disorder in which cognitive and sleep disturbances have been described. In this study we analyzed different characteristics of sleep spindles in a group of children with AS and compared them with sleep spindles of a group of children with typical development paired by age; both groups ranged from 6 to 12 years of age and were all male. We observed a statistically significant decrease in sleep spindles intrinsic frequency in different brain regions in the AS group in relation to the typical development group. This finding could be due to immaturity in brain regions related to the integration of sleep spindles; and this immaturity could be related with cognitive aspects in these patients.

Benign epilepsy with centrotemporal spikes: Is there a thalamocortical network dysfunction present?

IntroductionBenign epilepsy of childhood with centrotemporal spikes (BECTS) is one of the most frequently seen epileptic syndromes in childhood. It is characterized by centrotemporal spikes (CTS) on electroencephalography (EEG) that are typically activated by drowsiness and stage N2 sleep. The location, frequency, and amplitude of the spikes may vary in different EEG records of the same patient, supporting the presence of a global pathology rather than a focal one. Despite the well-known relation between BECTS and stage N2 sleep, the results of sleep studies have been diverse and have mainly focused on sleep cycles. The characteristics of sleep spindles in the interictal periods have not been studied well. MethodsA retrospective study involving patients with BECTS who were admitted to the Gazi University, Faculty of Medicine, Department of Pediatric Neurology from January 2017 to October 2018 was conducted herein. Patients with BECTS and age-matched controls who had stage N2 sleep records of 10 min were enrolled for spindle amplitude (peak-to-peak difference in spindle voltage), frequency (number of waveforms per second), and duration and density (number of spindle bursts/minute of stage N2 sleep). ResultsA total of 30 children with BECTS and 20 age-matched healthy peers were enrolled in the study. There were no significant differences between the age and sex of the patients. Statistically significant lower mean values of the amplitude, and duration and density of the spindle activity were observed in patients with BECTS when compared to the controls (P: 0.034, P: 0.016, and 0.020, respectively). Additionally, the risk of epilepsy was found to increase by 1.9 %, by the decrease of the mean amplitude of the spindles by 1 mV when compared to control group. ConclusionThe interictal records of stage N2 sleep differed in the patients with BECTS when compared to the controls. Findings related to the stage N2 sleep of the present study may suggest a network problem involving the thalamus and thalamocortical pathways in patients with BECTS.

Frequency-temporal characteristics of sleep spindles in IGE with variable phenotypes in adults

A Mathematical Wave Analysis was conducted to study the frequency-temporal characteristics of sleep spindles in idiopathic generalized epilepsy (IGE) with variable phenotypes in adults. In resistant generalized tonic-clonic seizures (GTCS), the maximum duration of the stationary part of the sleep spindle in the 10–12Hz frequency band in the frontal and parietal regions was greater with Juvenile Absence Epilepsy compared with Juvenile Myoclonic Epilepsy and IGE with isolated GTCS. In patients with GTCS remission who took antiepileptic drugs (AED’s) in the anamnesis, the frequency-time characteristics of the sleep spindle were not different. In the entire group, the maximum duration of the stationary part of the sleep spindles in patients with IGE with a variable phenotype receiving AED’s was significantly less than in patients who stopped receiving AED’s. The revealed differences in the duration of the stationary part of the sleep spindles are due to various pathogenetic mechanisms underlying the different types of generalized seizures in adults, and can be used to refine the subtype of the IGE and evaluate the efficacy of the AED’s.

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.

The reciprocal relation between sleep and memory in infancy: Memory-dependent adjustment of sleep spindles and spindle-dependent improvement of memories.

Sleep spindle activity in infants supports their formation of generalized memories during sleep, indicating that specific sleep processes affect the consolidation of memories early in life. Characteristics of sleep spindles depend on the infant's developmental state and are known to be associated with trait‐like factors such as intelligence. It is, however, largely unknown which state‐like factors affect sleep spindles in infancy. By varying infants’ wake experience in a within‐subject design, here we provide evidence for a learning‐ and memory‐dependent modulation of infant spindle activity. In a lexical‐semantic learning session before a nap, 14‐ to 16‐month‐old infants were exposed to unknown words as labels for exemplars of unknown object categories. In a memory test on the next day, generalization to novel category exemplars was tested. In a nonlearning control session preceding a nap on another day, the same infants heard known words as labels for exemplars of already known categories. Central–parietal fast sleep spindles increased after the encoding of unknown object–word pairings compared to known pairings, evidencing that an infant's spindle activity varies depending on its prior knowledge for newly encoded information. Correlations suggest that enhanced spindle activity was particularly triggered, when similar unknown pairings were not generalized immediately during encoding. The spindle increase triggered by previously not generalized object–word pairings, moreover, boosted the formation of generalized memories for these pairings. Overall, the results provide first evidence for a fine‐tuned regulation of infant sleep quality according to current consolidation requirements, which improves the infant long‐term memory for new experiences.

O212 Shortening of the duration of sleep spindles; A diagnostic biomarker for post-traumatic epilepsy

Objective We previously showed that almost 100% of the electroencephalographic generalized seizures after lateral fluid-percussion (FPI) induced traumatic brain injury (TBI) occurred in the transition between stage III and REM sleep. Our objective was to investigate whether the change in the characteristics of sleep spindles would serve as diagnostic biomarkers for post-traumatic epilepsy (PTE). Methodology Analysis groups included 26 TBI rats with epilepsy, 60 TBI rats without epilepsy, and 24 sham-operated controls. A 24-h epoch of a continuous 3-wk video-EEG recorded at 3 months after lateral FPI-induced was divided into 2947 epochs (30 seceach), andsleep stages were identified. Then, the graphoelements (spindles) occurring during the transition stage III and REM sleep were identified and traced, and their duration was measured. Results Spindle duration (SD) was shorter in the TBI than the Sham group (p = 0.029). In the TBI group, rats with epilepsy had shorter SD than rats without epilepsy (p = 0.0001). ROC analysis showed that spindle duration differentiated TBI animals with or without epilepsy with high sensitivity and specificity as the area under the curve (AUC) was 0.884 (sensitivity 81% at 97% specificity; SD Conclusion Our data show that the shortening of SDs during the transition from stage III to REM sleep differentiates epileptic from non-epileptic animals after TBI. Significance Shortening of spindle duration in the transition between stage III and REM sleep is a diagnostic biomarker for post-traumatic epilepsy.

Age-Dependent Increase of Absence Seizures and Intrinsic Frequency Dynamics of Sleep Spindles in Rats.

The risk of neurological diseases increases with age. In WAG/Rij rat model of absence epilepsy, the incidence of epileptic spike-wave discharges is known to be elevated with age. Considering close relationship between epileptic spike-wave discharges and physiologic sleep spindles, it was assumed that age-dependent increase of epileptic activity may affect time-frequency characteristics of sleep spindles. In order to examine this hypothesis, electroencephalograms (EEG) were recorded in WAG/Rij rats successively at the ages 5, 7, and 9 months. Spike-wave discharges and sleep spindles were detected in frontal EEG channel. Sleep spindles were identified automatically using wavelet-based algorithm. Instantaneous (localized in time) frequency of sleep spindles was determined using continuous wavelet transform of EEG signal, and intraspindle frequency dynamics were further examined. It was found that in 5-months-old rats epileptic activity has not fully developed (preclinical stage) and sleep spindles demonstrated an increase of instantaneous frequency from beginning to the end. At the age of 7 and 9 months, when animals developed matured and longer epileptic discharges (symptomatic stage), their sleep spindles did not display changes of intrinsic frequency. The present data suggest that age-dependent increase of epileptic activity in WAG/Rij rats affects intrinsic dynamics of sleep spindle frequency.

Time-frequency characteristics and dynamics of sleep spindles in WAG/Rij rats with absence epilepsy

In rat models of absence epilepsy, epileptic spike-wave discharges appeared in EEG spontaneously, and the incidence of epileptic activity increases with age. Spike-wave discharges and sleep spindles are known to share common thalamo-cortical mechanism, suggesting that absence seizures might affect some intrinsic properties of sleep spindles. This paper examines time–frequency EEG characteristics of anterior sleep spindles in non-epileptic Wistar and epileptic WAG/Rij rats at the age of 7 and 9 months. Considering non-stationary features of sleep spindles, EEG analysis was performed using Morlet-based continuous wavelet transform. It was found, first, that the average frequency of sleep spindles in non-epileptic Wistar rats was higher than in WAG/Rij (13.2 vs 11.2Hz). Second, the instantaneous frequency ascended during a spindle event in Wistar rats, but it was constant in WAG/Rij. Third, in WAG/Rij rats, the number and duration of epileptic discharges increased in a period between 7 and 9 months of age, but duration and mean value of intra-spindle frequency did not change. In general, age-dependent aggravation of absence seizures in WAG/Rij rats did not affect EEG properties of sleep spindles; it was suggested that pro-epileptic changes in thalamo-cortical network in WAG/Rij rats might prevent dynamic changes of sleep spindles that were detected in Wistar.

Iron-deficiency anemia is associated with altered characteristics of sleep spindles in NREM sleep in infancy.

To determine the effects of iron-deficiency anemia on the development of non-rapid-eye-movement (NREM) sleep stages, as indexed by sleep spindles. Patterns of sleep spindles during NREM sleep stages 2 and 3-4 (slow-wave-sleep, SWS) were compared in 26 otherwise healthy 6-month-old Chilean infants with iron-deficiency anemia and 18 non-anemic control infants. From polygraphic recordings, EEG activity was analyzed for sleep spindles to assess their number (density), duration, frequency, and inter-spindle interval. Iron-deficient anemic infants differed from the control group by having sleep spindles with reduced density, lower frequency, and longer inter-spindle intervals in NREM sleep stage 2 and SWS. These results provide evidence of delayed sleep spindle patterns in iron-deficient anemic infants, suggesting that iron is an essential micronutrient for the normal progression of NREM sleep pattern development in the human.

Daytime naps, motor memory consolidation and regionally specific sleep spindles.

BackgroundIncreasing evidence demonstrates that motor-skill memories improve across a night of sleep, and that non-rapid eye movement (NREM) sleep commonly plays a role in orchestrating these consolidation enhancements. Here we show the benefit of a daytime nap on motor memory consolidation and its relationship not simply with global sleep-stage measures, but unique characteristics of sleep spindles at regionally specific locations; mapping to the corresponding memory representation.Methodology/Principal FindingsTwo groups of subjects trained on a motor-skill task using their left hand – a paradigm known to result in overnight plastic changes in the contralateral, right motor cortex. Both groups trained in the morning and were tested 8 hr later, with one group obtaining a 60–90 minute intervening midday nap, while the other group remained awake. At testing, subjects that did not nap showed no significant performance improvement, yet those that did nap expressed a highly significant consolidation enhancement. Within the nap group, the amount of offline improvement showed a significant correlation with the global measure of stage-2 NREM sleep. However, topographical sleep spindle analysis revealed more precise correlations. Specifically, when spindle activity at the central electrode of the non-learning hemisphere (left) was subtracted from that in the learning hemisphere (right), representing the homeostatic difference following learning, strong positive relationships with offline memory improvement emerged–correlations that were not evident for either hemisphere alone.Conclusions/SignificanceThese results demonstrate that motor memories are dynamically facilitated across daytime naps, enhancements that are uniquely associated with electrophysiological events expressed at local, anatomically discrete locations of the brain.

Characteristics of human EEG sleep spindles assessed by Gabor transform

The aim of this study is to show an application of the Gabor transform on the detection and characterization of human sleep EEG spindles in a sample of 10 healthy young adults, trying to identify the most useful parameters that can be used for the automatic detection and characterization of such events.

The effects of normal aging on sleep spindle and K-complex production

Despite a relatively large body of literature describing the characteristics of sleep spindles and K-complexes in young adults, relatively little research has been conducted in older individuals. The general consensus from the few studies that have addressed this issue is that there is a progressive decrease in the number of spindles and K-complexes with age, although there is large intra-individual variation. Whether or not these changes are an inevitable consequence of the aging process can be addressed by studying healthy older adults who provide an example of the effects of age independently from those of disease. Fourteen young adults (mean age=21.4+/-2.5 years) and 20 older adults (mean age=75.5+/-6.3 years) participated in the study. All subjects were neurologically and medically healthy and were not taking any medications with a known effect on the central nervous system or sleep. For each subject, a number of characteristics were determined including the number, density (SS/min), amplitude and frequency of all spindles as well as the number and density of K-complexes (KC/min). Spindle number, density and duration as well as K-complex number and density were all significantly lower in the elderly compared to the young adults. The EEG frequency within the spindles was significantly higher in the elderly, although the absolute difference was less than 0.5 Hz. Multiple regression analysis indicated that spindle duration and K-complex density were able to predict over 90% of the variance in age. The age-related decrease in sleep spindle and K-complex density is consistent with previous reports and may be interpreted as an age-related alteration of thalamocortical regulatory mechanisms.

Sleep spindle characteristics in healthy subjects of different age groups

Objectives: Few studies have quantified the various characteristics of sleep spindles (SS) in groups of normal human subjects. The aim of the present study was to look at the effects of age on the number, density, duration, intra-spindle frequency, and periodicity of SS during stage 2 sleep in normal subjects of different age groups.Methods: Thirty-six healthy subjects participated in the study. They were divided into 6 age groups: 10–19, 20–29, 30–39, 40–49, 50–59 and 60–69 years.Results: The results show that there is a progressive decrease in SS number, density, duration and a progressive increase in intra-spindle frequency with age. These changes occur mainly in the first 4 decades, except for SS number and density, for which the changes seem to continue until the sixth decade. The present study also reveals a clear periodicity of SS in human sleep. SS occur every 3–6 s, and the modal value of inter-spindle intervals increases with aging.Conclusions: The progressive decrease in the number of SS and slow-wave sleep time with age suggests that SS are part of sleep promoting mechanisms. The negative correlation found between SS density and sleep efficiency in the present study is congruent with the sleep maintenance role of SS.