The aging slow wave: a shifting amalgam of distinct slow wave and spindle coupling subtypes define slow wave sleep across the human lifespan

Study ObjectivesSlow wave and spindle coupling supports memory consolidation, and loss of coupling is linked with cognitive decline and neurodegeneration. Coupling is proposed to be a possible biomarker of neurological disease, yet little is known about the different subtypes of coupling that normally occur throughout human development and aging. Here we identify distinct subtypes of spindles within slow wave upstates and describe their relationships with sleep stage across the human lifespan.MethodsCoupling within a cross-sectional cohort of 582 subjects was quantified from stages N2 and N3 sleep across ages 6–88 years old. Results were analyzed across the study population via mixed model regression. Within a subset of subjects, we further utilized coupling to identify discrete subtypes of slow waves by their coupled spindles.ResultsTwo different subtypes of spindles were identified during the upstates of (distinct) slow waves: an “early-fast” spindle, more common in stage N2 sleep, and a “late-fast” spindle, more common in stage N3. We further found stages N2 and N3 sleep contain a mixture of discrete subtypes of slow waves, each identified by their unique coupled-spindle timing and frequency. The relative contribution of coupling subtypes shifts across the human lifespan, and a deeper sleep phenotype prevails with increasing age.ConclusionsDistinct subtypes of slow waves and coupled spindles form the composite of slow wave sleep. Our findings support a model of sleep-dependent synaptic regulation via discrete slow wave/spindle coupling subtypes and advance a conceptual framework for the development of coupling-based biomarkers in age-associated neurological disease.     

Spindles are highly heritable as identified by different spindle detectors

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

Analysis of oscillatory patterns in the human sleep EEG using a novel detection algorithm

The different brain states during sleep are characterized by the occurrence of distinct oscillatory patterns such as spindles or delta waves. Using a new algorithm to detect oscillatory events in the electroencephalogram (EEG), we studied their properties and changes throughout the night. The present approach was based on the idea that the EEG may be described as a superposition of stochastically driven harmonic oscillators with damping and frequency varying in time. This idea was implemented by fitting autoregressive models to the EEG data. Oscillatory events were detected, whenever the damping of one or more frequencies was below a predefined threshold. Sleep EEG data of eight healthy young males were analyzed (four nights per subject). Oscillatory events occurred mainly in three frequency ranges, which correspond roughly to the classically defined delta (0-4.5 Hz), alpha (8-11.5 Hz) and sigma (11.5-16 Hz) bands. Their incidence showed small intra- but large inter-individual differences, in particular with respect to alpha events. The incidence and frequency of the events was characteristic for sleep stages and non-rapid eye movement (REM)-REM sleep cycles. The mean event frequency of delta and sigma (spindle) events decreased with the deepening of sleep. It was higher in the second half of the night compared with the first one for delta, alpha and sigma oscillations. The algorithm provides a general framework to detect and characterize oscillatory patterns in the EEG and similar signals.     

Improvements in cognitive function and quantitative sleep electroencephalogram in obstructive sleep apnea after six months of continuous positive airway pressure treatment

Study ObjectivesUntreated obstructive sleep apnea (OSA) is associated with cognitive deficits and altered brain electrophysiology. We evaluated the effect of continuous positive airway pressure (CPAP) treatment on quantitative sleep electroencephalogram (EEG) measures and cognitive function.MethodsWe studied 167 patients with OSA (age 50 ± 13, AHI 35.0 ± 26.8) before and after 6 months of CPAP. Cognitive tests assessed working memory, sustained attention, visuospatial scanning, and executive function. All participants underwent overnight polysomnography at baseline and after CPAP. Power spectral analysis was performed on EEG data (C3-M2) in a sub-set of 90 participants. Relative delta EEG power and sigma power in NREM and EEG slowing in REM were calculated. Spindle densities (events/min) in N2 were also derived using automated spindle event detection. All outcomes were analysed as change from baseline.ResultsCognitive function across all cognitive domains improved after six months of CPAP. In our sub-set, increased relative delta power (p < .0001) and reduced sigma power (p = .001) during NREM were observed after the 6-month treatment period. Overall, fast and slow sleep spindle densities during N2 were increased after treatment.ConclusionsCognitive performance was improved and sleep EEG features were enhanced when assessing the effects of CPAP. These findings suggest the reversibility of cognitive deficits and altered brain electrophysiology observed in untreated OSA following six months of treatment.     

Effect of prolonged wakefulness on electroencephalographic oscillatory activity during sleep

The human sleep electroencephalogram (EEG) is characterized by the occurrence of distinct oscillatory events such as delta waves, sleep spindles and alpha activity. We applied a previously proposed algorithm for the detection of such events and investigated their incidence and frequency in baseline and recovery sleep after 40 h of sustained wakefulness in 27 healthy young subjects. The changes in oscillatory events induced by sleep deprivation were compared to the corresponding spectral changes. Both approaches revealed, on average, an increase in low frequency activity and a decrease in spindle activity after sleep deprivation. However, the increase of oscillatory events in the delta range and decrease in the sigma range occurred in a more restricted frequency range compared to spectral changes. The mean relative power spectra showed a significant increase in theta and alpha activity after sleep deprivation while, on average, the event analysis showed only a weak effect in the theta band. The reason for this discrepancy is that the spectral analysis does not distinguish between diffuse activity and clearly visible temporally localized oscillations, while the event analysis would detect only the latter. Additionally, only a few individuals clearly showed activity in the theta or alpha frequency bands. Conversely, event analysis revealed that some individuals showed an increased rate of sleep spindles after sleep deprivation, a fact that was not evident in the relative power spectra due to a decrease in background activity. The two methods complement each other and facilitate the interpretation of distinct changes induced by prolonged wakefulness in sleep EEG.     

Changes in electroencephalographic power and bicoherence spectra according to depth of dexmedetomidine sedation in patients undergoing spinal anesthesia

Background: Assessment the depth of dexmedetomidine sedation using electroencephalographic (EEG) features can improve the quality of procedural sedation. Previous volunteer studies of dexmedetomidine-induced EEG changes need to be validated, and changes in bicoherence spectra during dexmedetomidine sedation has not been revealed yet. We aimed to investigate the dexmedetomidine-induced EEG change using power spectral and bicoherence analyses in the clinical setting.Patients and Methods: Thirty-six patients undergoing orthopedic surgery under spinal anesthesia were enrolled in this study. Dexmedetomidine sedation was conducted by the stepwise increase in target effect site concentration (Ce) while assessing sedation levels. Bispectral index (BIS) and frontal electroencephalography were recorded continuously, and the performance of BIS and changes in power and bicoherence spectra were analyzed with the data from the F3 electrode.Results: The prediction probability values for detecting different sedation levels were 0.847, 0.841, and 0.844 in BIS, 95% spectral edge frequency, and dexmedetomidine Ce, respectively. As the depth of sedation increased, δ power increased, but high β and γ power decreased significantly (P <0.001). α and spindle power increased significantly under light and moderate sedation (P <0.001 in light vs baseline and deep sedation; P = 0.002 and P <0.001 in moderate sedation vs baseline and deep sedation, respectively). The bicoherence peaks of the δ and α-spindle regions along the diagonal line of the bicoherence matrix emerged during moderate and deep sedation. Peak bicoherence in the δ area showed sedation-dependent increases (29.93%±7.38%, 36.72%±9.70%, 44.88%±12.90%; light, moderate, and deep sedation; P = 0.008 and P <0.001 in light sedation vs moderate and deep sedation, respectively; P = 0.007 in moderate sedation vs deep sedation), whereas peak bicoherence in the α-spindle area did not change (22.92%±4.90%, 24.72%±4.96%, and 26.96%±8.42%, respectively; P=0.053).Conclusions: The increase of δ power and the decrease of high-frequency power were associated with the gradual deepening of dexmedetomidine sedation. The δ bicoherence peak increased with increasing sedation level and can serve as an indicator reflecting dexmedetomidine sedation levels.     

Evaluation of Allergenicity on a ω-5 Gliadin-Deficient Cultivar in Wheat-Dependent Exercise-Induced Anaphylaxis

Purposeω-5 gliadin is the major allergen that causes wheat-dependent exercise-induced anaphylaxis (WDEIA). Recently, a missing mutant wheat cultivar at 1B chromosome Glu-B3 and closely linked Gli-B1 loci was bred. This cultivar (ω5D) has a deficiency in ω-5 and γ-gliadins as well as some low-molecular-weight glutenins. We evaluated specific immunoglobulin E (sIgE) reactivity of the ω5D in WDEIA patients compared to wild-type cultivar.MethodsSerum samples from 14 WDEIA and 7 classic wheat allergy patients were used to compare the allergenicity of ω5D and wild-type cultivars using immunoglobulin E immunoblotting, enzyme-linked immunosorbent assay (ELISA), and ImmunoCAP inhibition assays.ResultsImmunoblotting revealed that ω5D extracts had less sIgE binding to gliadins and glutenins in WDEIA sera than wild-type extracts. Immunoblot inhibition assay for gliadin sIgE reactivity also showed that ω5D gliadins had less allergenicity than wild-type gliadins. ELISA inhibition assay showed stronger allergenicity of gliadins than glutenins, although they had cross-reactivity. This assay also showed that the 50% inhibitory concentrations (IC50) of ω5D extracts against gliadin- or glutenin-sIgE reactivity were approximately 4-fold higher in WDEIA patients than those of wild-type extracts. The inhibition capacity of ω5D gliadins against recombinant ω-5 gliadin-sIgE reactivity was also lower in WDEIA patients than that of wild-type.ConclusionsThe allergenicity of the ω5D cultivar is markedly lower for WDEIA patients in the sIgE inhibition tests. These results suggest that the ω5D cultivar may be a safe alternative for WDEIA patients.     

Vitrification of in vitro matured oocytes: effects on meiotic spindle configuration and mitochondrial function

Background: In the assisted reproductive technique, cryopreserving in vitro-matured oocytes is a new strategy to extend the pool of total oocytes. However, oocyte cryopreservation technique is still unsatisfied. So the assessment of cyro-damage on meiotic spindle and mitochondrial function is necessary to evaluate and refine the current protocols. Material and Methods: The immature oocytes were donated from women undergoing ICSI cycles. Cytoskeleton was assessed by α-tubulin and mitochondria through the fluorescent ΔΨm reporter JC-1. Results: Relative inner membrane potential in MII oocytes from vIVM group sharply decreased, compared with the control (n=30) (1.397 vs. 1.019, P<0.05). 45.2% defective spindles were observed in fIVM group, compared with 48.0% in vIVM group (P>0.05). Oocytes in fIVM (35.5%, 11/31) and vIVM (40.0%, 10/25) displayed abnormal chromosome (P>0.05). Conclusion: In vitro maturation (IVM) has an adverse effect on the organization of spindle and chromosome, and no significantly effect on spindle and chromosome was discovered after vitrification-thaw cycle, while there was obvious damage of oocyte mitochondrial function of in vitro-matured oocyte detected after warming, which may be the reason of the low following developmental potential.     

Development and comparison of four sleep spindle detection methods

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

Genetic influence of Apolipoprotein E gene ε2/ε3/ε4 isoforms on odds of mesial temporal lobe epilepsy

ObjectiveThe potential correlation between the ε2/ε3/ε4 variants of the ApoE (Apolipoprotein E) gene and the odds of mesial temporal lobe epilepsy was investigated.MethodsThe database searching for eligible studies was performed in October 2020. A series of pooling analyses were conducted.ResultsWe enrolled a total of twelve case-control studies for pooling. Within the pooling analysis of ε4, there was an increased risk of mesial temporal lobe epilepsy in cases under the models of carrier ε4 vs. ε3, ε3ε4 vs. ε3ε3, and ε3ε4+ε4ε4 vs. ε3ε3 [P < 0.05, odds ratio (OR) > 1], compared with controls. Moreover, we observed similar positive results in the subgroup analyses of “China” and “Population-based control” under the genetic models of ε4 (P < 0.05, OR > 1). Nevertheless, we did not detect the significant difference between the mesial temporal lobe epilepsy cases and controls in the pooling analyses of ε2 (all P > 0.05).ConclusionThe ε3ε4 genotype of ApoE seems to be linked to the risk of mesial temporal lobe epilepsy for patients in China. More sample sizes are required to confirm the potential role of ApoE isoforms in the susceptibility to diverse types of epilepsy from different origins.     

Characteristics and reproducibility of novel sleep EEG biomarkers and their variation with sleep apnea and insomnia in a large community-based cohort

Study ObjectivesNew electroencephalogram (EEG) features became available for use in polysomnography and have shown promise in early studies. They include a continuous index of sleep depth (odds-ratio-product: ORP), agreement between right and left sleep depth (R/L coefficient), dynamics of sleep recovery following arousals (ORP-9), general EEG amplification (EEG Power), alpha intrusion and arousal intensity. This study was undertaken to establish ranges and reproducibility of these features in subjects with different demographics and clinical status.MethodsWe utilized data from the two phases of the Sleep-Heart-Health-Study (SHHS1 and SHHS2). Polysomnograms of 5,804 subjects from SHHS1 were scored to determine the above features. Feature values were segregated according to clinical status of obstructive sleep apnea (OSA), insomnia, insomnia plus OSA, no clinical sleep disorder, and demographics (age, gender, and race). Results from SHHS visit2 were compared with SHHS1 results.ResultsAll features varied widely among clinical groups and demographics. Relative to participants with no sleep disorder, wake ORP was higher in participants reporting insomnia symptoms and lower in those with OSA (p < 0.0001 for both), reflecting opposite changes in sleep pressure, while NREM ORP was higher in both insomnia and OSA (p<0.0001), reflecting lighter sleep in both groups. There were significant associations with age, gender, and race. EEG Power, and REM ORP were highly reproducible across the two studies (ICC > 0.75).ConclusionsThe reported results serve as bases for interpreting studies that utilize novel sleep EEG biomarkers and identify characteristic EEG changes that vary with age, gender and may help distinguish insomnia from OSA.     

Sleep Spindle Activity Is Correlated With Reading Abilities in Developmental Dyslexia

Study Objectives:

To analyze sleep architecture of children with dyslexia, by means of conventional parameters and EEG spectral analysis and to correlate sleep parameters and EEG spectra with neuropsychological measures.

Design:

Cross-sectional study involving validated sleep questionnaires, neuropsychological scales, and polysomnographic recordings.

Setting:

Sleep laboratory in academic center.

Participants:

Sixteen subjects with developmental dyslexia (mean age 10.8 years) and 11 normally reading children (mean age 10.1 years). All the subjects underwent overnight polysomnographic recording; EEG power spectra were computed from the Cz derivation and spindle density was calculated during sleep stages N2.

Intervention:

N/A

Measurements and Results:

Dyslexic children showed an increase in power of frequency bands between 0.5–3 Hz and 11–12 Hz in stage N2 and between 0.5–1 Hz in stage N3; they also showed significantly increased spindle density during N2. The power of the sigma band in N2 was positively correlated with the Word reading and MT reading tests; similarly, spindle density was significantly correlated with the Word reading test. The increased spindle activity and EEG sigma power in dyslexic subjects were found to be correlated with the degree of dyslexic impairment.

Conclusions:

The correlation found between sleep spindle activity and reading abilities in developmental dyslexia supports the hypothesis of a role for NREM sleep and spindles in sleep-related neurocognitive processing.

Citation:

Bruni O; Ferri R; Novelli L; Terribili M; Troianiello M; Finotti E; Leuzzi V; Curatolo P. Sleep spindle activity is correlated with reading abilities in developmental dyslexia. SLEEP 2009;32(10):1333-1340.     

Mean platelet volume is associated with disease severity in patients with obstructive sleep apnea syndrome

OBJECTIVE:Obstructive sleep apnea syndrome is associated with cardiovascular diseases and thromboembolic events. The mean platelet volume (MPV) is a predictor of cardiovascular thromboembolic events. The aim of the present study is to investigate the association between the MPV and disease severity in patients with obstructive sleep apnea syndrome.METHODS:We prospectively included 194 obstructive sleep apnea syndrome patients without cardiovascular disease (mean age 56.5±12.5 years) who were undergoing sleep tests. An overnight full laboratory polisomnography examination was conducted on each patient. The patients were divided into 3 groups according to the apnea-hypopnea index (AHI): (1) AHIlow group: 5≤AHI<15, (2) AHImid group: 15<AHI≤30, and (3) AHIhigh group: AHI>30.RESULTS:The highest MPV values were found in the AHIhigh group compared with other groups (p<0.05 for all). Multiple linear regression analysis indicated that the MPV was associated with the AHI (β=0.500, p<0.001) and the high sensitivity C-reactive protein (hs-CRP) level (β=0.194, p=0.010).CONCLUSION:The MPV is independently associated with both disease severity and inflammation in patients with obstructive sleep apnea syndrome.     

The Dreem Headband compared to polysomnography for electroencephalographic signal acquisition and sleep staging

Study ObjectivesThe development of ambulatory technologies capable of monitoring brain activity during sleep longitudinally is critical for advancing sleep science. The aim of this study was to assess the signal acquisition and the performance of the automatic sleep staging algorithms of a reduced-montage dry-electroencephalographic (EEG) device (Dreem headband, DH) compared to the gold-standard polysomnography (PSG) scored by five sleep experts.MethodsA total of 25 subjects who completed an overnight sleep study at a sleep center while wearing both a PSG and the DH simultaneously have been included in the analysis. We assessed (1) similarity of measured EEG brain waves between the DH and the PSG; (2) the heart rate, breathing frequency, and respiration rate variability (RRV) agreement between the DH and the PSG; and (3) the performance of the DH’s automatic sleep staging according to American Academy of Sleep Medicine guidelines versus PSG sleep experts manual scoring.ResultsThe mean percentage error between the EEG signals acquired by the DH and those from the PSG for the monitoring of α was 15 ± 3.5%, 16 ± 4.3% for β, 16 ± 6.1% for λ, and 10 ± 1.4% for θ frequencies during sleep. The mean absolute error for heart rate, breathing frequency, and RRV was 1.2 ± 0.5 bpm, 0.3 ± 0.2 cpm, and 3.2 ± 0.6%, respectively. Automatic sleep staging reached an overall accuracy of 83.5 ± 6.4% (F1 score: 83.8 ± 6.3) for the DH to be compared with an average of 86.4 ± 8.0% (F1 score: 86.3 ± 7.4) for the 5 sleep experts.ConclusionsThese results demonstrate the capacity of the DH to both monitor sleep-related physiological signals and process them accurately into sleep stages. This device paves the way for, large-scale, longitudinal sleep studies.Clinical Trial Registration{"type":"clinical-trial","attrs":{"text":"NCT03725943","term_id":"NCT03725943"}}NCT03725943.     

Optimization of sigma amplitude threshold in sleep spindle detection

Sleep spindles are transient EEG waveforms of non-rapid eye movement sleep. There is considerable intersubject variability in spindle amplitudes. The problem in automatic spindle detection has been that, despite this fact, a fixed amplitude threshold has been used. Selection of the spindle detection threshold value is critical with respect to the sensitivity of spindle detection. In this study a method was developed to estimate the optimal recording-specific threshold value for each all-night recording without any visual scorings. The performance of the proposed method was validated using four test recordings each having a very different number of visually scored spindles. The optimal threshold values for the test recordings could be estimated well. The presented method seems very promising in providing information about sleep spindle amplitudes of individual all-night recordings.     

The Relationship between HIF-2α and VEGF with Radiographic Severity in the Primary Osteoarthritic Knee

PurposeThe aim of this study was to determine the relationship of hypoxia-inducible factor-2 (HIF-2α) and vascular endothelial growth factor (VEGF) with radiographic severity in primary osteoarthritis (OA) of the knee. Expression of these two factors in cartilage samples from OA knee joints was examined at mRNA and protein levels.ResultsCartilage degeneration correlated with the radiographic severity grade. OA severity, determined using the Mankin scale, correlated positively with the KL grade (r=0.8790, p<0.01), and HIF-2α and VEGF levels with the radiographic severity of knee OA (r=0.7001, p<0.05; r=0.6647, p<0.05).ConclusionIn OA cartilage, HIF-2α and VEGF mRNA and protein levels were significantly and positively correlated. The expression of both factors correlated positively with the KL grade. HIF-2α and VEGF, therefore, may serve as biochemical markers as well as potential therapeutic targets in knee OA.     

Individual Physical Activity Behaviour and Group Composition as Determinants of the Effectiveness of a Childhood Obesity Intervention Program

IntroductionUp to now, there is limited clarity on factors that determine the effectiveness of childhood obesity interventions.ObjectiveThis study intends to uncover individual- and program-level predictors of BMI-SDS and fitness to achieve significant, sustainable health improvements.MethodsData of 249 children with obesity or overweight who participated in an outpatient multidisciplinary program were analysed and compared to 54 waitlist controls. Linear regression models were used to examine associations between individual- and group-level variables and BMI-SDS and fitness.ResultsAmong intervention children, BMI-SDS decreased by 0.19 units and physical fitness increased by 11.5%, versus a BMI-SDS decrease of 0.07 and a 1.8% decrease in fitness in the control group. Participants who reported being physically active before the program start achieved greater improvements in BMI-SDS (β = −0.177, p < 0.05) and physical fitness (β = 0.174, p < 0.05) than inactive peers. BMI-SDS decreased significantly more for members of gender-heterogeneous groups (β = 0.194, p < 0.05) with a narrow age range (β = 0.152, p < 0.05).ConclusionsThe program under review is effective in counteracting juvenile obesity. The results give reason to believe that forming mixed-gender groups with a small age range and providing increased support for reportedly inactive children may improve program effectiveness.     

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

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