Spindle Frequency Research Articles

Sleep-spindles as a marker of attention and intelligence in dogs

The sleep spindle-generating thalamo-cortical circuitry supports attention capacity in awake humans and animals, but using sleep spindles to predict differences in attention has not been tried in either. Of the more commonly examined cognitive correlates of spindle occurrence and amplitude, post-sleep recall, and general intelligence, only post-sleep recall had been studied in dogs, rats and mice. Here, we examined a sample of companion dogs (N = 58) for whom polysomnographic recordings and several cognitive tests were performed on two occasions each, with a three-month break in-between. Five of the tests were used to extract a factor analogous to human g (general mental ability). A sixth test in the battery measured sustained attention. Both attention and g-factor scores were linked to higher slow spindle occurrence and absolute sigma power detected in polysomnographic recordings over the central electrode. These effects persisted across measurement occasions. Higher intrinsic spindle frequency was, in turn, linked to lower g-factor scores but displayed no relationship with attention scores. The overlap in localization and direction for the effects of slow spindle density (spindles/minute) and sigma power supports that they tap into the same underlying cognition-relevant aspects of spindling. Given earlier large sample and meta-analysis validations of sigma power as a reliable predictor of cognitive performance in humans, we thus conclude that the currently handled method for quantifying spindle density in dogs indeed measures cognition-relevant spindle activity by virtue of its agreement with the sigma power alternative.

Recent Evidence of Non-Rapid Eye Movement Sleep Oscillation Abnormalities in Psychiatric Disorders.

We review recent studies published from 2019 to 2024 examining slow waves and sleep spindles abnormalities across neurodevelopmental, mood, trauma-related, and psychotic disorders using polysomnography and Electroencephalogram (EEG). Individuals with attention-deficit/hyperactivity disorder (ADHD) showed higher slow-spindle activity, while findings on slow-wave activity were mixed. Individuals with autism spectrum disorder (ASD) showed inconsistent results with some evidence of lower spindle chirp and slow-wave amplitude. Individuals with depression displayed lower slow-wave and spindle parameters mostly in medicated patients. Individuals with post-traumatic stress disorder (PTSD) showed higher spindle frequency and activity, which were associated with their clinical symptoms. Psychotic disorders demonstrated the most consistent alterations, with lower spindle density, amplitude, and duration across illness stages that correlated with patients' symptom severity and cognitive deficits, whereas lower slow-wave measures were present in the early phases of the disorders. Sleep spindle and slow-wave abnormalities are present across psychiatric populations, with the most consistent alterations observed in psychotic disorders. Larger studies with standardized methodologies and longitudinal assessments are needed to establish the potential of these oscillations as neurophysiological biomarkers and/or treatment targets.

Objective sleep enhancement in Parkinson's disease: A sham-controlled trial of low-frequency repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex

IntroductionParkinson's disease (PD) is often accompanied by sleep disturbances, impacting patients' quality of life. While repetitive transcranial magnetic stimulation (rTMS) shows promise in improving self-reported sleep quality, its effects on objective sleep architecture in PD remain understudied. Sleep disturbances, including rapid eye movement (REM) and slow-wave sleep disturbances, correlate with cognitive decline and motor symptoms. This study investigated the effect of low-frequency rTMS targeting the right dorsolateral prefrontal cortex (DLPFC) modifying objective sleep architecture and explored symptom improvement mechanisms in PD patients. MethodsIn this randomized, double-blind, sham-controlled trial, 67 PD patients received 10 consecutive days of 1-Hz rTMS over the right DLPFC. Polysomnography assessed sleep microstructure, while electroencephalogram recordings evaluated power spectral density and sleep spindle activity. Clinical scales measured sleep quality, motor symptoms, and cognition at baseline, post-treatment, and 3 months post-rTMS. ResultsThe rTMS group exhibited improvements in sleep quality, motor symptoms, and cognition post-treatment, persisting at the 3-month follow-up. There was a notable increase in the REM sleep proportion post-rTMS. The rTMS group exhibited elevated low-frequency (0.5–2 Hz) slow-wave electroencephalogram spectral density during non-REM sleep. Cognitive enhancement correlated with increased lower delta power, while motor symptom progression correlated with spindle frequency and slow-wave sleep percentage changes. ConclusionLow-frequency rTMS targeting the right DLPFC holds promise for improving clinical symptoms and modulating sleep architecture in PD. These findings suggest a link between symptom improvement and sleep structure enhancement, highlighting the need for further investigation into the therapeutic potential of rTMS in PD management.

Possible mechanisms to improve sleep spindles via closed loop stimulation during slow wave sleep: A computational study.

Sleep spindles are one of the prominent EEG oscillatory rhythms of non-rapid eye movement sleep. In the memory consolidation, these oscillations have an important role in the processes of long-term potentiation and synaptic plasticity. Moreover, the activity (spindle density and/or sigma power) of spindles has a linear association with learning performance in different paradigms. According to the experimental observations, the sleep spindle activity can be improved by closed loop acoustic stimulations (CLAS) which eventually improve memory performance. To examine the effects of CLAS on spindles, we propose a biophysical thalamocortical model for slow oscillations (SOs) and sleep spindles. In addition, closed loop stimulation protocols are applied on a thalamic network. Our model results show that the power of spindles is increased when stimulation cues are applied at the commencing of an SO Down-to-Up-state transition, but that activity gradually decreases when cues are applied with an increased time delay from this SO phase. Conversely, stimulation is not effective when cues are applied during the transition of an Up-to-Down-state. Furthermore, our model suggests that a strong inhibitory input from the reticular (RE) layer to the thalamocortical (TC) layer in the thalamic network shifts leads to an emergence of spindle activity at the Up-to-Down-state transition (rather than at Down-to-Up-state transition), and the spindle frequency is also reduced (8-11 Hz) by thalamic inhibition.

Interhemispheric coherence of EEG rhythms in children: Maturation and differentiation in corpus callosum dysgenesis

ObjectivesTo evaluate the evolution of interhemispheric coherences (ICo) in background and spindle frequency bands during childhood and use it to identify individuals with corpus callosum dysgenesis (CCd). MethodsA monocentric cohort of children aged from 0.25 to 15 years old, consisting of 13 children with CCd and 164 without, was analyzed. The ICo of background activity (ICOBckgrdA), sleep spindles (ICOspindles), and their sum (sICO) were calculated. The impact of age, gender, and CC status on the ICo was evaluated, and the sICO was used to discriminate children with or without CCd. ResultsICOBckgrdA, ICOspindles and sICO increased significantly with age without any effect of gender (p < 10−4), in both groups. The regression equations of the different ICo were stronger, with adjusted R2 values of 0.54, 0.35, and 0.57, respectively. The ICo was lower in children with CCd compared to those without CCd (p < 10−4 for all comparisons). The area under the precision recall curves for predicting CCd using sICO was 0.992 with 98.9 % sensitivity and 87.5 % specificity. DiscussionICo of spindles and background activity evolve in parallel to brain maturation and depends on the integrity of the corpus callosum. sICO could be an effective diagnostic biomarker for screening children with interhemispheric dysfunction.

Attention and executive function impairments in obstructive sleep apnea are associated with decreased sleep spindles.

Sleep spindles play a key role in sleep-mediated cognitive processes. Cognitive functions are well-known to be affected in obstructive sleep apnea (OSA). Here, we analyzed attention and executive functions in patients with OSA and investigated the relationship between sleep spindles and cognitive abilities. Sixty patients with OSA (18-65years, 19 females and 41 males) and a control group (n = 41) including age-and sex-matched healthy individuals were consecutively and prospectively enrolled. All participants had a full-night polysomnography, and sleep spindles were analyzed using a semi-automated program. For the evaluation of short-term memory, attention and executive functions, Stroop test, forward and backward digit span tests were applied to all participants upon awakening following polysomnography. Scores of forward and backward digit span and Stroop tests were worse in OSA patients in compared to those in controls. Mean density of sleep spindles was decreased in OSA patients than those in controls (p = 0.044). A positive correlation was found between fast sleep spindle frequency and forward digit span (r = 2.222; p = 0.038) and backward digit span test scores (r = 2,157; p = 0.042) in OSA patients. In patients with moderate to severe OSA, sleep spindle density was positively correlated with forward (r = 2.323, p = 0.029) and backward (r = 2.500, p = 0.016) DSTs, and the duration of sleep spindles had positive correlation with backward DST (r = 2.452, p = 0.010). Our findings demonstrated that the disturbances in sleep spindle characteristics in OSA are associated with the cognitive impairments in attention, short-term memory, and executive functions, especially in patients with moderate to severe OSA.

Sleep alterations as a function of 88 health indicators

BackgroundAlterations in sleep have been described in multiple health conditions and as a function of several medication effects. However, evidence generally stems from small univariate studies. Here, we apply a large-sample, data-driven approach to investigate patterns between in sleep macrostructure, quantitative sleep EEG, and health.MethodsWe use data from the MrOS Sleep Study, containing polysomnography and health data from a large sample (N = 3086) of elderly American men to establish associations between sleep macrostructure, the spectral composition of the electroencephalogram, 38 medical disorders, 2 health behaviors, and the use of 48 medications.ResultsOf sleep macrostructure variables, increased REM latency and reduced REM duration were the most common findings across health indicators, along with increased sleep latency and reduced sleep efficiency. We found that the majority of health indicators were not associated with objective EEG power spectral density (PSD) alterations. Associations with the rest were highly stereotypical, with two principal components accounting for 85–95% of the PSD-health association. PC1 consists of a decrease of slow and an increase of fast PSD components, mainly in NREM. This pattern was most strongly associated with depression/SSRI medication use and age-related disorders. PC2 consists of changes in mid-frequency activity. Increased mid-frequency activity was associated with benzodiazepine use, while decreases were associated with cardiovascular problems and associated medications, in line with a recently proposed hypothesis of immune-mediated circadian demodulation in these disorders. Specific increases in sleep spindle frequency activity were associated with taking benzodiazepines and zolpidem. Sensitivity analyses supported the presence of both disorder and medication effects.ConclusionsSleep alterations are present in various health conditions.

Fundamentals of sleep regulation: Model and benchmark values for fractal and oscillatory neurodynamics

Homeostatic, circadian and ultradian mechanisms play crucial roles in the regulation of sleep. Evidence suggests that ratios of low-to-high frequency power in the electroencephalogram (EEG) spectrum indicate the instantaneous level of sleep pressure, influenced by factors such as individual sleep-wake history, current sleep stage, age-related differences and brain topography characteristics. These effects are well captured and reflected in the spectral exponent, a composite measure of the constant low-to-high frequency ratio in the periodogram, which is scale-free and exhibits lower interindividual variability compared to slow wave activity, potentially serving as a suitable standardization and reference measure. Here we propose an index of sleep homeostasis based on the spectral exponent, reflecting the level of membrane hyperpolarization and/or network bistability in the central nervous system in humans. In addition, we advance the idea that the U-shaped overnight deceleration of oscillatory slow and fast sleep spindle frequencies marks the biological night, providing somnologists with an EEG-index of circadian sleep regulation. Evidence supporting this assertion comes from studies based on sleep replacement, forced desynchrony protocols and high-resolution analyses of sleep spindles. Finally, ultradian sleep regulatory mechanisms are indicated by the recurrent, abrupt shifts in dominant oscillatory frequencies, with spindle ranges signifying non-rapid eye movement and non-spindle oscillations – rapid eye movement phases of the sleep cycles. Reconsidering the indicators of fundamental sleep regulatory processes in the framework of the new Fractal and Oscillatory Adjustment Model (FOAM) offers an appealing opportunity to bridge the gap between the two-process model of sleep regulation and clinical somnology.

Risk stratification for phenoconversion in patients with isolated REM sleep behavior disorder. A follow-up study from Turkey.

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is one of the strongest prodromal markers of alpha-synucleinopathies. We aimed to investigate non-invasive clinical and quantitative predictors of phenoconversion from iRBD to parkinsonism. We prospectively followed-up a total of 45 patients (57.8% men) for eight years. Clinical assessments, Sniffin' Sticks Odor Identification Test, Farnsworth-Munsell 100 Hue Color Vision test, Beck Depression Inventory and Rome III Criteria for constipation were performed. Polysomnographic parameters, sleep spindles, electroencephalographic (EEG) spectral analysis, heart rate variability (HRV) were analyzed. Eight patients (17.8%) showed phenoconversion to parkinsonism after a mean duration of 3.2 ± 1 years. Odds ratio for predicting phenoconversion was highest for patients =60 years of age with anosmia and constipation -44.8 (4.5-445.7); kappa = 4.291-. Duration, frequency or density of sleep spindles failed to demonstrate significant correlations. In EEG spectral analysis, lower alpha power in occipital region during wakefulness and REM sleep was significantly correlated with phenoconversion. Slowing in EEG spectrum power, together with age =60 years, anosmia and constipation, resulted in the highest odds ratio -122.5 (9.7-1543.8); kappa = 3.051-. It is of great importance to have a world-wide perspective of phenoconversion rates from iRBD to overt neurodegeneration, since racial and geographical factors may play important modifying roles. Relatively younger age and shorter disease duration may also be confounding factors for lower rate in our study. Neurophysiological biomarkers seem to be important predictors of phenoconversion, though more research is needed to establish subtypes of iRBD with different probabilities of evolution to overt synucleinopathy.

Sleep Spindle Alterations in Children With Migraine

BackgroundThe modulation of thalamocortical activity is the most important site of several levels of interference between sleep spindles and migraine. Thalamocortical circuits are responsible for the electrophysiological phenomenon of sleep spindles. Spindle alterations may be used as a beneficial marker in the diagnosis and follow-up of children with migraine. We aimed to formulate the hypothesis that there is a shared mechanism that underlies migraine and sleep spindle activity. MethodsWe analyzed the amplitude, frequency, duration, density, and activity of sleep spindles in non-rapid eye movement stage 2 sleep in patients with migraine without aura when compared with healthy control subjects. ResultsThe amplitudes of average, slow, and fast sleep spindles were higher in children with migraine without aura (P = 0.020, 0.013, and 0.033, respectively). The frequency of fast spindles was lower in children with migraines without aura when compared with the control group (P = 0.03). Although not statistically significant, the fast sleep spindle duration in the migraine group was shorter (P = 0.055). Multivariate analysis revealed an increased risk of migraine associated with increased mean spindle amplitude and decreased fast spindle frequency and duration. ConclusionsOur data suggest that spindle alterations may correlate with the vulnerability to develop migraine and may be used as a model for future research about the association between the thalamocortical networks and migraine.

Mechanisms underlying Myosin 10's contribution to the maintenance of mitotic spindle bipolarity.

Myosin 10 (Myo10) couples microtubules and integrin-based adhesions to movement along actin filaments via its microtubule-binding MyTH4 domain and integrin-binding FERM domain, respectively. Here we show that Myo10-depleted HeLa cells and mouse embryo fibroblasts (MEFs) both exhibit a pronounced increase in the frequency of multipolar spindles. Staining of unsynchronized metaphase cells showed that the primary driver of spindle multipolarity in Myo10-depleted MEFs and in Myo10-depleted HeLa cells lacking supernumerary centrosomes is pericentriolar material (PCM) fragmentation, which creates y-tubulin-positive acentriolar foci that serve as extra spindle poles. For HeLa cells possessing supernumerary centrosomes, Myo10 depletion further accentuates spindle multipolarity by impairing the clustering of the extra spindle poles. Complementation experiments show that Myo10 must interact with both microtubules and integrins to promote PCM/pole integrity. Conversely, Myo10 only needs interact with integrins to promote supernumerary centrosome clustering. Importantly, images of metaphase Halo-Myo10 knockin cells show that the myosin localizes exclusively to the spindle and the tips of adhesive retraction fibers. We conclude that Myo10 promotes PCM/pole integrity in part by interacting with spindle microtubules, and that it promotes supernumerary centrosome clustering by supporting retraction fiber-based cell adhesion, which likely serves to anchor the microtubule-based forces driving pole focusing.

Sleep spindles in adolescents with major depressive disorder

Sleep spindle differences in adolescents with major depressive disorder (MDD) compared to healthy adolescents is an ongoing debate. Results mostly indicate decreased sleep spindle activity in adolescents with MDD. Given that sleep spindles predominate NREM and that acutely delaying the sleep period via a “sleep delay challenge” (SDC) increases non-rapid eye movement (NREM) sleep duration, it may be possible to increase spindle density in adolescents with MDD, which may provide a therapeutic benefit to depression symptoms. Here, we examined the impact of a SDC on spindle density and depression symptomology in adolescents with MDD (n = 66) and healthy controls (n = 62) tested across three nights: adaptation, normal sleep, and a SDC night which delayed bedtime by three hours. The results showed that; (1) there was no difference in spindle density between groups on the normal sleep night, (2) following the SDC, both males and females with MDD had a decrease in the frequency of slow spindles, while only females with MDD had an increase in the frequency of fast spindles, (3) acute SDC reduced depression symptoms in both groups, and (4) light sleep on the normal sleep night and slow spindle frequency at SDC predicted an 8 % improvement in depression symptoms, regardless of sex or MDD diagnosis. Taken together, these results suggest that; (a) spindles may be a useful biological marker of depression symptomatology regardless of clinical MDD diagnosis, and (b) that acute SDC may help alleviate depression symptoms in adolescents with MDD.

Electroencephalographic markers from routine sleep discriminate individuals who are vulnerable or resilient to sleep loss.

Sleep loss impairs cognition; however, individuals differ in their response to sleep loss. Current methods to identify an individual's vulnerability to sleep loss involve time-consuming sleep-loss challenges and neurobehavioural tests. Here, we sought to identify electroencephalographic markers of sleep-loss vulnerability obtained from routine night sleep. We retrospectively analysed four studies in which 50 healthy young adults (21 women) completed a laboratory baseline-sleep phase followed by a sleep-loss challenge. After classifying subjects as resilient or vulnerable to sleep loss, we extracted three electroencephalographic features from four channels during the baseline nights, evaluated the discriminatory power of these features using the first two studies (discovery), and assessed reproducibility of the results using the remaining two studies (reproducibility). In the discovery analysis, we found that, compared to resilient subjects, vulnerable subjects exhibited: (1) higher slow-wave activity power in channel O1 (p < 0.0042, corrected for multiple comparisons) and in channels O2 and C3 (p < 0.05, uncorrected); (2) higher slow-wave activity rise rate in channels O1 and O2 (p < 0.05, uncorrected); and (3) lower sleep spindle frequency in channels C3 and C4 (p < 0.05, uncorrected). Our reproducibility analysis confirmed the discovery results on slow-wave activity power and slow-wave activity rise rate, and for these two electroencephalographic features we observed consistent group-difference trends across all four channels in both analyses. The higher slow-wave activity power and slow-wave activity rise rate in vulnerable individuals suggest that they have a persistently higher sleep pressure under normal rested conditions.

Sleep-physiological correlates of brachycephaly in dogs

The shape of the cranium is one of the most notable physical changes induced in domestic dogs through selective breeding and is measured using the cephalic index (CI). High CI (a ratio of skull width to skull length > 60) is characterized by a short muzzle and flat face and is referred to as brachycephaly. Brachycephalic dogs display some potentially harmful changes in neuroanatomy, and there are implications for differences in behavior, as well. The path from anatomy to cognition, however, has not been charted in its entirety. Here, we report that sleep-physiological markers of white-matter loss (high delta power, low frontal spindle frequency, i.e., spindle waves/s), along with a spectral profile for REM (low beta, high delta) associated with low intelligence in humans, are each linked to higher CI values in the dog. Additionally, brachycephalic subjects spent more time sleeping, suggesting that the sleep apnea these breeds usually suffer from increases daytime sleepiness. Within sleep, more time was spent in the REM sleep stage than in non-REM, while REM duration was correlated positively with the number of REM episodes across dogs. It is currently not clear if the patterns of sleep and sleep-stage duration are mainly caused by sleep-impairing troubles in breathing and thermoregulation, present a juvenile-like sleeping profile, or are caused by neuro-psychological conditions secondary to the effects of brachycephaly, e.g., frequent REM episodes are known to appear in human patients with depression. While future studies should more directly address the interplay of anatomy, physiology, and behavior within a single experiment, this represents the first description of how the dynamics of the canine brain covary with CI, as measured in resting companion dogs using a non-invasive sleep EEG methodology. The observations suggest that the neuroanatomical changes accompanying brachycephaly alter neural systems in a way that can be captured in the sleep EEG, thus supporting the utility of the latter in the study of canine brain health and function.

Sleep Spindle Generation Before and After Epilepsy Surgery: A Source Imaging Study in Children with Drug-Resistant Epilepsy.

Literature lacks studies investigating the cortical generation of sleep spindles in drug-resistant epilepsy (DRE) and how they evolve after resection of the epileptogenic zone (EZ). Here, we examined sleep EEGs of children with focal DRE who became seizure-free after focal epilepsy surgery, and aimed to investigate the changes in the spindle generation before and after the surgery using low-density scalp EEG and electrical source imaging (ESI). We analyzed N2-sleep EEGs from 19 children with DRE before and after surgery. We identified slow (8-12Hz) and fast spindles (13-16Hz), computed their spectral features and cortical generators through ESI and computed their distance from the EZ and irritative zone (IZ). We performed two-way ANOVA testing the effect of spindle type (slow vs. fast) and surgical phase (pre-surgery vs. post-surgery) on each feature. Power, frequency and cortical activation of slow spindles increased after surgery (p < 0.005), while this was not seen for fast spindles. Before surgery, the cortical generators of slow spindles were closer to the EZ (57.3 vs. 66.2mm, p = 0.007) and IZ (41.3 vs. 55.5mm, p = 0.02) than fast spindle generators. Our data indicate alterations in the EEG slow spindles after resective epilepsy surgery. Fast spindle generation on the contrary did not change after surgery. Although the study is limited by its retrospective nature, lack of healthy controls, and reduced cortical spatial sampling, our findings suggest a spatial relationship between the slow spindles and the epileptogenic generators.

Effect of Acute Enriched Environment Exposure on Brain Oscillations and Activation of the Translation Initiation Factor 4E-BPs at Synapses across Wakefulness and Sleep in Rats.

Brain plasticity is induced by learning during wakefulness and is consolidated during sleep. But the molecular mechanisms involved are poorly understood and their relation to experience-dependent changes in brain activity remains to be clarified. Localised mRNA translation is important for the structural changes at synapses supporting brain plasticity consolidation. The translation mTOR pathway, via phosphorylation of 4E-BPs, is known to be activate during sleep and contributes to brain plasticity, but whether this activation is specific to synapses is not known. We investigated this question using acute exposure of rats to an enriched environment (EE). We measured brain activity with EEGs and 4E-BP phosphorylation at cortical and cerebellar synapses with Western blot analyses. Sleep significantly increased the conversion of 4E-BPs to their hyperphosphorylated forms at synapses, especially after EE exposure. EE exposure increased oscillations in the alpha band during active exploration and in the theta-to-beta (4-30 Hz) range, as well as spindle density, during NREM sleep. Theta activity during exploration and NREM spindle frequency predicted changes in 4E-BP hyperphosphorylation at synapses. Hence, our results suggest a functional link between EEG and molecular markers of plasticity across wakefulness and sleep.

The association between sleep spindles and cognitive function in middle-aged and older men from a community-based cohort study

ObjectivesPrevious studies examining associations between sleep spindles and cognitive function attempted to account for obstructive sleep apnea without consideration for potential moderating effects. To elucidate associations between sleep spindles, cognitive function, and obstructive sleep apnea, this study of community-dwelling men examined cross-sectional associations between sleep spindle metrics and daytime cognitive function outcomes following adjustment for obstructive sleep apnea and potential obstructive sleep apnea moderating effects. MethodsFlorey Adelaide Male Ageing Study participants (n = 477, 41-87 years) reporting no previous obstructive sleep apnea diagnosis underwent home-based polysomnography (2010-2011). Cognitive testing (2007-2010) included the inspection time task (processing speed), trail-making tests A (TMT-A) (visual attention) and B (trail-making test-B) (executive function), and Fuld object memory evaluation (episodic memory). Frontal spindle metrics (F4-M1) included occurrence (count), average frequency (Hz), amplitude (µV), and overall (11-16 Hz), slow (11-13 Hz), and fast (13-16 Hz) spindle density (number/minute during N2 and N3 sleep). ResultsIn fully adjusted linear regression models, lower N2 sleep spindle occurrence was associated with longer inspection times (milliseconds) (B = −0.43, 95% confidence interval [−0.74, −0.12], p = .006), whereas higher N3 sleep fast spindle density was associated with worse TMT-B performance (seconds) (B = 18.4, 95% confidence interval [1.62, 35.2], p = .032). Effect moderator analysis revealed that in men with severe obstructive sleep apnea (apnea-hypopnea index ≥30/hour), slower N2 sleep spindle frequency was associated with worse TMT-A performance (χ2 = 12.5, p = .006). ConclusionsSpecific sleep spindle metrics were associated with cognitive function, and obstructive sleep apnea severity moderated these associations. These observations support the utility of sleep spindles as useful cognitive function markers in obstructive sleep apnea, which warrants further longitudinal investigation.

Frequency Analysis of EEG Microstate Sequences in Wakefulness and NREM Sleep

The majority of EEG microstate analyses concern wakefulness, and the existing sleep studies have focused on changes in spatial microstate properties and on microstate transitions between adjacent time points, the shortest available time scale. We present a more extensive time series analysis of unsmoothed EEG microstate sequences in wakefulness and non-REM sleep stages across many time scales. Very short time scales are assessed with Markov tests, intermediate time scales by the entropy rate and long time scales by a spectral analysis which identifies characteristic microstate frequencies. During the descent from wakefulness to sleep stage N3, we find that the increasing mean microstate duration is a gradual phenomenon explained by a continuous slowing of microstate dynamics as described by the relaxation time of the transition probability matrix. The finite entropy rate, which considers longer microstate histories, shows that microstate sequences become more predictable (less random) with decreasing vigilance level. Accordingly, the Markov property is absent in wakefulness but in sleep stage N3, 10/19 subjects have microstate sequences compatible with a second-order Markov process. A spectral microstate analysis is performed by comparing the time-lagged mutual information coefficients of microstate sequences with the autocorrelation function of the underlying EEG. We find periodic microstate behavior in all vigilance states, linked to alpha frequencies in wakefulness, theta activity in N1, sleep spindle frequencies in N2, and in the delta frequency band in N3. In summary, we show that EEG microstates are a dynamic phenomenon with oscillatory properties that slow down in sleep and are coupled to specific EEG frequencies across several sleep stages.

0551 Predicting Daytime Alertness Impairment in Obstructive Sleep Apnea

Abstract Introduction Obstructive sleep apnea (OSA) reduces daytime alertness leading to social and occupational impairment. The Maintenance of Wakefulness Test (MWT), a gold-standard test for daytime alertness, is time-consuming and not routinely available in clinical practice. We examined EEG-based and clinical parameters derived from diagnostic polysomnography (PSG) as predictors of alertness impairment in adults with OSA. Methods Eighty-two participants with untreated OSA on diagnostic PSG (apnea hypopnea index, AHI ≥5/hour), enrolled in a two-center clinical trial were included. The day following PSG, each participant completed four 40-minute MWT and four 10-minute Psychomotor Vigilance Tests (PVT). The outcomes were MWT mean sleep latency (MSL) and PVT lapses (reaction time ≥500 milliseconds, square root transformed). Three multiple linear regression models were used: 1. “standard predictors” (total sleep time, TST, percent REM and slow wave sleep, AHI, time &amp;lt; 90% oxygen saturation, and arousal index), 2. “novel predictors” derived by spectral analysis and averaged across right and left central EEG (normalized EEG power, odds ratio product; ORP parameters, and spindle characteristics), and 3. combined standard and novel predictors. Age, sex, and body mass index (BMI) were included in each model, and backward elimination (step AIC) was used for models 2 and 3. Results Participants were middle-aged (mean ± standard deviation, SD 53.5±8.7 years), with moderate OSA (AHI 33.8±18.2) and daytime sleepiness (Epworth Sleepiness Scale 11.7±3.9), and 86% were men. The adjusted r2 for MSL were: model 1=0.09, model 2=0.16, and model 3=0.27, and PVT lapses were: model 1=0.09, model 2=0.31, and model 3=0.34. For MSL, the significant predictors in model 3 included TST (t-statistic -3.59, p=0.0007), REM% (2.51, p=0.01), ORP-9 (2.95, p=0.004), ORP NREM (-3.15, p=0.002), spindle frequency (-2.95, p=0.004), and normalized EEG power (-2.59, p=0.01). For PVT lapses, model 3 predictors included 2.25-2.5 ORP% (-2.91, p=0.005), normalized EEG power (3.22, p=0.002), spindle power (-4.30, p&amp;lt; 0.0001), spindle frequency (2.83, p=0.006), and sex (men vs. women, -2.56, p=0.01). Conclusion We have identified several novel PSG EEG-based predictors of impaired daytime alertness in OSA that will improve occupational evaluation and prognostication in OSA after future validation. Support (if any) National Institutes of Health, UM1-HL112856, UL1TR001422, and UL1TR002003.

Functional MRI reveals brain-wide actions of thalamically-initiated oscillatory activities on associative memory consolidation

As a key oscillatory activity in the brain, thalamic spindle activities are long believed to support memory consolidation. However, their propagation characteristics and causal actions at systems level remain unclear. Using functional MRI (fMRI) and electrophysiology recordings in male rats, we found that optogenetically-evoked somatosensory thalamic spindle-like activities targeted numerous sensorimotor (cortex, thalamus, brainstem and basal ganglia) and non-sensorimotor limbic regions (cortex, amygdala, and hippocampus) in a stimulation frequency- and length-dependent manner. Thalamic stimulation at slow spindle frequency (8 Hz) and long spindle length (3 s) evoked the most robust brain-wide cross-modal activities. Behaviorally, evoking these global cross-modal activities during memory consolidation improved visual-somatosensory associative memory performance. More importantly, parallel visual fMRI experiments uncovered response potentiation in brain-wide sensorimotor and limbic integrative regions, especially superior colliculus, periaqueductal gray, and insular, retrosplenial and frontal cortices. Our study directly reveals that thalamic spindle activities propagate in a spatiotemporally specific manner and that they consolidate associative memory by strengthening multi-target memory representation.