Stage N2 Sleep Research Articles

Mouth Leak is Associated with Sleep Fragmentation During Nasal CPAP Treatment of OSA and May Be Detected by Leak Waveform Analysis.

Mouth air leak is a major cause of low adherence to nasal CPAP in patients with obstructive sleep apnea (OSA). However, CPAP reports do not distinguish mouth from mask leak. We hypothesized that mouth air leak is terminated abruptly by an arousal from sleep and mouth closing that can be detected by CPAP leak waveform analysis. Describe patterns of mouth air leak waveform during polysomnography (PSG) in patients with OSA treated with well-fitted nasal CPAP. PSG recordings with a jaw motion sensor to detect mouth opening were performed in OSA patients treated with nasal CPAP with suspected mouth air leak. Careful mask fitting and visual inspection excluded mask leak. Mouth leak episodes were characterized by an increase (≥ 20%) above the intentional leak. Leak episodes were classified as intermittent (< 5 minutes) or continuous (≥ 5 minutes). Twenty patients (80% men; age: 63±11 years; body mass index: 29.9±6 kg/m2; baseline apnea hypopnea index: 46.9±19 events/h) treated with nasal CPAP and documented mouth leak completed the study. All but one patient experienced an overlap of intermittent and continuous mouth leak. Most mouth leak episodes ended with mouth closure (97.7%) and an arousal (52.7%) or awakening (38.6%). Only 34.9% of the leak episodes were associated with respiratory events. Intermittent mouth air leak was more common in sleep stages N1+ N2 (P<0.01), while continuous leak was more common in sleep stage N3 (P<0.01). Continuous episodes of air leak were associated with a higher amplitude of mouth opening. CPAP report waveform was able to detect only 29.6% of the leak episodes detected by PSG. Only 10 patients (50%) had a high unintentional leak according to the criterion adopted by ResMed and only 2 patients (10%) presented large leak according to the Philips criterion. Intermittent and continuous mouth leak during nasal CPAP frequently co-exist and contribute to sleep fragmentation. Identification of leak waveform patterns may help detect mouth air leak which in turn is an important cause of poor CPAP adherence.

Sleep Characteristics of Patients Admitted to Intensive Care Units after Major Abdominal Surgery

Purpose : The aim of this study was to investigate sleep parameters and architecture in patients admitted to the intensive care unit (ICU) on the day of abdominal surgery. Methods : A total of ten patients who underwent laparotomy under general anesthesia at the hepatopancreatobiliary surgery department of a general hospital in Busan, South Korea participated in this observational study. We measured total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), and sleep stages on their first night in the ICU using the WatchPAT300. Furthermore, we used nonparametric statistics to examine differences in postoperative sleep based on sedative administration. Results : The Median (IQR) TST for the participants was 399.50(263.80) minutes; the SE was 75.1 (30.4)%; the WASO rate was 27.8(30.6)%; and the WASO frequency was 5.50(8.50) times. Patients’ rapid eye movement (REM) sleep time was 114.31(87.88) minutes, with 55.8(11.9)% of N1, 18.2(5.3)% of N2, and 24.8 (11.7)% of N3 sleep stages. The sedation group had a longer TST (Z=-2.619, &lt;i&gt;p&lt;/i&gt; =.008), higher SE (Z=-2.611, &lt;i&gt;p&lt;/i&gt; =.008), lower WASO rate (Z=-2.611, &lt;i&gt;p&lt;/i&gt; =.008), smaller number of WASOs (Z=-2.627, &lt;i&gt;p&lt;/i&gt; =.008), and longer REM sleep (Z=-2.617, &lt;i&gt;p&lt;/i&gt; =.008) compared to the non-sedation group. Conclusion : We observed a high rate of light sleep and awakenings during sleep in patients admitted to the ICU after surgery. Moreover, non-sedated patients lacked either deep or REM sleep. Sleep-improving interventions are needed for non-sedated surgical patients who are admitted to the ICU.

Impaired Sleep-Dependent Memory Consolidation in Pediatric Narcolepsy Type 1.

Disrupted nighttime sleep (DNS) is common in pediatric Narcolepsy type 1, yet its cognitive impact is unknown. As N2 sleep spindles are necessary for sleep-dependent memory consolidation, we hypothesized that Narcolepsy Type 1 impairs memory consolidation via N2 sleep fragmentation and N2 sleep spindle alterations. We trained 28 pediatric Narcolepsy Type 1 participants and 27 healthy controls (HC) on a spatial declarative memory task before a nocturnal in-lab polysomnogram and then gave them a cued recall test upon awakening in the morning. We extracted wake and sleep stage bout numbers and N2 spindle characteristics from the polysomnogram and conducted mixed model analysis of sleep-dependent memory consolidation to identify group differences. Narcolepsy Type 1 participants had shorter N2 bout durations and associated shorter N2 spindles vs. HC, but other N2 spindle features were similar. Narcolepsy Type 1 participants had worse memory performance post-sleep than HCs after adjusting for age and gender (mean memory consolidation HC: -3.1% ± 18.7, NT1: -15.6 ± 24.8, main effect group x time of testing F=5.3, p=0.03). We did not find significant relationships between sleep-dependent memory consolidation and N2 spindle characteristics. Notably, increased N1% was associated with worse sleep-dependent memory consolidation with results driven by the Narcolepsy Type 1 group. Sleep-dependent memory consolidation is mildly impaired in youth with Narcolepsy Type 1 and findings may be attributed to increases in N1 sleep. Further studies are needed to determine if these findings are generalizable and reversible with sleep-based therapies.

Caffeine Intake Alters Recovery Sleep after Sleep Deprivation.

Caffeine is a well-known psychostimulant reputed to alleviate the deleterious effects of sleep deprivation. Nevertheless, caffeine can alter sleep duration and quality, particularly during recovery sleep. We evaluated the effects of acute caffeine intake on the duration and quality of recovery sleep following total sleep deprivation (TSD), taking into account daily caffeine consumption. Forty-one participants performed a double-blind, crossover TSD protocol (38 h of continuous wakefulness) with acute caffeine or placebo. Caffeine (2.5 mg/kg) or placebo was administered twice during continuous wakefulness (last treatment 6.5 h before bedtime for the recovery night). Polysomnographic measurements were recorded using a connected headband. TSD was associated with a rebound in total sleep time (TST) on the recovery night (+110.2 ± 23.2 min, p < 0.001). Caffeine intake decreased this recovery TST (-30.2 ± 8.2 min p = 0.02) and the N3 sleep stage duration (-35.6 ± 23.2 min, p < 0.01). Caffeine intake altered recovery sleep continuity (increased number of long awakenings), stability (higher stage transition frequency), and organization (less time spent in complete sleep cycle) and decreased the delta power spectral density during NREM sleep. On the recovery night, habitual daily caffeine consumption was negatively correlated with TST in caffeine and placebo conditions and positively correlated with wake after sleep onset (WASO) duration and with the frequency of long (>2 min) awakenings in the caffeine condition only. Acute caffeine intake during TSD affects nighttime recovery sleep, with an interaction with daily consumption. These results may influence advice on caffeine intake for night-shift workers. (NCT03859882).

Polysomnographic and clinical characteristics of sleep apnea headache patients.

Sleep apnea headache can be defined as a persistent, widespread, throbbing headache that occurs recurrently, is not accompanied by any additional symptoms after waking up, and usually resolves within four hours. Diagnosis of the condition requires confirmation through polysomnography with an apnea-hypopnea index of at least 5, indicating the presence of obstructive sleep apnea syndrome (OSAS). While sleep apnea headaches are common in 10-15% of individuals with OSAS, morning headaches are experienced by 5% of this population. The aim of this study is to examine both polysomnographic and clinical features associated with sleep apnea headache in individuals confirmed to have OSAS by polysomnography. The study was conducted in the sleep center of University of Health Science, Erenköy Mental and Nervous Disease Training and Research Hospital. We have examined the clinical and polysomnographic data of the patients with sleep apnea headache (SAH) diagnosed according to IHS-3 criteria retrospectively and grouped the patients as mild, moderate and severe OSAS. Patients with morning headache except sleep apnea headache and under PAP titration treatment were excluded. The differences between the sleep macro structures of patients with (WSAH) and without sleep apnea headache (WOSAH) were examined. The WSAH group consisted of 384 participants and the control group (WOSAH) consisted of 294 participants The mean age was 46.29 ± 12.18 and 45.08 ± 12.62 years, respectively. Patients in the WSAH group had significantly higher scores on the Epworth Sleepiness Scale (ESS) (p = 0.004) and higher periodic limb movement index (PLMI) (p = 0.014) compared to the WOSAH group. WSAH patients exhibited shorter wake times after sleep onset (WASO) and lower scores on the sleep quality index, in contrast to WOSAH patients. Additionally, within the WSAH group, there was a negative correlation between age and several sleep parameters, including total sleep parameters. A positive correlation was observed between sleep duration (p = 0.009), waking up after sleep (p = 0.043), sleep efficiency (p = 0.001) and apnea-hypopnea index (AHI) (p = 0.018). Additionally, ESS scores were positively correlated with AHI and total awake time (p = 0.000 and p = 0.008, respectively), while negatively correlated with stage N3 sleep percentage and mean minimum oxygen level (p = 0.001 and p = 0.020, respectively) in the WSAH group. The causes and possible mechanisms of sleep apnea headache are not fully clarified and the underlying processes are not fully understood. Sleep apnea headaches appear to be related to disturbances in nocturnal sleep. Dysregulation in regions that modulate sleep and nociception may be one possible mechanism.

Temporal Lobe Epilepsy with Bitemporal Interictal Epileptiform Discharges: Effects of Sleep and Wakefulness

Introduction. Independent bitemporal interictal discharges are often found in patients with temporal lobe epilepsy. The likelihood of registering epileptiform activity (EA) is higher during sleep. Assessment of bitemporal interictal epileptiform discharges (BIEDs) with various discharge predominance ratio is used for presurgical evaluation of epilepsy patients and prediction of surgical outcomes. Our objective was to determine the predominant side (PS) in patients with bitemporal epilepsy using the incidence of epileptiform discharges for each sleep stage. Materials and methods. We analyzed 45 recordings of 10–24 h long-term video-EEG monitoring (LTM) in patients with bitemporal EA. For each recording, the total incidence of EA (IEA) and EA incidence for wakefulness and for each sleep stage were calculated individually. We also assessed the discharge predominance index (DPI) as a ratio of IEA in the predominant and contralateral sides for the entire recording and for each sleep stage. Results. We observed an IEA increase with sleep deepening, with maximum values observed during N2 and N3 sleep stages. The minimum IEA values were recorded during REM sleep; nevertheless, most of the REM sleep discharges were detected on the PS. DPI values were the highest and the most stable during N2 and N3 stages. Conclusion. The findings of our study demonstrate an increase in DPI values with non-rapid eye movement (NREM) sleep deepening in patients with bitemporal localization of EA. Despite the protective effects of REM sleep (i.e., reducing the likelihood of EA), it may be pivotal in lateralization of EA in patients with BIEDs. The PS is generally determined by a higher DPI during N2 and N3 stages.

Impact of mini-dose dexmedetomidine supplemented analgesia on sleep structure in patients at high risk of obstructive sleep apnea: a pilot trial.

Obstructive sleep apnea (OSA) is common in surgical patients and associated with worse perioperative outcomes. To investigate the effect of mini-dose dexmedetomidine supplemented analgesia on postoperative sleep quality pattern in patients at high risk of OSA. A pilot randomized, double-blind, placebo-controlled trial. A tertiary university hospital in Beijing, China. One hundred and fifty-two adult patients who had a STOP-Bang score ≥3 and a serum bicarbonate level ≥28 mmol/L and were scheduled for major noncardiac surgery between 29 January 2021 and 20 September 2022. After surgery, patients were provided with high-flow nasal cannula and randomized in a 1:1 ratio to receive self-controlled opioid analgesia supplemented with either mini-dose dexmedetomidine (median 0.02 μg/kg/h) or placebo. We monitored polysomnogram from 9:00 pm to 6:00 am during the first night. Our primary outcome was the percentage of stage 2 non-rapid eye movement (N2) sleep. Secondary and exploratory outcomes included other postoperative sleep structure parameters, sleep-respiratory parameters, and subjective sleep quality (Richards-Campbell Sleep Questionnaire; 0-100 score range, higher score better). All 152 patients were included in intention-to-treat analysis; 123 patients were included in sleep structure analysis. Mini-dose dexmedetomidine supplemented analgesia increased the percentage of stage N2 sleep (median difference, 10%; 95% CI, 1 to 21%; p = 0.029); it also decreased the percentage of stage N1 sleep (median difference, -10%; 95% CI, -20% to -1%; p = 0.042). Other sleep structure and sleep-respiratory parameters did not differ significantly between the two groups. Subjective sleep quality was slightly improved with dexmedetomidine on the night of surgery, but not statistically significant (median difference, 6; 95% CI, 0 to 13; p = 0.060). Adverse events were similar between groups. Among patients at high risk of OSA who underwent noncardiac surgery, mini-dose dexmedetomidine supplemented analgesia may improve sleep quality without increasing adverse events. Clinicaltrials.gov, identifier NCT04608331.

Age-related changes in sleep spindle characteristics in individuals over 75 years of age: a retrospective and comparative study

BackgroundSleep and its architecture are affected and changing through the whole lifespan. We know main modifications of the macro-architecture with a shorter sleep, occurring earlier and being more fragmented. We have been studying sleep micro-architecture through its pathological modification in sleep, psychiatric or neurocognitive disorders whereas we are still unable to say if the sleep micro-architecture of an old and very old person is rather normal, under physiological changes, or a concern for a future disorder to appear. We wanted to evaluate age-related changes in sleep spindle characteristics in individuals over 75 years of age compared with younger individuals.MethodsThis was an exploratory study based on retrospective and comparative laboratory-based polysomnography data registered in the normal care routine for people over 75 years of age compared to people aged 65–74 years. We were studying their sleep spindle characteristics (localization, density, frequency, amplitude, and duration) in the N2 and N3 sleep stages. ANOVA and ANCOVA using age, sex and OSA were applied.ResultsWe included 36 participants aged > 75 years and 57 participants aged between 65 and 74 years. An OSA diagnosis was most common in both groups. Older adults receive more medication to modify their sleep. Spindle localization becomes more central after 75 years of age. Changes in the other sleep spindle characteristics between the N2 and N3 sleep stages and between the slow and fast spindles were conformed to literature data, but age was a relevant modifier only for density and duration.ConclusionWe observed the same sleep spindle characteristics in both age groups except for localization. We built our study on a short sample, and participants were not free of all sleep disorders. We could establish normative values through further studies with larger samples of people without any sleep disorders to understand the modifications in normal aging and pathological conditions and to reveal the predictive biomarker function of sleep spindles.

Exploring Sleep Architecture in Polish Patients with Multiple Sclerosis: A Polysomnography Study.

Sleep disturbances are a prevalent phenomenon in patients with multiple sclerosis (PwMS). The present study employs polysomnography (PSG) to quantify sleep efficiency and architecture in PwMS, aiming to elucidate the relationships between PSG parameters and factors including gender, disability level, brain lesion location, and subjective measures of insomnia, excessive daytime sleepiness (EDS), fatigue, pain, and mood disorders. The study cohort comprised 51 adult PwMS, of whom 31 underwent overnight PSG. The demographic and clinical characteristics, including age, gender, and Expanded Disability Status Scale (EDSS), were collated. The Athens Insomnia Scale, the Epworth Sleepiness Scale, the Fatigue Severity Scale, the Modified Fatigue Impact Scale (MFIS), the Numerical Pain Rating Scale, and the Hospital Anxiety and Depression Scale were employed for the assessment of insomnia, EDS, fatigue, pain, and mood disorders. The brain and spinal cord magnetic resonance imaging (MRI) were evaluated. A reduced sleep efficiency was observed among 30 PwMS (aged 38.9 ± 12.9), with a mean of 80 ± 12%, especially in those with brainstem demyelinating lesions. In those PwMS aberrant sleep onset latency (SOL) and wake after sleep onset were also noted (p < 0.05). The prevalence of sleep fragmentation, as measured by the total arousal index, was greater in male PwMS than in female (p < 0.05). Higher disability according to the EDSS correlated with longer SOL (ρ = 0.48, p < 0.05), and reduced N2 sleep stage correlated with cognitive fatigue according to MFIS (ρ = -0.46, p < 0.05). Age, disease duration, insomnia, EDS, physical fatigue, and mood disorders did not impact PSG parameters. The study demonstrated the disruption of sleep architecture in PwMS, and highlighted the importance of a comprehensive PSG assessment of sleep disturbances in this population.

Network analysis of the relationship between different heart rate variability metrics during sleep

AbstractHeart rate variability (HRV) refers to the physiological phenomenon of variation in heartbeat duration, which can be characterized using various metrics. Considering a complex systems approach, in this study we used network modeling to quantitatively evaluate the relationship between different HRV metrics during sleep. Polysomnography recordings were performed on 24 healthy participants and their cardiac activity was sampled from the N2, N3, and REM sleep stages. Fifty-eight HRV metrics were calculated, and the relationship between each was assessed using mutual information (MI). One network was created for each sleep stage; HRV metrics constituted its nodes, and MI values were used to establish its edges. Repeated measures ANOVA was applied to each metric to assess variation between sleep stages. It was found that all three networks had characteristics of complex networks. Several communities of shared similar metrics were found across the three sleep stages. Of these, one community had the same metrics in stages N2 and N3, but in REM sleep was divided into three communities. REM sleep exhibited significant differences compared to the other sleep stages in several metrics. These preliminary findings allow us to suggest the application of this method in other HRV research contexts, which will determine its scope and limitations.

Construction and validation of clinical prediction model of tongue base collapse under drug-induced sleep endoscopy in OSA patients

Objective: To analyze the correlation between drug-induced sleep endoscopy (DISE), results, polysomnography (PSG) indicators, and clinical parameters in patients with obstructive sleep apnea (OSA), and to establish and validate a predictive model for tongue base plane obstruction. Methods: This retrospective study analyzed 117 OSA patients diagnosed via PSG and treated at the Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, between October 2014 and March 2022. The cohort comprised of 114 males and 3 females, with an age range of 20 to 54 years (mean age 38.1±8.4 years). Data on DISE results, PSG results, and clinical indicators were collected for all 117 patients. Logistic regression analysis was performed to identify relevant indicators, and a predictive model for tongue base plane obstruction was constructed and internally validated using the R programming language. Results: Univariate logistic regression analysis identified four independent risk factors for predicting tongue root plane obstruction: tonsil grading, N2, N3, and rapid eye movement sleep(REM) stage [OR:0.412(0.260~0.652),1.045(1.012~1.079),0.943(0.903~0.984),0.961(0.925~0.998),P <0.05]. Multivariate logistic regression analysis confirmed tonsil grading and N3 sleep stage (12.48±12.22%) as significant predictors. A nomogram model incorporating these factors demonstrated good predictive performance, with an area under curve(AUC) of 0.82 (95%CI: 0.548-1.000), an optimal cutoff of 0.519, a specificity of 80.0%, and a sensitivity of 86.7%. Internal validation of the model in the validation cohort yielded an AUC of 0.751 (95%CI: 0.625-0.876). Conclusions: Tongue base plane obstruction observed during DISE in OSA patients is associated with tonsil grading and N3 sleep stage duration. The predictive model developed for tongue base plane obstruction based on DISE demonstrates good efficacy, as evidenced by its internal validation.

NREM sleep brain networks modulate cognitive recovery from sleep deprivation.

Decrease in cognitive performance after sleep deprivation followed by recovery after sleep suggests its key role, and especially non-rapid eye movement (NREM) sleep, in the maintenance of cognition. It remains unknown whether brain network reorganization in NREM sleep stages N2 and N3 can uniquely be mapped onto individual differences in cognitive performance after a recovery nap following sleep deprivation. Using resting state functional magnetic resonance imaging (fMRI), we quantified the integration and segregation of brain networks during NREM sleep stages N2 and N3 while participants took a 1-hour nap following 24-hour sleep deprivation, compared to well-rested wakefulness. Here, we advance a new analytic framework called the hierarchical segregation index (HSI) to quantify network segregation across spatial scales, from whole-brain to the voxel level, by identifying spatio-temporally overlapping large-scale networks and the corresponding voxel-to-region hierarchy. Our results show that network segregation increased in the default mode, dorsal attention and somatomotor networks during NREM sleep compared to wakefulness. Segregation within the visual, limbic, and executive control networks exhibited N2 versus N3 sleep-specific voxel-level patterns. More segregation during N3 was associated with worse recovery of working memory, executive attention, and psychomotor vigilance after the nap. The level of spatial resolution of network segregation varied among brain regions and was associated with the recovery of performance in distinct cognitive tasks. We demonstrated the sensitivity and reliability of voxel-level HSI to provide key insights into within-region variation, suggesting a mechanistic understanding of how NREM sleep replenishes cognition after sleep deprivation.

Effects of post-learning nap in the recognition memory for faces in habitual nappers

This study investigated the effects of diurnal nap in the recognition memory for faces in habitual nappers. Thirty volunteers with habitual midday napping (assigned as the sleep group) and 28 non-nappers (assigned as the wake group) participated in this study. Participants were instructed to memorize faces, and subsequently to perform two recognition tasks before and after nap/wakefulness, i.e., an immediate recognition and a delayed recognition. There were three experimental conditions: same faces with the same view angle (S-S condition); same faces with a different view angle (22.5°) (S-D condition); and novel faces (NF condition). A mixed repeated-measures ANOVA revealed that the sleep group exhibited significantly longer reaction times (RT) following their nap compared to those of the wake group; no significant between-group differences were observed in accuracy or sensitivity (d’). Furthermore, both groups were more conservative in the delayed recognition task compared to the immediate recognition task, but the sleep group was more conservative after their nap (vs pre-nap), reflected by the criterion (β, Ohit/Ofalse alarm). Further stepwise regression analysis revealed a positive relationship between duration of stage N3 sleep and normalized RT difference before/after nap on the S-S condition. These findings suggest that an immediate nap following face learning is associated with memory reorganization during N3 sleep in habitual nappers, rendering the memories not readily accessible.

Vortioxetine’s impact on the autonomic nervous system in depressed children and adolescents: analysis of the heart rate variability

Relationship between depressive disorder and autonomic nervous system has been already discussed. Reduced emotional regulation is supposed to be associated with prefrontal hypofunction and subcortical hyperactivity. The aim of this study was to determine the effect of vortioxetine on heart rate variability (HRV), a parameter of cardiac autonomic regulation, in depressed hospitalized paediatric patients and assess the clinical effectiveness of the drug in this population. We performed repeated polysomnography analyses at admission and after a short treatment in hospital (15.2 days on average) and measured various HRV parameters (RRi, pNN50, RMSSD, LF-HRV, HF-HRV) during wakefulness, N3 and REM sleep stages. Out of 27 study subjects, 67% have improved depression symptoms as well as anxiety and subjective sleep quality after short vortioxetine treatment. We have found a significant decrease in parasympathetic parameters pNN50, RMSSD and HF-HRV during N3 sleep phase, though not exclusively among vortioxetine responders. The anticipated increase in cardiovagal regulation after vortioxetine treatment was not demonstrated in this pilot study, possibly due to the drug’s multimodal mechanism and impact on the nucleus tractus solitarii, particularly its antagonism on 5HT-3 receptors. Application of selective drugs could further explain the effect of vortioxetine on HRV in depressed patients.

Pharmacologic Sleep Aids in the Intensive Care Unit: A Systematic Review.

Background: Patients in the intensive care unit (ICU) often experience poor sleep quality. Pharmacologic sleep aids are frequently used as primary or adjunctive therapy to improve sleep, although their benefits in the ICU remain uncertain. This review aims to provide a comprehensive assessment of the objective and subjective effects of medications used for sleep in the ICU, as well as their adverse effects. Methods: PubMed, Web of Science, Scopus, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from their inception until June 2023 for comparative studies assessing the effects of pharmacologic sleep aids on objective and subjective metrics of sleep. Results: Thirty-four studies with 3498 participants were included. Medications evaluated were melatonin, ramelteon, suvorexant, propofol, and dexmedetomidine. The majority of studies were randomized controlled trials. Melatonin and dexmedetomidine were the best studied agents. Objective sleep metrics included polysomnography (PSG), electroencephalography (EEG), bispectral index, and actigraphy. Subjective outcome measures included patient questionnaires and nursing observations. Evidence for melatonin as a sleep aid in the ICU was mixed but largely not supportive for improving sleep. Evidence for ramelteon, suvorexant, and propofol was too limited to offer definitive recommendations. Both objective and subjective data supported dexmedetomidine as an effective sleep aid in the ICU, with PSG/EEG in 303 ICU patients demonstrating increased sleep duration and efficiency, decreased arousal index, decreased percentage of stage N1 sleep, and increased absolute and percentage of stage N2 sleep. Mild bradycardia and hypotension were reported as side effects of dexmedetomidine, whereas the other medications were reported to be safe. Several ongoing studies have not yet been published, mostly on melatonin and dexmedetomidine. Conclusions: While definitive conclusions cannot be made for most medications, dexmedetomidine improved sleep quantity and quality in the ICU. These benefits need to be balanced with possible hemodynamic side effects.

Large muscle group movements during sleep in restless leg syndrome: neurophysiological and clinical implications.

Recently, criteria have been drawn up for large muscle group movements during sleep (LMM), defined as movements lasting for 3-45 seconds in adults, which are often accompanied by changes in sleep stage, arousals, and increases in heart rate. The aim of this study was to characterize LMM in restless legs syndrome (RLS) in order to better evaluate their impact on the neurophysiology of the disorder and, therefore, the possible clinical implications. Consecutive, drug-free patients diagnosed with RLS and controls, aged 18 years or more, were retrospectively enrolled. Leg movement activity-short-interval (SILMS), periodic (PLMS), and isolated (ISOLMS) leg movements during sleep-and LMM were detected and scored. In total, 100 patients and 67 controls were recruited. All movement measures were significantly higher in RLS. A significant positive correlation was found between LMM and ISOLMS index but not PLMS index in both groups. LMM index showed a significant negative correlation with total sleep time, sleep efficiency, and percentage of sleep stages N3 and R, as well as a significant positive correlation with the number of awakenings, and percentage of sleep stages N1 and N2 only in patients with RLS. No significant correlation was found between either LMM or PLMS index and RLS severity. Different types of movements, including SILMS, ISOLMS, and LMM, play somewhat distinct roles in sleep neurophysiology in RLS. Notably, LMM, a newly recognized category of movements, demonstrates associations with sleep architecture instability and fragmentation, arousals, and awakenings, suggesting potential clinical implications.

Nocturnal Heart Rate Response to Spontaneous Arousals Following Sleep Restriction

Short sleep duration is associated with future cardiovascular disease including hypertension, especially in females, but mechanistic evidence is largely lacking. Experimental sleep restriction has been shown to cause short sleep-mediated tachycardia and reduced heart rate variability, indicative of autonomic cardiac instability, in some but not all studies. Heart rate (HR) response to spontaneous cortical arousals can be regarded as an index of autonomic cardiac control given its characteristic temporal pattern. Whether the HR response to cortical arousals is altered during experimental sleep restriction remains unknown. We hypothesized that sleep restriction would result in augmented HR reactivity to spontaneous arousals, and that this response would be more marked in females. We studied 19 young, healthy subjects (eight females, age: 23.5 ± 5 years, body mass index [BMI]: 24.5 ± 3.6 kg/m2). In a randomized, crossover design, participants were tested during a normal sleep (NS, 9 hr sleep opportunity) or sleep restriction (SR, 4 hr sleep opportunity) study arm. Each 16-day study visit consisted of a 4-day study acclimation phase, 9-day experimental sleep perturbation segment, followed by a 3-day recovery period. An overnight polysomnography (PSG) study was conducted on study days 2, 5 and 11 (at baseline and after 1 and 7 days of restricted versus control sleep). A registered PSG technician provided sleep staging and spontaneous arousal scoring, which was confirmed by an investigator with sleep expertise (IMG). For each identified spontaneous arousal, the HR change was quantified for 30 cardiac cycles post-arousal onset and compared to a pre-arousal baseline (average HR 5 – 10 cardiac cycles prior to arousal). An arousal was considered valid for analysis if at least one minute of stage N2 or rapid eye movement (REM) sleep occurred following sleep stage transition and was at least 30 seconds apart from other sleep disturbance-related events (e.g., limb movement, apneic event, etc.). Given low prevalence of slow wave sleep (SWS) arousals, arousals occurring in that sleep stage were excluded from present analysis. Statistical analysis, including repeated measures ANOVA (RMANOVA, p &lt; 0.05) with condition and time (cardiac cycles) as within-subjects factors and sex as the between-subjects factor, was conducted to compare the beat-to-beat HR response to arousal between study conditions. Additionally, average and peak HR responses to spontaneous arousals were compared via RMANOVA with condition and time (study days) as within-subjects and sex as between-subjects factors. HR response to spontaneous arousal in stage two and REM sleep was similar between NS and SR on study day 5 or day 11 (condition × time: p = 0.943, 0.865). Secondary analysis of average and peak HR responsiveness to spontaneous arousals in stage two and REM sleep between conditions and study days was also not statistically different (condition × time: p = 0.193, 0.185). Last, no significant sex differences were detected across comparisons (condition × time × sex: p &gt; 0.05 for all). These findings suggest that a 9-day sleep restriction paradigm may not alter cardiac autonomic function in otherwise healthy adults. Future work is warranted to determine whether these results extend to individuals with established cardiovascular risk factors or cardiovascular disease. Support: NIH T32-DK007013, R01-114676, and CTSA grant UL1-TR002377. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Inverse association between slow-wave sleep and low-grade inflammation in children and adolescents with major depressive disorder

ObjectiveTo investigate the relationship between both self-reported and objective sleep variables and low-grade inflammation in children and adolescents with major depressive disorder (MDD) of moderate to severe symptom severity. MethodsIn this cross-sectional study, we examined twenty-nine children and adolescents diagnosed with MDD and twenty-nine healthy controls (HC). Following a one-week actigraphy assessment, comprehensive sleep evaluations were conducted, including a one-night sleep EEG measurement and self-reported sleep data. Plasma high-sensitivity C-reactive protein (hsCRP) was employed as a marker to assess low-grade inflammation. ResultsNo significant difference in hsCRP levels was observed between participants with MDD and HC. Furthermore, after adjusting for sleep difficulties, hsCRP exhibited no correlation with the severity of depressive symptoms. In HC, levels of hsCRP were not linked to self-reported and objective sleep variables. In contrast, depressed participants showed a significant correlation between hsCRP levels and increased subjective insomnia severity (Insomnia Severity Index; r = 0.41, p < 0.05), increased time spent in the N2 sleep stage (r = 0.47, p < 0.01), and decreased time spent in slow-wave sleep (r = − 0.61, p < 0.001). Upon additional adjustments for body mass index, tobacco use and depression severity, only the inverse association between hsCRP and time spent in slow-wave sleep retained statistical significance. Moderation analysis indicated that group status (MDD vs. HC) significantly moderates the association between slow-wave sleep and hsCRP. ConclusionOur findings suggest that alterations in the architecture of slow-wave sleep may have a significant influence on modulating low-grade inflammatory processes in children and adolescents with MDD.

Modulation index predicts the effect of ethosuximide on developmental and epileptic encephalopathy with spike-and-wave activation in sleep

PurposeIn developmental and epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS), the thalamocortical network is suggested to play an important role in the pathophysiology of the progression from focal epilepsy to DEE-SWAS. Ethosuximide (ESM) exerts effects by blocking T-type calcium channels in thalamic neurons. With the thalamocortical network in mind, we studied the prediction of ESM effectiveness in DEE-SWAS treatment using phase-amplitude coupling (PAC) analysis. MethodsWe retrospectively enrolled children with DEE-SWAS who had an electroencephalogram (EEG) recorded between January 2009 and September 2022 and were prescribed ESM at Okayama University Hospital. Only patients whose EEG showed continuous spike-and-wave during sleep were included. We extracted 5-min non-rapid eye movement sleep stage N2 segments from EEG recorded before starting ESM. We calculated the modulation index (MI) as the measure of PAC in pair combination comprising one of two fast oscillation types (gamma, 40–80 Hz; ripples, 80–150 Hz) and one of five slow-wave bands (delta, 0.5–1, 1–2, 2–3, and 3–4 Hz; theta, 4–8 Hz), and compared it between ESM responders and non-responders. ResultsWe identified 20 children with a diagnosis of DEE-SWAS who took ESM. Fifteen were ESM responders. Regarding gamma oscillations, significant differences were seen only in MI with 0.5–1 Hz slow waves in the frontal pole and occipital regions. Regarding ripples, ESM responders had significantly higher MI in coupling with all slow waves in the frontal pole region, 0.5–1, 3–4, and 4–8 Hz slow waves in the frontal region, 3–4 Hz slow waves in the parietal region, 0.5–1, 2–3, 3–4, and 4–8 Hz slow waves in the occipital region, and 3–4 Hz slow waves in the anterior-temporal region. SignificanceHigh MI in a wider area of the brain may represent the epileptic network mediated by the thalamus in DEE-SWAS and may be a predictor of ESM effectiveness.

Alpha anteriorization and theta posteriorization during deep sleep.

Brain states (wake, sleep, general anesthesia, etc.) are profoundly associated with the spatiotemporal dynamics of brain oscillations. Previous studies showed that the EEG alpha power shifted from the occipital cortex to the frontal cortex (alpha anteriorization) after being induced into a state of general anesthesia via propofol. The sleep research literature suggests that slow waves and sleep spindles are generated locally and propagated gradually to different brain regions. Since sleep and general anesthesia are conceptualized under the same framework of consciousness, the present study examines whether alpha anteriorization similarly occurs during sleep and how the EEG power in other frequency bands changes during different sleep stages. The results from the analysis of three polysomnography datasets of 234 participants show consistent alpha anteriorization during the sleep stages N2 and N3, beta anteriorization during stage REM, and theta posteriorization during stages N2 and N3. Although it is known that the neural circuits responsible for sleep are not exactly the same for general anesthesia, the findings of alpha anteriorization in this study suggest that, at macro level, the circuits for alpha oscillations are organized in the similar cortical areas. The spatial shifts of EEG power in different frequency bands during sleep may offer meaningful neurophysiological markers for the level of consciousness.