Feasibility and Acceptability of Using Wireless Limited Polysomnography to Capture Sleep Before, During, and After Hospitalization for Patients With Planned Cardiothoracic Surgery.

BACKGROUND: Sleep disruption, a common symptom among patients requiring cardiovascular surgery, is a potential risk factor for the development of postoperative delirium. Postoperative delirium is a disorder of acute disturbances in cognition associated with prolonged hospitalization, cognitive decline, and mortality. OBJECTIVE: The aim of this study was to evaluate the feasibility and acceptability of using polysomnography (PSG) to capture sleep in patients with scheduled cardiothoracic surgery. METHODS: Wireless limited PSG assessed sleep at baseline (presurgery at home), postoperatively in the intensive care unit, and at home post hospital discharge. Primary outcomes were quality and completeness of PSG signals, and acceptability by participants and nursing staff. RESULTS: Among 15 patients, PSG data were of high quality, and mean percentage of unscorable data was 5.5% ± 11.1%, 3.7% ± 5.4%, and 3.7% ± 8.4% for baseline, intensive care unit, and posthospitalization measurements, respectively. Nurses and patients found the PSG monitor acceptable. CONCLUSIONS: Wireless, limited PSG to capture sleep across the surgical continuum was feasible, and data were of high quality. Authors of future studies will evaluate associations of sleep indices and development of postoperative delirium in this high-risk population.

Polysomnographic characteristics of excessive daytime sleepiness phenotypes in obstructive sleep apnea: results from the international sleep apnea global interdisciplinary consortium.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is a major symptom of obstructive sleep apnea (OSA). Traditional polysomnographic (PSG) measures only partially explain EDS in OSA. This study analyzed traditional and novel PSG characteristics of two different measures of EDS among patients with OSA. METHODS: Sleepiness was assessed using the Epworth Sleepiness Scale (>10 points defined as "risk of dozing") and a measure of general sleepiness (feeling sleepy ≥ 3 times/week defined as "feeling sleepy"). Four sleepiness phenotypes were identified: "non-sleepy," "risk of dozing only," "feeling sleepy only," and "both at risk of dozing and feeling sleepy." RESULTS: Altogether, 2083 patients with OSA (69% male) with an apnea-hypopnea index (AHI) ≥ 5 events/hour were studied; 46% were "non-sleepy," 26% at "risk of dozing only," 7% were "feeling sleepy only," and 21% reported both. The two phenotypes at "risk of dozing" had higher AHI, more severe hypoxemia (as measured by oxygen desaturation index, minimum and average oxygen saturation [SpO2], time spent < 90% SpO2, and hypoxic impacts) and they spent less time awake, had shorter sleep latency, and higher heart rate response to arousals than "non-sleepy" and "feeling sleepy only" phenotypes. While statistically significant, effect sizes were small. Sleep stages, frequency of arousals, wake after sleep onset and limb movement did not differ between sleepiness phenotypes after adjusting for confounders. CONCLUSIONS: In a large international group of patients with OSA, PSG characteristics were weakly associated with EDS. The physiological measures differed among individuals characterized as "risk of dozing" or "non-sleepy," while "feeling sleepy only" did not differ from "non-sleepy" individuals.

New insights and potential clinical implications of the odds ratio product.

The odds ratio product (ORP) is a continuous metric of sleep depth that ranges from 0 (very deep sleep) to 2. 5 (full wakefulness). Its advantage over the conventional method recommended by AASM is that it discloses different levels of stage wake (sleep propensity) and different sleep depths within the same sleep stage. As such, it can be used to identify differences in sleep depth between subjects, and in the same subjects under different circumstances, when differences are not discernible by conventional staging. It also identifies different sleep depths within stage rapid-eye-movement sleep, with possible implications to disorders during this stage. Epoch-by-epoch ORP can be displayed graphically across the night or as average values in conventional sleep stages. In addition, ORP can be reported as % of recording time in specific ORP ranges (e.g., deciles of the total ORP range) where it produces distinct distribution patterns (ORP-architecture) that have been associated with different clinical disorders and outcomes. These patterns offer unique research opportunities to identify different mechanisms and potential therapy for various sleep complaints and disorders. In this review I will discuss how ORP is measured, its validation, differences from delta power, and the various phenotypes, and their postulated mechanisms, identified by ORP architecture and the opportunities for research to advance management of sleep-disordered breathing, insomnia and idiopathic hypersomnia.

An approach for determining the reliability of manual and digital scoring of sleep stages.

STUDY OBJECTIVES: Inter-scorer variability in sleep staging is largely due to equivocal epochs that contain features of more than one stage. We propose an approach that recognizes the existence of equivocal epochs and evaluates scorers accordingly. METHODS: Epoch-by-epoch staging was performed on 70 polysomnograms by six qualified technologists and by a digital system (Michele Sleep Scoring [MSS]). Probability that epochs assigned the same stage by only two of the six technologists (minority score) resulted from random occurrence of two errors was calculated and found to be <5%, thereby indicating that the stage assigned is an acceptable variant for the epoch. Acceptable stages were identified in each epoch as stages assigned by at least two technologists. Percent agreement between each technologist and the other five technologists, acting as judges, was determined. Agreement was considered to exist if the stage assigned by the tested scorer was one of the acceptable stages for the epoch. Stage assigned by MSS was likewise considered in agreement if included in the acceptable stages made by the technologists. RESULTS: Agreement of technologists tested against five qualified judges increased from 80.8% (range 70.5%-86.4% among technologists) when using the majority rule, to 96.1 (89.8%-98.5%) by the proposed approach. Agreement between unedited MSS and same judges was 90.0% and increased to 92.1% after brief editing. CONCLUSIONS: Accounting for equivocal epochs provides a more accurate estimate of a scorer's (human or digital) competence in scoring sleep stages and reduces inter-scorer disagreements. The proposed approach can be implemented in sleep-scoring training and accreditation programs.

Sleep Architecture Patterns in Critically Ill Patients and Survivors of Critical Illness: A Retrospective Study.

Rationale: Sleep abnormalities are very frequent in critically ill patients during and after intensive care unit (ICU) stays. Their mechanisms are poorly understood. The odds ratio product (ORP) is a continuous metric (range, 0.0-2.5) of sleep depth measured in 3-second intervals and derived from the relationship of powers of different electroencephalographic frequencies to one another. When expressed as the percentage of epochs within 10 ORP deciles covering the entire ORP range, it provides information about the mechanism(s) of abnormal sleep. Objectives: To determine ORP architecture types in critically ill patients and survivors of critical illness who had previously undergone sleep studies. Methods: Nocturnal polysomnograms from 47 unsedated critically ill patients and 23 survivors of critical illness at hospital discharge were analyzed. Twelve critically ill patients were monitored also during the day, and 15 survivors underwent subsequent polysomnography 6 months after hospital discharge. In all polysomnograms, each 30-second epoch was characterized by the mean ORP of the 10 3-second epochs. The number of 30-second epochs with mean ORP within each of 10 ORP deciles covering the entire ORP range (0.0-2.5) was calculated and expressed as a percentage of total recording time. Thereafter, each polysomnogram was characterized using a two-digit ORP type, with the first digit (range, 1-3) reflecting increasing degrees of deep sleep (ORP < 0.5, deciles 1 and 2) and the second digit (range, 1-3) reflecting increasing degrees of full wakefulness (ORP > 2.25, decile 10). Results from patients were compared with those from 831 age- and gender-matched community dwellers free of sleep disorders. Results: In critically ill patients, types 1,1 and 1,2 (little deep sleep and little or average full wakefulness) dominated (46% of patients). In the community, these types are uncommon (<15%) and seen primarily in disorders that preclude progression to deep sleep (e.g., very severe obstructive sleep apnea). Next in frequency (22%) was type 1,3, consistent with hyperarousal. Day ORP sleep architecture was similar to night results. Survivors had similar patterns, with little improvement after 6 months. Conclusions: Sleep abnormalities in critically ill patients and survivors of critical illness result primarily from stimuli that preclude progression to deep sleep or from the presence of a hyperarousal state.

Contribution of obstructive sleep apnea to disrupted sleep in a large clinical cohort of patients with suspected obstructive sleep apnea.

STUDY OBJECTIVES: The response of sleep depth to CPAP in patients with OSA is unpredictable. The odds-ratio-product (ORP) is a continuous index of sleep depth and wake propensity that distinguishes different sleep depths within sleep stages, and different levels of vigilance during stage wake. When expressed as fractions of time spent in different ORP deciles, nine distinctive patterns are found. Only three of these are associated with OSA. We sought to determine whether sleep depth improves on CPAP exclusively in patients with these three ORP patterns. METHODS: ORP was measured during the diagnostic and therapeutic components of 576 split-night polysomnographic (PSG) studies. ORP architecture in the diagnostic section was classified into one of the nine possible ORP patterns and the changes in sleep architecture were determined on CPAP for each of these patterns. ORP architecture was similarly determined in the first half of 760 full-night diagnostic PSG studies and the changes in the second half were measured to control for differences in sleep architecture between the early and late portions of sleep time in the absence of CPAP. RESULTS: Frequency of the three ORP patterns increased progressively with the apnea-hypopnea index. Sleep depth improved significantly on CPAP only in the three ORP patterns associated with OSA. Changes in CPAP in the other six patterns, or in full diagnostic PSG studies, were insignificant or paradoxical. CONCLUSIONS: ORP architecture types can identify patients in whom OSA adversely affects sleep and whose sleep is expected to improve on CPAP therapy.

The sleep homeostatic response to sleep deprivation in humans is heritable.

STUDY OBJECTIVES: Following sleep deprivation, increases in delta power have historically been used to index increases in sleep pressure. Research in mice has demonstrated that the homeostatic delta power response to sleep deprivation is heritable. Whether this is true in humans is unknown. In the present study, we used delta power and ORP, a novel measure of sleep depth, to investigate the effects of acute sleep deprivation on sleep depth and to assess the heritability of sleep homeostasis in humans. METHODS: ORP and delta power were examined during baseline and recovery sleep following 38 h of sleep deprivation in 57 monozygotic and 38 dizygotic same-sex twin pairs. Two complementary methods were used to estimate the trait heritability of sleep homeostasis. RESULTS: During recovery sleep, ORP was lower and delta power was higher than at baseline, indicating deeper sleep. However, at the end of the recovery night, delta power reached baseline levels but ORP demonstrated incomplete recovery. Both ORP and delta power showed a broad sense heritability of sleep homeostasis following sleep deprivation. The classical approach demonstrated an h2 estimate of 0.43 for ORP and 0.73 for delta power. Mixed-effect multilevel models showed that the proportion of variance attributable to additive genetic transmission was 0.499 (95% CI = 0.316-0.682; p < .0001) for ORP and 0.565 (95% CI = 0.403-0.726; p < .0001 for delta power. CONCLUSIONS: These results demonstrate that the homeostatic response to sleep deprivation is a heritable trait in humans and confirm ORP as a robust measure of sleep depth.

Adherence Index: sleep depth and nocturnal hypoventilation predict long-term adherence with positive airway pressure therapy in severe obstructive sleep apnea.

STUDY OBJECTIVES: Treatment of obstructive sleep apnea with positive airway pressure (PAP) devices is limited by poor long-term adherence. Early identification of individual patients' probability of long-term PAP adherence would help in their management. We determined whether conventional polysomnogram (PSG) scoring and measures of sleep depth based on the odds ratio product would predict adherence with PAP therapy 12 months after it was started. METHODS: Patients with obstructive sleep apnea referred to an academic sleep center had split-night PSG, arterial blood gases, and a sleep questionnaire. Multiple linear regression analysis of conventional PSG scoring and the odds ratio product both during diagnostic PSG and PAP titration provided an "Adherence Index," which was correlated with PAP use 12 months later. RESULTS: Patients with obstructive sleep apnea (n = 236, apnea-hypopnea index 72.2 ± 34.1 events/h) were prescribed PAP therapy (82% received continuous PAP, 18% received bilevel PAP). Each patient's adherence with PAP therapy 12 months later was categorized as "never used," "quit using," "poor adherence," and "good adherence." PSG measures that were most strongly correlated with PAP adherence were apnea-hypopnea index and odds ratio product during nonrapid eye movement sleep; the additional contribution of nocturnal hypoxemia to this correlation was confined to those with chronic hypoventilation treated with bilevel PAP. The Adherence Index derived from these measures, during both diagnostic PSG and PAP titration, was strongly correlated with PAP adherence 12 months later. CONCLUSIONS: Long-term adherence with PAP therapy can be predicted from diagnostic PSG in patients with severe obstructive sleep apnea, which may facilitate a precision-based approach to PAP management. CITATION: Younes MK, Beaudin AE, Raneri JK, Gerardy BJ, Hanly PJ. Adherence Index: sleep depth and nocturnal hypoventilation predict long-term adherence with positive airway pressure therapy in severe obstructive sleep apnea. J Clin Sleep Med. 2022:18(8):1933-1944.

A novel EEG marker predicts perceived sleepiness and poor sleep quality.

STUDY OBJECTIVES: To determine if a novel EEG-derived continuous index of sleep depth/alertness, the odds ratio product (ORP), predicts self-reported daytime sleepiness and poor sleep quality in two large population-based cohorts. METHODS: ORP values which range from 0 (deep sleep) to 2.5 (fully alert) were calculated in 3s intervals during awake periods (ORPwake) and NREM sleep (ORPNREM) determined from home sleep studies in the HypnoLaus (N = 2162: 1106 females, 1056 males) and men androgen inflammation lifestyle environment and stress (MAILES) cohorts (N = 754 males). Logistic regression was used to examine associations between ORPwake, ORPNREM, and traditional polysomnography measures (as comparators) with excessive sleepiness (Epworth sleepiness scale >10) and poor sleep quality (Pittsburgh sleep quality index >5) and insomnia symptoms. RESULTS: High ORPwake was associated with a ~30% increase in poor sleep quality in both HypnoLaus (odds ratio, OR, and 95% CI) 1.28 (1.09, 1.51), and MAILES 1.36 (1.10, 1.68). High ORPwake was also associated with a ~28% decrease in excessive daytime sleepiness in the MAILES dataset. ORPNREM was associated with a ~30% increase in poor sleep quality in HypnoLaus but not in MAILES. No consistent associations across cohorts were detected using traditional polysomnography markers. CONCLUSIONS: ORP, a novel EEG-derived metric, measured during wake periods predicts poor sleep quality in two independent cohorts. Consistent with insomnia symptomatology of poor perceived sleep in the absence of excessive daytime sleepiness, ORPwake may provide valuable objective mechanistic insight into physiological hyperarousal.

Sleep architecture based on sleep depth and propensity: patterns in different demographics and sleep disorders and association with health outcomes.

STUDY OBJECTIVES: Conventional metrics of sleep quantity/depth have serious shortcomings. Odds-Ratio-Product (ORP) is a continuous metric of sleep depth ranging from 0 (very deep sleep) to 2.5 (full-wakefulness). We describe an ORP-based approach that provides information on sleep disorders not apparent from traditional metrics. METHODS: We analyzed records from the Sleep-Heart-Health-Study and a study of performance deficit following sleep deprivation. ORP of all 30-second epochs in each PSG and percent of epochs in each decile of ORPs range were calculated. Percentage of epochs in deep sleep (ORP < 0.50) and in full-wakefulness (ORP > 2.25) were each assigned a rank, 1-3, representing first and second digits, respectively, of nine distinct types ("1,1", "1,2" … "3,3"). Prevalence of each type in clinical groups and their associations with demographics, sleepiness (Epworth-Sleepiness-Scale, ESS) and quality of life (QOL; Short-Form-Health-Survey-36) were determined. RESULTS: Three types ("1,1", "1,2", "1,3") were prevalent in OSA and were associated with reduced QOL. Two ("1,3" and "2,3") were prevalent in insomnia with short-sleep-duration (insomnia-SSD), but only "1,3" was associated with poor sleep depth and reduced QOL, suggesting two phenotypes in insomnia-SSD. ESS was high in types "1,1" and "1,2", and low in "1,3" and "2,3". Prevalence of some types increased with age while in others it decreased. Other types were either rare ("1,1" and "3,3") or high ("2,2") at all ages. CONCLUSIONS: The proposed ORP histogram offers specific and unique information on the underlying neurophysiological characteristics of sleep disorders not captured by routine metrics, with potential of advancing diagnosis and management of these disorders.

Impact of intermittent hypoxia on human vascular responses during sleep.

Exposure to intermittent hypoxia (IH) ≥15 times per hour is believed to be the primary mechanism for the increased risk of cerebrovascular and cardiovascular disease in patients with moderate to severe sleep apnea. Human experimental models of IH used to investigate this link have been predominantly employed during wakefulness, which limits extrapolation of findings to sleep apnea where IH occurs during sleep. Moreover, how IH impacts vascular regulation during sleep has not been measured quantitatively. Therefore, the objective of this study was to assess the impact sleep accompanied by IH on vascular responses to hypoxia and hypercapnia during sleep. Ten males performed two randomly scheduled 6-h overnight sleep studies. One sleep study was performed in room air (normoxia) and the other sleep study was performed during isocapnic IH (60 s hypoxia-60 s normoxia). On each night, cerebrovascular (peak blood velocity through the middle cerebral artery (V¯P); transcranial Doppler ultrasound) and cardiovascular (blood pressure, heart rate) responses to hypoxia and hypercapnia were measured before sleep onset (PM-Awake), within the first 2 h of sleep (PM-Asleep), in the 5th (out of 6) hours of sleep (AM-Asleep) and after being awoken in the morning (AM-Awake). Sleep accompanied by IH had no impact on the V¯P and blood pressure responses to hypoxia and hypercapnic at any timepoint (p ≥ 0.103 for all responses). However, the AM-Awake heart rate response to hypoxia was greater following sleep in IH compared to sleep in normoxia. Independent of the sleep environment, the V¯P response to hypoxia and hypercapnia were reduced during sleep. In conclusion, cerebral blood flow responses are reduced during sleep compared to wakefulness, but 6 h of sleep accompanied by IH does not alter cerebrovascular and cardiovascular response to hypoxia and hypercapnia during wakefulness or sleep in healthy young humans. However, it is likely that longer exposure to IH during sleep (i.e., days-to-weeks) is required to better elucidate IH's impact on vascular regulation in humans.

Association of a novel EEG metric of sleep depth/intensity with attention-deficit/hyperactivity, learning, and internalizing disorders and their pharmacotherapy in adolescence.

STUDY OBJECTIVES: Psychiatric/learning disorders are associated with sleep disturbances, including those arising from abnormal cortical activity. The odds ratio product (ORP) is a standardized electroencephalogram metric of sleep depth/intensity validated in adults, while ORP data in youth are lacking. We tested ORP as a measure of sleep depth/intensity in adolescents with and without psychiatric/learning disorders. METHODS: Four hundred eighteen adolescents (median 16 years) underwent a 9-hour, in-lab polysomnography. Of them, 263 were typically developing (TD), 89 were unmedicated, and 66 were medicated for disorders including attention-deficit/hyperactivity (ADHD), learning (LD), and internalizing (ID). Central ORP during non-rapid eye movement (NREM) sleep was the primary outcome. Secondary/exploratory outcomes included central and frontal ORP during NREM stages, in the 9-seconds following arousals (ORP-9), in the first and second halves of the night, during REM sleep and wakefulness. RESULTS: Unmedicated youth with ADHD/LD had greater central ORP than TD during stage 3 and in central and frontal regions during stage 2 and the second half of the sleep period, while ORP in youth with ADHD/LD on stimulants did not significantly differ from TD. Unmedicated youth with ID did not significantly differ from TD in ORP, while youth with ID on antidepressants had greater central and frontal ORP than TD during NREM and REM sleep, and higher ORP-9. CONCLUSIONS: The greater ORP in unmedicated youth with ADHD/LD, and normalized levels in those on stimulants, suggests ORP is a useful metric of decreased NREM sleep depth/intensity in ADHD/LD. Antidepressants are associated with greater ORP/ORP-9, suggesting these medications induce cortical arousability.

Traffic noise-induced changes in wake-propensity measured with the Odds-Ratio Product (ORP).

Nocturnal traffic noise can disrupt sleep and impair physical and mental restoration, but classical sleep scoring techniques may not fully capture subtle yet clinically relevant alterations of sleep induced by noise. We used a validated continuous measure of sleep depth and quality based on automatic analysis of physiologic sleep data, termed Wake Propensity (WP), to investigate temporal changes of sleep in response to nocturnal noise events in 3-s epochs. Seventy-two healthy participants (mean age 40.3 years, range 18-71 years, 40 females, 32 males) slept for 11 nights in a laboratory, during which we measured sleep with polysomnography. In 8 nights, participants were exposed to 40, 80 or 120 road, rail and/or aircraft noise events with maximum noise levels of 45-65 dB LAS,max during 8-h sleep opportunities. We analyzed sleep macrostructure and event-related change of WP during noise exposure with linear mixed models. Nocturnal traffic noise led to event-related shifts towards wakefulness and less deep, more unstable sleep (increase in WP relative to pre-noise baseline ranging from +29.5% at 45 dB to +38.3% at 65 dB; type III effect p < 0.0001). Sleep depth decreased dynamically with increasing noise level, peaking when LAS,max was highest. This change in WP was stronger and occurred more quickly for events where the noise onset was more rapid (road and rail) compared to more gradually time-varying noise (aircraft). Sleep depth did not immediately recover to pre-noise WP, leading to decreased sleep stability across the night compared to quiet nights, which was greater with an increasing number of noise events (standardized ß = 0.053, p = 0.003). Further, WP was more sensitive to noise than classical arousals. Results demonstrate the usefulness of WP as a measure of the effects of external stimuli on sleep, and show WP is a more sensitive measure of noise-induced sleep disruption than traditional methods of sleep analysis.

Effects of Sedatives on Sleep Architecture Measured With Odds Ratio Product in Critically Ill Patients.

Evaluation of sleep quality in critically ill patients is difficult using conventional scoring criteria. The aim of this study was to examine sleep in critically ill patients with and without light sedation using the odds ratio product, a validated continuous metric of sleep depth (0 = deep sleep; 2.5 = full wakefulness) that does not rely on the features needed for conventional staging. DESIGN: Retrospective study. SETTINGS: A 16-bed medical-surgical ICU. PATIENTS: Twenty-three mechanically ventilated patients who had previously undergone two nocturnal sleep studies, one without and one with sedation (propofol, n = 12; dexmedetomidine, n = 11). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sleep architecture was evaluated with odds ratio product analysis by the distribution of 30-second epochs with different odds ratio product values. Electroencephalogram spectral patterns and frequency of wake intrusions (3-s odds ratio product > 1.75) were measured at different odds ratio product levels. Thirty-seven normal sleepers were used as controls. Compared with normal sleepers, unsedated critically ill patients spent little time in stable sleep (percent odds ratio product < 1.0: 31% vs 63%; p < 0.001), whereas most of the time were either in stage wake (odds ratio product > 1.75) or in a transitional state (odds ratio product 1.0-1.75), characterized by frequent wake intrusions. Propofol and dexmedetomidine had comparable effects on sleep. Sedation resulted in significant shift in odds ratio product distribution toward normal; percent odds ratio product less than 1.0 increased by 54% (p = 0.006), and percent odds ratio product greater than 1.75 decreased by 48% (p = 0.013). In six patients (26%), sedation failed to improve sleep. CONCLUSIONS: In stable critically ill unsedated patients, sleep quality is poor with frequent wake intrusions and little stable sleep. Light sedation with propofol or dexmedetomidine resulted in a shift in sleep architecture toward normal in most, but not all, patients.

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

STUDY OBJECTIVES: New 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. METHODS: We 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. RESULTS: All 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). CONCLUSIONS: The 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.

Sex and Pubertal Differences in the Maturational Trajectories of Sleep Spindles in the Transition from Childhood to Adolescence: A Population-Based Study.

Sleep spindles, bursts of electroencephalogram (EEG) activity in the σ-frequency (11-16 Hz) range, may be biomarkers of cortical development. Studies capturing the transition to adolescence are needed to delineate age-related, sex-related, and pubertal-related changes in sleep spindles at the population-level. We analyzed the sleep EEG of 572 subjects 6-21 years (48% female) and 332 subjects 5-12 years (46% female) followed-up at 12-22 years. From 6 to 21 years, spindle density (p quadratic = 0.019) and fast (12-16 Hz) spindle percent (p quadratic = 0.016) showed inverted U-shaped trajectories, with plateaus after 15 and 19 years, respectively. Spindle frequency increased (p linear < 0.001), while spindle power decreased (p linear < 0.001) from 6 to 21 years. The trajectories of spindle density, frequency, and fast spindle percent diverged between females and males, in whom density plateaued by 14 years, fast spindle percent by 16 years, and frequency by 18 years, while fast spindle percent and spindle frequency continued to increase until 21 years in females. Males experienced a longitudinal increase in spindle density 31% greater than females by 12-14 years (p = 0.006). Females experienced an increase in spindle frequency and fast spindle percent 2% and 41% greater, respectively, than males by 18-22 years (both p = 0.004), while males experienced a 14% greater decline in spindle power by 18-22 years (p = 0.018). Less mature adolescents (86% male) experienced a longitudinal increase in spindle density 36% greater than mature adolescents by 12-14 years (p = 0.002). Overall, males experience greater maturational changes in spindle density in the transition to adolescence, driven by later pubertal development, and sex differences become prominent in early adulthood when females have greater spindle power, frequency, and fast spindle percent.

Maturational trajectories of non-rapid eye movement slow wave activity and odds ratio product in a population-based sample of youth.

BACKGROUND: Brain maturation is reflected in the sleep electroencephalogram (EEG) by a decline in non-rapid eye movement (NREM) slow wave activity (SWA) throughout adolescence and a related decrease in sleep depth. However, this trajectory and its sex and pubertal differences lack replication in population-based samples. We tested age-related changes in SWA (0.4-4 Hz) power and odds ratio product (ORP), a standardized measure of sleep depth. METHODS: We analyzed the sleep EEG of 572 subjects aged 6-21 y (48% female, 26% racial/ethnic minority) and 332 subjects 5-12 y followed-up at 12-22 y. Multivariable-adjusted analyses tested age-related cross-sectional and longitudinal trajectories of SWA and ORP. RESULTS: SWA remained stable from age 6 to 10, decreased between ages 11 and 17, and plateaued from age 18 to 21 (p-cubic<0.001); females showed a longitudinal decline 23% greater than males by 13 y, while males experienced a steeper slope after 14 y and their longitudinal decline was 21% greater by 19 y. More mature adolescents (75% female) experienced a greater longitudinal decline in SWA than less mature adolescents by 14 y. ORP showed an age-related increasing trajectory (p-linear<0.001) with no sex or pubertal differences. CONCLUSIONS: We provide population-level evidence for the maturational decline and sex and pubertal differences in SWA in the transition from childhood to adolescence, while introducing ORP as a novel metric in youth. Along with previous studies, the distinct trajectories observed suggest that age-related changes in SWA reflect brain maturation and local/synaptic processes during this developmental period, while those of ORP may reflect global/state control of NREM sleep depth.