Odds Ratio Product Research Articles

Association between sleep microarchitecture and cognition in obstructive sleep apnea

Abstract Study Objectives Obstructive sleep apnea (OSA) increases the risk of cognitive impairment. Measures of sleep microarchitecture from EEG may help identify patients at risk of this complication. Methods Participants with suspected OSA (n = 1142) underwent in-laboratory polysomnography and completed sleep and medical history questionnaires, and tests of global cognition (Montreal Cognitive Assessment, MoCA), memory (Rey Auditory Verbal Learning Test, RAVLT) and information processing speed (Digit–Symbol Coding, DSC). Associations between cognitive scores and stage 2 non-rapid eye movement (NREM) sleep spindle density, power, frequency and %-fast (12–16Hz), odds-ratio product (ORP), normalized EEG power (EEGNP), and the delta:alpha ratio were assessed using multivariable linear regression (MLR) adjusted for age, sex, education, and total sleep time. Mediation analyses were performed to determine if sleep microarchitecture indices mediate the negative effect of OSA on cognition. Results All spindle characteristics were lower in participants with moderate and severe OSA (p ≤ .001, vs. no/mild OSA) and positively associated with MoCA, RAVLT, and DSC scores (false discovery rate corrected p-value, q ≤ 0.026), except spindle power which was not associated with RAVLT (q = 0.185). ORP during NREM sleep (ORPNREM) was highest in severe OSA participants (p ≤ .001) but neither ORPNREM (q ≥ 0.230) nor the delta:alpha ratio were associated with cognitive scores in MLR analyses (q ≥ 0.166). In mediation analyses, spindle density and EEGNP (p ≥ .048) mediated moderate-to-severe OSA’s negative effect on MoCA scores while ORPNREM, spindle power, and %-fast spindles mediated OSA’s negative effect on DSC scores (p ≤ .018). Conclusions Altered spindle activity, ORP and normalized EEG power may be important contributors to cognitive deficits in patients with OSA.

1120 Measuring Sleep Depth with Odds Ratio Product (ORP) and In-ear EEG Earbuds

1120 Measuring Sleep Depth with Odds Ratio Product (ORP) and In-ear EEG Earbuds

0427 Assessment of First-Night Effect in Patients with Insomnia Using the Odds-Ratio-Product (ORP)

0427 Assessment of First-Night Effect in Patients with Insomnia Using the Odds-Ratio-Product (ORP)

0583 Improvement in Sleep Depth on CPAP Is Related to Odds-Ratio-Product (ORP) Type and Apnea-Hypopnea-Index at Baseline

0583 Improvement in Sleep Depth on CPAP Is Related to Odds-Ratio-Product (ORP) Type and Apnea-Hypopnea-Index at Baseline

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.

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

Sleep abnormalities are very frequent in critically ill patients during and following ICU stay. Their mechanisms are poorly understood. The odds ratio product (ORP) is a continuous metric (0.0-2.5) of sleep depth measured in 3-sec intervals and derived from the relationship of powers of different EEG frequencies to each other. When expressed as percent of epochs within 10 ORP deciles covering the entire ORP range, it provides information about mechanism(s) of abnormal sleep. To determine ORP architecture types in critically ill patients and survivors of critical illness who had previously undergone sleep studies. Nocturnal polysomnograms of 47 un-sedated 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 another polysomnogram 6 months after hospital discharge. In all polysomnograms each 30-sec epoch was characterized by the mean ORP of the ten 3-sec epochs. The number of 30-sec epochs with mean ORP within each of 10 ORP deciles covering the entire ORP range (0.0-2.5) was calculated and expressed as % of total recording time. Thereafter, each polysomnogram was characterized by a 2-digit ORP type with the first digit (range 1-3) reflecting increasing levels of deep sleep (ORP<0.5, deciles 1 and 2) and the second digit (range 1-3) reflecting increasing levels of full wakefulness (ORP>2.25, decile 10). Results of patients were compared to 831 age- and gender-matched community dwellers free of sleep disorders. 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 OSA). 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. Sleep abnormalities in critically ill patients and survivors of critical illness result primarily from stimuli that preclude progression to deep sleep or from presence of a hyperarousal state.

0807 The Odds Ratio Product as a Metric of Obstructive Sleep Apnea Severity in Adolescents

Abstract Introduction Although the apnea-hypopnea index (AHI) remains the gold-standard metric of the severity of obstructive sleep apnea (OSA), it is often criticized for its limitations. The odds ratio product (ORP), a continuous standardized measure of sleep depth that ranges from 0 (deep sleep) to 2.5 (full wakefulness), has been proposed as a potential EEG-based alternative to assess the severity of OSA, including its association with cardiovascular outcomes such as elevated blood pressure (eBP). Methods We extracted ORP during rapid eye movement (REM) and non-REM sleep stages from the sleep EEG of 421 adolescents (median 16y) from the Penn State Child Cohort. Higher ORP indicates lower sleep depth. Systolic and diastolic BP levels were measured in the seated position and eBP was identified using American Heart Association guideline-recommended pediatric criteria. OSA was defined as an AHI of 2 or greater events per hour of sleep. Logistic regression models examined the joint of effect of AHI and ORP on eBP, while adjusting for sex, age, race/ethnicity and body mass index, and stratified by the presence of OSA. Results We found a significant interaction between AHI and ORP on eBP (p-interaction=0.016). Among adolescents with OSA, each additional 0.5-point increase in ORP was associated with 6.3-fold odds (95%CI=1.9-20.6, p=0.003) of eBP. Specifically, each additional 0.5-point increase in ORP was associated with 6.4 mmHg (SE=3.0, p=0.036) higher systolic BP among adolescents with OSA. These associations were not significant among adolescents without OSA (eBP: OR=0.8, 95%CI=0.4-1.8, p=0.602 for each additional 0.5 increase in ORP). Conclusion Our data support ORP as a prognostic sleep-EEG metric of OSA in youth. Future clinical trials should examine the added value of ORP in OSA endophenotyping, its response to treatment and role in improving cardiovascular outcomes. Support (if any) National Institutes of Health (R01HL136587, R01MH118308, UL1TR000127)

0100 Developmental trajectories of SWA and ORP since childhood in young adults: association with psychiatric/behavioral disorders

Abstract Introduction Declines in non-rapid eye movement (NREM) sleep slow wave activity (SWA) in the transition to adolescence are indicative of brain maturational changes that parallel a decline in sleep depth, as measured by the novel sleep EEG biomarker odds ratio product (ORP). However, these developmental trajectories and their psychiatric/behavioral associations have lacked replication across multiple time points during the lifespan. Methods We determined the developmental trajectories (median follow-up 15y) of SWA and ORP among 150 participants from the Penn State Child Cohort studied in childhood (median age 9y) through adolescence (median age 16y) into young adulthood (median age 24y). Discrete mixture models for clustering of longitudinal data series was used to compute the probability of a subject belonging to mutually-exclusive 2 or 3 trajectory groups, which were selected based on Bayesian and Akaike Information Criteria. Cochran-Mantel-Haenszel tests were used to compare the proportion of subjects with psychiatric/behavioral disorders across the three developmental trajectories in each sleep EEG biomarker. Results Age-related declines in SWA were observed across two developmental groups, of which one followed a cubic trajectory and one a linear trajectory. This decline in SWA was coupled with age-related increases in ORP across three developmental groups, two of which were quadratic and one was linear. Compared to the shallowest trajectories, the SWA and ORP trajectories with the greatest slopes in the transition to young adulthood had a significantly higher proportion of participants with a history of psychiatric/behavioral disorders (78.6% vs. 53.2% and 80.0% vs. 50.7%, respectively, both p&amp;lt; 0.01). Conclusion Our novel data provide replication for the maturational trajectories of SWA and ORP by including time points across three distinct developmental stages, including young adulthood. Also, our data provide evidence linking the developmental trajectories of SWA and ORP with psychopathology. Young adults with psychiatric/behavioral disorders are associated with a steeper developmental decline in sleep intensity (SWA) and sleep depth (ORP) after adolescence. Support (if any) National Institutes of Health (R01HL136587, R01MH118308, UL1TR000127)

0390 Cracking the EEG Code on Insomnia: How Odds Ratio Product Architecture Relates to Number of Insomnia Symptoms

Abstract Introduction Objective markers of insomnia have remained largely elusive. Odds ratio product (ORP; a marker of objective sleep quality), is currently being investigated for a potential role in assisting in insomnia diagnosis. Recent research has shown how patients with insomnia may present with hyperarousal and may be identified by looking at ORP architecture. In the current study, we aimed to investigate how ORP architecture, and specifically time spent in the lowest two (deep sleep) and last decile (full wakefulness) of ORP, relate to the number of insomnia symptoms. Methods 403 participants (age 46.3±12.3, range 18-79, 172 females) recorded their sleep with in-home PSG using the Cerebra Sleep System and completed sleep questionnaires. Sleep quality was measured using the odds ratio product (ORP) derived from micro-analyzing frontal EEG channels. On the questionnaires, participants reported whether they experienced any of the following insomnia symptoms at least three times a week: trouble falling asleep, trouble staying asleep, and waking up too early. Statistical analyses included number of insomnia symptoms as a dependent variable in a multiple linear regression, time spent in the lowest two deciles of ORP and the highest decile of ORP as independent variables, and age as a covariate in a separate model. Results 60 participants reported 1 symptom of insomnia, 82 reported 2 symptoms, and 68 reported 3 symptoms. The full model was significant (F2,399=4.675, p=0.010, R=0.228, R2 adj=0.052) and indicated that time spent in the highest decile of ORP was the only significant predictor of number of insomnia symptoms (t399=2.321, p=0.021, β=0.131) after controlling for age. Time spent in the lowest two deciles of ORP (deep sleep) was not a significant predictor (p &amp;gt;0.05). Conclusion Time in the highest ORP decile, indicative of full wakefulness, is positively associated with insomnia symptoms after controlling for age. Individuals reporting more insomnia symptoms spent more time in full wakefulness. Time spent in deep sleep was not associated with insomnia symptoms. This may indicate hyperarousal and low sleep drive in participants with subjective insomnia complaints, which is consistent with insomnia etiology. Support (if any)

0329 Wake Intrusions in the EEG: A Novel Application of the Odds Ratio Product in Identifying Subthreshold Arousals

Abstract Introduction Arousal scoring is controversial, due to its lack of objectivity and dependency on other intrinsic characteristics of sleep. Conventional arousal measurements have not consistently predicted insomnia severity. The present study used a novel application of the Odds Ratio Product (ORP), a measure of sleep depth ranging from 0 (deep sleep) to 2.5 (fully awake), to identify subtle wake intrusions in sleep (i.e., subthreshold arousals). We assessed whether these intrusions are better predictors of frequent insomnia symptoms when compared to conventional arousal measurements. Methods Using cross-sectional data from the Sleep Heart Health Study with high-quality ORP data (SHHS1; n = 5,771), accessed through the National Sleep Research Resource, we defined ‘wake intrusions’ as the number of times the ORP spiked above a wake threshold of 2.0 (99% agreement in wake scoring among sleep scorers) during sleep. The wake intrusion index (WII) was derived by calculating the quotient of the number of intrusions by total sleep time. Insomnia was defined from self-reported frequency of &amp;gt;15x/month of insomnia symptoms: delayed sleep onset, difficulty maintaining sleep, and/or early morning awakenings (n = 617). Linear models were used to examine the associations between insomnia and WII, as well as arousal index. Analyses were adjusted for age, sex, body mass index (BMI), and apnea-hypopnea index (AHI). Results There was a weak, but significant correlation between conventional arousal index and WII (r=0.25, 95%CI [0.22, 0.27], p&amp;lt; 0.001). After adjusting for age, sex, BMI and AHI, frequent insomnia symptoms were associated with WII (β=9.47, 95%CI [2.07, 16.87], p=0.012), but not with arousal index (β=0.16, 95%CI [-0.59,0.91], p=0.217). Conclusion Results suggest that the ORP WII may be more sensitive than the arousal index. Moreover, frequent insomnia symptoms were independently associated with WII in adjusted analysis, while not with the arousal index. The role of the ORP WII as a potential physiological marker of insomnia deserves further investigation. Support (if any) NIH (U01HL53916, U01HL53931, U01HL53934, U01HL53937, U01HL64360, U01HL53938, U01HL53940, U01HL53941, U01HL63463, R24HL114473, 75N92019R002).

0534 How objective sleep quality with Odds Ratio Product differs by diagnosis of COMISA, OSA, and insomnia

Abstract Introduction Recent research has highlighted differences in sleep quality for comorbid insomnia and obstructive sleep apnea (COMISA). We investigated how COMISA affects objective sleep quality measured with odds ratio product (ORP) compared to individuals without insomnia or moderate to severe OSA. Methods 410 participants (age 46.4±12.3; 174 females) recorded their sleep with in-home PSG using the Cerebra Sleep System and completed questionnaires. Sleep quality was measured using ORP derived from micro-analyzing frontal EEG channels. On the questionnaires, participants reported whether they experienced insomnia symptoms at least three times a week. Participants were classified as having no diagnosis if their RDI on the home PSG was &amp;lt; 15 and no insomnia symptoms. They were classified as insomnia only if they reported at least one insomnia symptom with an RDI &amp;lt; 15. They were classified as OSA only if they had an RDI ≥15 and reported no insomnia symptoms. Finally, they were classified as COMISA if they had an RDI ≥15 and reported at least one insomnia symptom. All analyses controlled for age and were corrected for multiple comparisons. Results 113(27.6%) patients were classified as having no diagnosis, 109(26.6%) as insomnia only, 83(20.2%) as OSA only, and 105(25.6%) as COMISA. There was a significant effect of diagnosis on ORPNREM (F3,405= 6.042, p&amp;lt;.001) and ORPTRT (F3,405= 3.799, p= 0.010). Participants with no diagnosis had lower ORPNREM than patients with OSA only (p= 0.039) and patients with COMISA (p&amp;lt;.001) and had lower ORPTRT than COMISA (p= 0.009). OSA severity based on the AHI was the only significant predictor of ORPNREM (p &amp;lt;.001, β= 0.321). Both AHI (p &amp;lt;.001, β=0.176) and number of insomnia symptoms (p=0.002, β=0.141) were significant predictors of ORPTRT. Conclusion Participants with no diagnosis had the lowest ORP indicative of better sleep quality than participants with evidence of sleep disorders. Having COMISA may have greater impacts on sleep quality than insomnia symptoms alone. OSA severity was the only predictor of poor sleep quality when looking at ORPNREM. Yet both OSA severity and insomnia symptoms were associated with higher ORPTRT indicating that individuals with COMISA may show alterations of sleep quality in different states throughout the night. Support (if any)

0419 Sensitivity of ORP to classify individuals with insomnia based on subjective complaints

Abstract Introduction The diagnosis of insomnia is currently based on subjective complaints. Previous research has demonstrated limited benefits of polysomnography in improving diagnostic accuracy with no evident differences in sleep macro-architecture and traditional indices of sleep quality. In this study, we aimed to assess the ability of a novel index of sleep quality, the Odds Ratio Product (ORP), to correctly identify individuals with insomnia, based on subjective complaints. Methods We analyzed responses to a custom sleep survey from 510 participants (age 46.2±12.4; 229 females). We entered 13 outcomes to a principal component analysis (PCA). These included age, body mass index (BMI), Epworth Sleepiness Scale (ESS) scores, sex, questions about snoring, subjective hours of sleep, satisfaction with own sleep, movement symptoms, problems falling asleep, staying asleep and waking up early. Based on the correlations between the original outcomes, the PCA extracted 3 factors that were interpreted as 3 different phenotypes: 1) insomnia (e.g., sleep initiation and maintenance complaints, satisfaction with sleep, lower subjective sleep duration); 2) OSA (e.g., bed partner snoring complaints, snoring self-awareness, sleepiness, respiratory complaints); 3) movement disorder (e.g., movements, female, lower age, higher BMI). We then computed the pre-test probability of insomnia (factor 1 scores &amp;gt;80%) and conducted a series of ROC analyses to assess specificity of PSG indices traditionally used to evaluate the presence of insomnia, and of ORP metrics. Results The AUC values assessing the ability of ORP metrics to predict 80% pre-test probability of insomnia were: ORPwake (0.592, 95% CI 0.499-0.685), ORPNREM (0.465, 95% CI 0.362-0.558), ORPREM (0.542, 95% CI 0.447-0.636), and ORPTRT (0.567, 95% CI 0.475-0.659). When looking at traditional indices like total sleep time (TST), wake after sleep onset (WASO), and number of awakenings, the AUC values were 0.471 (95% CI 0.385-0.556), 0.612 (95% CI 0.528-0.697) and 0.509 (95% CI 0.421-0.597), respectively. Conclusion WASO, ORPwake and ORPTRT have the highest sensitivity to detect insomnia in participants with &amp;gt;80% pretest probability measured by subjective complaints. These analyses indicate the value of EEG metrics of sleep quality to correctly identify individuals with insomnia and the need to investigate both sleep and wake states. Support (if any)

0195 The association of electronic device use before bedtime on objective sleep quality measured with Odds Ratio Product

Abstract Introduction Previous research has shown mixed results when it comes to electronic device use and the impact on sleep quality. The use of electronic devices before bedtime can impact sleep quality through engaging content and the impact of blue light on melatonin secretion. In the present study, we assessed the relationship between electronic device use and sleep under real-world conditions. Methods Nineteen participants (age 41.1±10.9; 9 females) recorded their sleep with in-home PSG using the Cerebra Sleep System for 18 to 31 nights (21.5±3.4). Sleep quality was measured using odds ratio product (ORP) derived from spectral analysis of the frontal EEG channels during wake, NREM and REM sleep. Participants completed a nighttime questionnaire within one hour of bedtime where they were asked “Did you do any of these activities today” and indicated “social media or surfed the internet in the last hour before bedtime”. The Karolinska Sleepiness Scale (KSS) was also completed during the before bedtime test battery. Results Across the 19 participants, 17 participants reported using social media or surfing the internet within an hour before bedtime for at least one night. Participants reported usage for 9.6 ± 8.2 nights on average (n=165) but no usage for 11.7 ± 7.9 nights on average (n=210). On nights that internet or social media usage before bedtime was reported, participants had lower levels of evening sleepiness on the Karolinska Sleepiness Scale than on nights where no usage was reported (p &amp;lt;.001). On these nights, participants also had higher ORPNREM (p &amp;lt;.001), higher ORPREM (p&amp;lt;.001), higher ORPTRT (p&amp;lt;.001), higher ORP-9 (p&amp;lt;.001) which is an indication of poorer sleep depth after an EEG arousal. Conclusion On the nights when electronic devices were used before bedtime, participants experienced less sleepiness and had worse objective sleep quality during the night. These results indicate the utility of ORP to be sensitive enough to detect changes in sleep quality after electronic device use. Support (if any)

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

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. 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. 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. ORP architecture types can identify patients in whom OSA adversely affects sleep and whose sleep is expected to improve on CPAP therapy.

0536 Association of a Novel EEG Biomarker of Sleep Depth with Sleep Disordered Breathing in Adolescents

Abstract Introduction The odds ratio product (ORP) provides a standardized, continuous measure of sleep depth that ranges from 0 (deep sleep) to 2.5 (full wakefulness). ORP has been shown to increase during adolescence, representing the decline in sleep depth that occurs during this developmental period. In adults, higher ORP has been associated with sleep disordered breathing (SDB), including obstructive sleep apnea (OSA), while there have been no studies in youth. We aimed to determine the association of ORP with SDB in adolescents. Methods We extracted ORP from the sleep EEG of 261 typically developing adolescents aged 12-23y (median 16y) from the Penn State Child Cohort. Higher ORP during rapid eye movement (REM) and non-REM sleep indicates less deep sleep, while higher ORP-9 (i.e., average ORP in the 9-seconds following non-REM cortical arousals) indicates greater arousability. We used general linear models, adjusted for sex, age and race/ethnicity, to examine mean differences in ORP metrics among clinically meaningful groups of SDB based on the apnea/hypopnea index (AHI) consisting of no SDB (AHI&amp;lt;2 and no snoring, n=100), primary snoring (AHI&amp;lt;2 and snoring, n=75), 2≤AHI&amp;lt;5 (n=64), and AHI≥5 (n=22). Results Adolescents with primary snoring or 2≤AHI&amp;lt;5 did not significantly differ in ORP metrics from those without SDB (all p≥0.12). Adolescents with AHI≥5 had higher ORP-NREM compared to those without SDB, with primary snoring or with 2≤AHI&amp;lt;5 (all p≤0.01), while ORP-REM was significantly higher compared to those without SDB (p=0.02). ORP-9 was significantly greater in adolescents with AHI≥5 compared to those with no SDB (p&amp;lt;0.01) and those with primary snoring (p=0.02), but not when compared to those with 2≤AHI&amp;lt;5 (p=0.07). Conclusion Our data suggest that adolescents with OSA experience lower REM and non-REM sleep depth/intensity (higher ORP) compared to those without SDB. In addition, these adolescents experience a slower progression back to deep sleep following cortical arousals (higher ORP-9), which suggests they remain in a high arousability state and, thus, are more likely to repeat arousals. Commensurate with previous studies in adults, our data show that ORP is a useful sleep EEG biomarker able to capture decreased sleep depth in adolescents with OSA. Support (If Any) National Institutes of Health (R01MH118308, UL1TR000127)

0254 Association of Slow Wave Activity and Odds Ratio Product with Internalizing and Externalizing Problems in Children and Adolescents

Abstract Introduction The association of metrics of sleep microstructure with internalizing and externalizing problems in youth has remained elusive. While one study found increased frontal slow wave activity (SWA) in depressed adolescents, there is lack of evidence for a relationship between dimensional measures of behavior and metrics of sleep depth/intensity. We examined the association between two measures of sleep depth/intensity, slow wave activity (SWA) and odds ratio product (ORP), with internalizing and externalizing problems in children and adolescents. Methods We calculated SWA and ORP during non-rapid eye movement (NREM) sleep at central, frontal and fronto-occipital derivations in 639 children (5-12y, median 9y) and 418 adolescents (12-23y, median 16y) from the Penn State Child Cohort via in-lab polysomnography. ORP provides a standardized measure of NREM sleep depth, while ORP-9 (average ORP in the 9-seconds following NREM arousals) provides a metric of arousability. SWA (0.4-4Hz) absolute power (µV2) was determined during NREM sleep. Internalizing and externalizing problems were assessed on Achenbach’s Behavior Checklist by parent (subjects≤17y) or self-report (subjects≥18y). For each scale, T-scores with a mean of 50 and standard deviation of 10 were obtained following standardized scoring. Multivariable-adjusted linear regression models examined the association between SWA/ORP and clinical outcomes. Results At ages 5-12, fronto-occipital SWA was negatively associated with externalizing behaviors (p=0.05), while fronto-occipital and frontal ORP, and frontal ORP-9 were positively associated with internalizing symptoms (all p&amp;lt;0.01). At ages 12-23, central SWA was negatively associated with internalizing symptoms (p=0.05), while central (p=0.05) and frontal (p=0.03) ORP and central ORP-9 (p=0.03) were positively associated with externalizing behaviors. Conclusion Reductions in SWA in childhood or adolescence are associated with developmentally appropriate behavioral problems, as depression/anxiety are more prevalent in adolescence. In contrast to SWA, increased ORP (lighter sleep) and ORP-9 (greater arousability) are associated with more anxiety/depression in childhood, yet more externalizing behaviors in adolescence. These distinct associations, such as SWA with externalizing behaviors and ORP with internalizing symptoms during childhood, may reflect how SWA captures local/synaptic control, while ORP global/state control, of sleep depth, making both sleep EEG biomarkers important from a developmental standpoint. Support (If Any) National Institutes of Health (R01MH118308, UL1TR000127)

0174 The Odds Ratio Product as a Marker of Sleep Homeostasis

Abstract Introduction Classic EEG markers of sleep homeostasis (process S) usually study the level and amount of slow wave activity (SWA). In recent years, the odds ratio product (ORP) has been described as a novel quantitative measure of sleep depth (and conversely, arousability), which is derived from a four-digit permutation of the power in four respective frequency bands. Therefore, we sought to determine whether the ORP can also be used as a novel quantitative marker of process S. Methods Utilizing C3/C4 electrodes with TP9/TP10 reference, ORP was calculated from 25 nights in 15 patients. We used ORP from REM and NREM1-3 segments/bouts in each person’s night(s) with varying number of data points per REM segment(s) in each night(s). Artifacts and wake segments were discarded from analysis. Average ORP is calculated for an individual bout per night per patient. Generalized Estimating Equation (GEE) modelling used GEEQBOX MATLAB toolbox to identify change in sleep depth over bouts. Resultant beta (β) values represented change in nightly sleep depth over sequential NREM/REM segments per patient. Significance was p≤0.000833. Results From 15 people in the epilepsy monitoring unit, 3 did not have epilepsy. In NREM, the average ORP for C3/C4 is 1.26/1.19 (n=146307/125709). Average number of nightly NREM segments for C3/C4 are 4.64/4.9 (n=1261.27/1282.74 average ORP values per nightly segment). In REM, the average ORP for C3/C4 is 1.44/1.44 (n=47629/43528). Average number of nightly REM segments for C3/C4 are 4.36/4.38 (n=418.68/453.33 average ORP values per nightly segment). Signifying the change in sleep depth the beta values from C3/C4 were consistently positive: REM (epilepsy 0.033/0.018, non-epilepsy 0.096/0.053), NREM (epilepsy 0.047/0.053, non-epilepsy 0.026/0.064). Conclusion As a marker of sleep homeostasis, SWA decreases across a period of sleep. Consistently positive beta values derived from ORP in both REM and NREM are comparable because they demonstrate shallower sleep depth (i.e. greater arousability) across segments over nights as sleep debt is repaid. Also as expected, REM has a higher ORP than NREM. Furthermore, our findings of positive beta values are robust against sleep stage and pathology (i.e. epilepsy). Therefore, these findings may represent a novel quantitative marker of sleep homeostasis that includes REM. Support (If Any)

0439 A Polysomnographic Marker of Sleep Quality using Odds Ratio Product are Associated with Insomnia Symptoms in a Dose-Response Relationship

Abstract Introduction Insomnia is primarily diagnosed with subjective complaints because objective biomarkers are limited. In the current study, we assessed whether a polysomnographic marker of sleep quality (odds ratio product; ORP) was associated with different types of insomnia symptoms. Methods 416 participants (age 46.2±12.5; 176 females) recorded their sleep with an in-home Type 2 PSG test using the Cerebra Sleep System and filled out sleep questionnaires. Sleep quality was measured using odds ratio product (ORP) derived from frontal EEG channels across the duration of the recording (ORPTRT). On the questionnaires, participants reported whether they experienced any of the following insomnia symptoms at least three times a week: trouble falling asleep, trouble staying asleep, and waking up earlier than desired. Participants were then classified based on the total number of insomnia symptoms reported. An ANOVA, controlling for age, was performed to compare the effect of the number of insomnia symptoms on ORP. Results 199 participants reported no insomnia symptoms, while the remaining 217 reported at least one symptom three nights a week (1 symptom: n = 62, 2 symptoms: n = 83, 3 symptoms: n = 70). There was a significant effect of number of insomnia symptoms on ORPTRT F(3,414)=3.45, p =.017. There were significant differences between ORPTRT in participants who reported 0 symptoms (.991±.267), and participants who reported 2 symptoms (1.11±.259) (t(282) = -3.57, p &amp;lt;.001), and between 0 and 3 symptoms (1.13±.31 (t(269) = -3.46, p &amp;lt;.001). Even within individuals reporting insomnia symptoms, there were significant differences in ORPTRT between participants who reported 1 and 2 symptoms (p=.024), and 1 and 3 symptoms (p=.029). Conclusion The more insomnia symptoms that were reported, the greater the impairment in sleep quality using ORP were found. Further research could explore if treatment interventions aimed at reducing ORPTRT might be useful to help treat insomnia. Support (If Any)

0417 Odds Ratio Product reveals distinct sleep phenotypes in idiopathic hypersomnia

Abstract Introduction The pathophysiology of idiopathic hypersomnia with long sleep times (IH) remains an enigma. Alternate methods to characterize sleep such as the Odds Ratio Product (ORP), a continuous measure of sleep depth, has the potential to improve understanding of IH. Methods The Odds ratio product is a continuous measure of sleep depth and propensity ranging 0 (very deep sleep) to 2.5 (Least sleep propensity). The difference between 2.5 and ORP in any epoch indicates extent of wake suppression (sleep depth) for that epoch. The cumulative sleep index (CSI) is the integral of sleep suppression across recording time thereby reflecting both the duration and depth of sleep over specified intervals (higher value is deeper and longer sleep). 36 patients with long sleep (600 minutes or longer) recorded through unconstrained polysomnography were analyzed using ORP across the full study (12.7±1.7 hours). Participants were divided into quartiles, 9 patients each(Q1-Q4) based on accumulated sleep across the entire study. Results The mean age for the cohort was 35.8 ± 16.2, of which 29/36 were females. Total sleep time by visual scoring was 679.4 ± 96.4 minutes (range: 601.5 - 1145) minutes). The whole night CSI mean was 989.39 ± 271.64 units (range: 345 to 1427). The quartile values were 618.33 ± 178.83, 919.33 ± 67.27, 1142.89 ± 39.01, and 1277 ± 69.39 units, and not related to total recording or sleep time. The NREM sleep ORP was 1.43± 0.32, 1.06 ± 0.22, 0.73± 0.13 and 0.67 ± 0.19, respectively. This distribution was true for REM sleep ORP also: 1.52 ± 0.30, 1.26 ± 0.19, 1.05 ± 0.25, and 0.84 ± 0.21, respectively. The trait-like ORP-9 (9 seconds post-arousal), and a reflection of sleep fragmentation propensity, was also similarly distributed: 1.60 ± 0.30, 1.29 ± 0.27, 0.92 ± 0.15, and 0.80 ± 0.18, respectively. All comparisons were statistically significant by Tukey multiple comparisons. Conclusion Patients with IH are not homogenous, showing a range of sleep depth in both NREM and REM sleep regardless of total sleep time. These phenotypes of IH could reflect unique endotypic mechanisms, requiring different therapies or have differential treatment responses. Support (If Any)

0426 Shallower sleep depth in the laboratory is not related to insomnia severity

Abstract Introduction In insomnia, classical sleep scoring parameters are often uncorrelated with symptom severity and may not fully capture more subtle alterations in the polysomnogram (PSG) that could contribute to clinical symptoms. The odds ratio product (ORP) is a well-validated, continuous index of sleep depth (range 0=deep sleep; 2.5=full wakefulness) that offers an alternative to traditional staging. It is unknown whether ORP is related to self-reported insomnia severity. We hypothesized that individuals with insomnia would exhibit higher ORP values than healthy controls (reflecting less deep sleep) which would be associated with greater insomnia severity. Methods This is a secondary analysis of data from a study in which n=15 participants with chronic insomnia disorder and n=15 age- and sex-matched healthy controls completed an in-laboratory protocol (N=30; 66% female; 36±8 years; 63% White). Participants had their sleep monitored with in-lab PSG. The Insomnia Severity Index (ISI) was used to estimate sleep disturbance severity. PSG were used to calculate classical sleep scoring parameters as well as the average ORP in each sleep stage. Independent samples t-tests compared means between the insomnia and healthy control groups and Pearson’s correlations assessed relations between PSG/ORP outcome measures and ISI scores. Results The insomnia group’s mean (SD) ISI score was 14.13 (6.00) and significantly higher than the control group’s (1.73 (2.37); corrected p &amp;lt; 0.001). There were no statistically significant between-group differences for classically-scored sleep parameters or average ORP values after correcting for multiple comparisons. Interestingly, means for the insomnia group’s average ORP values tended to be higher than those of the control group’s. ISI scores were not significantly associated with average ORP values across or within groups. Conclusion Insomnia does not appear to be associated with alterations in global sleep depth when measured in a laboratory setting, but there is a need to conduct more detailed analyses on patterns across the night. Support (If Any) Merck, Inc. Investigator Studies Program