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 418 adolescents (median 16y) 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 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. Conclusion 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.

Sleep Depth and Patterns of In-Flight Sleep Behavior Across Time During Global Pandemic Conditions

Fatigue risk to commercial pilots operating under global pandemic conditions had not been in-vestigated prior to COVID-19. Examining how pilots slept during COVID-19 pandemic-specific flights can provide a precedent for estimating fatigue risk for future public health emergencies. Twenty (n=20) pilots flying across five COVID-19 humanitarian missions between Brazil and China wore a sleep-tracking device (the Zulu watch), which has been validated for the estimation of sleep timing (sleep onset and offset), duration, efficiency, and sleep depth (Wake, Interrupted, Light, or Deep Sleep) throughout the mission period. Pilots also reported sleep timing, duration and subjective quality of their in-flight rest periods using a sleep diary. To our knowledge, this is the first report of commercial pilot sleep behavior during ultra-long-range operations under COVID-19 pandemic conditions. Moreover, these analyses provide an estimate of sleep depth during in-flight sleep, which has not been reported previously in the literature.

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 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 5804 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.

Exposure to relaxing words during sleep promotes slow-wave sleep and subjective sleep quality

Our thoughts alter our sleep, but the underlying mechanisms are still unknown. We propose that mental processes are active to a greater or lesser extent during sleep and that this degree of activation affects our sleep depth. We examined this notion by activating the concept of “relaxation” during sleep using relaxation-related words in 50 healthy participants. In support of our hypothesis, playing relaxing words during non-rapid eye movement sleep extended the time spent in slow-wave sleep, increased power in the slow-wave activity band after the word cue, and abolished an asymmetrical sleep depth during the word presentation period. In addition, participants reported a higher sleep quality and elevated subjective alertness. Our results support the notion that the activation of mental concepts during sleep can influence sleep depth. They provide a basis for interventions using targeted activations to promote sleep depth and sleep quality to foster well-being and health.

628 Longitudinal Association between NREM Sleep Depth and Arousability with ADHD and Internalizing Disorders in Adolescence

Introduction Sleep depth decreases in the transition from childhood to adolescence, even in typically developing (TD) youth. However, it remains unknown whether this developmental trajectory in NREM sleep depth differs across adolescents with psychiatric/behavioral disorders. Methods We analyzed the sleep EEG of 392 subjects aged 5–12 at baseline and 12–22 at follow-up (45.2% female, 23.2% racial/ethnic minority), of whom 246 were TD adolescents (controls), 62 were diagnosed with a psychiatric/behavioral disorder and were taking stimulant, anti-depressant, anxiolytic, sedative and/or anti-psychotic medications, and 84 were un-medicated. NREM sleep depth was measured at both time points using the odds ratio product (ORP), which provides a standardized continuous EEG measure of NREM sleep depth/arousability (higher ORP reflects lighter NREM sleep). General linear models examined mean differences between groups on the percent change in ORP between baseline and follow-up (ΔORP) while adjusting for sex, race/ethnicity, age, BMI and AHI at follow-up, and PSG system, psychiatric/behavioral disorders, psychoactive medications and ORP at baseline as well as time-to-follow-up. Results Overall, medicated (80.4%, 95%CI=66.2–94.6) and un-medicated (66.1%, 95%CI=53.0–79.1) subjects showed a higher ΔORP compared to controls (52.2%, 95%CI=40.0–64.5, p<0.01 and p<0.05, respectively) but did not differ between each other (p=0.134). Specifically, un-medicated subjects with ADHD (n=56) showed a higher ΔORP (77.3%, 95%CI=62.4–92.1) compared to controls (p<0.01), while subjects with ADHD on stimulant medication (n=36) did not differ (66.1%, 95%CI=48.9–93.2) from controls (p=0.268) or from un-medicated ADHD subjects (p=0.303). Subjects with internalizing disorders on psychoactive medications (n=29) showed a higher ΔORP (104.9%, 95%CI=82.8–127.0) compared to controls (p<0.01) and to un-medicated subjects (n=27) with internalizing disorders (60.1%, 95%CI=36.8–83.3, p<0.01), who did not differ from controls (p=0.772). Conclusion The greater increase in ORP in the transition to adolescence in un-medicated youth with ADHD suggests that decreased NREM sleep depth may be a biomarker of the disorder. In contrast, the greater increase in ORP in medicated youth with internalizing disorders suggests that psychoactive medications impact NREM sleep depth in these children as they transition to adolescence. These data have important implications for sleep EEG studies that include medicated and un-medicated youth with comorbid psychiatric disorders. Support (if any) NIH Awards Number R01MH118308, R01HL136587, R01HL97165, R01HL63772, UL1TR000127

035 Activating the concept of “relaxation” during sleep using relaxation-related words

Introduction Cognitive processes (e.g., rumination, perception of an unfamiliar sleeping environment, relaxation techniques) alter our sleep, but the underlying mechanisms are still unknown. Theories of embodied or grounded cognition assume that semantic meaning is stored in multimodal neuronal networks. We therefore assume that cognitive concepts are closely linked to related bodily functions. We propose that mental processes are active to a greater or lesser extent during sleep and that this degree of activation affects our sleep depth. Methods We examined this notion by activating the concept of “relaxation” during sleep using relaxation-related words in 50 healthy participants. After an adaption night, subjects slept in the sleep laboratory for two experimental nights according to a within-subject cross-over design. During one experimental night, relaxing words (e.g., “sea”, “relax”) were presented to promote sleep depth. During the other experimental night, control words were presented (e.g., “produce”, “materials”). As the amount of SWS peaks within the first sleep cycle, words were presented during NREM sleep starting with the second sleep cycle (at the latest 120 min after sleep onset). In addition, a mood and a subjective sleep quality questionnaire was conducted. Results In support of our hypothesis, playing relaxing words during non-rapid eye movement sleep extended the time spent in slow-wave sleep during the period, when words were presented. Furthermore, power in the slow-wave activity band was increased several seconds after the cue for relaxing compared with control words. The increased sleep depth by means of relaxing words was accompanied by a reduced interhemispheric asymmetry of SWA and slow-wave density in the during-cueing period. The changes observed in objective sleep translated to the subjective level with an increase in subjective sleep quality and alertness ratings. Conclusion The present study showed that the semantic meaning of words presented during NREM sleep is capable of affecting sleep physiology, SWS maintenance and the subjective evaluation of sleep quality. Our results support the notion that the activation of mental concepts during sleep can influence sleep depth and provide a basis for interventions using targeted activations to promote sleep depth and sleep quality to foster well-being and health. Support (if any):

The determinants of the subjective perception of sleep: insights from a high-density EEG study with serial awakenings

What determines the feeling of being asleep? Standard sleep recordings only incompletely reflect subjective aspects of sleep and some individuals with so-called sleep misperception frequently feel awake although sleep recordings indicate clear-cut sleep. Here we performed 787 awakenings in 20 good sleepers and 10 individuals with severe sleep misperception to interview them about their subjective sleep depth while they underwent high-density EEG sleep recordings (256-channels). Surprisingly, in good sleepers, sleep was subjectively lightest in the first two hours of Non-rapid eye movement (NREM) sleep, generally considered the ′deepest′ sleep, and deepest in rapid eye movement (REM) sleep. Compared to good sleepers, sleep misperceptors felt more frequently awake during sleep, reported overall lighter REM sleep and had more thought-like conscious experiences. In both groups, subjective sleep depth positively correlated with dream-like features of conscious experiences. At the EEG level, spatially widespread high-frequency power was inversely related to subjective sleep depth in NREM sleep in both groups and in REM sleep in misperceptors. Taken together, these findings challenge the widely held notion that ′deep′ (slow wave) sleep best accounts for feeling soundly asleep. Instead, they suggest that subjective sleep depth is inversely related to a neurophysiological process that predominates in NREM sleep early in the night, becomes quiescent in REM sleep and is reflected in high-frequency EEG-activity. In sleep misperceptors, this neurophysiological process is more active and spatially widespread, and abnormally persists into REM sleep. Thus, it is not the presence of ′sleep rhythms′ but rather the absence of ′wake-like′ EEG activity that predicts the feeling of being deeply asleep. These findings will help identify the neuromodulatory systems involved in subjective sleep depth and are therefore relevant for future studies aiming to improve subjective sleep quality.