bluuebunny/crossref_metadata_2025 huggingface dataset:
0190 Impact of Menopause-Related Sleep Fragmentation on Daytime Sleepiness and Neurobehavioral Performance: Results of an Experimental Model
Authors: Grant L K , Cohn A , Abramson M , Russell J A , Wiley A , Coborn J E , Nathan M D , Scheer F A , Klerman E B , Kaiser U B , Rahman S A , Joffe H
Published: May 2020

Introduction

Cognitive performance may be adversely affected during the menopause transition from hot flash-induced sleep fragmentation even without changes in sleep duration. We examined the effects of experimentally-induced sleep fragmentation without shortened sleep duration on daytime sleepiness and neurobehavioral performance in women in a high and low estradiol (E2) state.

Methods

Seven pre-menopausal women (29.4 ± 3.8 years) participated in two 6-day inpatient studies repeated in a high-E2 (mid-to-late follicular phase) then low-E2 state (gonadotropin-releasing hormone agonist-induced E2 suppression - similar to levels during menopause) ~6 weeks apart. Sleep was uninterrupted on nights 1–2 [8-h time-in-bed (TIB)] and fragmented on nights 3–5 (9-h TIB) using an auditory stimulus delivered every 15 min that sustained wake for 2 minutes, producing 1-h total wake after sleep onset. Wakefulness was confirmed by event-markers during polysomnographically-recorded sleep episodes. Daytime subjective sleepiness (Karolinska Sleepiness Scale; KSS) and neurobehavioral performance (Psychomotor Vigilance Task; PVT) were assessed every 2–3 hours on study days 2–5. The effects of study day and E2 state on KSS scores and PVT measured reaction time (RT) and attentional failures (RT>500ms) were examined using linear mixed models.

Results

Participants reported feeling sleepier (+10%), had longer RTs (+22ms), and more attentional failures (+53%) after sleep fragmentation than after uninterrupted sleep (all p<0.001). While there was no main effect of E2 state, there was a differential effect of sleep fragmentation by E2 state on PVT, but not sleepiness, such that the increase in RT and attentional failures in response to sleep fragmentation was only observed in the high-E2 state (p<0.001).

Conclusion

Eight hours of total sleep time may not be sufficient to maintain subjective sleepiness and PVT performance levels when sleep is not consolidated. These findings have important implications for understanding the role of sleep and E2-modulated cognitive impairment during the menopause transition.

Support

This work was supported by the NIH: 5R01 AG053838-02 (HJ) and K24-HL105664 (EBK).
0245 Relationship of Chronotype with Sleep Duration, Daytime Sleepiness, and Sustained Attention in High School Students: A Pilot Study
Authors: Morrison S W , Scheer F A , Mason I C
Published: May 2020

Introduction

People with a later chronotype typically sleep later and perform better later in the day. In an early high school schedule, students with later chronotypes earn lower average grades than those with earlier chronotypes. However, other effects of late chronotype on high school students are poorly understood. This study examined the relationship of chronotype with sleep duration, daytime sleepiness and sustained attention in high school students.

Methods

This study was conducted at Byram Hills High School in Armonk, NY, where classes begin at 7:45am. During three class periods, 36 participants (female n=24, n=12, 14–17 years old) completed the Morning-Eveningness Questionnaire (MEQ), Karolinska Sleepiness Scale (KSS), and Psychomotor Vigilance Test (PVT) during their class. Subjects recorded time spent on homework/extracurricular activities and bedtime/waketime from the night prior to the assessment.

Results

Later chronotype (lower MEQ score) was significantly associated with later bedtime, shorter sleep duration, and increased sleepiness (r=-0.82, p<0.001; r=0.72, p<0.001; and r=-0.40, p=0.016; respectively). Shorter sleep duration was significantly correlated with increased sleepiness (r=-0.34, p=0.045). Increased workload (time on homework/extracurriculars) was significantly associated with later bedtime (r=0.42, p=0.011). Chronotype, sleep duration, and sleepiness showed no significant association with PVT scores (r=-0.16, p=0.360; r=-0.10, p=0.933; r=0.09, p=0.619, respectively); however, increased workload was significantly associated with increased PVT scores (r=-0.35, p=0.041).

Conclusion

These results are important for the wellbeing of high school students, as they show relationships between late chronotype, short sleep, and increased sleepiness during class in an early school schedule. Further research is needed to determine the best school schedule for high school students based on individual differences in chronotype.

Support

We thank the Authentic Science Research program at Byram Hills High School, specifically teachers Mrs. Stephanie Greenwald, Dr. Caroline Matthew, and Mrs. Megan Salomone.
0267 School Night Sleep Duration Effect on Risk for In-and-Out of School Suspensions: An Investigation in a Middle-School Aged Sample
Authors: Cook J D , Peppard P E , Blair E E , Tran K M , Plante D T
Published: May 2020

Introduction

Sleep plays an important role in adolescent education and development. Sleep impacts student school attendance, academic performance, and daytime behaviors. There has been limited investigation into the impact on sleep duration (SD) on school suspension risk. Given the growing public health and policy focus on altering school start times to increase SD, this study assessed SD association with school suspension risk using a middle-school aged sample from the Madison (Wisconsin) Metropolitan School District (MMSD), prior to implementation of a planned district-wide delay in middle school start times.

Methods

4,175 middle-school aged students from 12 MMSD schools completed a sleep survey, which included school-night SD (SNSD). Self-reported SNSD between 4-and-12 hours served as criterion for inclusion in final sample. Mixed effects modeling was employed with students nested within school. Logistic regression determined SNSD association with in-school (ISS) and out-of-school (OSS) suspensions. ISS and OSS were dichotomized (No ISS/OSS = 0; nonzero ISS/OSS = 1) to serve as outcome variables. Full model covariates included age, sex, race, circadian preference, parent educational level, homelessness, free and reduced lunch, and special education status.

Results

Final sample included 3,860 students. Shorter SNSD associated with greater likelihood of OSS [OR = 0.83, 95% CI (-0.28, -0.09), X2 = 16.1, p < 0.0001], but not ISS [OR = 0.97, 95% CI (-0.14, -0.070), X2 = 0.44, p = 0.51]. Significance between SNSD and OSS was maintained in the full model [OR = 0.84, 95% CI (-0.27, -0.08), X2 = 13.2, p = 0.0003]. Each additional hour of sleep associated with 16% lower risk of OSS.

Conclusion

These results suggest that students with shorter SD are at increased risk for OSS, which further highlights the potential deleterious impact of short SD on adolescent educational experience.

Support

This research was generously supported by a grant from the Madison Education Partnership (MEP).
0293 Sleep Deprivation Affects the Acoustic Properties of Human Speech
Authors: Thoret E , Gauriau C , Andrillon T , Pressnitzer D , Leger D
Published: May 2020

Introduction

Lack of sleep drastically aﬀects many aspects of human behavior. The early detection of sleepiness is thus a major challenge for health and security reasons. Here we investigated the eﬀect of sleep deprivation on the acoustic properties of human speech.

Methods

Twenty-four participants were sleep deprived for two days (two successive nights with only 3 hours of sleep). They were recorded reading a short text aloud before and after sleep deprivation. An auditory model, based on spectro-temporal modulations, was used to analyse the acoustic properties of their speech and served as a front-end to machine-learning classiﬁers.

Results

Results showed that sleepiness could be accurately detected with individually-trained classiﬁers. However,we were not able to ﬁt a generic classiﬁer for all participants. As we relied on an auditory-inspired model,we could identify and interpret the acoustic features impacted by sleep deprivation. Again,no simple diagnostic feature could be easily identiﬁed in the group- level analyses of the speech signals. We therefore developed a novel probing method, combining signal detection theory and noise activation of the classiﬁer, to understand what made the classiﬁer successful for each participant. This led to a diagnostic map for each participant, specifying which frequency region and modulation rates were impacted by sleep deprivation for this particular individual

Conclusion

In addition to suggesting a practical machine learning algorithm to detect sleep deprivation, combining our probing method with considerations about voice production could help uncover the physiological impact of sleep deprivation at the level of each individual.

Support
0296 Less Self-Reported Alertness and Motivation During Sleep Restriction are Associated with Decreased Attentional Performance
Authors: Mathew G M , Strayer S M , Ness K , Bailey D S , Buxton O M , Chang A
Published: May 2020

Introduction

Some individuals demonstrate more performance decrements on the psychomotor vigilance task (PVT) after sleep restriction (SR). We investigated whether individuals who reported less alertness and/or less motivation after SR demonstrated poorer performance on the PVT.

Methods

Fifteen healthy men (22.3±2.8 years) participated in a 10-night inpatient protocol with three nights of 10-hour baseline time in bed (TIB), five nights of SR (5-hour TIB), then two recovery (10-hour TIB) nights. Participants completed the 10-minute PVT (Joggle Research® battery) approximately every two hours during wake. Outcomes included number of false starts (<100 ms reaction time, RT) and number of lapses (≥500 ms RT). Participants reported alertness and motivation levels after each PVT. Median splits were used to characterize changes in alertness (“sleepy,” n=8, versus “alert,” n=7) and motivation (“unmotivated,” n=7, versus “motivated,” n=8) from the last day of baseline to the last day of SR. Outcomes were analyzed in mixed models with the predictor day*alertness or day*motivation, excluding the first three baseline days to preclude practice effects.

Results

There were significant interactions between day and alertness (p=.025) and day and motivation (p=.043) for false starts. False starts followed a quadratic inverted-U shape across days in sleepy (b=-0.16, p=.003) and unmotivated (b=-0.16, p=.004) participants, but not in alert or motivated participants (p>.05). There was a significant interaction between day and alertness for lapses (p=.008); lapses followed a quadratic inverted-U shape across days with a stronger effect in sleepy (b=-0.43, p<.001) versus alert (b=-0.15, p=.031) participants. There was no interaction between day and motivation for lapses.

Conclusion

Participants reporting less alertness were more likely to make both false starts and lapses after SR; those reporting less motivation were more likely to make false starts, but not lapses. Findings suggest greater motivation is sufficient to preserve inhibitory control but not vigilance after sleep restriction. In contrast, greater alertness despite sleep restriction was sufficient to preserve inhibitory control and resulted in lower vigilance decrements.

Support

This study was funded by grant UL1TR000127 from the Clinical and Translational Science Institute and the College of Health and Human Development at the Pennsylvania State University (Chang PI).
0314 Resilience to Inhibitory Deficits During Sleep Deprivation is Predicted by Gray Matter Volume in the Ventrolateral and Ventromedial Prefrontal Cortex
Authors: Killgore W D , Dailey N S , Raikes A C , Vanuk J R , Taylor E , Grandner M A , Alkozei A
Published: May 2020

Introduction

Stable, trait-like inter-individual resilience to sleep loss has been demonstrated for psychomotor vigilance, mood, subjective sleepiness, and some reasoning tasks, some of which have been associated with specific genetic or neurobiological markers. Resilience to executive control deficits induced by sleep deprivation (SD) has not been explored in terms of neurobiological markers. We, therefore, collected magnetic resonance imaging (MRI) scans of healthy individuals when well rested and correlated gray matter volume with resistance to inhibitory declines during 29 hours of SD.

Methods

Forty-five healthy individuals (22 female) ranging in age from 20 to 43 underwent structural MRI. Within 2-4 days after scanning, participants returned to the lab to undergo one night of SD, during which they completed a standard go/no-go task involving inhibitory processing every 4 hours. Scores were calculated as throughput (correct responses per working minute). The difference between performance in the evening (22:45) versus the performance the next morning (06:45) was calculated as an index of “inhibitory resilience.” Gray matter volume was regressed against the inhibitory resilience measure. Based on prior research, regions were constrained to the ventrolateral prefrontal cortex and ventromedial prefrontal cortex.

Results

Greater resilience against declines in inhibitory capacity during SD was predicted by 1) larger gray matter volume within the ventrolateral prefrontal cortex and 2) reduced volume within the ventromedial prefrontal cortex (p<.05, FWE cluster corrected). These two clusters contributed significant unique explanatory variance to the model (R2=.45, p<.0001).

Conclusion

The ability to sustain performance during an inhibitory go/no-go task during SD was predicted by greater gray matter volume within the ventrolateral prefrontal cortex, a region that has been previously associated with inhibitory capacity, and reduced volume within an area of the ventromedial prefrontal cortex, which is often related to the default mode network. Findings suggest that specific brain networks may confer task-specific resistance to SD.

Support

Defense Advanced Research Projects Agency, DARPA Young Faculty Award: DARPA-12-12-11-YFA-FP-029
0327 NREM Sleep EEG in Typically Developing and Drug-Naïve ADHD Adolescents: Data from a Longitudinal Study
Authors: Basishvili T , Eliozishvili M , Oniani T , Tchintcharauli T , Sakhelashvili I , Oniani N , Campbell I G , Feinberg I , Darchia N
Published: May 2020

Introduction

Structural MRI studies suggest delayed brain maturation in children with attention deficit hyperactivity disorder (ADHD). The steep adolescent decline in sleep slow wave EEG activity provides an opportunity to investigate brain electrophysiological evidence for this maturational delay. Most ADHD sleep EEG studies have been cross-sectional. Here we present data from an ongoing longitudinal study of the maturational trajectories of sleep EEG in drug-naïve ADHD and typically developing adolescents.

Methods

Nine children diagnosed with ADHD (combined subtype, DSM-V criteria, mean age 12.39±0.61 years), and nine typically developing controls (12.07±0.35 years) were recruited. Subjects underwent an adaptation night and all night polysomnography twice yearly at the Laboratory. Sleep EEG was analyzed using fast Fourier transform. NREM delta and theta EEG activity were compared across first two recordings.

Results

Group effects (ADHD vs. control) on all night delta and theta energy, and delta power were not significant (p>0.2 for all). All night theta power was lower (p=0.035) for the ADHD group, and all night NREM sleep duration trended (p=0.060) toward being lower for the ADHD group. Controlling for sleep duration differences by examining only the first 5 h of NREM sleep showed no group effect on delta power (p=0.77) and a trend toward lower theta power (p=0.057) for the ADHD group.

Conclusion

At age 12 to 13 years, NREM sleep delta EEG did not differ between ADHD and control subjects. Theta power, which declines at a younger age than delta, was lower in control subjects. The two recordings thus far differ only by 6 months. The entire study will provide 5 semiannual recordings and allow us to determine if the higher theta power in the ADHD group will hold and if delta power will be greater as well, and thus provide electrophysiological support for the delayed brain maturation suggested by MRI findings.

Support

Shota Rustaveli National Science Foundation Grant FR17_94; Subjects Recruitment Support - Mental Health Service in Tbilisi “Kamara”.
0358 Sleep Among Transgender and Cisgender Adolescents
Authors: Levenson J C , Thoma B C , Hamilton J L , Choukas-Bradley S , Salk R H
Published: May 2020

Introduction

Sleep problems are germane to the majority of adolescents, but stigmatized youth may experience poorer sleep than those who have not experienced stigma. However, no prior studies have examined sleep among transgender adolescents (TGAs). Investigating these sleep disparities is critical, since low sleep duration and poor sleep quality are predictive of depressive symptoms and suicidality among adolescents, two mental health outcomes experienced disproportionately by TGAs. Using a nationwide survey of adolescents, we examined sleep duration, sleep quality, and rates of insufficient sleep among a sample of adolescents, and we compared those parameters between TGAs and cisgender adolescents (CGAs).

Methods

Adolescents (n=1784) ages 14-18 completed an anonymous survey including measures of sleep, sexual and gender identity, depressive symptoms, and demographic variables. Participants were grouped as TGA or CGA. Unadjusted associations between gender identity and sleep outcomes were examined, followed by multivariate regression models examining associations adjusted for demographics and depressive symptoms.

Results

TGAs reported sleeping fewer hours, higher odds of being a ‘poor sleeper’, and lower odds of getting the right amount of sleep and getting ‘enough sleep’ than CGAs. After adjusting for key demographic variables, TGAs were still more likely to report that they were poor sleepers and less likely to report getting enough sleep compared to CGAs. When adding depressive symptoms as a covariate, the finding that TGAs reported they got enough sleep less often than CGAs remained marginally significant.

Conclusion

Transgender adolescents reported receiving poorer sleep than cisgender adolescents. Future studies should focus on longitudinally examining the emergence of sleep problems among TGAs and CGAs, which may also serve to identify specific biopsychosocial pathways that contribute to heightened risk for sleep problems among TGAs. Sleep disparities may be a promising target for prevention and intervention programs to improve health outcomes among stigmatized youth.

Support

This study was funded by the University of Pittsburgh Central Research Development Fund through an award to Drs. Salk, Choukas-Bradley, and Thoma. Dr. Levenson was supported by grant K23HD087433. Dr. Thoma was supported by grants T32MH018951 and K01MH117142, Dr. Salk was supported by grant T32MH018269, and Dr. Hamilton was supported by grant T32HL082610.
0363 Racial/Ethnic Differences in Actigraphy, Questionnaire, and Polysomnography-Measured Indicators of Sleep Health and Sleep Quality: The Multi-Ethnic Study of Atherosclerosis
Authors: Chung J , Goodman M O , Huang T , Wallace M , Bertisch S , Johnson D , Redline S
Published: May 2020

Introduction

Paradigm shifts in sleep research suggest the importance of considering multi-dimensional sleep health, compared to single metrics, to promote physical and mental well-being and to understand racial/ethnic disparities in sleep.

Methods

We used data from the Multi-Ethnic Study of Atherosclerosis (MESA; n = 1,740) to create a Sleep Health Score (SHS), including questionnaire (quality, sleepiness); 7-day actigraphy (total sleep time, sleep continuity [sleep maintenance efficiency], timing consistency [midpoint variability], fragmentation, wake after sleep onset, sleep onset latency); and in-home polysomnography (%N3 sleep, %REM sleep, AHI). Sleep parameters were dichotomized based on prior literature or by healthiest quartile(s), with positive values denoting healthier sleep (e.g. Epworth scores < 10). All 11 dichotomized parameters were summed to calculate the SHS (mean=4.9, sd=1.58). We used modified Poisson and linear regression for individual sleep outcomes and the SHS, respectively, adjusting for age and sex.

Results

The sample was older (mean age=68.28, sd=9.08) and 54% female. SHSs were associated with Black race (β=-0.60 [-0.78, -0.42]) and Hispanic ethnicity (β=-0.40 [-0.59, -0.21]), but not Chinese ethnicity (β=-0.16 [-0.41, 0.08]). Compared to Whites (n=644), Blacks (n=485) showed lower adjusted probability of obtaining favorable levels of: sleep continuity, fragmentation, timing consistency, alertness/sleepiness, and sleep depth (%N3 sleep). Chinese respondents (n=202) had lower probability of obtaining favorable levels of: sleep continuity and timing consistency, but higher probability of quality. Hispanics (n=409) had lower probability of obtaining healthy levels of: sleep continuity, timing consistency, and fragmentation. Neither healthy total sleep time (middle quartiles) nor AHI (<30) differed by race/ethnicity.

Conclusion

Among MESA-Sleep participants, summary SHSs were lowest in Blacks, followed by Hispanics. Multiple dimensions of sleep - particularly related to continuity and timing consistency - were less favorable across race/ethnic minority groups. A summary SHS may help monitor sleep health across populations, while measurement of specific sleep components may help identify modifiable targets.

Support

Joon Chung is supported by a T-32 NIH training grant.
0370 Objective Differences in Sleep Timing Between African Americans and Non-Hispanic Whites
Authors: Combs D , Patel S , Mashaqi S , Estep L , Provencio-Dean N , Lopez S , Parthasarathy S
Published: May 2020

Introduction

Prior studies have shown a morning circadian preference for African Americans compared to Non-Hispanic whites, but prior research has shown that self-reported sleep timing is delayed in African Americans compared to whites. No prior studies have evaluated this difference in sleep timing using objective measures of habitual sleep such as actigraphy.

Methods

We analyzed the sleep data from the Multi-Ethnicity Study of Atherosclerosis (MESA), a multi-site community-based cohort with both self-reported and actigraphic measures of habitual sleep variables. Self-reported sleep timing, chronotype as measured by the modified Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ) and actigraphic sleep timing were examined using logistic regression and independent t-tests.

Results

1,430 participants had self-reported sleep data, and 1,405 participants had complete actigraphy data as well. There was no self-reported difference in circadian preference between African Americans and whites (mean MEQ score 17.1 ± 3.6 vs. 17.0 ± 4.0). African Americans were 76% more likely to report a bedtime after midnight on weekdays (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.4, 2.3, p<0.001), and 50% more likely on weekends (OR 1.5, 95% CI 1.2, 1.9, p=0.001) as compared to whites. Actigraphic data showed similar results. African Americans were 80% more likely to have actigraphic sleep onset after midnight on weekdays (OR 1.8, 95% CI 1.4, 2.2) and 137% more likely (OR 2.4,95% CI 1.9, 3.0, p<0.001) on weekends as compared to whites. Actigraphic mid-sleep time was delayed 42 (95% CI 20, 64, p<0.001) minutes on weekdays and 24 (95% CI 6,42, p=0.01) minutes on weekends in African Americans compared to whites.

Conclusion

African Americans had delayed sleep timing compared to whites even though no significant racial differences in chronotype were present. Delayed sleep timing in African Americans may be related to factors other than self-reported circadian preference.

Support

Funding to DC from the American Heart Association, University of Arizona Health Sciences Center and NIH-NHLBI. MESA data obtained from NIH-NHLBI BioLINCC and the National Sleep Research Resource.
0383 Outdoor Artificial Light at Night, Sleep Duration, and Sleep Quality in the California Teachers Study Cohort
Authors: Zhong C , Franklin M , Wiemels J , Chung N , Benbow J , Wang S S , Lacey J V , Longcore T
Published: May 2020

Introduction

Artificial light at night (ALAN) is believed to disrupt sleep by suppressing melatonin and altering normal circadian patterns. We assessed the association between self-reported sleep measures and outdoor ALAN in a large cohort of women.

Methods

The California Teachers Study (CTS) is a prospective cohort of 133,479 current and former Californian female public school professionals recruited and given a baseline questionnaire in 1995-1996. A follow-up questionnaire in 2012-2014 assessed self-reported measures of sleep habits, quality, and chronotype. Using geocoded residential addresses, participants were assigned exposures to outdoor ALAN based on the New World Atlas of Artificial Night Sky Brightness to assess the association between ALAN and self-reported sleep initiation, duration, and quality.

Results

Of the 42,706 women who completed the follow-up questionnaire and reported the same sleep patterns over the previous year, 5,968 reported poor sleep quality. The median outdoor ALAN was 2.16 (IQR: 1.04-3.61) millicandela per meter squared (mcd/m2). After adjusting for self-reported chronotype, use of sleep medication, age, race, and socioeconomic status, residing in the highest ALAN quintile was associated with poor sleep (OR 1.16, 95% CI 1.07-1.26). There did not appear to be an association between outdoor ALAN and time taken to fall asleep (OR 1.02, 95% CI 0.96-1.08), but it was associated with sleeping less than 8 hours (OR 1.41, 95% CI 1.33-1.50).

Conclusion

CTS participants who self-reported shorter sleep and poorer sleep quality were more likely to reside in areas with greater levels of outdoor ALAN. We did not see an association with ALAN and time to fall asleep, suggesting ALAN may be contributing to later sleep time or earlier waking. As we continue to follow this cohort, the data collected over the past 20 years provide a rich resource for studying both factors related to sleep and its effect on health.

Support

The California Teachers Study and the research reported in this publication were supported by the National Cancer Institute of the National Institutes of Health under award number U01-CA199277; P30-CA033572; P30-CA023100; UM1-CA164917; R01-CA077398; and R01-CA207020.
0395 “Doctor, I Can’t Sleep”, How Intensivist Cannot Restore Their Sleep Debt
Authors: Chhor V , Leger D , Pepin E , Elbaz M
Published: May 2020

Introduction

Since 2001, intensivist physicians working in France have been organized in 24-hour shifts (in order to provide 24/7 support), followed by a mandatory rest period of at least 24 hours between shifts.. The goal was to survey how intensivists cope with maintaining enough sleep throughout their 24-hour shifts.

Methods

During twelve months, the whole medical staff of our ICU, i.e. 29 individuals (11 senior physicians and 18 residents), agreed to participate in this study. They were allowed to settle into a typical work period of 7 days and 7 nights (i.e. 3 days before and 3 days following the 24-hour shift), separated by at least 5 days from any previous 24-hour shifts. A 24-hour shift typically started at 8:30am in the morning and finished 24 hours later. All physicians wore a wrist actigraphy device (MotionWatch 8) assessing total sleep time (TST) on a 24-hour period. We retained several criteria such as:

The reference TST, i.e. the mean of the TST during the first three days preceding the 24-hour shift

The sleep debt, through the comparison between the average of the TST during the 24-hour shift and the 24 (SD24) or 72 following hours (SD72) and the reference TST.

Results

Twenty nine actigraphy records from 29 individuals were analyzed. The reference TST preceding the shift was 377 min (IQR25-75: 346-396). Doctors participating in the study slept very little during a 24-hour shift: 181 min (IQR25-75: 134-260). Subsequently, we observed that intensivists were unable to completely recover their sleep debt, even after 72 hours. Average TST was significantly shorter at 72 hours compared to reference (343 min [IQR25-75: 304-367], Mann-Whitney test, p=0.015).

Conclusion

These findings raise the question of whether it is possible for intensivist doctors to maintain their energy and intensity in their jobs without sleeping enough. This remains an open question and we are currently unable to respond with only a simple study.

Support

No support
0396 Prevalence of Delayed Sleep Phase Syndrome (DPSP) Among Omani People
Authors: Al-Abri M A , Al-Kindi T
Published: May 2020

Introduction

Delayed sleep phase syndrome (DSPS) is a circadian rhythm sleep disorder with a definition of delayed night sleep by two or more hours beyond the socially acceptable or conventional bedtime. The general reported prevalence of DSPS is 7% to 16%. However, there is no previous study which assess DSPS prevalence in Oman or nearby regions. This study aimed to assess the prevalence of DSPS among Omani population and to establish a connection between demographics and DSPS.

Methods

This community-based study included 186 subjects aged from 18 to 64 who had one week of actigraphy records along with their demographical data in Sultan Qaboos University hospital.

Results

Among the 186, 19 (10.2%) subjects were identified of having DSPS in weekdays, and 15 (11.4%) subjects have DSPS in weekends. The results indicated that marital status had significant relation (P=0.02) more with unmarried group (62.50%, N=10). No significant relationship was found between DSPS and age, gender, BMI, education and employment status in either weekdays or weekends (P>0.05)

Conclusion

A consistent rates of DSPS was found among Omanis which are 10.2% in weekdays and 11.4% in weekends. Also, DSPS have significantly higher rates among unmarried subjects in weekdays. Further studies in DSPS are needed to assess risk factors and possible health impacts.

Support

The research Council of Oman
0404 Jewish-Arab Disparities in Sleep Behaviors and Differential Ethnic Impact on Daytime Functioning, Driving Safety, and Health in Israel
Authors: Rosenberg E , Perlis M L , Parthasarathy S , Jean-Louis G , Chakravorty S , Grandner M A
Published: May 2020

Introduction

In Israel, those with Arabic as compared to Jewish ethnicity, exhibit poorer health and motor vehicle safety behaviors. Their ethnic differences in sleep duration and quality may modulate their vulnerabilities to these behaviors.

Methods

7,230 Israeli individuals (N=5,880 Jewish and N=1350 Arabic) responded to the 2017 Israeli Bureau of Statistics population-based survey of households. Variables were self-reported. Outcomes included sleepiness, sleep medications, functional impairment, drowsy driving, overall health, 1-year health change, and obesity. Predictors included categorical sleep duration (<=5, 6, 7, 8 [reference], or >=9 hours) and sleep disturbance in the past month (none [reference], mild [1/week], moderate [2-3/week], or severe [>3/week]). Covariates included age, sex, and financial status. Ethnicity (Jewish/Arabic) was treated as a predictor of sleep and behavioral outcomes.

Results

When compared to normal (8-hour) sleepers, Jewish as compared to Arabic individuals were more likely to to sleep <=5h (RRR=3.99, p<0.0005), 6h (RRR=4.65, p<0.0005), and 7h (RRR=3.34, p<0.0005), and were more likely to report severe sleep difficulties (RRR=1.49, p<0.0005) and sleepiness (oOR=1.52, p< 0.0005). Yet, they were less likely to report functional impairment (oOR=0.65, p<0.0005), drowsy driving (OR=0.58, p<0.0005), worse health (oOR=0.51, p<0005), worsening health (oOR=0.70, p<0.0005), or obesity (OR=0.64, p<0.0005). Significant ethnicity by sleep duration interactions (p<0.05) characterized sleepiness, sleep medications, functional impairment, health, and health change. Moreover, significant ethnicity by sleep disturbance interactions (p<0.05) characterized the same outcomes, in addition to drowsy driving. Overall, the impact of sleep duration and sleep difficulties was generally greater among Arabs for all variables.

Conclusion

Despite Jewish individuals endorsing relatively shorter sleep and more severe sleep difficulties, Arabs seem to be more vulnerable to the health and functional outcomes. This finding may explain some of the discrepancies in the health and safety outcomes between these ethnic groups.

Support

Dr. Grandner is supported by R01MD011600
0415 Metabolic Dysfunction and Sleep Disruption in Models of Alzheimer’s Disease
Authors: Carroll C M , Stanley M , Macauley S L
Published: May 2020

Introduction

Metabolic perturbations and sleep disruptions are a cause and consequence of Alzheimer’s disease pathophysiology. A bidirectional relationship exists where impairments in sleep and metabolism contribute to the development of Alzheimer’s disease while the presence of Alzheimer’s disease pathology leads to decreased cerebral metabolism, peripheral glucose intolerance, and disrupted sleep. While the effects of type 2 diabetes (T2D) and Alzheimer’s disease on sleep have been explored separately, no previous studies have examined the effect of acute glycemic variability, a defining feature of T2D, on sleep in the context of Alzheimer’s disease. The goal of this study is to determine how glycemic variability drives sleep disruptions by modifying the relationship between cerebral glucose metabolism and neuronal activity.

Methods

Biosensors are implanted bilaterally into the hippocampus of APP/PS1, a model of amyloid-beta (Aβ) overexpression, and P301S, a model of tau deposition and neurodegeneration, mice to measure ISF glucose and lactate, markers of cerebral metabolism and neuronal activity, respectively. Simultaneous cortical EEG/EMG recordings are used for sleep/wake scoring and analysis.

Results

Glycemic fluctuations cause a decoupling of the typical relationships between cerebral metabolism and neuronal activity, while also increasing arousal in 3-month-old, wildtype mice. The presence of AD-like pathology results in a similar, albeit muted cerebral metabolic response to peripheral glycemic variability, but a diminished effect on wakefulness, likely due to age- and pathology-dependent increases in overall time spent awake. Conversely, in aged, P301S mice, cerebral metabolic responsiveness is lost and a ceiling effect on wakefulness emerges, suggesting differential effects on sleep with tau accumulation. Moreover, aged mice show progressive disruptions to overall sleep quality and quantity, highlighting the synergism existing between AD-like pathology and glucose intolerance in sleep dysfunction. Lactate seems to be a common driver of disruption in this synergistic cycle.

Conclusion

This study represents a novel approach to defining the dynamic interplay between risk factors for AD and T2D and suggests a feedforward loop of disease progression where disrupted sleep can alter the relationship between neuronal activity, metabolism, and pathology.

Support

NIH/NIA 1K01AG050719.

Harold and Mary Eagle Fund for Alzheimer’s Research

New Vision Award through Donors Cure Foundation
0446 A Novel System for Enabling High-Density EEG Recordings in a Mouse
Authors: Thankachan S , Gerashchenko L , Gerashchenko D
Published: May 2020

Introduction

Recent advances in micro-electromechanical system (MEMS) technology have promoted the development of microelectrode arrays (MEA) that allow high resolution recordings in neuroscience research. However, applying MEA in studies in freely moving mice remains very challenging due to the large number of electrical connections required in this type of studies. The use of commutators for a large number of connections is not practical, and headmounts/loggers placed on the animal head are too heavy for small animals such as mice. Therefore, there is a need for a better compact system for using MEA in mice. Herein, we designed such a system and successfully recorded high-density-EEG in freely moving mice.

Methods

We designed a system in which forty flexible ultrathin wires are connected to the headstage enclosed in a container held close to the mouse. The container also houses a logger and battery connected to the headstage. This recording system allows minimizing weighted pressure on the animal using a counterbalance, so that the animal can freely move in the cage.

Results

We tested the system using a signal generator and mouse EEG arrays (NeuroNexus). When potentials produced by the signal generator were recorded via the wires, recorded traces were indistinguishable from the traces that were recorded when the signal generator was connected directly to the logger. We then implanted mice with EEG electrode arrays under surgical anesthesia. The high-density EEG recordings were performed one and four weeks after the surgery. High-quality EEG signals were observed in all the channels of the 32-channel logger (SpikeGadgets) in freely moving mice.

Conclusion

We successfully developed and tested a novel system for enabling high-density EEG recordings in freely moving mice. We expect that this system will be useful for recording biopotentials from different types of MEA in freely moving mice.

Support

NIH 1R43OD023231 (LG), NIH 1RF1AG061774 (DG), and NIH 5R21NS106406 (DG)
0447 ResTNet: A Robust End-to-End Deep Learning Approach to Sleep Staging of Self Applied Somnography Studies
Authors: Jónsson S Æ , Gunnlaugsson E , Finssonn E , Loftsdóttir D L , Ólafsdóttir G H , Helgadóttir H , Ágústsson J S
Published: May 2020

Introduction

Sleep stage classifications are of central importance when diagnosing various sleep-related diseases. Performing a full PSG recording can be time-consuming and expensive, and often requires an overnight stay at a sleep clinic. Furthermore, the manual sleep staging process is tedious and subject to scorer variability.

Here we present an end-to-end deep learning approach to robustly classify sleep stages from Self Applied Somnography (SAS) studies with frontal EEG and EOG signals. This setup allows patients to self-administer EEG and EOG leads in a home sleep study, which reduces cost and is more convenient for the patients. However, self-administration of the leads increases the risk of loose electrodes, which the algorithm must be robust to. The model structure was inspired by ResNet (He, Zhang, Ren, Sun, 2015), which has been highly successful in image recognition tasks. The ResTNet is comprised of the characteristic Residual blocks with an added Temporal component.

Methods

The ResTNet classifies sleep stages from the raw signals using convolutional neural network (CNN) layers, which avoids manual feature extraction, residual blocks, and a gated recurrent unit (GRU). This significantly reduces sleep stage prediction time and allows the model to learn more complex relations as the size of the training data increases.

The model was developed and validated on over 400 manually scored sleep studies using the novel SAS setup. In developing the model, we used data augmentation techniques to simulate loose electrodes and distorted signals to increase model robustness with regards to missing signals and low quality data.

Results

The study shows that applying the robust ResTNet model to SAS studies gives accuracy > 0.80 and F1-score > 0.80. It outperforms our previous model which used hand-crafted features and achieves similar performance to a human scorer.

Conclusion

The ResTNet is fast, gives accurate predictions, and is robust to loose electrodes. The end-to-end model furthermore promises better performance with more data. Combined with the simplicity of the SAS setup, it is an attractive option for large-scale sleep studies.

Support

This work was supported by the Icelandic Centre for Research RANNÍS (175256-0611).
0457 Insomnia and Cause-Specific Mortality in Men and Women
Authors: He F , Fernandez-Mendoza J , Vgontzas A N , Calhoun S L , Liao D , Bixler E O
Published: May 2020

Introduction

The association of insomnia with an increased risk of mortality has remained inconsistent across studies, which contrasts with accumulating evidence linking this prevalent and chronic sleep disorder with cardiovascular, cerebrovascular, oncologic, and psychiatric morbidity. The higher prevalence of insomnia in women compared to men may be an important contributor to the different survival rates reported in large, population-based studies.

Methods

The Penn State Adult Cohort is a random, general population sample of 1,741 adults (48.8±13.6y, 52.2% women) who were studied in the sleep laboratory and followed-up for their cause of death up to December 31, 2018. Insomnia was defined as a chronic complaint lasting at least 1 year (n=199). We assessed the risk of all-cause mortality (n=664) and the two most common causes of death: cardiovascular/cerebrovascular (n=275) and cancer (n=161). Cox proportional hazard models adjusted for age, race, sex, education, smoking, alcohol, BMI, AHI, cognitive impairment, mental health problems and physical health problems, including hypertension, diabetes, heart disease, stroke and cancer at baseline.

Results

The risk of all-cause mortality associated with insomnia was significantly increased in men (HR=1.84, 95%CI=1.18-2.87) but not in women (HR=0.80, 95%CI=0.57-1.13; p for sex-interaction<0.01). Insomnia was significantly associated with an increased risk of cardiovascular/cerebrovascular mortality in men (HR=2.11, 95%CI=1.14-3.99), but not in women (HR=0.98, 95%CI=0.59-1.63; p for sex-interaction=0.06). Insomnia was not significantly associated with an increased risk of cancer mortality either in men (HR=1.41, 95% CI=0.56-3.56) or in women (HR=0.90, 95% CI=0.45-1.80), after adjusting for hypertension, diabetes, heart disease, stroke and cancer at baseline.

Conclusion

Men with chronic insomnia are at an increased risk of mortality, particularly that of cardiovascular/cerebrovascular origin. There is a need for translational studies focused on sex-differences that can disentangle the biological and behavioral mechanisms underlying women’s resilience.

Support

American Heart Association (14SDG19830018), National Institutes of Health (R01HL51931, R01HL40916)
0474 Long-Term Efficacy and Safety of Lemborexant in Elderly Adults with Insomnia Disorder: Results from SUNRISE-2
Authors: Moline M , Inoue Y , Pinner K , Perdomo C , Filippov G , Kubota N , Yardley J
Published: May 2020

Introduction

In SUNRISE-2 (NCT02952820; E2006-G000-303), the dual orexin receptor antagonist lemborexant (LEM) demonstrated significant benefit versus placebo (PBO) on subjective sleep endpoints over 6mo in subjects age ≥18y; benefits were sustained over 12mo. Here we present 12mo efficacy and safety data for LEM from the elderly (≥65y) subgroup.

Methods

SUNRISE-2 was a 12mo, randomized, double-blind, PBO-controlled (first 6mo [Period 1]), global phase 3 study. During Period 1, subjects were randomized to PBO or LEM (5mg, [LEM5]; 10mg, [LEM10]). During Period 2 (second 6mo), LEM subjects continued their assigned dose while PBO subjects were rerandomized to LEM5 or LEM10 (not reported here). Patient-reported (subjective) sleep endpoints were assessed from sleep diary data (sleep onset latency [sSOL]; sleep efficiency [sSE]; wake after sleep onset [sWASO]).

Results

Of the 949 subjects in the Full Analysis Set, 262 were age ≥65y. At 6mo, in subjects ≥65y, median sSOL significantly decreased from baseline for LEM5 (−21.7) and LEM10 (−26.0) versus PBO (−10.8; P<0.0001, P<0.01, respectively). At 12mo, LEM5 and LEM10 subjects maintained decreases in median sSOL (−29.3, −34.3, respectively). At 6mo, the mean (SD) increase from baseline in sSE was significantly larger versus PBO (8.5[13.3]) for LEM5 (16.9[13.6]; P<0.001) and LEM10 (14.9[15.9]; P<0.01). At 12mo, mean (SD) increase in sSE was maintained for LEM5 (18.1[12.5]) and LEM10 (18.0[16.8]). At 6mo, mean (SD) change from baseline in sWASO was significantly decreased versus PBO (−26.5 [52.9]) for LEM5 and LEM10 (−54.8[64.4], P<0.01; −51.4[69.3], P<0.05, respectively). At 12mo, mean (SD) decrease in sWASO was maintained for LEM5 (−58.6[46.0]) and LEM10 (−60.9[80.4]). Over 12mo, the most common (>10% either group) treatment emergent adverse events with LEM5 and LEM10, respectively, were somnolence (9.3%, 19.0%), nasopharyngitis (9.3%, 10.7%), and headache (10.5%, 6.0%).

Conclusion

In elderly subjects, LEM demonstrated efficacy at 6mo, which persisted at 12mo; LEM was well tolerated.

Support

Eisai Inc.
0500 Evaluation of the Human Abuse Potential of Single Oral Doses of V117957, a Novel, Highly Potent and Selective Partial Agonist for Nociceptin/Orphanin-FQ Peptide (NOP) Receptors
Authors: Harris S , Zhou M , Cipriano A , Kapil R , Shet M , He E , Apseloff G
Published: May 2020

Introduction

The satisfactory safety/tolerability profile of V117957, an investigational NOP receptor partial agonist, has been previously established in ~200 healthy subjects with maximum doses at 30mg following a single oral administration and 10mg once daily for 2 weeks. V117957 exhibited linear plasma exposures at doses up to 10mg. In patients with insomnia disorder, V117957 demonstrated dose-dependent improvement in sleep efficiency and sleep maintenance between 0.5mg and 10mg as measured by polysomnography and patient diaries. The current study evaluated the abuse potential and safety of V117957 in healthy, nondependent recreational polydrug users with a history of central nervous system (CNS) depressant use.

Methods

The abuse potential of V117957 (1mg, 6mg, 10mg), placebo, and triazolam (0.5mg, 1mg) were assessed in a randomized, double-blind, double-dummy, placebo- and positive-controlled crossover study. Triazolam was utilized as a positive control based on its comparable pharmacokinetic and pharmacodynamic characteristics. V117957 doses (1mg, 6mg, 10mg) were selected to represent therapeutic, mid-range supratherapeutic, and maximum-tolerated supratherapeutic doses, respectively. Subjects were qualified based on pharmacodynamic responses following a single oral 0.75mg triazolam dose. Drug liking was measured through 24 hours, including the primary endpoint of maximum “at the moment” Drug-Liking Visual Analog Scale, as recommended by FDA. Secondary endpoints included Divided Attention Test (DAT) and Choice Reaction Time (CRT).

Results

The positive control (triazolam 0.5mg, 1mg) produced statistically significant greater abuse potential and cognitive/motor impairment versus placebo, which demonstrated study validity. In contrast, V117957 at 1mg was not statistically significantly different from placebo. At the supra-therapeutic doses of 6 and 10mg, V117957 was associated with abuse potential and cognitive/motor impairment greater than placebo, yet similar to those of triazolam 0.5 and 1mg.

Conclusion

Overall, in this valid study, V117957 1mg and placebo were associated with statistically significant lower potential for abuse and reduced cognitive/motor impairment compared with the two supratherapeutic doses of V117957 (6mg, 10mg), and triazolam (0.5mg, 1mg). V117957 1mg met FDA’s statistical criterion for similarity to placebo.

Support

Funded by Imbrium Therapeutics, a subsidiary of Purdue Pharma L.P.