bluuebunny/crossref_metadata_2025 huggingface dataset:
0200 Effects of Early-Life Sleep Disruption on Spatial Learning, Tau Burden, and Neurodegeneration in the PS19 Mouse Model of Tauopathy
Authors: Vetter Kenny , Pettibone Ward , Tejiram Rachel , Kam Korey , Varga Andrew
Published: May 2023

Introduction

Sleep disruption is thought to increase tau hyperphosphorylation and tangle formation. This study aims to identify the impact of chronic early-life sleep disruption on late-life tau burden, neurodegeneration, and spatial memory.

Methods

Eight-week-old PS19 (MAPT P301S) mice and wildtype littermates were subjected to chronic daily sleep disruption (SD) or allowed to sleep ad libitum (AL) for eight weeks. SD was achieved using an automated physical stimulus every 10 seconds for 18 hours daily between ZT 0 and 18. Spatial memory testing occurred at 6, 8, and 10 months of age using the Barnes maze where latencies to find and enter the escape box were recorded on 4 consecutive days (n: WT AL=22, WT SD=21, PS19 AL=15, PS19 SD=28). Brains were subsequently collected between 10 and 14 months of age and analyzed in a subset. Tau pathology was analyzed with AT8 immunohistochemistry on paraffin sections and quantified by counting tau-positive hippocampal neurons using QuPath software. Neurodegeneration was quantified by measuring the combined area of both the lateral and third ventricles.

Results

Spatial memory was equivalent among all genotypes and sleep conditions at 6 months. We observed a main effect of PS19 genotype with worse spatial memory at 8 and 10 months. Notably, early life SD imparted a protective effect on spatial memory at 8 and 10 months vs ad lib sleep in PS19 mice with no effect on controls. PS19 mice experiencing early life SD showed no difference in late-life hippocampal tau burden (SD: mean 462 AT8+ neurons (SEM: 268), n=5, AL: 284 AT8+ neurons (SEM: 98), n=5, p=0.56) as well as no difference in total ventricle area (SD: mean 1.2 square mm (SEM: 0.5), n=5, AL: 2.0 square mm (SEM: 0.4), n=5, p=0.26).

Conclusion

Counter to our initial hypothesis, early-life SD resulted in preservation of late-life spatial memory, without changes to neurodegeneration as measured by ventricle area or changes to tau hyperphosphorylation in the hippocampus. Dissociation of tau burden and memory has been observed in models of immune modulation suggesting further investigation regarding effects of sleep disruption on immune function in the context of neurodegenerative models.

Support (if any)
0201 Prebiotic Diet Impact on Cognitive Performance, Sleepiness, and Mood During Combined Sleep Restriction and Circadian Misalignment
Authors: Ekin Sarila , Withrow Dana , Kuppa Abhignya , Sprecher Kate , Fleshner Monika , Gonzalez Antonio , Lowry Christopher A , Turek Fred , Vitaterna Martha , Dorrestein Pieter C , Knight Rob , Wright Kenneth
Published: May 2023

Introduction

The gut microbiome plays a crucial role in health and affects mood and behavior. The composition and function of the gut microbiome can be modified by prebiotics, which are defined as substrates selectively utilized by host microorganisms conferring a health benefit. This study examined the effects of a prebiotic diet combination of polydextrose (PDX) and galacto-oligosaccharides (GOS) on cognitive performance and sleepiness during combined sleep restriction and circadian misalignment.

Methods

Eleven healthy adults (aged 24.6 ± 4.5, 6 females, 5 males) completed a randomized, double-blind, cross-over study lasting a total of 39 days. Participants consumed 14 days of prebiotic (7.5g/day each of PDX [Danisco] and GOS [FrieslandCampina]) or maltodextrin placebo diets at home(sachets dissolved in water with breakfast) while maintaining ~8h sleep per night at habitual times for two separate weeks before undergoing ~4 days of in laboratory testing under combined sleep restriction (3h sleep opportunity per day) and circadian misalignment (wakefulness at night) conditions. Prebiotic or placebo diet continued in-laboratory. Cognitive function testing occurred every 3h during scheduled wakefulness and included the Psychomotor Vigilance Task (PVT), Stroop Color and Word Test (STROOP) visual analog mood scales (VAS), positive and negative affect scales (PANAS), and the Karolinska sleepiness scale (KSS). Participants had a 3-day washout, then repeated the same procedure with the second condition.

Results

Sleepiness on the KSS was reduced, and positive mood on the PANAS and calm mood were increased under prebiotic versus placebo (all p < 0.05). Median reaction time on the PVT was faster, whereas median reaction times for congruent stimuli on the STROOP task were slower under the prebiotic diet versus placebo (all p < 0.05).

Conclusion

A prebiotic diet had beneficial effects on many performance, sleepiness and mood outcomes during combined sleep restriction and circadian misalignment. These findings have important implications for shift workers, emergency responders, and military personnel working under the demanding conditions of sleep restriction and circadian misalignment.

Support (if any)

Office of Naval Research MURI N00014-15-1-2809, NIH CTSA Grant UL1 TR002535 and Undergraduate Research Opportunities Grant, University of Colorado Boulder.
0202 Sleep Deprivation: Cognitive Decline and Hippocampal Neuroinflammation
Authors: Olsen Laura , McCubbins Hunter , Moore Raquel , Gargas Nathan , Rohan Joyce , Hatcher-Solis Candice
Published: May 2023

Introduction

A highly conserved biological process, sleep is imperative for healthy brain function. Sleep deprivation (SD) disrupts cognition and increases susceptibility to neurological disorders. The first step to developing mitigation strategies, this study investigated mechanisms underlying sleep-induced cognitive impairment, including hippocampal neuroinflammation.

Methods

All animal activities were approved under an IACUC protocol. Male Sprague-Dawley rats (N = 50) underwent 120 h of SD. Novel Object Recognition (NOR) and Passive-Avoidance Task (PAT) assessed cognitive performance (n = 6-12), followed by humane euthanization. Protein analysis of hippocampal tissue was performed using immunohistochemistry (IHC, n = 3-6) and enzyme-linked immunoassay (ELISA, n = 8-13). Microglia (Iba-1 marker) and astrocyte (GFAP marker) populations were quantified using IHC and ImageJ. The ELISA V-PLEX assay was used to assess concentration of pro-/anti-inflammatory mediators.

Results

Tested 24 h after training, SD rats had significantly lower cognitive performance in NOR (p< 0.05) and PAT (p< 0.01). Percentage of Iba-1+ microglia in the stratum radiatum of CA1 (p< 0.05) and CA2 (p< 0.05) hippocampal subregions was higher among SD rats. This SD-induced increase in microglia was not found in the pyramidal layer of CA1/2/3 (p>0.05). There was no SD-associated change in percentage of GFAP+ astrocytes in any hippocampal subregion (p>0.05). ELISA analysis found SD rats had higher levels of pro-inflammatory chemokine ligand 1 (CXCL1, p< 0.05) and anti-inflammatory interleukin-10 (IL-10, p=0.07) in the hippocampus.

Conclusion

SD-induced cognitive impairment was associated with increased microglia presence in CA1/2 subregions of the hippocampus. Increased expression of hippocampal CXCL1 after SD indicates these CA1/2 microglia are pro-inflammatory, leading to neuroinflammation in regions that mediate declarative memory. Although IL-10 trended to increase after SD, this neuroprotective anti-inflammatory factor did not prevent SD-induced performance decline or microglia recruitment. Based on these findings, it is suggested that blocking pro-inflammatory microglia pathways in the CA1/2 may prevent SD-induced cognitive dysfunction.

Support (if any)

AFOSR grant 20RHCOR04
0203 Time-In-Bed Classroom Challenges: Incentivizing Undergraduate Students to Improve Sleep During Final Exams Week
Authors: Cruz Andri , Nickel Allison , Barley Blake , Diaz Laurel , Scullin Michael
Published: May 2023

Introduction

Late bedtimes and all-nighters are ingrained into student culture, especially during final exam week. We previously found that extra credit incentives “to sleep 8 hours” encouraged longer sleep durations in small-sized classes. The current work investigated whether a modified approach—extending one’s time-in-bed—was scalable to larger-sized classes and dependent on the size of the incentive.

Methods

Across two studies, 129 undergraduate students completed baseline actigraphy and sleep diary monitoring early in Fall 2021 or Fall 2022. At the end of the semester, students could opt to take a time-in-bed challenge to earn large-sized (8 points; Study 1) or medium-sized (5 points; Study 2) extra credit on their final exam if they maintained an average time-in-bed of nine hours (or average total sleep time of eight hours). A smaller-sized extra credit (2 points) could be earned if the overall benchmarks were not met but one still improved on their baseline sleep duration by 20 minutes or sleep efficiency by 3%. Participants provided informed consent and the class instructor was kept blinded until after exams were graded.

Results

Most students attempted the time-in-bed sleep challenge (Study 1: 86.79%; Study 2: 92.11%). In Study 1, large-sized extra credit encouraged a 66 minute/night improvement in actigraphy-defined total sleep time from early-semester baseline (6.72 ± 1.18 hours) to final exams week (7.82 ± 0.89 hours; p<.001). In Study 2, a medium-sized extra credit opportunity improved actigraphy-defined total sleep time by 46 minutes/night from baseline (6.69 ± 0.80 hours) to finals week (7.46 ± 1.12 hours; p<.001). The interaction with incentive size was non-significant (p>.05). Sleep efficiency was similar across timepoints in Study 1 (83.6 ± 5.35 to 82.8 ± 5.18, p>.10) and Study 2 (82.9 ± 6.1 to 82.9 ± 6.47, p>.10). Students did not have to sacrifice total sleep time to perform well on their final exams (rs<.10); interestingly, students with higher sleep efficiencies performed better on their final exams (r=.28, p<.05).

Conclusion

The all-nighter culture of final exam week can be overcome by creating incentives for students to prioritize nighttime sleep.

Support (if any)

National Science Foundation (1920730 and 1943323).
0205 Catechol-O-methyltransferase Genotype, but not Dopamine Receptor D2 Genotype, Modulates Slow Wave Sleep
Authors: Muck Rachael , Van Dongen Hans , Satterfield Brieann
Published: May 2023

Introduction

Slow wave sleep (SWS), a putative marker of sleep homeostasis, robustly increases following total sleep deprivation (TSD). The neurotransmitter dopamine is substantively involved in sleep-wake regulation. Single nucleotide polymorphisms (SNP) in the dopaminergic genes of dopamine receptor D2 (DRD2) and catechol-O-methyltransferase (COMT) have been found to alter dopamine availability primarily in the striatum and prefrontal cortex (PFC), respectively. Here, we investigate if these SNPs are associated with changes in SWS at baseline and following TSD.

Methods

N=105 healthy adults (ages 26.5±5.0; 55 females) completed one of three 4-day/3-night in-laboratory studies with 10h baseline sleep opportunity (22:00–08:00), 38h TSD period, and 10h recovery sleep opportunity. Sleep periods were recorded polysomnographically and visually scored according to AASM criteria. DNA isolated from whole blood was assayed for DRD2 (C957T, rs6277) and COMT (Val158Met, rs4680) genotypes using real-time PCR. For each genotype, SWS duration was analyzed using mixed-effects ANOVA with fixed effects for genotype, night (baseline vs. recovery), and their interaction, controlling for study, and a random effect over subjects on the intercept.

Results

DRD2 genotypes (25 C/C, 52 C/T, 28 T/T) and COMT genotypes (23 Val/Val, 58 Val/Met, 24 Met/Met) were in Hardy-Weinberg Equilibrium. As expected, SWS was substantially increased during recovery sleep compared to baseline. There was no main effect of DRD2 (F[2,102]=2.78, p=0.07), nor interaction of DRD2 by night (F[2,102]=1.45, p=0.24). However, there was a significant main effect of COMT on SWS duration (F[2,102]=3.20, p=0.04), without interaction of COMT by night (F[2,102]=1.43, p=0.24). Compared to Met allele carriers, Val homozygotes displayed reduced SWS duration during both baseline and recovery sleep.

Conclusion

The DRD2 T allele is associated with decreased dopamine D2 receptors and decreased dopaminergic signaling in the striatum relative to the C allele. The COMT Val allele is associated with increased enzymatic activity and decreased dopaminergic signaling in the PFC relative to the Met allele. Our results indicate that compared to striatal dopamine, PFC dopamine may be a more prominent mediator of SWS regulation, with less PFC dopamine corresponding to less SWS. This needs to be confirmed in a larger sample.

Support (if any)

CDMRP W81XWH1610319; USAMRDC W81XWH1810100; ONR N000141310302; NIH R21CA16769; ARO W911NF2210223.
0207 Acute Total Sleep Deprivation Adversely Impacts Cardiovascular Measures across Long-Duration Intervals
Authors: Goel Namni , Rosendahl-Garcia Kathleen , Pasetes Lauren
Published: May 2023

Introduction

For the first time, we comprehensively investigated the effects of repeated exposures to baseline (BL), total sleep deprivation (TSD), and recovery (REC) phases at 2, 4, and 8 months on cardiovascular (CV) measures.

Methods

We conducted a five-day experiment twice (at months 2 and 4) in a 4-month study (N=6 healthy adults; 3 females), and a similar five-day experiment three times (at months 2, 4, and 8) in an 8-month study (N=5 healthy adults; 2 females). During these repeated experiments, CV measures were collected via echocardiography or blood pressure monitor [systolic and diastolic blood pressure (SBP and DBP)] at three assessment time points: 1) after two baseline 8h time in bed (TIB) nights (BL); 2) after a night of total sleep deprivation (TSD); and 3) after two recovery nights of 8-10h TIB (REC). CV measures were also collected once pre and post study. Seated stroke volume (SV), cardiac index (CI), left ventricular ejection time (LVET), SBP and DBP, systemic vascular resistance index (SVRI), and mean arterial pressure (MAP) were collected. Data did not significantly differ between the two studies and therefore were pooled together for analysis (N=11). Repeated measures ANOVA and post-hoc comparisons corrected for multiple testing examined CV measures across all time points.

Results

SV, CI, SVRI, LVET, and SBP, but not DBP or MAP, showed significant changes across time. SV increased with TSD compared to pre-study, BL, and post-study at month 2. CI increased with TSD compared to pre-study, BL, REC, and post-study at month 2. SVRI decreased with TSD compared to pre-study, BL, and REC at month 2 and LVET and SBP increased with TSD compared to BL at month 2. In the 8-month sample subset, SBP increased with TSD compared to BL at month 8.

Conclusion

TSD increased SV, CI, LVET, and SBP, and decreased SVRI, compared to BL at month 2. Notably, TSD also increased SBP compared to BL at month 8, indicating a sustained adverse effect after long-duration repeated exposure to TSD. Overall, SV, CI, SVRI, LVET, and SBP are reliable biomarkers for assessing the harmful long-term cardiovascular effects of TSD.

Support (if any)

NASA grants NNX14AN49G and 80NSSC20K0243 (NG)
0209 Cardiovascular Measures Display Robust Phenotypic Stability to Total Sleep Deprivation Across Long-Duration Intervals
Authors: Pasetes Lauren , Rosendahl-Garcia Kathleen , Goel Namni
Published: May 2023

Introduction

For the first time, we determined whether individual differences in cardiovascular (CV) measures are observed in response to total sleep deprivation as well as the stability of such responses across 4-month and 8-month long-duration studies.

Methods

We conducted a five-day experiment twice (at months 2 and 4) in a 4-month study (N=6 healthy adults; 3 females), and a similar five-day experiment three times (at months 2, 4, and 8) in an 8-month study (N=5 healthy adults; 2 females). During these repeated experiments, CV measures were collected via echocardiography or blood pressure monitor [systolic blood pressure (SBP)] at three assessment time points: 1) after two baseline 8h time in bed (TIB) nights (BL); 2) after a night of total sleep deprivation (TSD); and 3) after two recovery nights of 8-10h TIB (REC). Seated SBP, stroke volume (SV), heart rate (HR), cardiac index (CI), left ventricular ejection time (LVET), and systemic vascular resistance index (SVRI) were collected. Data did not significantly differ between the two studies and therefore were pooled together for analysis (N=11). Intraclass correlation coefficients (ICCs) assessed the stability of CV measures during TSD. Spearman’s rho assessed the relative rank of individuals’ averaged TSD-TSD responses across CV measures.

Results

TSD ICCs across months 2 and 4 were substantial to almost perfect for all CV measures (0.755-0.962). In the 8-month sample subset, TSD ICCs were moderate to almost perfect across 2, 4, and 8 months for all CV measures (0.643-0.944). Individuals also exhibited significant consistency of responses within CV measures: SV was positively correlated with LVET (ρ=0.791, P=0.004), HR was negatively correlated with LVET (ρ=-0.627, P=0.039) and CI was negatively correlated with SVRI (ρ=-0.936, P< 0.001).

Conclusion

Vulnerability to repeated TSD exposures showed trait-like stability in CV measures across months 2, 4, and 8, with significant consistency of responses within CV measures. For the first time, we demonstrate robust phenotypic stability of cardiovascular measures during total sleep deprivation across 2-month, 4-month and 8-month time points in long-duration studies. Our results herald the use of biomarkers and countermeasures for prediction and mitigation of this critical vulnerability.

Support (if any)

NASA grants NNX14AN49G and 80NSSC20K0243 (NG)
0212 Insufficient Sleep and Behavioral Health in the Military: A 5-Nation Perspective
Authors: Alger Sara , Bennett Clare , Bennett Neanne , Huebner Matthew , Lee Jennifer , Edge Heather McCuiag , Simms Amos , Adler Amy
Published: May 2023

Introduction

Insufficient sleep (< 7 hours per night) degrades both health and performance and constitutes a risk to military mission success. Accordingly, militaries across the globe are increasingly focusing on sleep management, including the role that leaders play in fostering and promoting a healthy sleep culture. In the present study, we assessed survey data from the militaries of five nations on: 1) sleep behavior, 2) the relationship between sleep behavior and mental health, and 3) the role leaders play in improving service member sleep. The goal was to determine the extent to which insufficient sleep, its link to behavioral health, and the role of leaders were relevant in militaries across allied English-speaking nations.

Methods

Data from five nations: Australia, Canada, New Zealand, the United Kingdom, and the United States were assessed. Each nation administered a survey to a military sample, including questions on sleep problems (e.g., Insomnia Severity Index) and mental health. In addition, some countries assessed how first-line leaders addressed sleep in their units using items from the sleep leadership scale. Each data collection differed in terms of scope, setting, and objective.

Results

Insufficient sleep (< 7 hours per night) was reported by 34.9%, 67.2% and 95.4% of survey respondents from the New Zealand Defence Force, Canadian Armed Forces, and the US Army, respectively. Those reporting shorter mean sleep durations also reported fewer sleep difficulties, likely reflecting higher sleep pressure from chronic sleep loss. Across all five nations, sleep problems (e.g., difficulty falling asleep) were positively correlated with behavioral health symptoms (e.g., depression and anxiety symptoms). Importantly, leader engagement in promoting healthy sleep was positively correlated with sleep duration and negatively correlated with sleep problems and behavioral health symptoms.

Conclusion

Insufficient sleep is pervasive in the militaries of the nations included in the present study – a finding that has serious implications for the behavioral health and resilience of service members, and more broadly for the overall effectiveness of these military forces. Across nations, militaries should attend to these risks and examine ways that first-line leaders can promote healthy sleep in their service members.

Support (if any)

Department of Defense Military Operational Medicine Research Program
0213 Sleep and well-being of culinary specialists on United States Navy ships
Authors: Shattuck Nita , Matsangas Panagiotis
Published: May 2023

Introduction

In the US Navy, “galley workers” are those sailors involved in cooking and preparing meals and maintaining the overall cleanliness and hygiene of the galley spaces and messdecks. These sailors begin their workday in the ship’s kitchen in the early morning, working until late in the evening, typically sleeping at night. The purpose of the current study was to assess the fatigue levels, work/rest patterns, health-related behaviors, and well-being of galley workers on US Navy ships while underway.

Methods

In this longitudinal field assessment, 80 fit-for-duty US Navy galley workers performed their normal duties on 11 surface ships. Participants wore actigraphs, and completed activity logs and questionnaires to include four standardized tools (Pittsburgh Sleep Quality Index – PSQI; Epworth Sleepiness Scale – ESS; Insomnia Severity Index – ISI; Profile of Mood States – POMS).

Results

Galley workers had a median age of 25 (IQR=11.8) years and most of them were male (68, 85.0%). Most galley workers reported drinking caffeinated beverages (60, 80.0%), with nicotine or tobacco products used by 22 (29.3%) participants. In terms of working out, 46 (61.3%) reported having an exercise routine. The typical schedule of the galley workers included sleeping at night with work hours extending from around 6:00 AM till 8:00 PM. Specifically, they slept on average 6.57±0.85 hours/day (~29% slept < 6 hours/day) and worked 12.8±2.43 hours/day (25% worked >14.5 hours/day). Approximately 84% were classified as poor sleepers, ~57% had excessive daytime sleepiness, and ~38% had elevated insomnia symptoms. Compared to adult norms for the POMS total and subscales scores, the mood of galley workers was worse in terms of total mood disturbance (84.1%), tension-anxiety (71.4%), anger-hostility (79.4%), vigor-activity (77.8%), fatigue (68.3%), and confusion-bewilderment (73.0%).

Conclusion

Galley workers on USN ships are chronically sleep-deprived and work long hours. To ameliorate the detrimental effects of these issues on sailor well-being, leaders should consider adopting strategies to improve sailor well-being. For example, appropriately timed short naps during the day, use of caffeine, and exposure to bright light may be viable methods to incorporate into the daily schedule of galley workers to alleviate the effects of their arduous work schedules.

Support (if any)
0216 The relationship between work and sleep in the naval operational environment
Authors: Matsangas Panagiotis , Shattuck Nita
Published: May 2023

Introduction

Several studies conducted by the Naval Postgraduate School Crew Endurance Team have shown that a sailor’s life at sea is characterized by limited opportunities to sleep and long work hours. In this environment, which is saturated with work duties, time is a rare commodity. This study assesses how work hours affect sleep duration. The information presented herein is a subset of the measures taken from multiple field assessments on sailors aboard nine different USN ships.

Methods

Longitudinal (average = 11 days; range = 7 to 18 days), prospective, naturalistic observations were made of sailors (N=675; 18-59 years of age, 79.3% males, 85.3% enlisted) while performing their normal underway duties on nine US Navy surface ships. Activity logs were used to assess work hours, messing (meals), and personal time. Sleep was objectively assessed by actigraphs.

Results

The average sailor’s workday was 11.6 hours (s.d.=2.48). Sailors slept on average 6.53 hours/day (s.d.=0.97), a median 1.34 hours/day (IQR=0.88) were spent messing/eating and a median 3.25 hours/day (IQR=2.50) were reported for personal time. Work hours were associated with daily sleep duration (F(1,602)=105, p < 0.001; R2=0.148), personal time (F(1,673)=1539, p < 0.001; R2=0.696), and messing time (F(1,673)=32.0, p< 0.001; R2=0.044). Within the range of our data, every extra hour of work was associated with an average of ~9 minutes less sleep, ~41 minutes less personal time, and ~3 minutes less time at meals. The association between work hours and sleep duration was evident (all p< 0.001) even after adjusting for confounding factors, i.e., watchstanding status (watchstander, non-watchstander), type of watch schedule (fixed, rotating), rank group (officer, enlisted), and detailed rank group (E1-E3, E4-E6, E7-E9, O1-O3, O4-O6).

Conclusion

The naval operational environment is dominated by long work hours that, in turn, lead to sleep deprivation. The competing relation between work and sleep, however, is ameliorated by the existence of personal time (i.e., spare time in which sailors do not work). More research should be focused on spare time and its importance for sailor wellbeing while underway.

Support (if any)
0217 Trait-Like Stability of Cardiovascular Measures Across Long-Duration Intervals after Baseline and Recovery Sleep Phases
Authors: Pasetes Lauren , Rosendahl-Garcia Kathleen , Goel Namni
Published: May 2023

Introduction

We determined for the first time whether individual differences in cardiovascular (CV) measures are observed after repeated baseline and recovery sleep (prior to and after exposure to total sleep deprivation) as well as the stability of such responses across 4-month and 8-month long-duration studies.

Methods

We conducted a five-day experiment twice (at months 2 and 4) in a 4-month study (N=6 healthy adults; 3 females), and a similar five-day experiment three times (at months 2, 4, and 8) in an 8-month study (N=5 healthy adults; 2 females). During these repeated experiments, CV measures were collected via echocardiography at three assessment time points: 1) after two baseline 8h time in bed (TIB) nights (BL); 2) after a night of total sleep deprivation (TSD); and 3) after two recovery nights of 8-10h TIB (REC). Seated stroke volume (SV), heart rate (HR), cardiac index (CI), left ventricular ejection time (LVET), and systemic vascular resistance index (SVRI) were collected. Data did not significantly differ between the two studies and therefore were pooled together for analysis (N=11). Intraclass correlation coefficients (ICCs) assessed the stability of CV measures after BL and REC. Spearman’s rho assessed the relative rank of individuals’ averaged BL and REC responses across CV measures.

Results

BL ICCs (0.821-0.944) and REC ICCs (0.806-0.869) comparing months 2 and 4 for all CV measures were almost perfect. The ICCs comparing BL vs. REC measures at month 2 (0.816-0.969) and at month 4 (0.816-0.927) for all CV measures were similarly almost perfect. In the 8-month sample subset, BL ICCs (0.693-939) and REC ICCs (0.770-960) comparing months 2, 4 and 8 for all CV measures were substantial to almost perfect. The ICCs comparing BL vs. REC measures at month 8 for all CV measures were fair to almost perfect (0.314-0.960). Individuals also exhibited significant consistency of responses within CV measures across 2 months and 4 months during BL and REC.

Conclusion

This is the first demonstration of remarkable robust phenotypic stability of a number of cardiovascular measures across repeated baseline and recovery sleep and across various CV measures in long-duration studies.

Support (if any)

NASA grants NNX14AN49G and 80NSSC20K0243 (NG)
0218 Changes in sleep architecture and topography of sleep EEG slow wave activity following acute wake extension in early adolescence
Authors: Mason Gina , Dionisos Victoria , Christiansen Taylor , Dickstein Daniel , Carskadon Mary , Saletin Jared
Published: May 2023

Introduction

A progression of peak sleep EEG slow wave activity (SWA; EEG power 0.5-4Hz) from posterior to anterior expression reflects brain development. Further, increased EEG SWA after extended wakefulness is a marker of sleep pressure. However, it is unclear whether recovery sleep SWA in later youth is expressed in a similar scalp topography as typical sleep. Using experimental wake-extension, we investigated homeostatic changes in sleep architecture and SWA topography in early adolescence.

Methods

Twenty-two young adolescents (M±SD: 12.03±1.14y, 12F) participated in two consecutive laboratory stays after at least a week of at-home actigraphy-monitored stabilization (9.5h in bed). A baseline night (BSL; 9.5h 21:00-06:30) was followed by wake-extension (WE) to 02:30 and a 4h recovery sleep opportunity (RS; 02:30-06:30), each monitored by polysomnography including a 25-channel EEG array. The current analyses examined R&K sleep architecture at BSL and RS. SWA in RS was compared to the first 4h of BSL in two ways: (1) absolute NREM power (µV2); (2) an index (TI) of the topographical distribution of midline SWA (FPz-AFz-Fz-FCz-Cz-CPz-Pz-POz-Oz) providing a score of 1 to 9 indicating frontal to occipital peak distribution.

Results

WE significantly altered RS sleep architecture, including an increase in slow-wave sleep (%TST) versus BSL (M±SD BSL: 26.76±5.69%, RS: 51.65±7.83%, t(21)=-17.09, p<.001, d=-3.65). SWA was also significantly greater in RS (channel-averaged SWA BSL: 11883.50±5142.17 µV2, RS: 18955.82±7451.20 µV2, t(21)=-8.67, p<.001) with 22/25 individual electrodes meeting Bonferroni-corrected significance (ps<.001). Finally, we observed a small frontal shift (t(21)=2.39, p=.027, d=.51) of maximal SWA in RS (TI: 4.46±2.58; i.e., FCz/Cz) compared to BSL (5.32±2.78, i.e., Cz/CPz).

Conclusion

These data indicate robust sleep homeostasis in young adolescents after wake extension, expressed as increased SWA across the scalp. The findings also add to existing literature by indicating that SWA topography may also be sensitive to homeostatic challenge. Specifically, a baseline centroparietal locus of maximal SWA typical to this age became more frontocentral in recovery sleep. This anterior shift may reflect a homeostatic need over developmentally sensitive prefrontal cortex. Next steps will assess how individual responses may reflect a child’s neurodevelopment (e.g., inattention symptoms) or manifested behavior after wake extension and recovery sleep.

Support (if any)

K01MH109854, P20GM139743, R01HD103655
0221 Time to wake up! Adolescents woken up by an alarm or family member get short sleep on schooldays and weekends/holidays
Authors: Gooley Joshua , Charoenthammanon Rachel
Published: May 2023

Introduction

Many adolescents get insufficient sleep on schooldays because they need to wake up early. It is often assumed that students can sleep in longer on non-schooldays (weekends and holiday periods) to recover their sleep debt. However, few studies have explored the degree to which adolescents are given the freedom to extend their nocturnal sleep. Here, (1) we investigated how often adolescents are awoken by an alarm or family member on schooldays and non-schooldays, and (2) we tested whether this results in shorter sleep even on non-school days.

Methods

Adolescents aged 13-18 years (n=66; 10 schools in Singapore) wore an actigraphy watch (Actigraph wGT3X-BT) and completed daily diaries for 7 days during their school and holiday periods. Each morning, students indicated their reason for having woken. Actigraphy-derived sleep parameters included sleep onset, sleep offset, and the nocturnal sleep period. Simple effect sizes (e.g., mean difference in sleep period) were calculated for schooldays versus non-schooldays, and for days waking up to an alarm or family member versus other reasons.

Results

Adolescents’ nocturnal sleep was about 1.7 hours shorter on schooldays (mean=6.50h, 95% CI=6.24h-6.75h) compared with non-schooldays (mean=8.17h, 95% CI=7.89h to 8.45h) because they woke up much earlier. Students were awoken by an alarm or family member on 78% of schooldays, and this was associated with shorter nocturnal sleep compared with waking up for other reasons (mean difference in sleep period=-1.16h, 95% CI=-1.59h to -0.80h). By comparison, adolescents were awoken by an alarm or family member on 41% of non-schooldays. In such instances, students also obtained shorter sleep by about an hour (mean difference in sleep period=-1.21h, 95% CI=-1.46h to -0.94h) and slept less than the recommended amount for their age group (mean sleep period=7.38h, 95% CI=7.18h to 7.59h).

Conclusion

Adolescents’ nocturnal sleep was frequently interrupted by an alarm or family member on both schooldays and non-schooldays. Chronic sleep restriction extends beyond schooldays if adolescents are not allowed to wake up naturally on their ‘free days’. This may have deleterious effects on students’ performance and wellbeing.

Support (if any)

The research was funded by the National Institute of Education, Singapore (OER 14/21 JJG).
0224 Chronic change in sleep oscillation expression in older adults with insomnia with zolpidem or lemborexant and its effect on memory
Authors: Barabadi Negin Sattari , Dave Abhishek , Niknazar Hamid , Chen Ivy , Neikrug Ariel , Benca Ruth , Mander Bryce
Published: May 2023

Introduction

Aging is accompanied by increased insomnia and memory decline. Enhancing GABAergic and antagonizing orexinergic function are both ways to treat insomnia, but how these mechanisms impact sleep oscillations, and consequently memory, among older adults with insomnia is unknown. Thus, chronic effects of zolpidem and lemborexant on quantitative sleep electroencephalography (EEG) and quality of memory among older adults with insomnia were evaluated.

Methods

116 older adults (71.01±4.81y, 78.67% female) with insomnia (Insomnia Severity Index 18.73±3.13) completed a phase 3 study (E2006-G000-304; NCT02783729) with placebo (n=29), zolpidem-extended-release (6.25mg,n=26;ZOL), and lemborexant (5mg,n=29[LEM5]; 10mg,n=32[LEM10]) using polysomnography before (at baseline) and 29-30 days after chronic treatment. Spectral analysis was performed on artifact-free EEG data during NREM sleep. Changes in relative power within canonical frequency bands (i.e., slow-oscillation[0.5-1Hz], delta[1-4.5Hz], theta[4.5-7.5Hz], alpha[7.5-11Hz], slow-sigma[11-13Hz], fast-sigma[13-16Hz], beta[16-28Hz] and gamma[28-35Hz]) from baseline were compared between groups at averaged frontal electrodes at each visit. Working (WM) and episodic memory (EM) were measured at waketime using ANOVA models and Pearson correlations.

Results

A significant main effect of intervention on frequency bands delta (p=0.02), slow-sigma (p<.001), and fast-sigma (p<.001) was found, with greater chronic suppression in power for ZOL compared to PBO for delta (p=0.002). Compared to PBO, ZOL showed greater increase in power for slow-sigma (p<.001), fast-sigma (p<.001) and beta (p=.03), and was also associated with greater increases in power compared to LEM5 for slow-sigma (p<.001) and fast-sigma (p=.006), and compared to LEM10 for alpha (p=.04), slow-sigma (p< 0.00), and fast-sigma (p<.001). LEM5 showed greater beta (p=.05) than PBO. WM was significantly higher (better) for LEM5 compared to PBO (p=0.04), while EM was higher for PBO compared to ZOL (p=0.01). Increase in beta with ZOL was related to decreased change-from-baseline-WM (r=-0.43, p=.03); increases in theta and alpha with LEM5 were related to decreased change-from-baseline-EM [r=-0.38, p=0.04; r=-0.39, p=0.03]; and increase in delta with LEM10 was related to increased change-from-baseline-EM (r=0.43, p=0.02).

Conclusion

In older adults with insomnia disorder, chronic treatment with lemborexant and zolpidem had distinct effects on sleep oscillation expression and between power and memory. Functional consequences of these differential effects on sleep-oscillation expression and memory in insomnia patients should be further considered.

Support (if any)

Eisai
0225 Effect of thermoneutral temperature exposure in the APP/PS1 knock-in mouse model of Alzheimer’s disease
Authors: Wang Jun , Iradukunda Diane , Huffman Dillon , McLouth Chris , Bachstetter Adam , Murphy Michael , O’Hara Bruce , Duncan Marilyn , Sunderam Sridhar
Published: May 2023

Introduction

There is growing evidence that disordered sleep in Alzheimer’s disease (AD) may accelerate neuropathology, thus promoting a vicious cycle. In a previous study, we found that improving sleep through thermoneutral ambient temperature exposure may slow disease progression in 3xTg-AD mice. However, the confounding effects of temperature on metabolism in addition to sleep remained an open question.

Methods

To test whether the effect of thermoneutral warming on amyloid pathology is mediated by sleep changes rather than other non-specific physiologic effects of temperature, we conducted a new study on APP/PS1 knock-in (KI) mice. First, 6-m.o. male APP/PS1-KI mice were instrumented for EEG/EMG sleep analysis. After a week-long baseline recording, we split the mice into 4 separate groups: 1. SE (n=8), which were exposed to 30°C thermoneutral ambient temperature during the 12-hour light period; 2. SE-SD (n=9), which received sleep disruption through mild intermittent cage vibration alongside thermoneutral temperature exposure; 3. SD (n=8), which received sleep disruption at room temperature (22°C); and 4. CTRL (n=8), which were undisturbed and at room temperature. This design aims to decouple the sleep-enhancing effect of thermoneutral exposure from other non-specific effects. After four weeks of treatment, the animals were euthanized and the brains dissected to assay Aβ levels by ELISA. Vigilance states, i.e., Wake, REM, NREM, and slow wave sleep (SWS) within NREM – were scored in 4-second epochs from the EEG/EMG recordings and sleep metrics computed.

Results

Initial analysis of sleep revealed some SE-induced increases in SWS similar to our findings in 3xTg-AD mice. Sleep disruption reduces SWS even when thermoneutral warming occurs. Biochemical assays are in progress to reveal the treatment effects on Aβ levels in the brain.

Conclusion

Sleep disruption through vibration seems to be an effective way to negate the sleep-specific effect of thermoneutral temperature exposure. Incorporation of the biochemical assay data will help uncover the correlation between SWS and AD progression.

Support (if any)

R01AG068215
0227 Impact of 5-night sleep restriction on actigraphy-estimated sleep in young adolescents: preliminary associations with ADHD traits
Authors: Mason Gina , Christiansen Taylor , Dionisos Victoria , Barker David , Dickstein Daniel , Carskadon Mary , Saletin Jared
Published: May 2023

Introduction

Prior research suggests that children with attention-deficit/hyperactivity-disorder (ADHD) may experience disrupted sleep. In typically developing children, short-term sleep restriction increases sleep pressure and efficiency; however, whether a similar homeostatic response occurs in children with ADHD is unknown. Here we explore the effects of 5 nights of experimental sleep restriction on actigraphy-estimated sleep of children with and without high ADHD characteristics.

Methods

Nineteen young adolescents (Mage=12.24yr, range 10.17-13.88yr; 10F/9M) participated in an at-home crossover protocol. After ≥5 nights of stabilization (10hr time-in-bed[TIB] set to habitual risetimes), participants had five nights of sleep optimization (SO; same stabilization schedule) or restriction (SR; 7.5hr TIB, sleep opportunity reduced by delaying bedtime and advancing risetime equally), a 2-3 night restabilization, and then the reverse schedule. Sleep was assessed via wrist-worn actigraphy (AMI Micro Motionlogger), sleep diaries, and twice-daily phone calls ensuring schedule adherence. Primary sleep variables included: total sleep time (TST; min), sleep period time (SPT; min), and sleep efficiency (TST/SPT*100). Children were grouped by parent-rated Conners 3 ADHD-Probability-Index: < 50% (low-ADHD; n=10, 8F) or >=50% (high-ADHD; n=9, 2F).

Results

Mixed-effects ANOVAs evaluating condition (SO vs. SR) and group (low- vs. high-ADHD) on schedule adherence indicated significant effects of condition; that is, SR reduced both SPT (M±SD SO=9.08[0.54]hr, SR=7.10[0.57]hr; F(1,17)=479.75, p<.001, ηp2=.97) and TST (M±SD SO=7.92[0.97]hr, SR=6.38[0.86]hr; F(1,17)=302.13, p<.001, ηp2=.95). No group or group-by-condition effects were significant (all ps>.21). For sleep efficiency, a group-x-condition interaction (F(1,17)=8.29, p=.01, ηp2=.33) revealed that SR significantly increased sleep efficiency in low-ADHD children (M±SD SO=85.08[9.95]%, SR=89.74[7.66]%, Bonferroni-p<.001) but not in high-ADHD children (M±SD SO=90.67[3.74]%, SR=91.21[3.19]%, Bonferroni-p=.61). Other between-group effects were not significant (all ps>.12).

Conclusion

These preliminary data indicate that our sleep restriction protocol successfully reduces sleep opportunity and sleep duration in peripubertal children, including those with high ADHD traits. Notably, sleep restriction improved sleep efficiency in low-ADHD children, whereas sleep efficiency was high and unchanging in our high-ADHD group. It is possible that high-ADHD children maintained higher sleep pressure even after stabilization. While data collection (matching groups on sex and age) continues, we are examining waking EEG markers to explore this possibility.

Support (if any)

R01HD103655, P20GM139743
0228 Investigating Application of Phase Contrast MRI to Study CSF Movement in Aging and Sleep Deprivation
Authors: Pedersen Taylor , Flores Jaqueline , Peskind Elaine , Iliff Jeffrey , Levendovzsky Swati
Published: May 2023

Introduction

The glymphatic system facilitates solute transport through the exchange of cerebral spinal fluid (CSF) and interstitial fluids using a brain-wide system of perivascular spaces. Such exchange is primarily active during sleep. Aging and sleep disruptions have been shown to decrease glymphatic clearance and increase risk of cognitive impairment. Here, we used phase contrast MRI (PC MRI) to measure CSF egress from the Aqueduct of Sylvius (AoS) as a marker of CSF circulation in the setting of sleep deprivation and aging.

Methods

Under approved IRB protocols six young adults (22±3 yo, 4F) underwent a night of full sleep and a night of sleep deprivation in a 3T Philips Ingenia Elition scanner with a 32-channel head coil. Additionally, six older adults (66±3 yo, 2F) were scanned using identical MRI protocol but only after full sleep. The PC MRI was a single slice acquisitions with 14 samples within a cardiac cycle. The slice was perpendicular to the AoS and care was taken to avoid any phase wrapping. All individuals also completed the General Practitioner’s assessment of cognition (GPCOG) in the morning prior to their scan. CSF velocity in cm/s was calculated from the phase data. Heart rate (HR) was recorded during the scan using a pulse-oximeter.

Results

CSF velocity was numerically lower after sleep deprivation (2.6±2.1 cm/s) than after a night of full sleep (3.1±2.0 cm/s) in young adults, but the difference was not significant. CSF velocity in the older adults was lower (2.0□0.5 cm/s, marginally significant at p = 0.10) than in young adults. HR in older adults (59±6) was significantly lower than the young adults under both conditions (full sleep: 68±4, sleep deprivation: (66±11) and, across all participants, HR was weakly correlated (r=-0.35) with CSF velocity. GPCOG was not significantly different across conditions or groups.

Conclusion

Although only marginally significant, CSF velocity in the AoS, measured by PC MRI is sensitive to HR variations and aging but not to sleep. Continued investigation with a larger sample size is underway to understand if these preliminary observations hold and if CSF velocity in the AoS is associated with glymphatic transport.

Support (if any)
0229 Reward motivation improves placekeeping performance after total sleep deprivation and a night of rest
Authors: Wernette Elle , Altmann Erik , Fenn Kimberly
Published: May 2023

Introduction

Sleep deprivation impairs some higher-order cognitive processes, but it is unclear if this reflects impaired ability to perform complex tasks, a reduction in motivation, or both. There is evidence that reward motivation attenuates the effect of sleep deprivation on lower-level cognitive processes, namely vigilant attention. We investigated the extent to which reward motivation would mitigate the effect of sleep deprivation on placekeeping, a higher-order cognitive process that plays a central role in accurate performance of procedural tasks. To conduct the study under pandemic conditions, we developed a novel method to conduct sleep deprivation research remotely.

Methods

Participants (N = 414) joined a Zoom meeting in the evening and completed the Psychomotor Vigilance Task (PVT) and a placekeeping task (UNRAVEL). At 00:00, we randomly assigned participants to stay awake in the meeting overnight (Deprivation) or leave the meeting and sleep (Rested). Two trained researchers stayed in the meeting overnight to monitor participants. At 08:30, Rested participants re-joined the meeting, and all participants completed the PVT and UNRAVEL again. Some participants (Motivated), but not others (Nonmotivated), could earn a monetary reward based on their morning UNRAVEL accuracy. Performance on the PVT was completed before the motivation manipulation.

Results

We examined morning UNRAVEL accuracy using a 2 (Sleep: Deprivation, Rested) x 2 (Reward: Motivated, Nonmotivated) between-participants design with evening performance as a covariate. Deprivation participants made more errors than Rested participants, Motivated participants made fewer errors than Nonmotivated participants, and there was no interaction between the factors.

Conclusion

Motivational interventions may be an effective way to mitigate some of the effects of sleep deprivation on higher-order cognitive tasks. However, reward motivation affected Deprivation and Rested participants similarly, and, therefore, did not compensate for impairments specific to sleep deprivation. Consistent with results of studies testing effects of naps and caffeine, the present results suggest that sleep deprivation impairs the ability to perform a procedural sequence accurately in a way that is difficult to mitigate.

Support (if any)

This work was funded by the Office of Naval Research (N00014-20-1-2739).