bluuebunny/crossref_metadata_2025 huggingface dataset:
0106 Unitization Improves Memory for Associations during Sleep Deprivation
Authors: Kurinec Courtney , Whitney Paul , Hinson John , Satterfield Brieann , Honn Kimberly , Van Dongen Hans
Published: May 2022

Introduction

Total sleep deprivation (TSD) impairs binding, i.e., the ability to form new associations. Unitization – when separate memory items are learned as a single unit (e.g., combining two words into a novel compound word) – reduces the need for binding. Unitization mitigates impaired memory for associations in amnesiacs, but whether it offsets binding problems from TSD is unknown.

Methods

N=23 healthy adults (ages 19-35, 8 women) participated in an ongoing, double-blind, 4-day/3-night in-laboratory study with a 10h baseline sleep opportunity, 38h TSD, and a 10h recovery sleep opportunity. During TSD, participants were randomized to four administrations of caffeine (200mg), modafinil (alternating between 200mg and 0mg), or placebo at 4h intervals beginning at 01:00. They completed a unitization task at 14:45 on day 2 (baseline, session 1), day 3 (TSD, session 2), and day 4 (recovery, session 3). The task began with a study phase where participants studied 60 pairs of words that were presented individually (e.g., “penny” and “tower”) or as new, unitized words (e.g., “pennytower”) (50% each). Afterward, in the test phase, participants indicated whether 60 presented pairs of individual words were old (presented together at study) or new (recombined into new pairs) (50% each).

Results

Repeated-measures ANOVA revealed significant effects of study pair type (individual or unitized), session (1–3), and their interaction (p<0.05). Performance did not differ by pair type in session 1 (p=0.46), and performance for pairs of individual words did not change across sessions (p=0.34). However, performance on unitized word pairs improved across sessions (p=0.003), and unitized word pairs were recognized better than individual word pairs in sessions 2 and 3 (p<0.05).

Conclusion

Across sessions, participants benefitted from practice on unitized word pairs, such that performance improved even during TSD. Although potentially partly attributable to drug condition (to which investigators are still blinded), no such practice effect was seen for word pairs studied individually. Whether this dissociation implies that unitization bypasses the need for binding and thus lessens the impact of TSD requires further investigation. Regardless, unitization may mitigate performance impairment from sleep loss in settings that require forming novel associations, such as eyewitness identifications.

Support (If Any)

USAMRDC W81XWH-18-1-0100 and CDMRP W81XWH-20-1-0442.
0113 Daily Patterns of Sleep and Metacognition in College Students
Authors: Costa Amy , McGovney Kevin , Liu Karina , McCrae Christina , Curtis Ashley
Published: May 2022

Introduction

Sleep problems have been associated with subjective cognitive complaints (a type of metacognition) in older adults, but little research has examined if this same relationship exists in younger adults. Additionally, college students have high intra-individual variability with their sleep, making day-to-day sleep an understudied parameter of interest in this population. Considering that metacognition has been associated with academic outcomes (e.g., GPA) in college students, it is important to understand how daily sleep patterns might impact metacognition. The present study examined how intra-individual variability in sleep is associated with metacognitive ratings in college students.

Methods

College students (N=81, Mage=18.8, SD = 1.1, 64 females) completed seven days of sleep diaries reporting total sleep time (TST), sleep onset latency (SOL), number of nighttime awakenings, and wake after sleep onset (WASO). Students also provided morning metacognitive ratings regarding the perceived quality of mental functioning from very poor (0) to very good (100). Multilevel modeling analyses tested whether intraindividual variability in daily sleep variables was associated with daily metacognitive ratings, after controlling for interindividual sleep patterns, age, sex, sleep medication usage, and anxiety symptoms (via the Hospital Anxiety and Depression Scale).

Results

Daily TST was associated with metacognitive ratings (B=2.35, p=0.003), in that those who slept less than their typical average reported worse metacognitive ratings. Similarly, daily number of nighttime awakenings (B=-1.92, p=0.02) and WASO (B=-0.13, p=0.009) were also associated with metacognitive ratings, in that those with more awakenings and greater WASO than their typical average reported worse metacognitive ratings.

Conclusion

Findings suggest that deviation in typical daily sleep patterns (shorter TST, a greater number of nighttime awakenings, greater WASO) may impact daily metacognitive ratings in college students. Similar patterns are not observed at the average/interindividual level, prompting the need for future studies to examine daily sleep in college students. These findings point to the need for research examining whether sleep interventions (e.g., Cognitive Behavioral Therapy for Insomnia) for college students who experience sleep variability, could improve metacognition, which in turn could improve academic outcomes.

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0116 Slow oscillations promote long range effective communication: the key for memory consolidation in a broken down network
Authors: Niknazar Hamid , Malerba Paola , Mednick Sara
Published: May 2022

Introduction

The relation between slow oscillations (SOs, <1Hz) during non-rapid eye movement (NREM) sleep and systems-level memory consolidation is one of the most robust findings in cognitive neuroscience. However, NREM is a brain state seemingly unfavorable to systems consolidation because a hallmark characteristic of this state is a breakdown in connectivity and reduction in synaptic plasticity with increasing depth of sleep. Our study addresses this apparent paradox and how SOs orchestrate neural communication.

Methods

We employed generalized partial directed coherence to estimate directional causal information flow between EEG channels across the electrode manifold during SO and non-SO periods. We examined the magnitude of causal information flow over the phase of SOs and found two peaks of flow preceding and following the trough of the SO. We categorized source-sink pairs of flows into three groups based on distance between source and sink of information flow. All the peak flows in each group were averaged and we tested relation between averaged magnitude of the flow and overnight episodic memory improvement using correlation test.

Results

The results reveal that NREM generally (non-SO periods) and during the SO trough show dampened neural communication. Causal communication during non-rapid eye movement sleep peaks during specific phases of the SO ( before and after SO trough), but only across long distances. Correlation test results showed that episodic memory improvement was predicted by peaks of information flow with longest distances between sinks and sources, and not by any other phase of the SO or non-SO period.

Conclusion

This work introduces a non-invasive approach to examine information processing during sleep, a behavioral stage whose function, until now, has been understood only at a delay. The findings represent a conceptual leap in understanding how slow oscillations unlock memory consolidation in a broken down network which is by promoting long range effective communication. This research will promote further investigations of understanding how brain oscillations alone and in nested rhythms promote network communication, as well as to investigate how these properties vary and predict patterns of deficits in clinical populations and aging humans.

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0118 Performance on a Computerized Threat Elimination Task in an Animated Environment during Total Sleep Deprivation
Authors: Moslener Emily , Honn Kimberly
Published: May 2022

Introduction

Military and law enforcement operators must make split-second decisions on whether to shoot during confrontations. Quick responses are crucial when force is necessary, but accurate decision-making is also imperative. Often, decisions are made while fatigued, which could impair speed and/or accuracy. Furthermore, the reliability of background information may impact performance. We investigated performance on a computerized shooting task during a total sleep deprivation (TSD) study.

Methods

N=86 healthy adults (39 males, age 21-38) completed a 4-day/3-night in-laboratory study, randomly assigned to a TSD (n=56) or control (n=28) condition. A custom task was administered after 32h or 8h of wakefulness (TSD and control groups). Participants were to shoot enemy robots (press spacebar) and not shoot friendly robots (no response) within 500ms of each robot being revealed inside shipping crates (1-5s inter-trial-interval). The task introduction described which crates would contain enemies, but the intel’s accuracy varied across four phases: 100% (20 trials), 80% (120 trials), and 20% (40 trials), then irrelevant in a new environment (60 trials). Reaction time (RT) and accuracy (hits and false alarms (FAs)) were analyzed using 2x4 mixed-effects ANOVAs to determine the effects of condition, phase, and their interaction.

Results

There was a significant effect of phase on RT (p<0.001); in both conditions, participants reacted faster in phase 1 than all other phases. However, there was no effect of condition (p=0.20) or phase-condition interaction (p=0.080) on RT. There were significant effects of condition on hits (p<0.001) and FAs (p=0.004); TSD had fewer hits and more FAs than the control group. There was an effect of phase on hits (p=0.045), with fewer hits in phase 1, and a condition-phase interaction (p=0.026) showing that the TSD group experienced less improvement in hits. For FAs, there was no effect of phase (p=0.86) or phase-condition interaction (p=0.86).

Conclusion

The results suggest a speed/accuracy tradeoff during TSD, where relative to the control group, RTs remained equivalent, but accuracy was worse. In both groups, the RT slowing from phase 1 to subsequent phases, suggests that participants initially used the intel to facilitate quicker decision-making, but disregarded it once it was not completely reliable.

Support (If Any)

CDMRP grants W81XWH-16-1-0319 and W81XWH-20-1-0442
0126 Zona incerta Lhx6 neurons are most active during NREM and REM sleep and after prolonged waking
Authors: Blanco-Centurion Carlos , Vidal-Ortiz Aurelio , Shiromani Priyattam
Published: May 2022

Introduction

Emerging data shows that GABA neurons in the zona incerta (ZI) play a prominent role in regulating sleep. Transfer of the orexin gene into ZI neurons blocks cataplexy in narcoleptic orexin-knockout mice (Liu et al., JNeurosci, 2011) and vGAT GABA neurons in the ZI anticipate onset of NREM (Blanco-Centurion et al., SLEEP, 2021). To identify the subtype of GABA neurons regulating sleep, we examined the activity of Lhx6 neurons. This study tests the hypothesis that Lhx6 neurons show peak calcium fluorescence during sleep, and that the fluorescence is further increased after prolonged waking.

Methods

In Lhx6-cre mice (mice=4; all females; 4-5 mo), rAAV-DIO-GCaMP6s was delivered stereotaxically to the ZI (isofluorane anesthesia) and a GRIN lens, along with EEG and EMG electrodes were implanted. 21d later a miniscope (INSCOPIX) was attached, and after 3d of adaptation, sleep and fluorescence in individual Lhx6 neurons were recorded for 4h (baseline). On another day, the mice were kept awake for 6h (gentle handling; 9a-3p) and fluorescence in Lhx6 neurons was recorded for 2h during recovery sleep. The imaged data from the two recording periods (baseline and recovery sleep) was combined into a single data file and the change in fluorescence was determined against the mean image frame (F0). Previously, we and others found that the GCamP calcium fluorescence is a direct measure of action potentials and serves as a marker of activity.

Results

97 neurons were automatically extracted (PCA-ICA analysis; blinded without knowledge of sleep state). In 66 neurons (68%) the average fluorescence was significantly higher during REM, NREM or both, compared to waking (Mixed Model ANOVA; SPSS25; P<0.01). In this population the fluorescence was significantly higher during recovery sleep compared to baseline (P<0.001) indicating increased activity of the sleep-active neurons during recovery sleep. With ensuing sleep, the increase in fluorescence gradually returned to baseline levels, attesting to the fluorescence as a marker of homeostatic sleep pressure. In 14 neurons (14%), fluorescence was highest in waking as compared to the other states during baseline, and in these neurons, fluorescence did not increase after sleep loss. Interestingly, six neurons (6%) were most active in waking and NREM but silent in REM (REM-off).

Conclusion

This is the first study to measure fluorescence in individual neurons after sleep loss. We find that the fluorescence in two-thirds of ZI Lhx6 neurons is tightly linked to sleep, and that the average fluorescence is further increased after prolonged waking. Microendoscopy is superior to indirect measures such as c-FOS or photometry in gauging sleep pressure in individual neurons.

Support (If Any)

VA BX000798, 1K6BX004216.
0131 Theta oscillations during REM sleep synchronize behavior and neural activity in the developing motor system
Authors: Dooley James , Sokoloff Greta , Blumberg Mark
Published: May 2022

Introduction

Myoclonic twitches are abundantly produced during REM sleep in skeletal muscles across the body. In infant rats, movements are produced by the red nucleus (RN), with the RN both sending motor commands and receiving sensory feedback from twitches. The RN’s role in producing twitches contrasts with that of primary motor cortex (M1), which does not generate motor commands at early postnatal ages. Instead, M1 functions as a sensory structure, processing sensory feedback from self-generated movements, including twitches. By postnatal day (P) 12, the RN (but not M1) also begins to exhibit a continuous theta rhythm (~6 Hz) during REM sleep that promotes sensorimotor integration with other brain areas. Given that the RN and M1 collaborate to control movement in adult rats, we hypothesized that theta emerges in M1 after P12, at which time theta synchronizes M1 and RN activity.

Methods

To determine if and when theta synchronizes activity in the RN and M1, we recorded local field potentials and unit activity in the RN and the forelimb region of M1 in unanesthetized preweanling rats at P12 and P20. Rats were head-fixed but were able to locomote and cycle freely between sleep and wake.

Results

Neurons in the RN and M1 continued to respond to twitches through P20. Further, as predicted, we observed the developmental emergence of REM-associated theta oscillations in M1 by P20 that were coherent with theta in the RN. Additionally, neural activity was phase-locked to theta; surprisingly, twitches were also phase-locked to theta, with twitches being more likely during the troughs of the oscillation. Finally, the temporal relationship between twitch-related activity in the two structures depended on the phase of theta, with twitch-related activity in M1 lagging behind twitch-related activity in the RN in the rising phase of theta. However, in the falling phase of theta, twitch-related activity in the RN and M1 showed similar time courses.

Conclusion

These results show how theta during REM sleep promotes the developmental integration of behavior with neural activity in the RN and M1. Because synchronous activity strengthens synaptic connectivity, and theta synchronized twitch-related activity in the RN and M1, these results also implicate twitches and twitch-related activity in the development of somatotopically precise functional connectivity between the RN and M1.

Support (If Any)

R37-HD081168 to M.S.B. and SRSF Career Development Award to J.C.D.
0132 Loss of Neurons in the Intermediate Nucleus is Related to Perturbed Sleep-Wake Rhythms in Older Adults
Authors: Wagner Max , Li Peng , Lim Andrew , Gao Lei , Gao Chenlu , Yang Hui-Wen , Yu Lei , Fan Wenqing , Bennett David , Buchman Aron , Schneider Julie , Saper Clifford , Hu Kun
Published: May 2022

Introduction

The ventrolateral preoptic nucleus (VLPO) is composed of neurons that are maximally active during sleep. In animal studies, VLPO lesion decreased the amount of sleep but only marginally attenuated circadian rhythm. The human intermediate nucleus (IN) is believed to be the homologue of the VLPO. Neuronal loss in IN has found to be associated with increased sleep fragmentation in older adults. We investigated whether IN neuronal loss is also associated with perturbed sleep-wake rhythms in humans.

Methods

We studied 50 deceased participants [age at death: 88.9±6.1 (mean±SD; female: 33 (66%)] from the Rush Memory and Aging Project, who had actigraphy assessment 1.6±1.3 years (range: 0.1-5.1 years) before death. Post-mortem immunohistochemical and stereological analysis was performed to quantify the count of galanin-immunoreactive neurons (Gal+) in the IN of them. Actigraphy data were used to calculate amplitude, acrophase, interdaily stability, and intradaily variability of the 24-h activity rhythms. Linear regression models were used to determine the associations of the four measures of sleep-wake rhythms with the GAL+ neuron counts, adjusting for age at death and sex. Further covariates considered included sleep fragmentation (derived from actigraphy) and the time interval between actigraphy assessment and death.

Results

The number of Gal+ neurons in IN was positively associated with interdaily stability and amplitude, and negatively associated with intradaily variability. Specifically, for one-SD decrease in Gal+ neurons, interdaily stability decreased by 0.06±0.02 (mean±standard error; equivalent to 40% SD of interdaily stability; p=0.009), amplitude decreased by 5.8±2.3 (equivalent to 35% SD of amplitude; p=0.014), and intradaily variability increased by 0.12±0.04 (equivalent to 36% SD of intradaily variability; p=0.009). Longer time interval between actigraphy and death showed a trend to attenuate these associations although not statistically significant (all p>0.1). These observations also remained statistically significant after adjusting for sleep fragmentation.

Conclusion

Neuronal loss in the IN was linked with perturbed sleep-wake rhythms in older adults. Further investigations are warranted to examine whether the observed associations are mediated by reduced sleep quantity or other aspects of sleep quality.

Support (If Any)

NIH RF1AG064312, RF1AG059867, R01AG017917, R01AG56352; and the BrightFocus Foundation A2020886S.
0133 Sleeping Well or Sleeping Poorly: Clues from Brain Neurochemistry
Authors: Killgore William , Grandner Michael , Dailey Natalie , Reign Deva , Silveri Marisa
Published: May 2022

Introduction

Sleep problems are prevalent throughout the population, but little is known about the brain mechanisms that differentiate good and poor sleepers. We studied the association between brain neurochemistry, as measured by proton magnetic resonance spectroscopy (1H-MRS), and sleep quality as measured by actigraphy. We hypothesized that better sleep quality would be predicted by brain metabolites indicative of greater neuronal health, neural inhibition, and reduced levels of excitatory neurotransmitters.

Methods

24 healthy adults (12 females25.4±5.6 years) wore an actigraph for seven consecutive days to collect Time in Bed (TIB), Total Sleep Time (TST), Sleep Efficiency (SE), Sleep Onset Latency (SOL), and Wake After Sleep Onset (WASO), and underwent 1H-MRS neuroimaging at 3T. Metabolite data from the medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (dlPFC), and medial parietal-occipital cortex (P-OCC) were entered stepwise into a series of multiple linear regression models to predict each actigraphic outcome.

Results

For SE, the regression analysis yielded a significant three predictor model (adjusted R2=.59), p=.0001, including mPFC choline (Cho; β=-.60), P-OCC N-Acetylaspartate (NAA ; β=.56), and P-OCC glutamate+glutamine (Glx; β=-.33). Better SE was associated with a combination of decreased Cho within the mPFC, and increased NAA and decreased Glx within the P-OCC. SOL was predicted by mPFC Cho alone (β =.60; adjusted R2 = .33), p=.002. This suggests that greater Cho within the mPFC was associated with a longer latency to fall asleep. Finally, for WASO, the regression analysis yielded a significant two predictor model, (adjusted R2 = .39), p=.002, including mPFC Cho (β = .56), P-OCC NAA (β = -.41). This suggests that a combination of greater Cho within the mPFC and decreased NAA in the P-OCC was associated with more minutes of wake after sleep onset.

Conclusion

Sleep quality was predicted from brain metabolites within the medial default mode network (DMN), an interconnected system of cortical regions that is normally deactivated during effortful cognitive processing. Sleep quality was predicted by a combined pattern of metabolites consistent with greater neuronal integrity, reduced cellular turnover, and lower excitatory neurotransmitters. Findings suggest potential metabolic and neuroanatomic targets for enhancing brain health to facilitate sleep quality.

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0150 Afternoon Napping Does Not Impact Autonomic Function in Healthy Adults
Authors: Nicevski Jennifer , Migliaccio Gianna , Bigalke Jeremy , Kerkering Emma , Greenlund Ian , Tikkanen Anne , Carter Jason
Published: May 2022

Introduction

Proper overnight sleep is important for autonomic nervous system function. However, less is known about the effects of daytime napping on wake autonomic regulation. In the present study, we assessed autonomic function following a daytime nap. We hypothesized that a 90-minute afternoon nap would significantly improve wake heart rate variability (HRV) and blood pressure (BP).

Methods

Fourteen participants (7 female, 24±1 years, 24 ±1 kg/m2) took part in the study. Subjects completed an autonomic function test after no nap (control condition) or a 90-minute nap opportunity (nap condition) on separate days using a randomized, crossover design. During the autonomic test, participants were fitted with three-lead electrocardiography (ECG), continuous beat-to-beat blood pressure (Finapres NOVA, Netherlands), and respiratory monitoring (pneumobelt). The autonomic function test consisted of 5-minutes of spontaneous breathing, 5-minutes of controlled breathing (15 breaths/min), and a 2-minute cold pressor test (CPT). Frequency-domain HRV in the low (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.4 Hz) components were determined via Fast Fourier transformation. Time-domain HRV was quantified using RMSSD and pNN50. Paired sample t-tests were completed between the control and nap sessions.

Results

Mean total sleep time (TST) for the nap session was 74±5 minutes. Contrary to our hypothesis, an afternoon nap did not change wake heart rate (HR, Control: 70±3 vs. Nap: 68±3 bpm, p = .31) or mean arterial pressure (MAP, Control: 77±3 vs. Nap: 83±3 mmHg, p = 0.70). Similarly, no differences were observed in HF (Control: 2632±628 vs. Nap: 2150±494 ms2, p = .33), LF (Control: 1702±373 vs. Nap: 1345±257 ms2, p = .20), or LF/HF (Control: 92±16 vs. Nap: 92±17%, p = .97) between conditions. RMSSD (Control: 82±12 vs. Nap: 79±11 ms, p = .723) and pNN50 (Control: 43±6 vs. Nap: 47±6%, p = .30) were not impacted by a daytime nap. Lastly, changes in HR (Control: ∆14±3 vs Nap: ∆18±3 bpm, p = .114) and MAP (Control: ∆23±4 vs. ∆Nap: 27±4 mmHg, p = .28) during CPT were not different between conditions.

Conclusion

An afternoon nap does not appear to significantly influence autonomic function at rest or during CPT in young healthy adults.

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0151 Subjective sleep onset latency is influenced by the sleep structure and body heat loss in human subjects
Authors: Iijima Ryusei , Kadooka Akari , Sugawara Kairi , Fushimi Momo , Hosoe Mizuki , Aritake-Okada Sayaka
Published: May 2022

Introduction

Humans can estimate the time that has elapsed during sleep (time estimation ability; TEA). Although research on the TEA during sleep has advanced in the field of sleep research, few studies have focused on the relationship between the subjective sleep onset latency (SOL), which is an indicator of TEA, and objective sleep structures, body heat loss, and body temperature. This paper investigates the association of the subjective SOL with sleep structures such as the objective SOL, duration of each sleep stage, subjective sleep parameters, and body heat loss in healthy young participants.

Methods

Twenty six participants (7 men and 19 women, mean age of 21.5 ± 0.5 years) having no sleep problems participated in a 1-hour polysomnographic recording that obtained objective sleep parameters during the daytime while temperatures of the skin (i.e., dorsum of the hand and foot, forehead, and subclavian) and eardrum were recorded at intervals of 1 min. The distal–proximal skin temperature gradient (DPG), which is a good predictor of body heat loss and sleepiness, was calculated. Subjective parameters, such as the subjective SOL, sleep time, sleep depth, sleepiness, and mood, were evaluated before and after sleep. We examined the association of the subjective SOL with objective sleep parameters, DPG, and other subjective parameters.

Results

Most participants estimated their sleep latency to be longer than their actual SOL (mean objective SOL of 7.6 min vs. subjective SOL of 13.7 min). The objective SOL was significantly correlated with each sleep stage parameter whereas the subjective SOL was negatively correlated with the stage N2 sleep duration (Rho = −0.454, p = 0.020) and correlated with the stage N2 sleep latency (Rho = 0.402, p = 0.051). Participants who estimated a shorter subjective SOL had a higher DPG before sleep periods than that after sleep onset (Rho = −0.692, p < 0.001). Additionally, the subjective SOL was correlated with the subjective sleep depth, subjective wake after sleep onset, and restorative sleep.

Conclusion

The subjective sleep onset latency in the healthy young participants was affected by the degree of body heat loss before sleep onset and stable shallow nonrapid-eye-movement sleep.

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0152 A functional role for global slow oscillations in major depressive disorder with hypersomnia
Authors: Malerba Paola , Dave Abhishek , Cook Jesse , Mednick Sara , Plante David
Published: May 2022

Introduction

Sleep slow oscillations (SOs, 0.5-1.5Hz) during stages N2 and N3 sleep facilitate cortical communication and are important to the restorative properties of sleep. Spatiotemporal clustering analysis of SOs on the electrode manifold has identified 3 topographically distinct patterns of SOs: Frontal, Local, and Global. Global SOs are spatially widespread cortical events implicated in anterior-posterior long-range communication. However, their precise functional significance is not fully understood. Patients experiencing Major Depressive Disorder (MDD) with comorbid hypersomnia show local deficits in parieto-central slow wave activity, suggesting that frontally-initiated SOs are not propagating to parietal-central regions. Hypersomnolence in MDD may therefore be connected to insufficiently restorative sleep. Here, we retrospectively examine associations between Global SOs in N2 and N3 sleep and hypersomnia severity in healthy controls and MDD patients.

Methods

MDD patients with (n=22) and without (n=22) hypersomnia, and age-gender balanced healthy controls (n=22) underwent overnight polysomnography studies with 256-channel hdEEG. After detection of SOs, our previously developed classification method was applied retrospectively to all SOs in this dataset, including leveraging a k-means clustering algorithm naïve to the MDD/Hypersomnia label. Fractions of global SOs during stages N2 and N3 were compared across healthy controls and MDD patients. Finally, the fraction of global SOs occurring during the night was correlated against all subjects’ individual scores on the Hypersomnia Severity Index (HSI).

Results

Analysis of EEG data revealed pronounced, but not statistically significant deficits in global SOs during N3 sleep in MDD patients with comorbid hypersomnia. These deficits were significantly correlated with HSI when examining MDD patients together (Pearson’s r = -0.397, p<0.01).

Conclusion

Our findings suggest that MDD patients with higher hypersomnia severity experience more pronounced deficits in Global SOs. Given the importance of SOs for the restorative properties of sleep, it is possible that MDD patients with hypersomnia might incur an enhanced sleep need driven by the homeostatic cost of a deficit in Global SOs.. Future studies are necessary to investigate causal mechanisms underlying these findings.

Support (If Any)

American Sleep Medicine Foundation (76-JF-12), Brain and Behavior Research Foundation (19193), and NIMH (K23MH099234) to DTP.
0158 Risk perception, outcome expectancy, and treatment self-efficacy among women and men with obstructive sleep apnea (OSA)
Authors: Sharma Akanksha , Byrne Sean , Deng Annan , Chu Jen-hwa , Sands Scott , Wellman Andrew , Redeke Nancy , Yaggi Henry , Zinchuk Andrey
Published: May 2022

Introduction

Continuous positive airway pressure (CPAP) is the first-line therapy for OSA. CPAP improves OSA severity, sleep architecture, and daytime symptoms. The effectiveness of CPAP, however, is limited to poor adherence. Individual's risk perception, outcome expectancy, and treatment self-efficacy predict CPAP adherence. CPAP adherence also differs by sex. However, it is unknown if predictors of CPAP use are different for women and men. We thus assessed sex differences in risk perception, outcome expectancy, and treatment self-efficacy among those with OSA.

Methods

Individuals enrolled to date (target n=267) in the NICEPAP study (NCT05067088), a prospective, observational cohort examining predictors of CPAP adherence, were included. Adults newly diagnosed with OSA prescribed CPAP therapy were included, while those with a need for non-CPAP therapy or unstable medical conditions (e.g., cancer receiving chemotherapy, severe lung, heart, or mental health disorders) were excluded. The exposure was sex. Co-primary outcomes were sub-scale scores from the Self-Efficacy Measure for Sleep Apnea (SEMSA) tool: Perceived Risk, Outcome Expectancies, and Treatment Self-Efficacy before starting CPAP. In addition, we assessed a comprehensive set of established psycho-social and biomedical CPAP adherence predictors using validated measures. SEMSA sub-scale scores for males and females were compared using Kruskal-Wallis statistics.

Results

We analyzed data for 33 females and 19 males. Females and males were 52 (41.0, 60.5) and 52 (35.0, 58) years old respectively (median [Q1, Q3]). Ten of 33 females and 4 of 19 males were Black with majority of others being White. The apnea-hypopnea index was 17.0 (9.1, 27.0) and 19.0 (13.3, 38.4), Epworth sleepiness scale and insomnia severity index scores were 9.0 (5.0, 12.0) & 15.0 (11.0, 18.0) and 6.0 (4.0, 9.0) & 17.0 (8.0, 19.5) for females and males respectively. There were no statistical differences in scores of Perceived Risk 2.4 (1.6, 2.9) vs 2.1 (1.8, 2.5) (p=0.717), Outcome Expectancies 2.8 (2.3, 3.4) vs 3.3 (2.4, 3.5) (p=0.371) or Treatment Self-Efficacy 3.1 (2.3, 3.7) vs 3.1 (2.0, 3.5) (p=0.977) for females vs. males.

Conclusion

We found no statistically significant differences in determinants of self-efficacy between women and men. Our findings may reflect a small sample size recruited to date or that self-efficacy of CPAP therapy is independent of sex.

Support (If Any)

This work was supported by Parker B. Francis Foundation and National Heart, Lung, and Blood Institute/NIH (1K23HL159259-01).
0159 Sleep-wake stability and variability in the middle-aged adult population: a UK Biobank study
Authors: Lok Renske , Weed Lara , Chawra Dwijen , Winer Joe , Zeitzer Jamie
Published: May 2022

Introduction

Given the increasing use of consumer, wrist-worn devices with triaxial accelerometry (actigraphy), understanding whether 24-hr activity patterns are associated with specific mental and physical health deficits is of paramount importance. The UK Biobank, a community-based sample of adults in the United Kingdom, provides an opportunity to examine this question given its size (more than 100,000 actigraphy records) and scope (association health records). As a first step in understanding these relationships, understanding the impact of missing data, ways to interpolate missing data, and the general characteristics of 24-hr patterns is necessary.

Methods

A subset (n=70) of complete (i.e., no missing data) actigraphy records from individuals participating in the UK Biobank were used to examine the impact of missing data on intradaily variability (IV; rhythm fragmentation) and interdaily stability (IS; rhythm regularity). Data were intentionally removed and imputed and the impact of the manipulations was examined with Bland-Altman statistics. After determining the best imputation method and the limits of the method, it was applied to missing data in the full cohort, resulting in 82,840 actigraphy records. These were examined for IV and IS, as well as relative amplitude and the timing of L5 and M10. Data were categorized by age, gender, ethnicity, BMI and material deprivation. ANOVA with eta² effect sizes were used for comparisons. Data shown as median (interquartile range).

Results

Relative to IV and IS, median and mean imputation methods corrected for missing data of up to 24 hours. Linear imputation of long (>3 hours) missing data worsened IV and IS scores. Non-parametric patterns in the general population were within expected range, with IV=0.89(0.74-1.05), IS=0.55(0.46-0.63), RA=0.90(0.85-0.99), L5-timing=00:52 (00:07-01:37), and M10-timing=08:25(07:40-09:20). Stratifying by gender, age, ethnicity, BMI and material deprivation resulted in significant differences within all groups (p<0.0001), but small effect sizes (0.0019-0.00052).

Conclusion

Median imputation is useful for correcting for missing data (<24 hours) when examining IV and IS. Non-parametric analysis of the general population indicated values within the expected range. Even though there were significant differences in non-parametric outcomes between genders, age groups, ethnicities, body-mass index and material deprivation, none of these had significant effect sizes.

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This research has been conducted using the UK Biobank Resource
0164 Overnight Oximetry in Generationally Un-Adapted Residents of High-Altitude
Authors: Stothard Ellen , Hickey Mark , Ebert-Santos Christine
Published: May 2022

Introduction

A recent population shift has increased residents of high-altitude locations. Additionally, travel infrastructure has created the opportunity for rapid displacement to high altitudes without adaptation. Residing at high-altitude is a physiological challenge, which increases the risk of overnight hypoxia from sleep disordered breathing. Sleep disordered breathing, including sleep apnea, is a risk factor for a variety of additional negative health outcomes. Additional information is needed to understand the physiology of high-altitude adaptation in generationally un-adapted residents and prevent negative health outcomes.

Methods

Healthy residents of high altitude participated in this community-supported observational study. Health and altitude history were gathered. Participants completed one night of overnight oxygen monitoring with finger pulse oximetry. Participants with BMI >30 kg/m2, sleep time <4 or >10 hours were excluded.

Results

Total of 41 participants included, 68.3% female, 44.9±13.0 years (SD), BMI 23.7±2.5 kg/m2. Participants resided at altitudes between 2500–3048 m. Participants were also characterized by their years at altitude and percent of life spent at altitude, average 15.9±12.2 years (median 13) and average 33.0±21.7% of life at altitude. Neither years or percent of life at altitude were predicted percent of time below 88% O2 on overnight pulse oximetry (R2 = 0.04 and 0.03, both p>0.12). Multiple Linear Regression indicated BMI was the only factor that explained a signification portion of the variance in adaptation (p<0.01).

Conclusion

In a generationally un-adapted population of high-altitude residents, years at altitude and percent of life at altitude do not explain the variance of adaptation to altitude as measured by percent of night spent hypoxic with less than 88% SpO2. While these data do not provide support for an adaptation response based on time at altitude, they indicate future directions in human altitude adaptation should focus on other covariates, potentially including genetic differences.

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0170 Slow Oscillation Power and Heart Rate Variability During Sleep Predicts Next-day Subjective Sleepiness in Healthy, Young Adults
Authors: Subramoniam Anjana , Chen Pin-Chun , Mednick Sara , Whitehurst Lauren
Published: May 2022

Introduction

High amplitude, slow oscillations in the electroencephalogram (EEG) often characterize the central nervous system’s homeostatic drive for sleep. Slow oscillations dominate the first part of the night and often dissipate as sleep need is satiated. These physiological changes are also reflected in next day subjective measures of sleepiness. Fluctuations in the autonomic nervous system, particularly parasympathetic activity, also coincide with slow wave sleep and are understood to represent bodily homeostasis. However, it is unclear if autonomic indicators effectively predict next-day sleepiness. Here, we investigated whether slow oscillatory (SO) power and cardiac autonomic activity during a night of sleep can predict next day subjective sleepiness.

Methods

88 young (aged 18-35), healthy participants spent the night in a University sleep lab. Before and after sleep, participants completed the Karolinska Sleepiness Scale (KSS) to measure subjective sleepiness. Each participant slept with polysomnography, including electroencephalography and electrocardiography. From these measures, we assessed slow oscillation power (0.5-1Hz) and high frequency heart rate variability (HRV; 0.15-0.45 Hz) --an indicator of parasympathetic, vagally-mediated cardiac tone-- during the first quartile of slow wave sleep. Paired T-tests compared the differences in KSS scores pre- and post-sleep. Pearson’s correlations assessed bivariate associations between slow oscillatory power, high frequency HRV, and KSS scores. Mixed linear models assessed the ability of SO power and high frequency HRV to predict next day subjective sleepiness.

Results

No significant differences were found in KSS ratings pre- (M±SD = 4.23±1.92) and post-sleep (4.38±1.80). No bivariate correlations were present between pre-sleep KSS, SO, or high frequency HRV. A significant correlation between KSS-post sleep and SO power emerged (r=0.286, p=0.001). In Model 1, we found that SO power was a predictor of subjective sleepiness (p<0.001; AIC: 777.469). In Model 2, we included high frequency HRV and reduced the AIC to 515.588. Both slow oscillatory power (p<0.001) and high frequency HRV (p<0.001) were significant predictors of KSS after sleep in Model 2.

Conclusion

We found evidence that both central and autonomic indicators of sleep predict psychological measures of sleepiness. Using autonomic indicators to characterize physiological sleepiness, compared to in-lab polysomnography, may be a more generalizable and cost-effective approach.

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0173 Kynurenine aminotransferase II inhibition improves sleep architecture in adult male and female rats exposed to kynurenic acid elevation during development
Authors: Milosavljevic Snezana , Rentschler Katherine , Wright Courtney , Pocivavsek Ana
Published: May 2022

Introduction

Dysregulated sleep and cognitive impairments are commonly reported in individuals with psychotic disorders, including schizophrenia (SZ) and bipolar disorder (BPD). Emerging evidence implicates the kynurenine pathway (KP) of tryptophan catabolism in the pathophysiology of psychotic disorders. Kynurenic acid (KYNA), a KP metabolite synthetized by kynurenine aminotransferases (KATs) from its biological precursor kynurenine, is elevated in brain tissue and the cerebrospinal fluid of patients with SZ and BPD. KYNA is hypothesized to play a key role in sleep disturbances, thus, we presently investigate if pharmacological inhibition of KAT II to reduce brain KYNA formation may overcome sleep.

Methods

We employed the embryonic kynurenine (EKyn) paradigm to induce KYNA elevation in the fetal brain (Pocivavsek et al 2014 Psychopharm). Wistar dams were fed either kynurenine (100 mg/day) (EKyn) or control wet mash (ECon) from embryonic day (ED) 15 to ED 22. Adult (postnatal day 56-85) male and female offspring were used in sleep studies (EEG/EMG telemetry) to evaluate the effectiveness of PF-04859989 (30 mg/kg, s.c.), an irreversible KAT II inhibitor. Each subject was treated at zeitgeber time (ZT) 0 with either vehicle or PF-04859989 and rapid-eye movement (REM) sleep, non-REM (NREM) sleep, and wakefulness parameters were assessed.

Results

KAT II inhibition significantly increased REM duration during the second half of the light phase in both male (P<0.01) and female (P<0.05) EKyn compared to vehicle treatment. PF-04859989 increased NREM duration and reduced wakefulness during the latter part of the dark phase in both ECon and EKyn male rats, accompanied with significant decrease in relative cage activity, but no differences were determined in female rats across 24 hr. Light phase analysis of spectral power during NREM sleep in EKyn rats revealed significant frequency by treatment interaction (P<0.0001) in males only, with enhanced delta power (0-4 Hz) after PF-04859989 treatment.

Conclusion

Acute decrease in brain KYNA mitigates sleep deficits and elicits higher quality sleep in male EKyn offspring, suggesting KAT II inhibition as a novel mechanistic approach to treating sleep deficiencies in a translationally-relevant preclinical paradigm.

Support (If Any)

This work was funded by National Institutes of Health Grant Nos. NIH R01 NS102209 & P50 MH103222.
0187 Brain Connectivity and Parenting: Association between Familial Factors and Sleep EEG Coherence in Infancy
Authors: Markovic Andjela , Schoch Sarah , Huber Reto , Kohler Malcolm , Kurth Salome
Published: May 2022

Introduction

Brain connectivity is tied to cognitive development and behavior. Previous work suggests that interactions with the environment tune the maturing patterns of brain connectivity. As the relevant environmental factors remain largely unknown, we examined whether the sleep-related familial context is associated with infant brain functional connectivity measured through sleep EEG coherence.

Methods

At-home 124-channel sleep EEG was recorded in 31 healthy infants aged 5.5 to 7.4 months (mean age=5.9±0.5mo; 15 females). Coherence was calculated for the first 80 20-second epochs of NREM sleep in delta (0.75–4.25Hz) and sigma (9.75–14.75Hz) bands, frequencies undergoing pronounced maturational dynamics. We averaged coherence within three regions over the frontal lobe (left, central, right) identified as regions with the strongest connectivity through data-driven clustering. For these regions and bands, linear regression models quantified the association between coherence and familial context, i.e., scores from the Brief Infant Sleep Questionnaire (i.e., sleeping arrangement and bedtime routine), Baby Care Questionnaire (i.e., Structure and Attunement subscales reflecting parental principles regarding infant sleep regularity), Maternal Cognitions about Infant’s Sleep (i.e., total score), age and sex. The best-fitting model was selected through backward selection (Akaike information criterion).

Results

Surprisingly, sex was the most consistent contributor across regions and bands, with girls exhibiting greater coherence than boys (FDR-corrected 0.004≤p≤0.038). Furthermore, older infants showed lower sigma coherence over the right frontal lobe (FDR-corrected 0.002≤p≤0.004). Additionally, infants co-sleeping with parents or siblings demonstrated lower delta and sigma coherence over the right frontal lobe than infants sleeping in their own bed (FDR-corrected 0.001<p≤0.025). Similarly, fewer maternal worries regarding the infant’s sleep were associated with lower sigma coherence in the right frontal region (FDR-corrected p=0.014). Finally, more regular bedtime routines were linked to increased delta coherence over the left frontal lobe (FDR-corrected p=0.014).

Conclusion

Based on previous observations indicating that in healthy children the right hemisphere develops first with a subsequent shift in asymmetry to the left, we propose that environmental factors such as co-sleeping, fewer parental worries, and more structured sleeping routines in infancy may serve as targets for early interventions to support this process and thereby healthy brain development.

Support (If Any)

This work was supported by the Swiss National Science Foundation (PCEFP1 181279) and the University of Zurich (Medical Faculty; Forschungskredit FK 18 047; Stiftung für wissenschaftliche Forschung STWF 17 008).
0192 Effects of emerging alcohol use on developmental trajectories of functional sleep measures in adolescents
Authors: Kiss Orsolya , de Zambotti Massimiliano , Yuksel Dilara , Goldstone Aimée , Colrain Ian , Schaefer Emil , Hasler Brant , Franzen Peter , Clark Duncan , Baker Fiona
Published: May 2022

Introduction

Adolescence is characterized by developmental changes in sleep timing and architecture as well as alcohol use initiation. While the effects of acute and chronic alcohol use on sleep in adults are well-documented, much less is known in adolescents. We used longitudinal data from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) to examine how emerging alcohol use affected sleep architecture in adolescents.

Methods

Overnight polysomnographic recordings were made each year, for 4 years, in 94 adolescents (12–21 years at baseline, 43% female) from the NCANDA cohort. All participants were no or low (youth adjusted Cahalan score of zero) alcohol users at baseline. These data were used to examine developmental trajectories of sleep macro-architecture and sleep electroencephalographic (EEG) measures using linear mixed effect models (LMMs), considering age, sex, family history of alcohol use, body mass index, ethnicity, and alcohol use class (i.e., no-to-low, moderate or heavy) at each annual assessment.

Results

There were strong developmental changes in sleep macro-structure and EEG, most notably, a decrease in slow wave sleep percentage and slow wave (delta) EEG activity with advancing age (p=0.02)​. Compared to those who remained no-to-low drinkers, participants who became moderate/heavy drinkers during the follow-up period, had different sleep trajectories, especially those older at baseline at baseline, including higher slow wave activity (p = 0.04), higher REM sleep percentage (p = 0.03), poorer sleep efficiency​ (p=0.003), and longer latency to sustained sleep (p = 0.03). The effects of alcohol use depended on sex, with male heavy drinkers having more REM sleep than female heavy drinkers (p = 0.04). Overall, a positive family history of alcohol use was associated with less NREM sleep and shorter sleep duration.

Conclusion

Our results present novel findings showing that emerging alcohol use during adolescence exerts complex effects on sleep macro- and micro-structure, over and above normal developmental changes in sleep. These effects could, in part, be alcohol effects on brain maturation processes underlying sleep regulation.

Support (If Any)

AA021696, AA021690