bluuebunny/crossref_metadata_2025_split huggingface dataset:
0059 Disruption of Circadian Clock Proteins in Obstructive Sleep Apnea Patients
Authors: Gabryelska A , Sochal M , Bialasiewicz P 
Published: May 2020

Abstract

Introduction
Circadian clocks are endogenous coordinators of 24-hour rhythm of behavioral and molecular processes in living organism. They are composed of set of genes, which function as activators - CLOCK and BMAL1, which through binding to regulatory elements containing E-boxes activate transcription of repressor proteins Period (PER1) and cryptochrome (CRY1). The aim of the study was to assess: CLOCK, BMAL1, PER1 and CRY1 in obstructive sleep apnea (OSA) patients.

Methods
The study included 20 individuals, who underwent PSG and based on apnea-hypopnea index (AHI) were divided into severe OSA group (n=10; AHI30; 90% male) and healthy control (n=10; AHI&lt;5; 70% male). All participants had their peripheral blood collected in the evening (9:00-10:00 pm) before and in the morning (6:00-7:00 am) after the PSG. CLOCK, BMAL1, CRY1 and PER1 protein concertation measurements were performed using ELISA.

Results
Increased level of following proteins was observed in OSA group: evening CLOCK (p=0.037), morning CLOCK (p=0.019), morning BMAL1 (p=0.0.16), evening PER1 (p=0.004), morning PER1 (p=0.029) and evening CRY1 (p=0.035). Yet, no significant difference was found between morning and evening level of any of the proteins in OSA and control group. Additionally, morning level of activator proteins CLOCK and BMAL1 had positive correlation with AHI (p=0.022, R=0.510 and p=0.010, R=0.560, respectively) and desaturation index (p=0.209, R=0.487 and p=0.009, R=0.570, respectively), while for repressor proteins PER1 and CRY1 significant correlations were found with desaturation index in the evening (p=0.025, R=0.500 and p=0.048, R=0.448, respectively), AHI in REM stage (p=0.009, R=0.569 and p=0.027, R=0.495, respectively) and AHI (for PER1 only p=0.014, R=0.540).

Conclusion
OSA patients have increased level of circadian clock proteins that corelates with severity of the disease. Further research is needed into the disruption of circadian clock should in OSA patients and possible effect of OSA treatment on concentrations of these proteins should be investigated.

Support
The study was financed by Polish National Centre Grant no. 2018/31/N/NZ5/03931.
0060 Morning Locus Coeruleus Activation During the PVT Predicts Later-Day Sleepiness
Authors: Lei H , Quan P , Liu W , Zhang X , Chai Y , Yang F , Dinges D , Rao H 
Published: May 2020

Abstract

Introduction
The locus coeruleus (LC) plays a key role in the regulation of arousal and autonomic function. Homeostatic sleep pressure refers to the drive for sleep that increases as a saturating exponential when we stay awake and decreases exponentially when we sleep. The current study used arterial spin labeling (ASL) functional magnetic resonance imaging (fMRI) to investigate the relationship between homeostatic sleep pressure (sleepiness) and LC activity during the psychomotor vigilance test (PVT).

Methods
We analyzed sleepiness and ASL imaging data from N=70 health adults (40 males, age range 21–50 years) who participated in a controlled in-laboratory sleep study. All participants were scanned at rest and during the PVT on the morning between 0700h-1000h after 9 hour time-in-bed (TIB) baseline sleep. LC regions-of-interest (ROI) were defined by standard templates from Keren et al. (2009). Sleepiness was assessed by the Karolinska Sleepiness Scale (KSS) every two hours from 10:30 am to 10:30 pm.

Results
Sleepiness scores gradually increased over wakefulness time and reached its peak in the evening at about 10:20pm. PVT-induced CBF changes did not correlate with sleepiness scores on the morning (p &gt; 0.05), but showed significant negative correlations with sleepiness scores on later day when sleep pressure became higher, especially during the night-time (r = -0.41, p &lt; 0.001). Specifically, LC CBF showed significant increases during the PVT scan as compared to the resting scan (p = 0.04) in individuals with less nigh-time sleepiness (KSS &lt; 4), but no differences (p &gt; 0.1) in individuals with greater nigh-time sleepiness (KSS ≥ 5). After controlling for age, gender, and total sleep time, PVT-induced regional CBF difference in the LC still negatively predicted sleepiness (β = -0.325, p = 0.005).

Conclusion
Our findings showed that individuals with greater LC CBF increases during the PVT were less sleepy during the night, supporting the key role of LC activity in promoting wakefulness and maintaining sleep homeostasis. PVT-induced LC activation may provide a non-invasive bio-marker of homeostatic sleep pressure in healthy adults.

Support
Supported in part by NIH grants R01-HL102119, R01-MH107571, R21-AG051981. CTRC UL1RR024134, and P30-NS045839.
0068 Circadian Alignment Predicts Neural Response to Monetary Reward in Late Adolescent Drinkers
Authors: Hasler B P , Soehner A M , Ngari W , Clark D B 
Published: May 2020

Abstract

Introduction
Abundant evidence from animal models implicates the circadian system in modulating the brain’s reward circuitry, but evidence in humans has been more limited. In particular, published evidence has relied on self-report and/or behavioral proxies of circadian misalignment and cross-sectional designs. Here, we employed objective measures and a prospective design to assess whether circadian alignment predicts the neural response to reward in a sample of late adolescent drinkers.

Methods
Participants included 23 late adolescents (18–22 y/o; 14 females) reporting weekly alcohol use. Participants completed pre-weekend (Thursday) circadian phase assessments via the dim light melatonin onset (DLMO). Sleep-wake timing was assessed via wrist actigraphy (midpoint of sleep on Tuesday and Wednesday prior to DLMO assessment). Circadian alignment was operationalized as the DLMO-midsleep interval. Neural response to reward was assessed via a card-guessing monetary reward fMRI task; analyzed on reward anticipation and reward win relative to neutral conditions. Mean BOLD signal was extracted from two regions-of-interest (striatum and medial prefrontal cortex, mPFC) for analyses in regression models, accounting for sex and scan order (participants also completed scans on Monday in counterbalanced order, not reported here).

Results
Shorter DLMO-midsleep intervals (i.e., greater misalignment) predicted lower striatal response to anticipated reward (beta=0.48,p=0.02) and showed a trend towards predicting lower mPFC response to anticipated reward (beta=0.39,p=0.06). No statistically-significant effects were found for reward win. Notably, a lower striatal response to anticipated reward correlated with more binge-drinking episodes in the past 30 days, but was not associated with alcohol use in the weekend immediately following the scan.

Conclusion
Our findings provide preliminary evidence of proximal associations between objectively-determined circadian alignment and the neural response to anticipated monetary reward. Ongoing work in a larger sample of adolescents aims to replicate this finding and more definitively determine its relevance to adolescent drinking.

Support
This work was supported by the National Institute on Alcohol Abuse and Alcoholism (R21 AA023209; R01 AA025626).
0069 Sleep in Drosophila is Regulated by the Chromatin Remodeling Factor ISWI
Authors: Gong N N , Dilley L C , Moscato E H , Williams C E , Kayser M S 
Published: May 2020

Abstract

Introduction
Sleep is commonly disrupted in patients with neurodevelopmental disorders (NDDs). Despite strong clinical associations between disrupted sleep and other NDD symptoms, we lack an understanding of how these are pathophysiologically related. Drosophila melanogaster exhibit essential characteristics of human sleep and have well-defined neural circuits underlying learning and social behaviors. This represents an ideal system to investigate the mechanistic interaction between disrupted sleep and other behavioral dysfunctions in NDDs.

Methods
We performed a reverse genetic RNAi-based screen targeting Drosophila homologs of human genes within NDD-associated risk loci. Pan-neuronal knockdown of risk genes was achieved using the Gal4-UAS system.

Results
Pan-neuronal knockdown of ISWI led to dramatic deficits in sleep and circadian arrhythmicity in the adult fly. Across species, ISWI and its homologs are ATP-dependent chromatin remodelers that regulate gene expression important for neural differentiation. We found that depleting ISWI also leads to memory and social deficits. ISWI functions during dissociable temporal windows of pre-adult development and in different circuits to establish different adult behaviors. The sleep phenotype associated with ISWI knockdown mapped to a specific population of cells. RNA-Seq of developing brains during the window important for sleep deficits revealed significant transcriptional changes in genes associated with nervous system development, suggesting ISWI acts in the development of sleep regulatory circuits. Finally, mutations in the human homologs of ISWI, SMARCA1/5, have been implicated in NDDs. Expressing either SMARCA1/5 in the setting of ISWI knockdown differentially rescued adult deficits.

Conclusion
Identification of ISWI provides a platform for unraveling pleiotropic behavioral effects from an NDD risk gene. Sleep, circadian rhythms, memory, and social behaviors are affected by ISWI knockdown, and map to different developmental periods and circuits. In addition, SMARCA1/5 differentially rescue adult behaviors, suggesting NDD-causing mutations in these genes may affect different behaviors. Current work aims to determine how human mutations in SMARCA1/5 affect behaviors.

Support
This work was supported by NIH K08 NS090461 (MSK) and T32 HL007953 (NNG), Hearst Foundation Fellowship 2018 (NNG), Burroughs Welcome Career Award for Medical Scientists, March of Dimes Basil O’Connor Scholar Award, and Sloan Research Fellowship (MSK).
0076 The Role of Preoptic Area GABAergic Axonal Projections to Tuberomammillary Nucleus in Sleep Homeostasis
Authors: Maurer J , Covarrubias I , Baik J , Weber F , Chung S 
Published: May 2020

Abstract

Introduction
Sleep deprivation has profound widespread physiological effects including cognitive impairment, compromised immune system function and increased risk of cardiovascular disease. The preoptic area (POA) of the hypothalamus contains sleep-active GABAergic neurons that respond to sleep homeostasis. We have shown that activation of POA GABAergic axons innervating the tuberomammillary nucleus (TMN, GABAergicPOA -&gt;TMN) are critical for sleep regulation but it is unknown if these projections modulate sleep homeostasis.

Methods
To monitor in vivo neural activity of GABAergicPOA -&gt;TMN projection neurons during sleep deprivation and rebound, fiber photometry was used. GAD2-Cre mice (n=6) were injected with AAV-DIO-GCaMP6S into the POA and an optic fiber was implanted into the TMN. An electroencephalogram (EEG) and electromyography (EMG) implant was mounted upon the skull to identify brain states. Calcium activity was measured for six hours starting at ZT4. Each mouse was recorded for three days to establish baseline sleep calcium activity with at least two days between sessions. During sleep deprivation sessions, an experimenter sleep deprived each mouse starting at ZT0 for six hours by gently brushing the animal with a small paintbrush to maintain wakefulness and minimize the stress to the animal.

Results
During baseline sleep recordings, GABAergicPOA -&gt;TMN projection neurons are most active during sleep (NREM and REM) which is maintained until wake onset. As sleep pressure increases, GABAergicPOA -&gt;TMN projection neurons display gradual increase in neural activity compared to time-matched points during baseline sleep recordings. Once mice were permitted to enter sleep rebound, GABAergicPOA -&gt;TMN projection neurons gradually displayed decreased activity as sleep pressure eased.

Conclusion
GABAergicPOA -&gt;TMN projection neurons show a strong increase in activity to drive homeostatic sleep need during periods of increased sleep pressure but subside once this pressure is reduced.

Support
This work is supported by NIH grant R01-NS-110865.
0077 Objective Sleep and Neural Response to Thermal Pain Testing Following Cognitive Behavioral Treatment in Patients with Comorbid Insomnia and Fibromyalgia: A Pilot Study
Authors: McCrae C , Craggs J , Curtis A , Staud R , Berry R , Robinson M 
Published: May 2020

Abstract

Introduction
Fibromyalgia (FM) is characterized by high rates of insomnia and abnormal central pain processing/heightened response to stimuli (i.e., central sensitization). This study examines whether cognitive behavioral treatments (CBTs) that target insomnia and pain improve central pain processing [indicated by decreased response to quantitative sensory testing (QST) using thermal stimuli] in patients with fibromyalgia and insomnia.

Methods
Before and after CBT-I, CBT-P or waitlist, adults (N=32, Mage=55.9, SD=12.2) with FM and insomnia completed QST during fMRI (Phillips Achieva 3T scanner), 14-daily pain ratings [least(0)-most(100) intense pain imaginable] and 1-night in-home polysomnography (AURA/Grass Technologies). Imaging data were processed using Brain Voyager (Brain Innovation/Netherlands). Random effects ANCOVA identified regions with significant group (3-CBT-I, CBT-P, waitlist) by time (baseline, post-treatment) interactions in brain hemodynamic response to QST. Linear regressions (using residualized change scores) were conducted for each significant region to examine how pain and sleep changes (%Stages 1–3 NREM, %REM) were related to brain response changes.

Results
Eleven regions exhibited significant interactions (ps&lt.00; large effects; right hemisphere: inferior frontal, superior temporal, mid-occipital, and cingulate gyri, lentiform nucleus; left hemisphere: angular, superior temporal, mid-frontal, inferior occipital, mid-temporal, and inferior frontal gyri). CBT-I decreased brain response to QST in 8 regions and CBT-P in 3 regions (CBT-I effects&gtCBT-P). Waitlist increased response in 6 regions. Pain ratings, %Stage 2 and %REM sleep were not significant for any region and were dropped from the models. Increased %Stage 1 and/or %Stage 3 predicted decreased brain response to QST in 8 of the 11 regions (ps&lt.01), accounting for 19–45% of the variance.

Conclusion
Compared to CBT-P, CBT-I prompted greater improvement in abnormal pain processing in patients with fibromyalgia and insomnia. Increased NREM sleep may underlie these pain processing improvements following treatment. Future research examining the potential role of NREM sleep in central sensitization and pain processing is warranted.

Support
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR055160 and R01AR005160-S1; McCrae, PI). Data collected as part of clinical trial NCT02001077 Sleep and Pain Interventions (SPIN) at the University of Florida (McCrae, PI).
0089 Sleep and Hippocampal Development in Early Childhood
Authors: Allard T L , Lokhandwala S , Spencer R M , Riggins T 
Published: May 2020

Abstract

Introduction
With sleep, memories are consolidated, leaving them less susceptible to interference. This process is believed to reflect transfer of memories from the hippocampus to the cortex. Research has established that naps benefit memory in typically napping children. This nap-benefit has been associated with sleep spindles during nREM2 sleep. Although research has separately related memory development to the hippocampus and to sleep, the association between hippocampal development and sleep physiology is not understood. The purpose of this investigation is to assess relations between sleep physiology and the hippocampus in early childhood.

Methods
Subjects are part of an ongoing longitudinal investigation. Preliminary analyses included 24 participants (Mage= 3.96 years, 14 females). Children participated in three consecutive visits, one week apart. During the first two visits, they completed a visuospatial memory task before and after a wake or nap period (order counterbalanced). Sleep physiology was assessed via polysomnography and hippocampal volumes were obtained via Freesurfer v5.1 using T1-weighted scans (.9 mm3).

Results
Preliminary results showed that total hippocampal volume was positively related to minutes spent in nREM2 sleep when controlling for age and gender (B=14.7, p=0.03). Further analysis showed that this relation held for left but not right hippocampus (B=10.1, p=0.01). Results also indicate a positive relation between sleep spindle count and left but not right hippocampal volume when controlling for age and gender (B=16.1, p=0.02).

Conclusion
Results show that greater time spent in nREM2 and greater sleep spindles across nREM2 are both related to a larger hippocampus in early childhood. These findings demonstrate an association between sleep physiology and the hippocampus during an important period of memory development, early childhood. Future analyses will assess differences in hippocampal volume between typical nappers and non-nappers at the second wave of data collection.

Support
Support was provided by NIH (HD094758) and NSF (BCS 1749280).
0102 The Relationship Between Overnight Consolidation and Next-Day Learning
Authors: Guttesen A V , Appleby G , Madden E , Gaskell M , Cairney S A 
Published: May 2020

Abstract

Introduction
Contemporary models of sleep-associated consolidation posit that overnight memory processing paves the way for next-day learning in hippocampus. However, the extent to which new hippocampal learning is dependent on overnight consolidation has yet to be investigated. In this study, we compared the impacts of sleep and sleep deprivation on the consolidation and encoding of hippocampus-dependent memories and, importantly, examined whether individual differences in consolidation were associated with individual differences in encoding.

Methods
Thirty healthy adults (17 females, mean age 20.1±1.65) were trained on a spatial memory task in the evening before a night of sleep or total sleep deprivation (repeated measures). Participants completed a spatial memory test the following morning, and then encoded a novel set of word-image pairs. Two days later (after recovery sleep), memory for the word-image pairs was tested. We predicted that participants’ spatial memory recall would predict performance on the word-image test, suggesting that overnight consolidation lays the groundwork for new encoding in hippocampus.

Results
Sleep (vs. sleep deprivation) improved spatial memory accuracy the following morning (t(29)=3.93, p&lt;.001, d=0.72) and word-image recall two days later (t(29)=12.19, p&lt;.001, d=2.23), suggesting that sleep facilitated the consolidation and encoding of hippocampus-dependent memories, respectively. However, the benefit of sleep for spatial memory recall was not significantly correlated with the benefit of sleep for word-image encoding (r(28)= 0.01, p=0.971), suggesting that hippocampal encoding was not contingent on foregoing overnight consolidation processes.

Conclusion
In support of previous findings, overnight sleep improved consolidation and next-day encoding, as compared to an equivalent period of sleep deprivation. However, the present results did not reveal any relationship between an individual’s sleep-associated consolidation and their next-day learning.

Support
Department of Psychology, University of York scholarship to A.áV.G. Medical Research Council Career Development Award (MR/P020208/1) to S.A.C.
1010 Individuals with Metabolic Syndrome and Unrecognized Sleep Apnea Can Be Identified by an Employer-Sponsored Healthcare Program and At-Home Sleep Study
Authors: Iakoubova O A , Tong C H , Arellano A R , Bare L A , Fragala M S , Devlin J J , Birse C E 
Published: May 2020

Abstract

Introduction
Obstructive sleep apnea (OSA) is common in individuals with metabolic syndrome (MetS) and increases risk of cardiovascular (CVD) events. Once recognized, therapeutic interventions can reduce OSA severity and associated CVD risk. Of the 25 million Americans with OSA, 80% are unaware of their disease. To facilitate and improve diagnosis of OSA, diagnostic devices for at-home OSA testing have been developed in clinical studies and approved by FDA. We evaluated an employer-sponsored healthcare outreach program and at-home OSA testing as a means of identifying individuals likely to have OSA and referring them into care.

Methods
Nine-hundred individuals with MetS, positive OSA Berlin questionnaire score and no prior diagnosis of OSA, as determined by annual workplace screening and health claims, were invited to participate in the sleep program. Those who agreed to participate (9.9%) received a diagnostic device for at-home OSA testing. Apnea-hypoapnea index (AHI) results recorded on returned diagnostic devices were evaluated by a sleep specialist. A telephone consultation with a program physician then provided each participant with an explanation of test results and referral into care. Based on AHI we identified individuals with moderate (AHI 16-30) to severe (AHI &gt;30) OSA and referred them to care.

Results
Of the 89 participating individuals, 21% had 3 MetS components, 53% had 4 components, and 20% had 5 components; 30% were diabetic; 83% had hypertension; and &gt;50% were obese. Moderate to severe OSA was diagnosed in 52 (58%) of participants. Of those, 50% had moderate OSA and 50%, had severe OSA. Among individuals with moderate to severe OSA, 29 (56%) had a physician consultation and were referred to treatment.

Conclusion
A personalized employer-sponsored healthcare outreach program identified individuals with unrecognized OSA and referred them into care.

Support
1018 Sleep and Fatigue: Examining the Impact on Cognitive Function in Older Adults Living with HIV
Authors: Frain J A , Chen L 
Published: May 2020

Abstract

Introduction
Poor sleep affects 75% of older adults living with HIV, negatively impacting health. The purpose of this study was to examine the associations between sleep, fatigue and cognitive function in older adults living with HIV with well-controlled HIV virus.

Methods
Forty-three adults aged 50 years and older living with HIV were recruited for this study. Participants provided demographic and health information. Participants wore actigraph watches continuously for one week, while completing a daily sleep diary, fatigue instrument, and Epworth Sleepiness Scale. After one week participants returned and completed the Pittsburgh Sleep Quality Index (PSQI) and performed cognitive testing including the NIH Toolbox Cognition Battery and the Montreal Cognitive Assessment (MoCA).

Results
Fluid cognition (measured with the Cognition Battery) positively correlated with hours of sleep measured via actigraph the night immediately prior to testing (p = .008), but not by average hours slept over the week. Average daily fatigue and daytime sleepiness were also correlated with fluid cognition (p = .012, p = .032 respectively). Similar results were found when cognition was measured using the MoCA, with sleep (p = .001), average fatigue (p = .017), and daytime sleepiness (p = .028) all correlated with cognition. When sleep was measured subjectively, Pearson correlation indicated that there was a statistically significant negative relationship of moderate strength between global sleep and cognitive function (r = -.47, p = .015).

Conclusion
The study provides evidence that poor sleep, measured objectively or subjectively, is associated with cognitive impairment. Despite we-controlled HIV virus, 86% of study participants had global sleep scores indicating poor sleep. Sleep measured objectively resulted in less nightly sleep than by subjective measure, 4.5 vs 6.07 average hours per night. Studying effective interventions to improve sleep should be a next step as a way of improving cognitive function for this population.

Support
This study was supported through a grant funded by Sigma Theta Tau International and the National Gerontological Nurses Association.