bluuebunny/crossref_metadata_2025_split huggingface dataset:
0067 An Anatomic Substrate for GABAergic Processes to Suppress Active Sleep and Promote Wakefulness in the Nucleus Pontis Oralis
Authors: Zhang J , Sampogna S , Xi M , Fung S J , Tobin C , Chase M H 
Published: May 2020

Abstract

Introduction
Our previous electrophysiologic data have provided compelling evidence that GABAergic processes in the nucleus pontis oralis (NPO) play a critical role in the generation and maintenance of wakefulness as well as active (REM) sleep (AS). We therefore hypothesized that one of the neuronal mechanisms of GABA actions in the NPO to promote wakefulness and suppress AS is due to a direct GABAergic inhibition of NPO neurons that generate AS (AS-generator neurons). However, the anatomical substrate for this inhibition is undetermined. Accordingly, the present study was undertaken to examine whether there is any direct interaction between GABAergic neurons and glutamatergic AS-generator neurons in the NPO.

Methods
Adult cats were deeply anesthetized and perfused transcardially. The brainstem containing the NPO was removed, postfixed and cut into 15 μm coronal sections with a Reichert-Jung cryostat. The sections were incubated with a mixture of a rabbit polyclonal antibodies against glutamine and GABA following the procedure of double fluorescence immunohistochemistry.

Results
There was a large number of neuronal somata labeled by anti-glutamine antibody and terminals labeled by anti-GABA antibody in the NPO. These glutamine-positive neurons were medium to large, multipolar cells (&gt; 20 μm), which resemble glutamatergic, AS-generator neurons that have been previously identified in the NPO. Specifically, majority of glutamatergic neuronal somata were closely apposed by multiple GABAergic terminals, indicating that AS-generator neurons in the NPO receive direct GABAergic inputs.

Conclusion
The present results demonstrate that a direct connection exists between glutamatergic AS-generator neurons and GABAergic processes in the NPO. These data provide the anatomical evidence which supports our hypothesis that the pontine GABAergic control of wakefulness and active sleep is partially mediated via GABAergic processes project to NPO AS-generator neurons that suppress the activity of these cells.

Support
NS092383
0074 Inhibitory Neurons in the Dorsomedial Medulla Promote REM Sleep
Authors: Stucynski J , Schott A , Baik J , Hong J , Weber F , Chung S 
Published: May 2020

Abstract

Introduction
The neural circuits controlling rapid eye movement (REM) sleep, and in particular the role of the medulla in regulating this brain state, remains an active area of study. Previous electrophysiological recordings in the dorsomedial medulla (DM) and electrical stimulation experiments suggested an important role of this area in the control of REM sleep. However the identity of the involved neurons and their precise role in REM sleep regulation are still unclear.

Methods
The properties of DM GAD2 neurons in mice were investigated through stereotaxic injection of CRE-dependent viruses in conjunction with implantation of electrodes for electroencephalogram (EEG) and electromyogram (EMG) recordings and optic fibers. Experiments included in vivo calcium imaging (fiber photometry) across sleep and wake states, optogenetic stimulation of cell bodies, chemogenetic excitation and suppression (DREADDs), and connectivity mapping using viral tracing and optogenetics.

Results
Imaging the calcium activity of DM GAD2 neurons in vivo indicates that these neurons are most active during REM sleep. Optogenetic stimulation of DM GAD2 neurons reliably triggered transitions into REM sleep from NREM sleep. Consistent with this, chemogenetic activation of DM GAD2 neurons increased the amount of REM sleep while inhibition suppressed its occurrence and enhanced NREM sleep. Anatomical tracing revealed that DM GAD2 neurons project to several areas involved in sleep / wake regulation including the wake-promoting locus coeruleus (LC) and the REM sleep-suppressing ventrolateral periaquaductal gray (vlPAG). Optogenetic activation of axonal projections from DM to LC, and DM to vlPAG was sufficient to induce REM sleep.

Conclusion
These experiments demonstrate that DM inhibitory neurons expressing GAD2 powerfully promote initiation of REM sleep in mice. These findings further characterize the dorsomedial medulla as a critical structure involved in REM sleep regulation and inform future investigations of the REM sleep circuitry.

Support
R01 HL149133
0080 Daytime Sleepiness Correlates with Increased Gray Matter Volume in the Right Middle Temporal Gyrus in Healthy Young Individuals
Authors: Burns A I , Bullock A , Raikes A C , Dailey N S , Grandner M A , Killgore W D 
Published: May 2020

Abstract

Introduction
Daytime sleepiness has been associated with some neuroimaging metrics, including altered functional connectivity within the default mode network and decreased gray matter volume (GMV) of the medial prefrontal cortex. Most prior studies, however, have focused on patients with sleep disorders or other pathologies. Here we examined the association between GMV and self-reported daytime sleepiness among a healthy group of young adults who reported no sleep-related problems.

Methods
Forty-five healthy adults (22 female; Mean Age=25.4, SD=5.6), who self-reported no history of sleep-related disorders or major medical conditions, completed the Epworth Sleepiness Scale (ESS), the Repeatable Battery for Neuropsychological Status (RBANS) and underwent high-resolution structural neuroimaging at 3T. Gray matter volumes were processed using standard procedures in SPM12. After controlling for age, sex, and intracranial volume, GMV was regressed against ESS scores.

Results
Greater ESS was associated with larger GMV within a cluster of voxels in the right middle temporal gyrus (MNI coordinates: 57, -9, -22; k=1344 voxels, p=.003, FWE cluster corrected). After controlling for ESS scores, larger GMV in this region was associated with poorer delayed memory performance (r=-.345, p=.022) and total neurocognitive performance on the RBANS (r=-.303, p=.046).

Conclusion
Greater daytime sleepiness in healthy normal sleepers was associated with greater GMV within a region of the right middle temporal gyrus. Greater volume of this region was also associated with poorer neuropsychological performance. Decreased GMV of this same region has previously been reported in patients with obstructive sleep apnea and insomnia, suggesting that it may be particularly sensitive to sleep disruption or may play a role in the etiology of sleep disorders, even among young individuals who deny any history of sleep-related dysfunction. Longitudinal work should focus on the potential of this region as a biomarker of vulnerability to sleep problems.

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0082 Hippocampal Gray Matter Volume in Healthy Adult Population is Associated with Habitual Sleep Duration
Authors: King R , Jecmen D , Alkozei A , Raikes A C , Grandner M A , Killgore W D 
Published: May 2020

Abstract

Introduction
The hippocampus is well known for its role in sleep and memory consolidation in adolescents, and has been shown to demonstrate neural plasticity and neuronal regeneration. However, the relationship between sleep and hippocampal gray matter volume in healthy adults remains to be fully characterized. We hypothesized that total sleep time (TST), as measured by actigraphy, would correlate positively with gray matter volume (GMV) in the hippocampus, a key memory region of the brain.

Methods
Forty-five healthy normal sleeping adults between 20–45 years of age wore an actigraph for seven days to quantify habitual sleep duration and underwent magnetic resonance imaging during the actigraphy period. Voxel based morphometry in SPM12 was used to estimate GMV at the whole brain level. A region-of-interest mask was used to constrain data analysis to the left and right hippocampi.

Results
Habitual sleep duration per night correlated positively with gray matter volume within part of the left hippocampus (x=-36,y=-20,z=-18; k=32, pFWE-corr=0.093), controlling for age, sex, total intracranial volume, intelligence scores and mood. No correlation was found between TST and hippocampal GMV in the right hippocampus.

Conclusion
Longer sleep time was associated with greater gray matter volume in the left hippocampus. This finding is consistent with what has been observed in healthy children and extend these findings to healthy normal sleeping adults. While TST and GMV are correlated, the causal association cannot be established here. Further research may explore the effects of sleep extension on GMV and how these volume differences associate with various aspects of cognition, particularly memory. It should be noted that this study only included healthy adults with sleep durations between 6–9 hours per night. Future studies would benefit from including adults with a greater variance in their sleep patterns to better understand the relationship between sleep and hippocampal volume, and its potential effects on memory performance.

Support
Defense Advanced Research Projects Agency Young Faculty Award: DARPA-12-12-11-YFA11-FP-029
0096 Future-Relevant Information is Enhanced After Sleep Despite Emotional Salience of Stimuli
Authors: Whitehurst L N , Sattari N , Mednick S C 
Published: May 2020

Abstract

Introduction
A substantial literature supports that sleep biases memory consolidation and retrieval for emotionally-salient stimuli. A smaller, yet growing, literature supports that information deemed relevant to future events may also be favored by sleep consolidation processes. However, it is unclear whether both emotion and predictability would act together to bias sleep-dependent memory formation. Here, we utilized a directed forgetting paradigm with negative and neutral word pairs to examine this open question.

Methods
Sixty young and healthy adults were exposed to word pair stimuli before a polysomnographically-recorded nap. Before the nap, participants were instructed to remember half of the word pairs presented for a later test, and for the other half of word pairs, participants were told to forget them as there would not be a test on them later. Additionally, during encoding, half of the subjects in the sample were exposed to negative valenced, high arousal word pairs while the other half were exposed to neutral, low arousal word pairs. After the nap, subjects were tested on all word pairs presented, regardless of previous instruction. This also included a set of novel word pairs to which participants had not been previously exposed.

Results
A series of 2x2 mixed measures ANOVAs revealed that individuals had better accuracy (p&lt;.001) and fewer misses (p&lt;.001) for the words they were told to remember compared to those they were instructed to forget. Additionally, participants had relatively few false alarms to novel stimuli, 7.14 times, on average (SD=6.10), out of a possible 50 word pairs. Importantly, contrary to predictions, post-nap performance was not dependent on the word pair valence (interaction p’s&gt;.70). No correlations between sleep stages and memory emerged.

Conclusion
These findings suggest that predictability of future events may be a relevant catalyst for sleep-related memory processing.

Support
This work was supported by an Office of Naval Research Young Investigators Award to Sara Mednick and a National Institutes of Mental Health Training grant to Lauren Whitehurst T32MH019391.
1006 Sleep Problems and Risk of Cancer Incidence and Mortality in the Cardiovascular Health Study (CHS)
Authors: Sillah A , Biggs M , Nieto J , Watson N , Gozal D , Peters U , Li C , Thornton T , Phipps A 
Published: May 2020

Abstract

Introduction
Even in the absence of a formal diagnosis, sleep problems (SP) are frequently indicative of an underlying sleep disorder, such as obstructive sleep apnea, which may be adversely associated with cancer risk and cancer outcomes.

Methods
We assessed the association of self-reported SP with incident cancer (N=4,997, excluding prevalent cancers) and cancer mortality (N=5849) among the participants of Cardiovascular Health Study (CHS), a population-based study of adults aged &gt;=65 years recruited from 4 US communities. Participants reported SP (daytime sleepiness, observed apnea and snoring) yearly from 1989-1994; these self-reported symptoms have been validated against objective sleep measures assessed within a subset of CHS participants (n= 1240) who received a home polysomnography as part of the Sleep Heart Health Study. Cancer incidence was ascertained through linkage with state cancer registries through 2005; cancer specific death was adjudicated through 2015. We used Cox proportional hazards regression to calculate hazard ratios (HR) and 95% confidence intervals (CI) for associations of baseline SP with subsequent cancer incidence and cancer mortality, adjusting for baseline sociodemographics, lifestyle factors, and medical history.

Results
The mean age (SD) of the study population was 73 (6) years, 56% were female, and 84% were white. The prevalence of SP was 17% for daytime sleepiness, 8% for observed apnea, and 24% for snoring; 63% reported none of the 3 SP. Overall, 1,130 first incident cancers and 1,014 cancer deaths were identified over median follow-up of 12 and 13 years, respectively. Compared to participants who reported no SP, the risk of incident cancer was inversely associated with daytime sleepiness (HR 0.86 [95% CI 0.70-1.04]), observed apnea (HR 0.74 [0.56-1.00]), and snoring (HR 0.80 [0.68-0.95]). Cancer mortality HR (95% CI) estimates were 1.00 (0.82-1.21) for daytime sleepiness, 0.77 (0.57-1.04) for observed apnea, and 0.88 (0.74, 1.04) for snoring.

Conclusion
Symptoms indicating SP reported at baseline were not associated with increased cancer incidence or cancer mortality. Ongoing analyses are focused on the impact of longitudinal SP (time dependent, cumulative average) to ensure an adequate latency period is incorporated into our analysis of the association between SP and cancer risk and mortality.

Support
NIHT32CA09488017
1014 Relationship Between Lung Function and Obstructive Sleep Apnea in Cystic Fibrosis
Authors: Shakkottai A , Nasr S Z , Hassan F , O’Brien L M , Chervin R D 
Published: May 2020

Abstract

Introduction
The frequency of obstructive sleep apnea (OSA) may be high among patients with cystic fibrosis (CF), a life-shortening, genetic respiratory disease that affects approximately 30,000 Americans. Yet, the potential relationship between OSA and lung function has not been thoroughly explored.

Methods
Single-center retrospective review of polysomnography (PSG) results from 2009-2017 in referred patients with CF and available pulmonary function data (PFTs) obtained at time of PSG and at 3, 6, 9, and 12-months prior.

Results
Mean ages were 11.1±3.9 (sd) and 37.1±14.1 years, among 18 children and 16 adults, respectively. Mean body mass index (BMI) was normal in both groups (62.5±26.6% in children; 25.1±6.4 kg/m2 in adults). Twenty-six subjects (76%) had OSA (apnea-hypopnea index &gt;1 in children, ≥5 in adults). Mean forced expiratory volume in 1 second percent predicted (FEV1 PPD) was higher among subjects with vs. without OSA at PSG and at each time-point in the year prior, independent of age and BMI at PSG (longitudinal mixed effects model, β=19.0, SE=8.1, p=0.028). While FEV1 PPD remained unchanged in the non-OSA group, FEV1 PPD at PSG was lower, in comparison to the year prior in subjects with OSA, with the greatest difference observed at 9-months prior to PSG (2-sample t-test, difference of -6.6% vs 0.6% in OSA vs. non-OSA groups respectively, p=0.078).

Conclusion
The PFTs, as daytime markers of CF lung disease severity, do not seem to reliably predict risk for OSA. In our sample, CF patients with vs. without OSA had better PFTs at baseline but they also showed a greater tendency for decline in PFTs over the year prior to OSA diagnosis. Larger sample size and longer duration of assessment may help, going forward, to assess any potential adverse impact of OSA on lung function decline.

Support
NIH Training Grant (T32NS007222, F32HL145915)
1020 Sleep and Glycemic Control in Adults With Long-Standing Type 1 Diabetes and Hypoglycemia Unawareness
Authors: Malone S K , Peleckis A J , Pack A I , Perez N , Yu G , Rickels M R , Goel N 
Published: May 2020

Abstract

Introduction
Nocturnal hypoglycemia is life threatening for individuals with type 1 diabetes (T1D) due to loss of hypoglycemia symptom recognition (hypoglycemia unawareness) and impaired glucose counterregulation. These individuals also show disturbed sleep, which may result from glycemic dysregulation. Whether use of a hybrid closed loop (HCL) insulin delivery system with integrated continuous glucose monitoring (CGM) designed for improving glycemic control, relates to better sleep across time in this population remains unknown.

Methods
Six adults (median age=58y,T1D duration=41y) participated in an 18-month ongoing clinical trial assessing the effectiveness of an HCL system. Sleep and glycemic control were measured concurrently using wrist actigraphs and CGM at baseline (1 week) and months 3 and 6 (3 weeks) following HCL initiation. BMI and hemoglobin A1c (HbA1c) were collected at all timepoints. Spearman’s correlations modeled associations between sleep, BMI, and glycemic control at each time point. Repeated ANOVAs modeled sleep and glycemic control changes from baseline to 3 months and to 6 months.

Results
Sleep and glycemic control indices showed significant associations at baseline and 3 months. More time-in-bed and later sleep offset related to higher HbA1c levels at baseline. Later sleep onset, midpoint and offset, and greater sleep efficiency associated with greater %time with hyperglycemia (glucose &gt;180 mg/dL) or hypoglycemia (glucose &lt;70 mg/dL) at baseline and 3 months. Longer sleep duration and greater sleep efficiency related to greater %time with hyperglycemia at 3 months. At 3 months, more wake after sleep onset associated with lower HbA1c levels and longer nocturnal awakenings and more sleep fragmentation associated with less glycemic variability. While both sleep and glycemic control improved from baseline to 3 and 6 months, these were not statistically significant.

Conclusion
Various dimensions of actigraphic sleep related to concurrently estimated glycemic indices indicative of poorer glycemic control and HbA1c across time in adults with long-standing T1D and hypoglycemia unawareness.

Support
This work was supported by NIH R01DK117488 (NG), R01DK091331 (MRR), and K99NR017416 (SKM).
1021 Effect of Dietary Nitrate Supplementation on Sleep in Chronic Obstructive Pulmonary Disease Patients
Authors: Wisor J P , Holmedahl N , West Saxvig I , Fjeldstad O , Weitzberg E , Gronli J , Engen H 
Published: May 2020

Abstract

Introduction
Chronic obstructive pulmonary disease (COPD) requires the use of accessory muscles to overcome inadequate ventilation. The activity of these voluntary muscles is compromised during sleep, resulting in insufficient ventilation, oxygen desaturation and disruption of sleep. Nitrate supplementation with dietary beetroot juice (DBJ) is known to increase the efficiency of oxygen utilization in non-COPD individuals; its therapeutic effect in COPD is uncertain.

Methods
In a repeated measured experiment involving 15 COPD patients, subjects consumed either 70 mL of beetroot juice containing nitrate (~6.2 mmol NO3-) or placebo (NO3--depleted juice) immediately before bedtime. Sleep states were defined based on F4-O2 electroencephalogram and masseter electromyogram. All subjects spent at least 6.2 hrs in bed; the data analysis was therefore restricted to the first 6 hrs in bed.

Results
Standard polysomnography indicated no changes in the amount of time spent in any sleep stages. Wake-to-N2 transitions were greater than two-fold more frequent after placebo (a total of 21 observed) than DBJ (9 observed), resulting in a significant main effect of treatment (F1,14=7.3, P=0.017). N2-to-wake transitions were nearly 3-fold more frequent after placebo (a total of 35 observed) than DBJ (12 observed), resulting in a significant main effect of treatment (F1,14=2.52, P=0.024). Direct wake-to-REMS transitions were observed four times after placebo and never after DBJ (F1,14=2.26, P=0.041). DBJ also resulted in sustained elevation of peripheral oxygen saturation (SpO2), measured by pulse oximetry, during episodes of wake after sleep onset (WASO). Two minutes into WASO after DBJ SpO2 was elevated by 1.09 + 0.31% relative to pre-WASO; two minutes into WASO after placebo SpO2 was elevated by 0.08 + 0.54% relative to pre-WASO (P=0.012).

Conclusion
Collectively, the reduced frequency of atypical transitions after DBJ are indicative of an improvement of sleep quality. DBJ is thus a potential adjunct therapy for disordered sleep in COPD.

Support
N/A
1033 Sleep and Patient-Reported Outcomes in Persons With Heart Failure With Preserved Ejection Fraction
Authors: Baniak L M , Atwood C W , Strollo P J , Forman D E , Chasens E R 
Published: May 2020

Abstract

Introduction
Sleep quality has a significant bearing on disease. A better understanding of sleep quality may help identify opportunities to improve patient-reported outcomes (PROs) in persons with heart failure with preserved ejection fraction (HFpEF). We aimed to explore the association between sleep and PROs in patients clinically diagnosed with HFpEF.

Methods
Cross-sectional study of 22 participants (71.2±7.2 years, 95% male, 86.4% white) with HFpEF, recruited from a heart failure (n=14) and sleep clinic (n=8). Sleep disordered breathing was measured objectively using one-night in-home obstructive sleep apnea (OSA) testing (ApneaLink). Actigraphy (7 days) was used to assess sleep duration, efficiency, and wake after sleep onset (WASO). Subjective sleep measures included the Insomnia Severity Index (ISI), Epworth Sleepiness scale (ESS), and Pittsburgh Sleep Quality Index (PSQI). PROs included functional status (Functional Outcomes Sleep Questionnaire [FOSQ]), depression (PROMIS Depression), fatigue (PROMIS Fatigue), and heart failure specific quality of life (Kansas City Cardiomyopathy Questionnaire [KCCQ]; overall summary score [KCCQ-os] and clinical summary score [KCCQ-cs]). The KCCQ-cs includes physical function and symptom scores to corresponds with NYHA Classification.

Results
Fifty percent of the participants had poor sleep quality (PSQI &gt;5) and 2 (9.1%) had ISI scores &gt;14. The majority (64%; n=14) had OSA; 10 currently on OSA therapy. Mean oxygen desaturation index (ODI) was 20.8±17.8. Mean actigraphy data indicated poor sleep (sleep duration 302±116 minutes, sleep efficiency 70.0±18.6%, and WASO 52±28 minutes) despite only 5 (22.7%) participants reporting excessive daytime sleepiness (ESS&gt;10). Greater insomnia symptom severity was associated with lower heart failure specific quality of life (KCCQ-os) and functional status, and, greater fatigue and depression (all p-values &lt;.05). FOSQ was negatively associated with PSQI (r= -.710, p= &lt;.001) and positively with sleep efficiency (r=.496, p=.026). The KCCQ-cs was positively associated with sleep duration (r=.496, p=.026) and negatively but not significantly associated with ODI (r= -.453, p=.07).

Conclusion
Impaired sleep and OSA are highly prevalent in patients with HFpEF and both are adversely associated with PROs. Goals to improve sleep is important for effective symptom management and for potential improvements in PROs.

Support
American Nurses Foundation, Preventative Cardiovascular Nurses Association