bluuebunny/crossref_metadata_2025_split huggingface dataset:
020 Sleep Quality Affects the Plasma Exosomal MicroRNA Expression Profile in Military Personnel with Traumatic Brain Injury
Authors: Mithani Sara , Leete Jacqueline , Pucci Josephine , Guedes Viivan , Kenney Kimbra , Gill Jessica , Werner J Kent 
Published: May 2021

Abstract

Introduction
Disordered sleep is a critical issue facing the US military due to its negative impact on maintaining force readiness, health, and well-being. Traumatic brain injury (TBI) is highly prevalent among military personnel and commonly co-occurs with disturbed sleep: up to 89% of military service members with TBI report poor sleep quality. Disturbed sleep is a hallmark of post-traumatic stress disorder (PTSD), which often coexists with TBI, with upward of 90% of patients with PTSD reporting some form of sleep disturbance. The pathophysiological mechanisms underlying sleep disturbances in TBI patients remain elusive. Exosomal microRNA (exomiRs), which are implicated in intracellular communication, may provide novel insight into molecular networks related to sleep disturbances in TBI patients.

Methods
ExomiR was extracted from plasma samples of 108 post-9/11 military personnel, and veterans with a history of mild TBI enrolled in a multicenter prospective longitudinal study. ExomiR profiling analysis was conducted using nCounter Human v3 miRNA Expression Panel with 798 microRNA probes. Sleep quality was assessed using the global score on the Pittsburgh Sleep Quality Index (PSQI), and symptoms of PTSD were measured with the PTSD Checklist for DSM-5 (PCL-5). Generalized linear models and Spearman’s correlations were constructed to analyze the relationship between levels of exomiR and global PSQI score.

Results
We found 17 exomiR that were significantly (P &lt; 0.05) associated with sleep quality and 11 exomiR significantly associated with PTSD symptoms. Two exomiR, has-miR-1268a and has-miR-139-5p, were significantly associated with both sleep quality and PTSD symptoms. The top three significant exomiR associated with sleep quality were hsa-miR-1250-5p (r = 0.2295, p = 0.0171), hsa-miR-3615(r = 0.2207, p = 0.0229), and hsa-miR-122-5p(r = 0.2069, p = 0.0132).

Conclusion
Overall, these findings suggest that analysis of exosomal miRNA expression may provide novel insights into the underlying pathobiology of sleep quality in military personnel with mild TBI, independent of PTSD symptoms. Further research is needed to understand the biological underpinnings of poor sleep quality in individuals with TBI and to determine causal links.

Support (if any)
Intramural Research Program at the NINR, Department of Defense, Chronic Effects of Neurotrauma Consortium (CENC) Award W81XWH-13-2-0095 and Department of Veterans Affairs CENC Award I01 CX001135.
030 The sleeping brain switches from frontal-subcortical working memory to hippocampal episodic memory processing during NREM sleep
Authors: Chen Pin-Chun , Niknazar Hamid , Whitehurst Lauren , Mednick Sara 
Published: May 2021

Abstract

Introduction
Working memory (WM) and long-term memory (LTM) serve separate functions. The former is a control process for planning and carrying out behavior that is information-independent, whereas the latter is an information-dependent vast store of knowledge and record of prior events. Both domains benefit from sleep. The overall picture emerging is that NREM sleep supports improvement in WM via strengthening of prefrontal-subcortical control networks, as well as the formation of LTM via thalamocortical sigma activity. Prior research suggests a potential antagonistic relation between the two neural processes during NREM sleep. Yet, how the sleeping brain performs both of these feats remain unknown.

Methods
Thirty-eight adults (age = 20.85 ± 2.97 years, 19 Females) were enrolled. We used a double-blind, placebo-controlled, within-subject design to investigate the role of autonomic and central activity on sleep-dependent LTM and WM improvement. We administered zolpidem, a GABA-A agonist, during PSG-recorded night and tested overnight LTM (word-paired-associates) and WM memory (operation-span) changes. We used effective connectivity to explore the causal information flow between central and autonomic sleep features and tested if the magnitude of this influence predicts the trade-off between overnight LTM and WM improvement.

Results
The intervention selectively suppressed vagal cardiac autonomic activity and increased sleep spindle sigma activity (12-15Hz) during non-rapid eye movement sleep (NREM). Behaviorally, the changes in sigma were associated with increased LTM and decreased WM improvement. Effective connectivity demonstrated a significantly decreased communication from autonomic to central regions with zolpidem compared with placebo, and this decrease in causal influence predicted the behavioral trade-off between LTM and WM.

Conclusion
Our results suggest evidence for a sleep switch that toggles between spindle-dependent and vagal-dependent processes during NREM. This switch supports enhancement of both LTM and WM during sleep via separate mechanisms. These results are consistent with prior studies reporting an antagonistic relation between neuromodulators governing the two systems, thalamocortical GABA and noradrenergic (NE) activity, respectively.
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033 The effect of sleep disturbance on cognition in late-life depression
Authors: Ricciardiello Andrea , Naismith Sharon , D’Rozario Angela , Kumfor Fiona , Wassing Rick 
Published: May 2021

Abstract

Introduction
Late-life depression is the most common psychiatric disorder in older adults and is associated with cognitive deficits, however, the role of sleep disturbance in cognitive deficits is poorly defined. In the current study we aimed to examine sleep macro and micro-architecture differences between those with late-life depression and controls. Secondly, we sought to determine how sleep changes relate to clinical memory and executive function measures in those with late-life depression and controls.

Methods
Using prior clinical data, this retrospective study assessed adults &gt;50 years who had completed an overnight PSG study and comprehensive psychiatric, neuropsychological, and medical assessment. Memory performance was measured using the Weschler Memory Scale logical Memory 1 and 2 components, Rey Auditory Verbal Learning Test (Senior) 30-minute recall and Rey Complex Figure 3-minute recall. Executive function was defined by z scores from Trail Making Test, D-KEFS Stroop Test and Controlled Oral Word Association Test. The sample comprised of 71 depressed participants, defined by a Geriatric Depression Scale score ≥6, and 101 non-depressed participants (GDS &lt;6 and no lifetime history of depression using DSM-IV criteria).

Results
Contrary to our hypothesis no significant macroarchitectural differences were observed between the groups. Less time spent in slow-wave sleep (SWS) was associated with worse delayed memory recall scores in the depression group (z=.342, p=0.008) although this was not seen in the control group. SWS and slow wave activity (SWA) were not related to measures of executive function performance. Depressed participants demonstrated a reduced level of sleep spindles (Dep= 159 ±142.8, con= 213±163, p=.03) although there were no associations with memory outcomes.

Conclusion
Compared to younger adults with depression, macroarchitectural differences in those with late-life depression are not as pronounced, due to a reduction of SWS and SWA power as a function of ageing. The efficiency of SWS hippocampal dependent memory processes in depression may be reduced, therefore, more time spent in SWS is related to better memory performance. This study assessed the density of sleep spindles but not spindle and slow wave oscillation coupling which may be more important for hippocampal dependent memory.
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051 Is Working Memory Associated with Ag- related Emotional Memory Bias?
Authors: Sattari Negin , Whitehurst Lauren , Mednick Sara 
Published: May 2021

Abstract

Introduction
Aging is accompanied by deterioration in both working memory (WM) and long-term memory (LTM), though the reason is not well understood. Sleep may play a role in young adults, but the findings in older adults are not as clear. In addition, older adults show better memory for positive memories, whereas youngers tend to hold on to negative memories. The prefrontal cortex has been implicated in this emotional memory bias. The current study investigated the role of working memory (a prefrontal task) on emotional memory consolidation across sleep and wake in young and older adults.

Methods
In the morning, 93 younger (18–39) and 121 older (60–85) adults took a WM task and encoded neutral or negative word pairs, and gave valence and arousal ratings for each pair. After a wake or polysomnography-recorded sleep condition, memory for the word pairs was tested plus valence and arousal ratings.

Results
Youngers had better overall memory (p&lt;.001), with older adults showing better memory for neutral compared to negative word pairs (p=.04), as well as increased positivity (p=.02), which was correlated with LTM performance (p=.009). In contrast, youngers performed better on the negative word pairs (p=.01), but no change in ratings and no association between emotional reactivity and LTM. Further, WM was positively related to memory in youngers (r=.38, p=.02), but not in older adults. Lastly, no role for sleep likely due to the lack of an immediate test.

Conclusion
we found that the positivity bias in aging in both memory and valence, with increasing positivity associated with better memory. We found a robust relation between WM and LTM in youngers but not older adults. Our findings are consistent with the socioemotional-selectivity theory that posits that aging is associated with a relative suppression of negative information while WM may play a role.
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060 Challenging the current assessment criteria for scoring central sleep apnea at altitude
Authors: Bird Jordan , Chan Jason , Rimke Alexander , Kalker Anne , Chan Garrick , Brutsaert Tom , Sherpa Mingma , Day Trevor 
Published: May 2021

Abstract

Introduction
Sleep disordered breathing comes in two forms: obstructive and central sleep apnea (SA). Obstructive sleep apnea (OSA) is caused by upper airway collapse during sleep, and is associated with increases in morbidity and mortality. Conversely, central sleep apnea (CSA) results from increases in respiratory chemosensitivity to blood gas challenges in the context of high-altitude ascent. CSA increases in severity and apneas shorten in duration with higher ascent and/or time spent at altitude. Although both types of SA are characterized by intermittent periods of apnea and hyperventilation, the underlying mechanisms and phenotypes between OSA and CSA are different. A universal scoring system for the two types of context-dependent SA may lead to errors in quantification. The American Association of Sleep Medicine (AASM) developed assessment criteria for SA, which are universally-utilized for all types of SA to quantify an apnea-hypopnea index (AHI; events/hour), where apneas are scored as cessation of breathing ≥10-sec. We aimed to assess the effect of reducing the apnea-detection threshold (ADT) to &lt;10-sec to quantitatively assess the extent that a shorter ADT affects the scoring of AHI in the context of high-altitude ascent, where CSA is universal.

Methods
We assessed CSA using portable polysomnography (ApneaLink, ResMed) during ascent to 5160m in the Nepal Himalaya over 10 days in 15 healthy participants. Files were archived digitally for later analysis using automated scoring software (ApneaLink Reporting Software, ResMed). We quantified and compared AHI using AASM criteria (i.e., 10-sec ADT) and a shorter 5-sec ADT.

Results
AHI was 3.9±4.1 events/hour at 1045m prior to ascent, with AHI increasing to 37.5±32.8 events/hour (P&lt;0.0001) at 5160m after 10 days of incremental ascent using AASM criteria (i.e., 10-sec ADT). When the ADT was reduced to 5-sec at 5160m, AHI was increased to 61.6±38.1 (+61%; P=0.0002).

Conclusion
This preliminary report suggests that the AASM criterion for scoring apneas, which is broadly applied to OSA at low altitude, may underestimate the assessment and quantification of CSA with ascent to and prolonged stays at high altitude. Development of distinct assessment criteria for OSA and CSA may be warranted.

Support (if any)
Natural Science sand Engineering Research Council of Canada
061 Sleep Hygiene as an Intervention to Lower Blood Pressure
Authors: Vazquez Michael , Yang Huan , Dang Rammy , Haack Monika , Mullington Janet 
Published: May 2021

Abstract

Introduction
Insufficient sleep has been shown to increase the risk of a person developing hypertension. Impaired baroreflex sensitivity (BRS) is one of the known underlying mechanisms involved that is responsible for increasing blood pressure (BP). This project investigates the relationship between sleep, BRS, and BP during Valsalva’s Maneuver (VM).

Methods
Fifty participants (59.8 ± 1.5 years; 31 women) completed 3 overnight in-hospital stays. The first stay (S1) was a baseline control; the second stay (S2) followed a 4-week wait-list control condition; the third stay (S3) followed an 8-week randomly assigned intervention that used sleep hygiene approaches and scheduling to either A) stabilize sleep timing, or B) stabilize and extend the bed period. The study is still ongoing, and we are blind to whether participants were randomized to arm A or B of the study. A linear regression model analyzing the R-R Interval (RRI) and corresponding systolic BP was used to calculate the BRS function and the maximum change in SBP (BPMax) during Early Phase II (EPII) of VM.

Results
There was an increasing BRS trend across the three stays during EPII (p=.051). There was no significant increase between S1 and S2 (p=.876), but BRS significantly increased following 8 weeks of intervention at S3 compared to S1 (p=0.033) and S2 (p=0.037). There was also a significant decrease in BPMax across the three stays during EPII (p&lt;.001). There was no significant decrease in EPII BPMax between S1 and S2 (p=.325), but BPMax significantly decreased in S3 compared to S1 (p&lt;0.001) and S2 (p=0.002).

Conclusion
While we are still blind to condition, both conditions are considered active as they both involve stabilizing the sleep period using sleep hygiene. These preliminary data suggest that stabilization of sleep timing and possibly duration, has a positive impact on BP regulation.

Support (if any)
NIH (R01HL125379 to Dr. Janet Mullington), Harvard Catalyst, Harvard Clinical and Translational Science Center (UL1TR001102).
062 Sex Differences in Slow Wave Sleep Following Evening Binge Alcohol Consumption
Authors: Greenlund Ian , Bigalke Jeremy , Tikkanen Anne , Nicevski Jennifer , Smoot Carl , Carter Jason 
Published: May 2021

Abstract

Introduction
Binge alcohol consumption alters normal sleep architecture, often via increased slow wave sleep (SWS) and decreased rapid eye movement (REM) sleep. Women may be more susceptible to the sedative effects of alcohol during blood alcohol content (BAC) decrease as they report higher subjective sleepiness scores prior to bedtime. The purpose of the present study was to examine changes in SWS between men and women following binge alcohol consumption and determine the relation between BAC change at lights out and subsequent sleep architecture.

Methods
Twenty-three participants (11 men, 12 women) between the ages of 21–45 years were tested twice, once after evening binge alcohol consumption and once after fluid control (randomized, cross-over design). The alcohol dose was based on body weight and sex (1g/kg in men, 0.85g/kg in women) and served as a 4–5 drink equivalent consumed over two hours. Breath alcohol content (BrAC) was monitored in 15-minute increments from first drink consumption to lights out. Overnight polysomnography (PSG) was recorded in each individual and scored by a board-certified sleep physician. Statistical analysis consisted of repeated measures ANOVA and Pearson correlation (p&gt;0.05).

Results
Age (24±4 vs. 26±6 years) and BMI (27±4 vs. 27±4 kg/m2) were similar between men and women. Peak BrAC (0.10±0.02% vs. 0.10±0.02%) and percent change (-19±11% vs. -19±11%) in BrAC from peak to lights out were also similar between the sexes. Peak BrAC was significantly correlated to the percentage of SWS in women (r=-0.71; p=0.01), but not men (r=-0.25; p=0.45). Similarly, the percent change in BrAC from peak to lights out was significantly correlated to the percentage of SWS in women (r=-0.66; p=0.02), but not men (r=-0.40; p=0.22). The SWS and REM latencies were not associated with either peak or lights out BrAC in both men and women.

Conclusion
Peak BrAC, and the rate of BrAC clearance prior to lights out, appear to impact SWS differently in men and women. Specifically, women appear to have more SWS in response to high BrAC than their male counterparts, suggesting a stronger depressor impact with regards to SWS in women.

Support (if any)
National Institutes of Health (AA-024892; U54GM115371; P20GM103474).
068 Morning Cardiovascular Function in Chronic Cannabis Users and Healthy Controls
Authors: Robinson LaTroy , Thosar Saurabh , Stewart Alicia , Clemons Noal , Chess Daniel , Herzig Maya , Gagnon Jacqueline , Ordaz-Johnson Omar , Emens Jonathan , Shea Steven , Bowles Nicole 
Published: May 2021

Abstract

Introduction
In the US cannabis is recreationally legal in 15 states and medically legal in 34 states. Preclinical studies suggest beneficial effects of cannabis on the cardiovascular system (e.g., vasorelaxation). Yet, acute cases of hospitalization after cannabis consumption indicate potential adverse cardiac effects. Vascular endothelial function is a marker of cardiovascular disease and is measured as a change in resting brachial artery diameter (flow-mediated dilation, FMD) during reactive hyperemia. Both resting diameter (positively) and FMD response (negatively) are associated with cardiovascular risk. Resting diameter likely depends on long-term structural changes, and FMD response mostly depends on nitric oxide. Reactive hyperemia is more complex and depends on numerous variables, including adenosine and prostaglandins. FMD is attenuated in the morning when the frequency of adverse cardiovascular events peaks. To begin to understand the effects of chronic cannabis use on the cardiovascular system, in this pilot study, we compared morning measurements of vascular endothelial function, blood pressure, and heart rate between chronic cannabis users and controls while controlling for prior nighttime sleep opportunities.

Methods
Participants, cannabis non-users (n=5) and users (n=4), 44% female, age 25.4 ± 3.6 years - no demographic differences between groups, kept a consistent 2-week sleep schedule at home followed by an 8h sleep opportunity at their habitual time in the laboratory. Upon-wakening, we measured resting blood pressure, heart rate, baseline diameter, hyperemic response, and FMD. Statistical differences between groups were calculated using a two-tailed t-test.

Results
Systolic and diastolic blood pressures (p=0.13 and 0.26 respectively), heart rate (p=0.97), and FMD response (p=0.99) did not differ between groups. However, chronic cannabis users had a significantly higher baseline brachial artery diameter (mean difference: 1.04 mm ± 0.26, p=0.005), and lower hyperemic response (mean difference: -7944 iu/s ± 2538, p=0.02) compared to non-users.

Conclusion
These preliminary findings suggest that chronic cannabis consumption may be associated with adverse structural and functional changes in the vasculature of otherwise healthy young adults. Based on these initial observations, cannabis may act on the cardiovascular system via non-nitric oxide mechanisms. However, it is necessary to increase our sample size to test the robustness of these findings.

Support (if any)
KL2TR002370, AASM
074 Basal Forebrain GABAergic Neurons Promote Arousal by Disinhibiting the Orexin Neurons via Local GABAergic Interneurons
Authors: Cristofolini Michela , De Luca Roberto , Venner Anne , Ferrari Loris , Grace Kevin , Fuller Patrick , Arrigoni Elda 
Published: May 2021

Abstract

Introduction
Optogenetic and chemogenetic studies have shown that activation of basal forebrain (BF) GABAergic neurons rapidly wakes up mice from non-REM (NREM) sleep. These wake-promoting responses have been attributed to BF GABAergic neurons projecting to the cerebral cortex and more specifically to the inhibition of cortical fast-spiking interneurons. Tracing studies have however found that BF GABAergic neurons also densely innervate the lateral hypothalamus (LH) perifornical area, although the role of this pathway in behavioral state control remains mostly unexplored.

Methods
We conducted in vivo and in vitro optogenetic studies. We selectively expressed channelrhodopsin-2 (ChR2) in BF GABAergic neurons by injecting a cre-dependent viral vector encoding for ChR2 into the BF of VGAT-cre mice. We photostimulated the BF GABAergic input to the LH with optical fibers placed into the LH of EEG instrumented mice. For in vitro recordings we expressed ChR2 in BF GABAergic neurons and we fluorescently labeled orexin or LH GABAergic neurons. We recorded in brain slices from identified orexin neurons or GABA neurons while photostimulating the BF GABAergic input.

Results
Optogenetic stimulation of the BF GABAergic fibers in the LH produced rapid arousals from NREM sleep. The same stimulation however did not wake up the mice if they were in REM sleep. We conducted additional studies in brain slices to identify the postsynaptic neurons in the LH targeted by the BF GABAergic input. We found that while optogenetic stimulation of the BF GABAergic input did not produce opto-evoked synaptic responses in the orexin neurons, it produced short-latency opto-evoked inhibitory postsynaptic currents (IPSCs) in LH GABAergic neurons. These opto-evoked IPSCs were GABAA receptor-mediated and were maintained in tetrodotoxin (TTX) indicating monosynaptic connectivity. We have previously found that orexin neurons are inhibited by local LH GABAergic neurons. Our hypothesis is that these local GABAergic interneurons are the target of the BF GABAergic arousal input.

Conclusion
BF GABAergic neurons drive arousal through projections to the LH. We propose that this arousal response is due to the inhibition of local GABAergic interneurons which in turn disinhibit the LH wake-promoting neurons including the orexin neurons.

Support (if any)
NS091126 and HL149630