bluuebunny/crossref_metadata_2025_split huggingface dataset:
014 Diurnal changes in perineuronal nets and parvalbumin neurons in the rat medial prefrontal cortex
Authors: Sorg Barbara , Harkness John , Gonzalez Angela , Bushana Priyanka , Jorgensen Emily , Hegarty Deborah , Nardo Ariel Di , Prochiantz Alain , Wisor Jonathan , Aicher Sue , Brown Travis 
Published: May 2021

Abstract

Introduction
Perineuronal nets (PNNs) surrounding fast-spiking, parvalbumin (PV) interneurons provide excitatory:inhibitory balance within cortical circuits. This balance is impaired in several disorders that are also associated with altered diurnal rhythms, yet few studies examined diurnal rhythms of PNNs or PV cells.

Methods
We measured the intensity and number of PV cells and PNNs labeled with Wisteria floribunda agglutinin (WFA) and also the oxidative stress marker 8-oxo-deoxyguanosine (8-oxo-dG) in rat prelimbic medial prefrontal cortex (mPFC) at Zeitgeber times (ZT) ZT0, 6, 12, and 18. To examine changes in inhibitory and excitatory inputs to PV cells, we measured GAD 65/67 and vGLUT1 puncta apposed to PV cells with and without PNNs. Whole-cell slice recordings in fast-spiking (PV) cells with PNNs was conducted to determine the ratio of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor:N-methyl-D-aspartate receptor (AMPA:NMDA) at ZT18 vs. ZT6. Finally, the number of PV cells and PV/PNN cells containing orthodenticle homeobox 2 (OTX2), which maintains PNNs, was also assessed.

Results
Relative to ZT0, the intensities of PNN and PV labeling were increased in the dark compared with the light phase. The intensity of 8-oxo-dG was decreased from ZT0 at all times. There were more excitatory puncta on PV cells with PNNs at ZT18 vs. ZT6, but no changes in PV cells without PNNs and no changes in inhibitory puncta. There was an increased AMPA:NMDA ratio at ZT18 vs. ZT6. The number of PV cells and PV/PNN cells containing OTX2 showed a strong trend toward an increase from ZT6 to ZT18, with no differences in non-PV-containing cells.

Conclusion
Diurnal fluctuations in PNNs and PV cells alter cortical excitatory:inhibitory balance. Detailed understanding of how these fluctuations are regulated should provide new insights into treatments for diseases impacted by disturbances in sleep and circadian rhythms. Ongoing studies are examining diurnal fluctuations in downstream signaling after PNN removal.

Support (if any)
Washington State University Alcohol and Drug Abuse Research Program, NIH GM134789 (JHH); NIH DA033404 (BAS), DA040965 (BAS, TEB, SAA); NIH NS078498 (JPW); NIH P30 NS061800 (SAA); and Agence Nationale de la Recherche ANR-18-CE16-0013-01 (AP and AAD).
016 Associations between Circadian Melatonin and Temperature Amplitudes during Constant Routine
Authors: Rodheim Katrina , Jung Christoper , Wright Kenneth 
Published: May 2021

Abstract

Introduction
Circadian amplitude measures the strength or robustness of a rhythm and changes in amplitude may have implications for health. Large individual differences in melatonin amplitude are recognized. Here we aimed to determine the strength of relationships between melatonin and the core body (CBT) and distal-proximal skin temperature gradient (DPG) amplitudes during a constant routine protocol. Additionally, we determined the best fitting harmonic model for the DPG circadian rhythm.

Methods
17 young healthy adults [13 males (22.3±3.9yr;mean±SD)] completed a 28-hr constant routine protocol after maintaining 8h habitual sleep schedules for one week at home. Endogenous circadian amplitudes of melatonin and CBT were fit with standard three- and dual-harmonic linear regression models, respectively. The DPG amplitude was analyzed with both dual and three-harmonic regression models to determine which model produced the best fit.

Results
The DPG was best fit by a three-harmonic regression model with significantly lower standard deviation and higher signal-to-noise ratio compared to the 2-harmonic model (both p&lt;0.05) as well as by visualization of the fitted curves. Melatonin, CBT and DPG amplitudes were not found to be associated with each other during constant routine (all r&lt;0.37; all p&gt;0.10).

Conclusion
While it is common for melatonin and body temperature circadian phase estimates to be used interchangeably, non-significant findings for associations between circadian amplitudes of melatonin, CBT and DPG indicate that these markers may not provide similar information about circadian amplitude. Further, research is needed to explore possible associations between individual differences in melatonin, CBT and DPG amplitudes with other physiological and behavioral outcomes to determine which measure(s) of circadian amplitude may be functionally relevant.

Support (if any)
NIH R01 HL081761
026 Vasoactive Intestinal Polypeptide Directly Excites Neurons of the Subparaventricular Zone
Authors: Raffin Francesca , Cristofolini Michela , Biella Gerardo Rosario , Fuller Patrick , Arrigoni Elda 
Published: May 2021

Abstract

Introduction
The suprachiasmatic nucleus (SCN) is responsible for generating the circadian rhythmicity in mammals. The ventral region or core of the SCN contains neurons that express the neuropeptide vasoactive intestinal polypeptide (VIP). VIP signaling is central for coherency and synchrony of SCN activity. VIP-expressing neurons in the SCN densely project to the ventral subregions of the subparaventricular zone (vSPZ). We studied the effects of VIP on vSPZ neurons in brain slices of mice with a combined calcium imaging and whole-cell patch-clamp recording techniques. We used calcium imaging to assess the effects of VIP on vSPZ neurons as a population and we acquired patch-clamp recordings to explore the effects of VIP on the electrical properties and the synaptic inputs to vSPZ neurons.

Methods
We expressed GCamp6 in vSPZ neurons by stereotaxically injecting AAV10-DIO-Ef1a-GCamp6 into the vSPZ of vGAT-IRES-Cre mice. Brain slices were prepared two weeks later and images were captured using a standard GFP filter set. We performed whole-cell recordings of the vSPZ neurons of wild-type mice. We assessed the effects of VIP on the membrane potential and the on excitatory synaptic input in vSPZ neurons.

Results
Using GCamp6-based in vitro calcium imaging we found that VIP excites 17% of vSPZ neurons and this effect was maintained in the presence of tetrodotoxin (TTX) and synaptic blockers for AMPA/NMDA and GABAA transmissions suggesting a direct effect of VIP on vSPZ neurons. We confirmed this result with patch-clamp recordings. We found that 29% of vSPZ neurons were excited by VIP. VIP produced a membrane depolarization of vSPZ neurons in the presence of antagonists for AMPA/NMDA and GABAA receptors. In addition, we found that in a small percentage of vSPZ neurons VIP increased the frequency of the glutamatergic excitatory postsynaptic currents, suggesting an additional excitatory mechanism.

Conclusion
Our results demonstrate that exogenous VIP directly excites the vSPZ neurons producing an increase in intracellular calcium and membrane depolarization. In addition, VIP increases glutamatergic afferent inputs to vSPZ neurons indicating an additional synergistic excitation. We conclude that when VIP is released from the SCN VIP fibers it can activate vSPZ neurons.

Support (if any)
NS091126 and HL149630.
065 Sleep and Gray Matter Volume: The Role of Physiological Arousal
Authors: Curtis Ashley , Nair Neetu , McGovney Kevin , Craggs Jason , McCrae Christina S 
Published: May 2021

Abstract

Introduction
Insomnia is associated with increased arousal. Brain regions involved in chronic insomnia are diffuse and the potential interactive role of physiological arousal in the association between insomnia symptoms and neural regions is unknown. This study examined whether physiological arousal (heart rate variability, HRV) moderated the association between sleep and gray matter (GM) volume of frontal [dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC)] and temporal [right/left (R/L) hippocampus] regions in adults with comorbid chronic widespread pain and insomnia (CWPI).

Methods
Forty-seven adults with CWPI (Mage=46.00, SD=13.88, 89% women) completed two weeks of diaries measuring sleep onset latency (SOL), wake time after sleep onset (WASO) and total sleep time (TST). Resting HRV was assessed via Holter monitoring (5 minutes). Root mean squared standard deviation of successive normal-to-normal heartbeats (RMSDNN) was computed. T1-weighted magnetic resonance images were obtained, segmented and co-registered to MNI space. GM volumes (DLPFC, ACC, R/L hippocampus) were estimated (FSL). Multiple regressions examined whether SOL, WASO or TST were independently associated with or interacted with RMSDNN in their associations with GM volumes, controlling for age.

Results
SOL interacted with RMSDNN in its association with ACC (B=-4.60, SE=2.06, p=.03, R-squared=.06). Longer SOL was associated with lower ACC volume at highest RMSDNN (lowest arousal; B=-103.54, SE=42.82, p=.02), not average/lowest RMSDNN (highest arousal, ps&gt;.05). TST interacted with RMSDNN in its association with R hippocampus (B=-.22, SE=.10, p=.04, R-squared=.07). Shorter TST was associated with lower R hippocampal volume at lowest RMSDNN (highest arousal; B=7.39, SE=2.29, p=.002) and average RMSDNN (B=4.18, SE=1.50, p=.008), not highest RMSDNN (lowest arousal; p=.64). There was a trending association between WASO and R hippocampus volume (B=-13.67, SE=7.28, p=.07).

Conclusion
In patients with CWPI and highest physiological arousal, achieving longer TST may be important in terms of associations with right hippocampus volume. Improving (reducing) SOL may only impact ACC volume in those with lower physiological arousal. Trends of association between longer WASO and reduced right hippocampus volume warrant follow-up in larger samples. Findings highlight the interactive role of physiological arousal (HRV) in the neural mechanisms associated with sleep in CWPI.

Support (if any)
National Institute of Nursing Research (NR017168; Clinical trial: NCT02001077; PI: McCrae).
071 Actigraphy-Derived Sleep Metrics are Not Related to Central Hemodynamics or Arterial Stiffness in Healthy Adults
Authors: Culver Meral , Montoye Alexander , McMillan Nathan , Cross Brett , Riemann Bryan , Flatt Andrew , Grosicki Gregory 
Published: May 2021

Abstract

Introduction
Insufficient sleep is an emerging risk factor for cardiovascular disease. To evaluate the hypothesis that decrements in vascular function, due to poor sleep, may serve as a mechanistic link between sleep and cardiovascular disease, we explored relationships of actigraphy-derived sleep metrics with central hemodynamics and arterial stiffness in healthy young adults.

Methods
A total of 23 women and 27 men (23±5 yrs), free of known cardiovascular, metabolic, and renal disease, and not using sleep medication, participated in this study. ActiGraph GT9X wrist-worn accelerometers were used to measure sleep efficiency, total sleep time, wake after sleep onset, and number of awakenings over a seven-day period. Vascular health measures including central pressures and augmentation index at a heart rate of 75 beats per minute (AIx@75) were quantified via pulse wave analysis, and carotid femoral pulse wave velocity (cf-PWV) was assessed using applanation tonometry. Gender-specific z-scores for each of the sleep metrics were summed to assign each participant a “sleep score” (higher score = better sleep), and relationships between sleep scores and vascular health measures were explored using Pearson correlation coefficients.

Results
In men, sleep score (range: -4.92 to 9.10) was not related (P&gt;0.05) to central systolic (114±15 mmHg, r=-0.26) or diastolic (72±7 mmHg, r=-0.21) pressures. Similarly, in women, sleep score (range: -5.02 to 5.34) was not related (P&gt;0.05) to central systolic (103±11 mmHg, r=-0.09) or diastolic (72±10 mmHg, r=-0.21) pressures. Sleep score also failed to predict (P&gt;0.05) indices of arterial stiffness, AIx@75 (men = 3.1±12.3, r=0.04; women = 5.2±9.5, r=-0.25) and cf-PWV (men = 6.2±0.8 m/s, r=-0.12; women = 5.7±0.5 m/s, r=-0.10).

Conclusion
In young healthy individuals, actigraphy-derived sleep characteristics were not related to central hemodynamics or non-invasive indices of arterial stiffness. Previously documented relationships between sleep and vascular function may be limited to less healthy populations, poorer sleepers, or only for certain sleep metrics.
Support (if any):
079 Sleep Quality Prediction During the Menstrual Cycle based on Daily Sleep Diary Reports
Authors: Sattari Negin , Mehrabadi Milad Asgari , Aqajari Seyed Amir Hossein , Zhang Jing , Simon Katharine , Alzueta Elisabet , Dulai Teji , de Zambotti Massimiliano , Baker Fiona , Rahmani Amir , Mednick Sara 
Published: May 2021

Abstract

Introduction
Estrogen and progesterone cycle through two main phases across a typical 28-day menstrual cycle: a perimense phase, when both hormones are low; and a non-perimenses phase, when both hormones are high. These fluctuations affect a range of daily activities, including sleep, mood, and physical feelings such as bloating. Here we aimed to predict differences in sleep quality during the perimenses and non-perimenses phases based on their daily reports.

Methods
We analyzed over 1200 nights of sleep diaries collected from 20 (18–35 yo) women across two months. We categorized days into perimenses when a night fell within 4 days prior to and 6 days after their self-reported first day of menses, and non-perimenses when a night fell 4 days before and 4 days after their reported positive ovulation. A random forest model was utilized in three different cases: 1) including the data associated with perimenses days 2) non-perimenses days and 3) considering the full data.

Results
Using the full data set we predicted subjects’ sleep quality with 70% accuracy. For the perimenses group our model predicted sleep quality with more than 80% accuracy while the prediction accuracy for non-perimenses was as high as 75%. Further, we observed that for perimenses women, overall alertness and alcohol consumption were among the most important features extracted from daily reports, while for the non-perimenses group, subjective happiness ratings and physical feelings of bloating were predicting sleep quality. Together our result showed that sleep quality reported on a daily basis can be predicted more accurately based on the phase of the menstrual cycle, where different daily features may play differential roles.

Conclusion
Sex hormones’ fluctuations across a month of menstrual cycle can affect a range of women’s daily functioning. We showed that the phase in menstrual cycle can influence women’s daily reports of their routines. Furthermore the fluctuations in these reports can be used to predict females’ sleep quality with higher accuracy compared to when the phase of menstrual cycle is not accounted for. Our results show the importance of considering the role of menstrual cycle when investigating sleep quality.
Support (if any):
091 The Feasibility of At-home Sleep Extension in Adolescents and Young adults: A Meta-Analysis and Systematic Review
Authors: Niu Xinran , Zhou Shijing , Casement Melynda 
Published: May 2021

Abstract

Introduction
Insufficient sleep duration has negative consequences for health and performance and is alarmingly common in adolescents and young adults. The primary aim of the meta-analysis and systematic review was to assess whether at-home sleep extension is a feasible means to improve sleep duration and daytime sleepiness without negative consequences for sleep quality or efficiency in adolescents and young adults. An additional aim of the review was to provide a qualitative summary of the health and performance outcomes associated with at-home sleep extension.

Methods
Peer-reviewed journal articles and doctoral dissertations available in English were searched and screened. Eligible studies had at least five consecutive days of at-home sleep extension, measurement of sleep duration during baseline/habitual sleep and extension of sleep opportunity, and participants 13–30 years of age. Information on primary sleep outcome (i.e., sleep duration), available secondary sleep outcomes (i.e., sleep opportunity, sleep efficiency, sleep quality, daytime sleepiness), and health and performance outcomes were extracted for quantitative synthesis and qualitative review.

Results
Of the 2254 articles assessed for eligibility, 17 studies (seven in adolescents and ten in young adults) met the eligibility criteria for this review. The average number of days of sleep manipulation was 14.29 (range: 5 to 49 nights). At-home extension of sleep opportunity reliably increased objective (ES = 0.97) and subjective sleep duration (ES = 2.19) and sleep quality (ES = 0.24), and decreased daytime sleepiness (ES = -0.39), when compared to unmanipulated sleep opportunity. Sleep extension was also found to have additional health (e.g., lower psychological stress) and performance benefits (e.g., better athletic performance) across ages and populations. A potential upward publication bias was found based on the distribution of within-subject effect sizes of actigraphic sleep duration.

Conclusion
The review indicates that at-home sleep extension is feasible in adolescents and young adults to improve sleep duration and daytime sleepiness, and maintain or improve sleep quality. However, the degree of improvement in sleep duration, sleep quality, and daytime sleepiness varied by study population and sleep extension method. Future research should investigate how variations in population and methods of sleep extension impact health and performance outcomes.
Support (if any):
112 Chronic sleep restriction disrupts slow-wave sleep homeostatic regulation and damages monoaminergic structures in the rat brain
Authors: Guzeev Mikhail , Kurmazov Nikita , Simonova Valentina , Belan Daria , Lapshina Ksenia , Pazi Maria , Ekimova Irina , Pastukhov Yuri 
Published: May 2021

Abstract

Introduction
The neurophysiological mechanisms underlying long-term neurological and cognitive disorders associated with chronic sleep restriction (CSR) are not fully understood. Here we evaluated how the sleep-wake cycle changes during and after a period of sleep restriction in rats, and whether CSR results in neurodegeneration in monoaminergic brain structures.

Methods
For CSR, 7-8-month-old Wistar rats underwent cycles of 3 h of sleep deprivation (SD) and 1 h of sleep opportunity (SO) continuously for 5 days on the orbital shaker. Telemetric sleep recordings were made before, during, and after CSR. Neurodegeneration in brain monoaminergic structures was assessed immunohistochemically.

Results
During SD, wakefulness comprised 85% of the total registration time; the remaining time was represented by drowsiness with low EEG delta power. Rapid eye movement sleep (REMS) was absent. During CSR, slow-wave sleep (SWS) and REMS were reduced by 62% and 57%. Total SWS time during SO periods increased on the first CSR day, but decreased to the baseline by the fifth CSR day. SWS EEG delta power (a measure of sleep intensity) decreased gradually from the first to the fifth CSR day. REMS total time remained elevated during all SO periods. During the first recovery day after CSR, SWS did not change, but REMS increased by 30%. No changes in total sleep time were found on the second recovery day but sleep intensity was decreased. In 14 days after CSR, all sleep parameters returned to the baseline. We revealed a loss of 24% of noradrenergic locus coeruleus neurons, 29% and 17% of dopaminergic neurons in the substantia nigra, the ventral tegmental area as well as in their striatal terminals.

Conclusion
We consider CSR as a damaging factor leading to a gradual suppression of homeostatic mechanisms governing sleep recovery. CSR can provoke neurodegeneration in monoaminergic structures involved in the regulation of emotional behavior, sleep, and autonomic functions.

Support (if any)
Ministry of Science and Higher Education of the Russian Federation grant (No. 075-15-2020-916 dated November 13, 2020) for the establishment and development of the Pavlovsky Center “Integrative Physiology for Medicine, High-Tech Healthcare and Stress Resilience Technologies”.
115 Age and Sex Differences in Behavioral Attention Across Baseline, Sleep Loss, and Recovery
Authors: Yamazaki Erika , Casale Courtney , Brieva Tess , Antler Caroline , Goel Namni 
Published: May 2021

Abstract

Introduction
There are established individual differences in performance resulting from sleep loss. However, differences in behavioral attention performance between demographic subgroups remain unclear, especially during recovery after sleep loss. Thus, we examined demographic subgroup performance differences during baseline, sleep loss (sleep restriction [SR] and total sleep deprivation [TSD]), and recovery (R).

Methods
Forty-one healthy adults participated in a 13-night experiment (2 baseline nights [10h-12h time-in-bed, TIB], 5 SR nights [4h TIB], 4 recovery nights [12h TIB], and 36h TSD). The 10-minute Psychomotor Vigilance Test (PVT), measuring behavioral attention, was administered every 2h during wakefulness. PVT lapses (reaction time [RT]&gt;500ms) and 1/RT (response speed) were measured. PVT performance differences were investigated by sex (18 females) and by median split on age (range: 21-49y; median: 32y). Repeated measures ANOVAs on each study day examined PVT performance with demographic groups as the between-subject factor.

Results
SR1-2 and R1-2 showed significant between-subject effects by age: the older group had faster mean 1/RT than the younger group. SR2 showed a significant time*age group interaction: the older group had faster 1/RT from 0800h-1400h. B2, SR1, and R1 showed significant between-subject effects by sex: males had faster mean 1/RT than females. SR3 showed a significant time*sex interaction: males had faster 1/RT at 0800h and 1200h. PVT lapses (log transformed) analyses by age and by sex revealed significant between-subject effects at SR1 and R1. The direction of effects for lapses paralleled those for 1/RT: the younger group and females had more lapses than the older group and males, respectively. No other study days showed significant between-subjects or interaction effects.

Conclusion
For both age and sex, significant between-subject effects and/or interactions were revealed only in the beginning half of SR or recovery and not during TSD. These findings suggest that group differences exist when the effects of sleep loss are mild (i.e., SR1-3) or when the post-effects of sleep loss have diminished (i.e., R3-4); however, when the effects of sleep loss become more severe (i.e., SR4-5 or after a night of TSD), the well-established individual differences in response to sleep loss may overwhelm group differences.

Support (if any)
ONR Award No.N00014-11-1-0361;NIH UL1TR000003;NASA NNX14AN49G and 80NSSC20K0243;NIH R01DK117488