bluuebunny/crossref_metadata_2025 huggingface dataset:
0260 Does multi-dimensional impulsivity mediate the relationship between poor sleep health and depressive symptoms in late adolescents?
Authors: Kwon Misol , Seo Young , Hasler Brant
Published: May 2022

Introduction

Abundant evidence links poor sleep health to problems with mental health, including depression. Poor sleep is also associated with deficits in impulse control, which have been linked in turn to depressive symptoms, perhaps most notably suicidality. However, whether impulsivity may partly account for the relationship between poor sleep health and depressive symptoms remains understudied. Here, we examined whether multi-dimensional impulsivity mediated the relationship between sleep health and depressive severity in a sample of late adolescent drinkers.

Methods

The sample consisted of 96 late adolescents (58.3% female; mean age 17.6 years) reporting regular alcohol use. Daily sleep duration, timing (sleep midpoint), and continuity (efficiency) were assessed using wrist actigraphy. Five facets of impulsivity (namely, negative urgency, lack of perseverance, positive urgency, lack of premeditation, and sensation seeking) were assessed via the UPPS-P Impulsive Behavior scale. Depressive symptoms were assessed via the Inventory of Depressive Symptomatology (IDS-SR-30).

Results

Mediation analyses showed that the associations between sleep health and depression severity were not mediated through impulsivity. However, results indicated that negative urgency and lack of perseverance were associated with increased severity in depression (B = .75, 95% CI, .27, 1.23 for negative urgency; B = .55, 95% CI, .12, .97 for lack of perseverance), whereas lack of premeditation was inversely associated with depression severity (B = -.72, 95% CI, -1.15, -.29).

Conclusion

Our findings suggest that sleep duration, timing and continuity were not related to any of the multi-dimensional impulsivity components used. However, findings show that negative urgency and lack of perseverance were related to heightened depressive severity but lack of premeditation was known to decrease depression severity. Further analysis may be needed to examine the mediational paths in the associations between sleep health and depressive symptoms, for example, by using latent constructs of sleep health and impulsivity, thus taking measurement errors into account.

Support (If Any)

This research was funded by R01 AA026249 (Hasler) by the National Institute of Alcohol Abuse and Alcoholism; and Sleep Research Society Mentor Mentee Award (Kwon).
0261 Pre-Sleep Arousal Predicts Subsequent Night’s REM Frontal Theta Power in a Naturalistic Context
Authors: ten Brink Maia , Yan Yan , Zhang Jinxiao , Manber Rachel , Kreibig Sylvia , Gross James
Published: May 2022

Introduction

Decreased rapid eye movement (REM) frontal theta spectral activity during sleep has been identified following intense negative experiences in both naturalistic and experimental settings. It is unknown, however, whether this spectral marker a) also appears following lower intensity naturalistic negative affective experiences, and b) whether it is responsive to arousal, to negative valence, or to both.

Methods

In a community sample of adults (N = 50, age range 21-49 [M = 30.30, SD = 7.85]) with no mental health or sleep disorders except bruxism, we separately measured naturalistic experiences of negative valence and arousal 40-60 minutes prior to bedtime, then assessed at-home sleep using a single night of ambulatory polysomnography with 8 electroencephalography channels. REM frontal theta was calculated as the mean relative spectral power density between 4.9-8 Hz at F3 and F4 during REM. Affective experience was assessed with a 0-100 slider rating filled out on participants’ smartphones. Negative valence was assessed by asking, “How negative are you feeling right now?” Arousal was assessed using a composite of somatic and cognitive arousal that reverse scored and averaged two ratings, “How calm is your body?” and “How quiet is your mind?” Analyses were conducted with Bayesian general linear models using flat priors.

Results

Contrary to our hypothesis, pre-sleep arousal was linearly associated with increased REM frontal theta (ß = 2.06 [0.95, 3.20], pMAP < 0.001). A quadratic association fit the data better than the linear model (Bayes Factor = 250.47), such that, for low to moderate pre-sleep arousal, REM frontal theta power increased as arousal ratings increased, but for moderate to high pre-sleep arousal, REM frontal theta power decreased as arousal ratings increased (ß = -2.04 [-3.18, -0.90], pMAP < 0.001). Both associations remained significant even adjusting for negative valence. Contrary to expectations, pre-sleep negative valence was not associated with REM frontal theta.

Conclusion

Separately measuring affect dimensions revealed that REM frontal theta power was selectively responsive to naturalistic pre-sleep arousal. At higher arousal ratings, our results matched prior findings. However, at lower arousal ratings, the association was reversed, suggesting that spectral markers may vary across affective intensities and contexts.

Support (If Any)

National Science Foundation Graduate FellowshipR56, National Institute of Dental and Craniofacial Research, “Emotion dysregulation and sleep-time masticatory muscle activity in sleep bruxism,” DE025321
0262 Sleep-wake cycle circadian disruption after chronic alcohol intake in a rat model of anxiety
Authors: Fierro Adriela , Cortés Carmen , Eguibar José
Published: May 2022

Introduction

Alcohol intake can produce disruptions in sleep-wake cycle, including circadian alterations like phase shifts. Alcohol intake is increased in subjects with anxiety to diminish its symptoms. We have selectively bred two sublines from Sprague-Dawley rats that differs on its yawning frequency. The high-yawning (HY) rats have a mean of 20 yawns/h, whereas the low-yawning (LY) rats have only 2 yawns/hour. LY male rats had high anxiety-like behavior in standardized tests and high preference for alcohol intake. The aim of this study was to assess circadian disruption of sleep-wake cycle after chronic alcohol consumption.

Methods

We used 8 male rats from HY and LY at 3 months of age. All rats were kept in acrylic boxes with food pellets and purified water ad libitum under a light-dark cycle of 12:12 (lights on at 0700) and temperature of 21 ± 1 °C. All subjects were implanted for EEG, EMG and EOG recordings to characterize sleep-wake phases. A basal sleep-wake recording was obtained for 24 h. A second and third recording were made after a 7 days of alcohol administration as a single source of hydration (AL1) and a 3 week two-bottle choice alcohol preference protocol (AL2) were carried out. We used COSINOR analysis to determine phase and cycle alterations of sleep-wake circadian rhythm of all subjects.

Results

After alcohol intake, there was a significant difference only in the acrophases of awake periods (P<0.01) and slow wave sleep (SWS, P<0.001) in both AL1 and AL2 conditions for the HY subline, with a phase delay of 90 min for awake, 30 min for SWS and an advanced phase of 40 min for rapid eye movement sleep (REM) with respect to basal condition. In the case of LY subline, there was a significant difference only in SWS (P<0.001) and REM sleep (P<0.05) acrophases for both AL1 and AL2 conditions, with a phase delay of 7 h for wake, 40 min for SWS and 1 h for REM sleep.

Conclusion

It has been reported that alcohol disrupt circadian synchronization of the sleep-wake cycle, producing a general delay of SWS and REM sleep phases. Additionally, subjects with basal circadian disruptions are more susceptible to increase their intake of alcohol and other addictive drugs. So, LY male rats are an adequate model for higher susceptibility to alcohol intake.

Support (If Any)

Partially supported by PRONACES-CONACYT grant and VIEP-BUAP 2021 to CA in Neuroendocrinología (BUAP-CA-288). AFR is PhD on Physiological Sciences fellowship from CONACYT No. 926368
0265 Samelisant (SUVN-G3031), a Histamine H3 Receptor Inverse Agonist in Animal Models of Narcolepsy
Authors: Benade Vijay , Abraham Renny , Palacharla Raghava Chowdary , Thentu Jagadeesh Babu , Petlu Surendra , Mekala Venkat Reddy , Pandey Santosh Kumar , Badange Rajesh Kumar , Bojja Kumar , Reballi Veena , Achanta Pramod Kumar , Choudakari Praveen kumar , Nirogi Ramakrishna
Published: May 2022

Introduction

Samelisant (SUVN-G3031) is a potent and selective H3 receptor (H3R) inverse agonist with hKi of 8.7 nM. It lacks measurable affinity against 70 other targets which includes GPCRs, ion channels, transporters, enzymes, peptides, steroids, second messengers, growth factors and prostaglandins. Samelisant exhibited desired pharmacokinetic properties and favorable brain penetration in preclinical species. Samelisant blocked R-α-methylhistamine induced dipsogenia in rats and increased tele-methylhistamine levels in brain and cerebrospinal fluid as well. Samelisant is currently being evaluated in a Phase-2 study as monotherapy for the treatment of excessive daytime sleepiness (EDS) in patients with narcolepsy with and without cataplexy (ClinicalTrials.gov Identifier: NCT04072380).

Methods

In brain microdialysis, samelisant was evaluated for its effects on modulation of neurotransmitters like histamine and norepinephrine in prefrontal cortex. In male orexin knockout mice, electroencephalography (EEG), electromyography and activity were monitored using telemetric device. Effects of samelisant on sleep/ wake profile and cataplexy episodes were evaluated during active period of animals. Animals were allowed three weeks of recovery from surgery prior to EEG recording.

Results

Samelisant significantly increased histamine, dopamine and norepinephrine levels in the prefrontal cortex. Samelisant did not change dopamine levels in the striatal and accumbal. These suggest that samelisant may not have propensity to induce abuse liability. Samelisant produced a significant increase in wakefulness with concomitant decrease in non-rapid eye movement sleep in orexin knockout mice. It also significantly decreased number of cataplectic episodes in orexin knockout mice.

Conclusion

The results from non-clinical studies presented here provide a strong evidence for the potential utility of samelisant for the treatment of EDS and cataplexy in patients with narcolepsy.

Support (If Any)

None
0268 Characterization of Neurodegenerative Disorder Subtypes Based on Non-REM Hypertonia and Sleep Spindle Duration
Authors: Levendowski Daniel , Boeve Bradley , Walsh Christine , Tsuang Debby , Salat David , Hamilton Joanne , Lee-Iannotti Joyce , Shprecher David , Berka Chris , Westbrook Philip , Mazeika Gandis , Neylan Thomas , St Louis Erik
Published: May 2022

Introduction

Increased non-REM hypertonia (NRH) and decreased sleep spindle-durations were found to be independently associated with patients broadly characterized as presumed Parkinsonian-spectrum disorder [i.e., dementia with Lewy Bodies/Parkinson Disease Dementia (DLB/PDD), Parkinson Disease (PD), progressive supranuclear palsy (PSP), or isolated REM sleep behavior disorder (iRBD)] when compared to subjects with Alzheimer Disease dementia (AD), mild cognitive impairment (MCI) and normal cognition (NC). In this investigation, the NRH and spindle-duration features were combined to determine whether these biomarkers could distinguish neurodegenerative disorder subtypes.

Methods

This multicenter investigation included analysis of several neurodegenerative disorder patient subtypes including: DLB/PDD (n=16), PD (n=16), iRBD (n=19), PSP (n=13), AD (n=22), MCI (n=35), and NC (n=61). Sleep Profiler (SP) studies were conducted in all participants. NRH was auto-detected based on persistently elevated electromyographic (EMG) power relative to delta, theta, and sigma bands, while spindles were recognized by temporal excursions in alpha and sigma power > 250-milliseconds. With NRH >5% of sleep-time and spindle-duration <1-minute considered abnormal, tallies were compared across neurodegenerative disorder subtypes with Fisher Exact tests.

Results

Combined SP features of Normal-NRH/normal-SpD were greater in the NC (56%), AD (46%), and MCI (43%) subtypes versus PSP (8%) and DLB/PDD (6%), and when iRBD (21%) was compared to NC (all P<0.05). Abnormal-NRH/abnormal-SpD were more frequent in PSP (85%) and DLB/PDD (75%) subtypes versus iRBD (26%), PD (25%), MCI (11%), AD (9%), and NC (8%)(all P<0.02). Abnormal-NRH/normal-SpD were greater in iRBD (47%) compared to MCI (14%), NC (8%), PSP (8%), DLB/PDD (6%), and AD (5%) subtypes, and in PD (31%) versus NC (all P<0.05). Normal-NRH/abnormal-SpD occurred more often in AD (41%) than iRBD (5%) and PSP (0%)(both P<0.05).

Conclusion

The combination of NRH and spindle-duration abnormality occurred more frequently in DLB/PDD and PSP subtypes. Abnormal NRH with normal sleep-duration was more frequent in iRBD and PD subtypes. Normal NRH and spindle-duration occurred most often in NC and MCI types. AD exhibited normal NRH with isolated cases of either normal or abnormal spindle-duration. Our preliminary findings suggest that auto-detected sleep biomarkers may aid in the characterization of neurodegenerative disorder subtypes. Larger prospective cohort studies are needed.

Support (If Any)

NIA grants: R44AG050326, R44AG054256, P30AG62677 and R34AG56639.
0269 Non-REM sleep Hypertonia in Parkinsonian-Spectrum Disorders
Authors: Levendowski Daniel , Walsh Christine , Boeve Bradley , Lee-Iannotti Joyce , Salat David , Hamilton Joanne , Tsuang Debby , Shprecher David , Westbrook Philip , Berka Chris , Mazeika Gandis , Neylan Thomas , Louis Erik St
Published: May 2022

Introduction

Non-REM hypertonia (NRH) was recently reported to be independently associated with the synucleinopathy-mediated neurodegenerative disorders: dementia with Lewy Bodies/Parkinson Disease Dementia (DLB/PDD), Parkinson Disease (PD), and isolated REM sleep behavior disorder (iRBD). In this NRH investigation, we included progressive supranuclear palsy (PSP), a Parkinsonian-spectrum disorder caused by tau pathology.

Methods

In this multicenter study, patients broadly characterized as presumed Parkinsonian-spectrum disorders (PSD) included DLB/PDD (n=16), PD (n=16), iRBD (n=19), and PSP (n=13). Presumed non-PSD subjects included Alzheimer’s Disease dementia (AD=22), mild cognitive impairment (MCI=35), and normal cognition (NC=61). Sleep Profiler studies were acquired in all participants. NRH, auto-detected based on persistently elevated electromyographic (EMG) power relative to delta, theta, and sigma bands in the differential Af7-Af8 signal, was measured as a percentage of sleep time and then weight-averaged in the 75% of in-home studies with two-nights of data. A >5% threshold characterized abnormal-NRH. Twenty-nine NC were longitudinally retested after 364- to 563-days. Statistical analyses included inter-class correlations (ICC), Bland-Altman plots, multiple logistic regression, and receiver-operating-characteristic curves (ROC).

Results

In the PSD=41 and non-PSD=95 records with two-nights of data, NRH-severity demonstrated moderate consistency (ICC=0.78, bias=0.6+/-6.2%, P<0.0001). Across the two-nights, NRH was classified consistently as normal or abnormal in 59.6% and 27.2% of the records, vs. normal/abnormal=4.4% or abnormal/normal=8.8%. The test-retest reliability of NRH-severity was good (ICC=0.84, bias=0.06+/-3.8%, P<0.0001), with all retest comparisons repeating as normal (73%) or abnormal (27%). The frequency of abnormal-NRH in PSP=92% was significantly greater than MCI=26%, AD=14%, and NC=16% (all P<0.0001) and PD=56% (P<0.05), but not DLB/PDD=81% and iRBD=74%. Abnormal-NRH was significantly associated with the PSD group (P<0.0001) and it differentiated PSD versus non-PSD group with an area under the curve of 0.78 (95%CI: 0.72-0.85) based on a sensitivity of 0.75 (95%CI: 0.63-0.84) and a specificity of 0.81 (85%CI: 0.73-0.87).

Conclusion

NRH independently discriminated PSD patients from age-sex similar non-PSD subjects, suggesting that NRH is a common sleep motor signature across clinical PSD phenotypes. We speculate that NRH could be related to pathological changes within the key non-REM sleep motor modulating center in synucleinopathies and PSP.

Support (If Any)

NIA grants: R44AG050326, R44AG054256, P30AG62677 and R34AG56639.
0277 Deep learning revealed associations between altered temporal correlations in motor activity and Parkinson’s risk
Authors: Zheng Xi , Sun Haoqi , Yang Jingyun , Yu Lei , Gao Lei , Buchman Aron , Bennett David , Westover M Brandon , Hu Kun , Li Peng
Published: May 2022

Introduction

Motor activity in healthy young adults displays fractal patterns with similar temporal correlations at different timescales. Altered fractal patterns were observed in patients with Parkinson’s disease. This study aimed to determine whether altered fractal patterns also predict the risk of Parkinsonism.

Methods

We studied 982 participants (age: 80.12±7.27 [SD]; 750 females) from the Rush Memory and Aging Project, who had at least one actigraphy assessment, had no symptoms of Parkinsonism at actigraphy baseline, and had follow-up clinical assessments. Detrended fluctuation analysis was performed on baseline actigraphy to determine the fractal patterns. Specifically, the activity fluctuation (around the trend) was computed at multiple timescales (n) ranging from 3-600 min. An exponential function with a variable scaling factor α was used to fit the local fluctuation function with respect to n. The α(n) that represented the temporal correlations was fed into a convolutional neural network (CNN) model whose output was further used as the input of a Cox proportional hazards model to predict the time to incident Parkinsonism. Covariates at baseline considered include age, sex, education, cognition, motor function, chronic health assessment, and actigraphy-derived measures including physical activity level, rest-activity/activity-rest transition probabilities, interdaily stability, and intradaily variability.

Results

There were 412 subjects who developed parkinsonism (in 4.75±3.13 [SD] years from baseline). Based on the gradient of hazard function (with respect to α) from the CNN model (estimated feature importance), the α in three timescale regions (i.e., 3-5 min, 12-20 min, and 270-600 min) contributed significantly to the prediction. Consistently, in separate Cox models with adjustment of age, sex, and education, the mean α at timescales 3-5 min was inversely associated with incident parkinsonism (for 1-SD increase, hazard ratio [HR]=0.82, 95% CI: 0.78-0.92, p<0.0001); The mean α at timescales 270-600 min was also inversely associated with incident Parkinsonism (HR=0.87, 95% CI: 0.78-0.96, p=0.008); And the mean α at timescales 10-25 min was marginally, positively associated with incident Parkinsonism (HR=1.10, 95% CI: 0.99-1.22, p=0.08).

Conclusion

Altered temporal correlations at specific timescales in motor activity predicted the risk of Parkinsonism.

Support (If Any)

NIH RF1AG064312, RF1AG059867, R01AG017917, R01AG56352, the BrightFocus Foundation A2020886S.
0279 Thermoneutral temperature exposure increases slow-wave sleep in the 3xTg-AD mouse model of Alzheimer’s Disease
Authors: Wang Jun , Huffman Dillon , Ajwad Asma’a , Bachstetter Adam , Murphy Michael , O’Hara Bruce , Duncan Marilyn , Sunderam Sridhar
Published: May 2022

Introduction

There is growing evidence that disordered sleep, which is known to be associated with Alzheimer’s disease (AD), may accelerate neuropathology, thus promoting a vicious cycle. Strategies for improving sleep quality may slow disease progression. Here we investigate the feasibility of sleep enhancement through ambient temperature regulation and examine the effect on amyloid pathology.

Methods

Female 3xTg-AD mice (~12 m.o.) were instrumented for EEG/EMG monitoring. After a week-long baseline, one half of the mice (n=8, EXPT) were exposed to stepwise diurnal increases in ambient temperature (Ta) to reach 30oC (thermoneutral for mice) during the light phase while the rest (n=8, CTRL) remained at room temperature (22oC). Vigilance state – i.e., Wake, REM, NREM, and slow wave sleep (SWS) within NREM – was scored in 4-second epochs and sleep metrics were computed.

Results

SWS percentage became significantly greater (p<0.05) in the light phase for EXPT mice over the course of treatment. These effects suggest better sleep consolidation and greater sleep depth with thermoneutral warming. After four weeks of treatment, the animals were euthanized, and the brains removed to assay amyloid pathology by ELISA. We found that thermoneutral warming caused a significant reduction in both Aβ40 and Aβ42 in the hippocampus, but not in the cortex.

Conclusion

These data imply that thermoneutral warming might have some regional specificity in its effects. The effects appear to be specific to some brain areas more than others, with implications for the cognitive and neuropathologic changes found in AD. Furthermore, since SWS and REM support memory, future studies should investigate the effects of thermoneutral enhancement of SWS and REM on cognition.

Support (If Any)

R01AG068215; seed funds UKY Department of Neuroscience
0280 Orexins play a dual role in immobility episodes on taiep rats a model of H-ABC
Authors: Cortes Carmen , Espinoza Karely , De Ovando Carlos , Hernandez Hugo , Piazza Valeria
Published: May 2022

Introduction

Leukodystrophies are a heterogenous group of congenital myelin alterations with more than 30 classified diseases was described until now. Among them there are several mutations in the a and b tubulins the so called tubulinophaties, that affect the central nervous system. The hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is due to a mutation in the tubulin b 4a (TUBB4A) and the taiep rats is the only available model of this human disease with similar magnetic resonance changes and a punctual mutation in the TUBB4A. Taiep rats had immobility episodes (IEs) with a peak between at 9 months of age. Importantly, electroencephalographic recordings shown that IEs had a rapid eye movement (REM) sleep characteristic pattern supporting that are equal to human cataplexy episodes that are key sign of narcolepsy. It is possible to induced IEs when taiep rats are manipulated from the tail or the thorax. Narcolepsy in humans and narcoleptic dogs had a significant decreased in orexin levels in the cerebrospinal fluid (CSF) and a concomitantly decreased of orexin neurons in the lateral hypothalamus.

Methods

We used 21 male rats from taiep at 9 months of age. All rats were kept in standard conditions and were implanted for EEG, EMG and EOG recordings to characterize IEs. We administered orexin A and B agonists and characterized the sleep-wake cycle and frequency of IEs, the peptides were administered by a intracerebroventricular (i.c.v.) injections diluted in artificial CSF. We also measured the number or positive orexin neurons in the lateral hypothalamus through immunohistochemistry.

Results

The i.c.v. administration of [Ala11, D-Leu 15] orexin B agonist significantly decrease the frequency of IEs with 3 and 10 nM doses (P≤0.05 and P≤0.03, respectively), without affecting the sleep-wake pattern. However, the i.c.v. administration of Orexin A (17-33) an agonist did not affect the sleep-wake pattern or the frequency of IEs. It is relevant that the number of orexins neurons did not differ between taiep and control Sprague-Dawley (SD) male rats.

Conclusion

Our results showed that IEs had a REM sleep EEG characteristic pattern with cataplexic-like atonia, there are sensible to orexin B agonist, but the number of orexin positive neurons do not differ with respect to SD male rats. In conclusion taiep rats a model of H-ABC is an adequate model of cataplexy-like episodes due to myelin disease.

Support (If Any)

Partially supported by PRONACES-CONACYT grant 194171, and VIEP-BUAP 2021 to CA in Neuroendocrinología. KGE is fellowship from CONACYT No. 772626.
0282 Elevated levels of Extracellular Vesicle Cytokines are Associated with Poor Sleep Quality in Warfighters with Chronic Mild TBI
Authors: Guedes Vivian , Gottshall Jackie , Mithani Sara , Leete Jackie , Lai Chen , Gill Jessica , Kenney Kimbra , Werner Kent
Published: May 2022

Introduction

Sleep disorders are common in military populations and frequently occur comorbidly with mild traumatic brain injury (mTBI), resulting in substantial health risks. Although inflammation and cytokine elevations have independently been reported both after traumatic brain injury (mTBI) and in association with sleep dysfunction, the impact of these factors on inflammatory processes in a combined context (i.e. post-mTBI sleep dysfunction) has yet to be explored. Extracellular vesicles (EVs) are a particularly promising source of these cytokines; EVs are lipid bilayer-enclosed particles released by cells to the extracellular environment, constituting a newly discovered form of cell-to-cell communication that may afford improved signal-to-noise ratio and more functionally specific protein biomarkers than free (soluble) sources. To determine whether mTBI and sleep dysfunction may bidirectionally regulate inflammatory processes, the present study examined associations between plasma and EV levels of cytokines and sleep quality in a cohort of warfighters with and without chronic mTBI.

Methods

Participants (n=182) were enrolled in the Chronic Effects of Neurotrauma Consortium (CENC) Multicenter Prospective Longitudinal Study/ Long-Term Impact of Military Brain Injury Consortium (LIMBIC). They were divided into control (no TBI history) or mTBI groups (positive history of mTBI). EV and plasma levels of interleukin (IL)-10, IL-6, and tumor necrosis factor-alpha (TNFα) were analyzed using a Simoa HD-1 analyzer. Sleep quality was evaluated using Pittsburgh Sleep Quality Index (PSQI).

Results

Within the mTBI group, patients reporting poor sleep quality (PSQI ≥10) had elevated EV levels of IL-10 (ß(SE) = 0.12(0.04), p<0.01) when compared to those reporting good sleep (PSQI<10). Sleep quality was associated with EV levels of IL-10 (ß(SE)=0.11(0.04), p=0.01) and TNFα (ß(SE)=0.07(0.03), p< 0.01) in mTBI patients. Plasma levels of cytokines were not significantly associated with sleep quality.

Conclusion

Our findings suggest that EV levels of IL-10 and TNFα, but not their plasma levels, are associated with self-reported sleep quality warfighters with history of mTBI. Our results suggest that EVs are relevant signaling mechanisms in sleep-related inflammatory responses following mTBI. Larger prospective studies are needed to further investigate the links between EV cytokines and sleep quality in participants with mTBI.

Support (If Any)

This work was supported by grant funding from: Department of Defense, Chronic Effects of Neurotrauma Consortium (CENC) Award W81XWH-13-2-0095 and Department of Veterans Affairs CENC Award I01 CX001135.
0284 Repetitive Weekly REM Sleep Deprivation-Recovery Cycle Obtained from a Large U.S. Sample by Home-Based Under-Mattress Monitoring Devices
Authors: Kushida Clete , Cotton-Clay Andrew , Baron Susan , Fava Laura , Easwar Venkat , Kinsolving Arthur , Kahn Philippe , Zitser Jennifer , Rama Anil , Ding Feihong
Published: May 2022

Introduction

American adults are typically sleep deprived during weekdays and attempt to recover sleep on the weekends. Technological advances in home sleep monitoring have provided the opportunity to analyze sleep patterns on a scale much larger than previously imaginable. This study explores the weekly REM sleep deprivation–recovery cycle in a large U.S. sample.

Methods

Estimated total sleep time (TST) and REM/TST (R%) were analyzed by a commercially-available home-sleep-monitoring device (Sleeptracker-AI Monitor, Fullpower Technologies, California, USA). The device passively monitors sleep using piezo-electric sensors that register the forces exerted through the mattress. The de-identified data from the devices were analyzed following review and exemption of the study (#57681) from the Stanford University IRB. Data from 07/2020–06/2021, from 101,442 individuals with 14,277,964 recorded nights, were available. The analytic dataset included individuals with at least 300 nights of sleep per year and 26 of 52 nights per each day of the week (excluding nights abutting federal holidays).

Results

A total of 21,543 individuals (11,095 men, 51±14 years; 9,821 women, 50±15 years; 627 unspecified genders) and 6,850,717 recorded nights met the inclusion criteria. There is a stepwise increase in R% from Sunday night to Friday night and a decrease back to Sunday night, following a cycle of weekday sleep deprivation and weekend recovery. The means and standard deviations (across individuals’ averages) of TST in hours and R% for each night were: Sunday (TST*:7.21±0.885, R%*:24.20±3.09), Monday (TST*:7.18±0.853, R%*:24.56±3.10), Tuesday (TST*:7.16±0.847, R%*:24.67±3.13), Wednesday (TST*:7.16±0.845, R%*:24.80±3.15), Thursday (TST*:7.18±0.845, R%*:24.87±3.15), Friday (TST*:7.51±0.904, R%*:25.05±3.15), and Saturday (TST*:7.59±0.897, R%*:24.83±3.12). Each statistic, when compared with the previous night of the week, was significant (p < 0.05/7, Bonferroni corrected) by paired t-test (denoted by an asterisk).

Conclusion

The use of advanced technology to estimate sleep-wake patterns in a large sample permits the validation of a repetitive REM sleep deprivation–recovery cycle. Individuals are, on average, partially sleep deprived starting Sunday night, which leads to a progressive REM sleep rebound that transitions into a REM recovery cycle on Friday and Saturday nights. Further work will focus on studying this cycle within different groups (e.g., age, gender), across seasons, and including other sleep parameters.

Support (If Any)
0285 Excessive daytime sleepiness with long sleep duration increases myocardial infarction risk
Authors: Wang Heming , Sofer Tamar , Saxena Richa , Purcell Shaun , Huang Tianyi , Zhu Xiaofeng , Rutter Martin , Redline Susan
Published: May 2022

Introduction

Excessive daytime sleepiness (EDS) affects 10-20% of the population and is associated with cardiovascular diseases (CVD) and mortality. However, EDS is heterogeneous, associated with both short and long sleep duration. It is unclear whether each subtype is related to CVD.

Methods

To understand the association of EDS subtypes (stratified by sleep duration) with incident myocardial infarction (MI), we perform multivariable Cox proportional hazards regression on MI using longitudinal medical record data of 471,991 individuals free of CVD at baseline from the UK Biobank. Baseline EDS and sleep duration were assessed by self-reported questionnaires.

Results

After adjusting for multiple social-demographic and behavioral factors, EDS with long sleep (³9 hours) was associated with a 91% increased incidence of MI (HR=1.91, 95% CI 1.34-2.71) compared to healthy sleep pattern (sleeping 6-9 hours without sleepiness), while EDS with normal (6-9 hours) or short sleep (≤6 hours) was not associated with incident MI. Long sleep without sleepiness was associated with a 39% increase in incident MI (HR=1.39, 95% CI 1.14-1.71). The association of EDS with long sleep was not explained by chronotype, insomnia, sleep apnea, depression, hypertension, or type 2 diabetes, but was confounded with self-reported overall health conditions (HR=1.46, 95% CI 1.02-2.08 after adjustment).

Conclusion

Our study suggests the previous association evidence of EDS increasing risk of MI may be primarily driven by its long sleep subtype (high “sleep propensity”), but the underlying mechanisms are unclear. Future work is needed to understand whether there are targetable interventions for this novel sleep phenotype that may improve cardiovascular health.

Support (If Any)

This research has been conducted using the UK Biobank Resource under Application Number 6818. Funding supports: NHLBI R35HL135818 and R01HL153814.
0286 Presence and Potential Impact of Demographically Based Attrition in Pediatric Sleep Manipulation Research
Authors: Beebe Dean , Rajput Gargi , Whitacre Catharine
Published: May 2022

Introduction

Pediatric sleep manipulation studies have mostly enrolled youth from dominant-culture, higher-income families. Studies with more diverse samples have been underpowered to detect differential attrition and demographic effect moderators. Here we pool data from two adolescent sleep manipulation protocols in a Midwest US city to better examine demographic differences in attrition rates and effect sizes.

Methods

Samples were pooled from studies detailed in Beebe et al. (2017; SLEEP, zsw035) and Duraccio et al. (2021; JSR, e13054). Both involved a sleep stabilization week, followed by 5-night periods of sleep restriction (6.5 hours/night in bed) and healthy sleep (9.5-10 hours/night in bed) in randomized counterbalanced order. Primary caregivers and 14-17 year-old adolescents each completed attention and sleepiness questionnaires for both conditions. Here we compare adolescents who were caregiver-identified as Black vs. White, the two largest local racial groups. Caregivers also reported their own education, family income, and household structure (single- vs. two-parent). Non-parametric tests looked for differential attrition and MANCOVA tested for racial differences in effects.

Results

Of the 257 initially enrolled, Black adolescents and those from households with one parent, lower income, or lower caregiver education were differentially lost to attrition (all p<.001), even though the racial makeup of the final sample approximated the regional population (36% Black, 64% White). In the final sample, Black and White youth were equally able to change their sleep (p>.90). Manipulation effects were significantly smaller for Black than White adolescents for inattention (self-report p=.026; parent-report p=.017) and sleepiness (self-report p=.002, parent-report p<.001), but these differential effects were non-significant after controlling for family income, household structure, and caregiver education (p>.05).

Conclusion

Even when a final study sample seemingly approximates the diversity of the local population, differential attrition may affect results. In this case, it superficially appeared that being in a non-dominant group (self-identified Black) was protective against the impact of short sleep. However, this effect disappeared after controlling for demographic risk factors. Participation in sleep manipulation studies can be challenging, so families facing higher burdens may need more support; otherwise, only the most resilient of those families may succeed, which could distort findings.

Support (If Any)

NIH (R01HL120879, R01HL092149)
0287 Effects of Sleep Restriction and Recovery on the Capacity of Glucocorticoids to Inhibit Inflammatory Marker Expression in Human Monocytes
Authors: Engert Larissa , Eske Annika , Buraks Olivia , Dang Rammy , Mullington Janet , Haack Monika
Published: May 2022

Introduction

Chronic low-grade systemic inflammation is involved in the pathogenesis of many human diseases. Common sleep patterns of restricting sleep during weekdays and catching up on sleep over the weekend induce inflammatory upregulation that may not resolve following weekend recovery sleep. We hypothesize that this sleep pattern leads to an inflammatory imbalance of markers regulating inflammatory homeostasis, including inflammatory markers (eg, interleukin-6 (IL-6) and cyclooxygenase 2 (COX-2)) and markers of counter-inflammation (eg, glucocorticoids (GCs)). The enzyme COX-2 is involved in prostaglandin synthesis and is the target of pain-relieving nonsteroidal anti-inflammatory drugs (NSAIDs). GCs are used in the treatment of many inflammatory diseases, including severe acute infection with SARS-CoV-2. We investigated if sleep restriction impairs the capacity of GCs to inhibit inflammatory COX-2 expression in a preliminary dataset.

Methods

The present preliminary dataset (N=6, 2F/4M) derives from an ongoing randomized controlled within-subjects trial consisting of three 11-day in-hospital protocols (2 restricted sleep arms, 1 control sleep arm). The ongoing study is blinded for administration of placebo or aspirin under sleep restriction. Under restricted sleep conditions, 2 nights of baseline sleep (8h/night) were followed by 5 nights of restricted sleep (4h/night), concluding with 3 nights of recovery sleep (8h/night). In the control condition, participants could sleep 8h/night throughout the entire protocol. Blood samples were taken after baseline sleep, after 5 nights of restricted or control sleep, and after 2 nights of recovery sleep. Data were analyzed using generalized linear mixed models.

Results

Sleep restriction was associated with decreased capacity of GCs to inhibit COX-2 expression in monocytes (p<.01) and has the expected inflammatory effect on IL-6 production in monocytes (p<.01). Moreover, sleep restriction has lasting inflammatory effects as shown in increased inflammation following 2 nights of recovery sleep (p<.01).

Conclusion

In conclusion, the present preliminary analysis suggests that in patients treated with GCs, sleep restriction potentially reduces their effectiveness in controlling inflammation, thus contributing to increased inflammation-related morbidity. Sample collection and data analysis is ongoing.

Support (If Any)

NIH/NHLBI R01-HL136310; NIH/NCRR UL1-RR02758, M01-RR01032; German Research Foundation (DFG) EN1291/1-1.
0288 Role of cofilin and calcium signaling in sleep-loss neural injury
Authors: Chou Allison Tzu-Han , Hollis Henry , Fenik Polina , Pullum Keelee , Slinger Michelle , Zamore Zachary , Zhu Yan , Anafi Ron , Veasey Sigrid
Published: May 2022

Introduction

Chronic sleep disruption (CSD) in young adult mice leads to phenotypes consistent with early (pre-plaque) Alzheimer’s Disease (AD), including increased Aβ and hippocampal neuron loss. Mechanisms underlying this injury are not known. Both acute sleep loss and AD activate cofilin, a regulator of actin dynamics. Activated cofilin (AC) in AD mouse models can impart neural injury, increase Aβ, and cofilin translocation to the mitochondria delays cytosolic Ca2+ clearance. We are critically testing the role of AC in chronic short sleep (CSS) and sleep fragmentation (SF) neural injury.

Methods

Synapse loss was studied using STED confocal microscopy and Imaris in CSS (n=9) and rested (n=10) mice. Synapses were identified as overlaps of pre- and postsynaptic densities. Percent area of cofilin was measured with FIJI. To further understand if and how wake-induced cofilin activation induces sleep-loss synapse and neural injury, we implanted AAV9CAMKII-GCaMP6f and then GRIN lenses, and later studied CAMKII calcium transients in CA1 of WT controls (n=4) and SF mice (n=4) by measuring GCaMP6f calcium transients. We developed a Shiny R application to analyze the frequency of Ca2+ spikes, ΔF/F0, and the rising and clearance patterns of spikes. To directly test cofilin’s role in delayed calcium clearance, we studied the calcium transients in hAPP mice (n=2) after injection of AAV-CAMKII-CofilinS3A to express AC and GCaMP6f. All data were analyzed with two-way ANOVA or unpaired t-tests.

Results

Results reveal significant synapse loss in CA1 of CSS mice (CSS=48.8±10.3; Rested=83.4±8.4), t(16)=2.63, p<0.02, and increased cofilin activation (AC=19.8±3.41; Rested=8.76±1.95), t(16)=8.43, p<0.0001. SF mice reveal an increase in NREM sleep firing rates, F(1,1)=22.0, p<0.001. In contrast, hAPP-AC mice show significantly increased ΔF/F0, F(1,1)=356, p<0.0001, prolonged calcium influx, F(1,1)=18.6, p<0.02, and prolonged calcium clearance duration, F(1,1)=23.9, p<0.01, but not increased firing frequencies.

Conclusion

CSS induces CA1 synapse loss and cofilin activation in WT mice. Increased CAMKII calcium ΔF/F0 occurs through different pathways in SF and AC, suggesting additional factors in CSD neural injury.

Support (If Any)

NIH AG054104; AG064231
0290 Associations between sleep duration and sedentary behavior in healthy, young adults
Authors: Melanson Edward , Depner Christopher , Wright Kenneth , Creasy Seth , Kubicki Michelle , Zimmerman Grace
Published: May 2022

Introduction

Chronic diseases are more prevalent among populations with greater daily sedentary time and among populations with insufficient sleep duration. Yet, little is known about the potential links between insufficient sleep and sedentary behavior. Early findings from recent studies show variable and bidirectional associations between sleep duration and sedentary behavior, based on the population studied. The purpose of this investigation was to measure associations between: (1) sleep duration and sedentary time the next day; and (2) sedentary time and sleep duration the same study day/night, during a sleep extension intervention.

Methods

Data collection are ongoing. To date, three participants (2 female; aged 24.7±4.04yr; BMI 21.73±2.38kg/m2) with self-reported habitual insufficient sleep (<6.5h per night) completed the study protocol in its entirety. Sedentary behavior (<1.5 METs, in seated or lying posture) and sleep duration were measured via activPALTM and wrist-actigraphy, respectively, at baseline for days 1-13. After baseline, participants completed a sleep extension intervention for study days 15-41, with sedentary behavior and sleep duration measured during study days 28-41. Only study days with full 24h activPAL™ wear time were included in statistical analyses. Associations between sedentary behavior and nightly sleep duration were analyzed by linear mixed-model regression. We focused this preliminary analysis of 3 participants on R2.

Results

Sleep duration was significantly increased (p<0.05) during sleep extension (7.6±1.5h) versus baseline (7.0±1.4h). Sedentary behavior was not significantly different (p=0.869) during sleep extension (8.4±1.6h) versus baseline (8.3±2.0h). The association between sleep duration to sedentary time the following day had p=0.683, R2=0.51, and =2.5±6.2h. The association between daily sedentary time to sleep duration the same study day/night had p=0.72, R2=0.12, and =2.3±6.2h.

Conclusion

Preliminary findings from 3 participants in this ongoing study suggest that sleep extension is not associated with changes in sedentary behavior.

Support (If Any)

NIH-UL1TR002535, NIH-K01HL145099, Colorado Clinical Translational Science Institute Pilot (CO-J-20-119), University of Utah Seed Grant-10060570
0291 Social Desirability Mediates Self-Reported Sleepiness during a Laboratory Total Sleep Deprivation Study
Authors: Scott Jonah , Muck Rachael , Van Dongen Hans , Honn Kimberly
Published: May 2022

Introduction

Total sleep deprivation (TSD) increases sleepiness and impairs vigilant attention. There are large individual differences in vulnerability to sleep loss, but individuals’ self-ratings of sleepiness often do not align with their objective performance impairment. Here we investigated whether the trait of social desirability – the desire to conform to social standards – plays a role.

Methods

N=39 healthy adults (ages 27.6±4.6y; 22 men) completed a 3-night/4-day in-laboratory study with 10h baseline and recovery sleep opportunities (22:00–08:00) preceding and following a 38h period of TSD. Every 2–4h during TSD, subjects completed the Karolinska Sleepiness Scale (KSS) and a 10min Psychomotor Vigilance Test (PVT) to assess subjective sleepiness and vigilant attention, respectively. Throughout the study, subjects were behaviorally monitored by the researchers. Prior to the study, subjects completed the Marlow-Crowne Social Desirability (MCSD) scale. Based on standard criteria, subjects were categorized post hoc into average (n=13) and high (n=26) social desirability groups (no subjects in the sample scored low on social desirability). Self-reported sleepiness scored on the KSS and lapses (reaction times ≥500ms) on the PVT were analyzed using mixed-effects ANOVA with fixed effects for time awake and MCSD group and their interaction.

Results

As expected, there was a main effect of time awake for KSS score (F[12,441]=31.48, p<0.001) and PVT lapses (F[12,441]=16.27, p<0.001), with sleepiness and lapses increasing during TSD. We found a main effect of MCSD group for KSS score (F[1,441]=4.56, p=0.033), with the high MCSD group reporting lower levels of sleepiness than the average MCSD group. However, there was no effect of MCSD group for PVT lapses (p=0.93) and no time awake by MCSD interaction for either KSS (p=0.86) or PVT (p=0.99).

Conclusion

Subjects high in social desirability reported less sleepiness during TSD than those with average social desirability yet their objective performance was equally degraded. This finding has implications for fatigue risk management because individuals with high social desirability may underreport their sleepiness. This may undermine the reliability of self-report assessments of sleepiness and ability to work safely. [ 1] Whether there is bias in self-reported sleepiness for individuals low in social desirability as well remains to be investigated.

Support (If Any)

Support: ONR N00014-13-1-0302 and PRMRP W81XWH-20-1-0442
0294 Voluntary Alcohol Consumption and Sleep Deprivation in Rats
Authors: Khan Aesha , Trice Catharine , Holt Daniel , Dyche Jeff
Published: May 2022

Introduction

Alcohol is one of the most common psychoactive drugs that has depressant effects on the central nervous system. The vast majority of research on alcohol and sleep indicates chronic alcohol consumption has a detrimental impact on sleep architecture and homeostasis. However, less research has explored the effects of sleep deprivation on alcohol consumption; that is, the relationship in the opposite direction. Previous animal studies have explored a potential bi-directional relationship between sleep and alcohol with promising results. However, there was concern that the potential relationship may be a result of stress as a by-product of the sleep deprivation method. The present study examines the effect of sleep deprivation on voluntary alcohol consumption using two sleep deprivation methods in the rat, forced exercise wheels and the automated sleep deprivation system.

Methods

Twelve male Sprague-Dawley rats had ad libitum access to a 7% alcohol solution and water. Alcohol and water consumption was measured daily at 0900. Baseline consumption levels were recorded in the home cage prior to introduction to the sleep deprivation equipment. Following baseline, rats were placed in the stationary equipment for the first sleep deprivation environment control. Rats were then subjected to 6hr/day of sleep deprivation for five consecutive days in either the forced exercise wheel (n=6) or the automated sleep deprivation system (n=6). After sleep deprivation, rats were placed back in the stationary equipment as a second control measure. In total, there were four conditions, home cage baseline, first sleep deprivation environment control, sleep deprivation, second environment control.

Results

Data indicates that rats consumed significantly more alcohol in the sleep deprivation condition and the second sleep deprivation control. There was no difference between the two sleep deprivation methods. The mean alcohol consumption (g/kg) significantly increased from the sleep deprivation condition to the second environment control indicating a cumulative effect.

Conclusion

The increase in alcohol consumption in the final condition rejects the hypothesis of a bi-directional relationship. Instead, the data suggests potential receptor downregulation due to alcohol exposure over time and a conditioned compensatory effect of the sleep deprivation environment. Research methodology issues also may have confounded results.

Support (If Any)