bluuebunny/crossref_metadata_2025_split huggingface dataset:
0259 Chronotype and affective response to sleep restriction, sleep deprivation, and circadian misalignment
Authors: Cox Rebecca , Ritchie Hannah , Sprecher Kate , Burke Tina , Smits Alexandra , Knauer Oliver , Guerin Molly , Stothard Ellen , Depner Christopher , Wright Kenneth 
Published: May 2022

Abstract

Introduction
Late chronotypes have been shown to have decreased positive affect during the day and during sleep loss. Findings for negative affect are inconsistent. The present analysis examined the effect of chronotype on positive and negative affect during two sleep and circadian challenges.

Methods
In both studies, chronotype was determined by habitual mid-sleep time. In Study 1, 10 healthy adults (5 early, 5 late chronotypes) completed a 10-day protocol of sleep restriction followed by total sleep deprivation. Participants maintained habitual 8h sleep schedules at home for 1 week, then completed a 2-day in-laboratory protocol: 4h of sleep restriction, followed by a 4h sleep opportunity, followed by 28h of sleep deprivation. Affect was assessed with the Positive and Negative Affect Schedule (PANAS) every hour during scheduled wakefulness. In Study 2, 14 healthy adults (7 early, 7 late chronotypes) completed a 39-day protocol of combined sleep restriction and circadian misalignment. Participants maintained habitual 8h sleep schedules at home for 2 weeks, then completed a 4-day in-laboratory protocol with the following sleep opportunities: 8h on night 1, 3h on night 2, and 3h on mornings 3 and 4. After 3 days of at-home unscheduled recovery sleep opportunities, the protocol was repeated. Affect was assessed with the PANAS every 3h during scheduled wakefulness. Data from each study were analyzed separately with mixed-model ANOVA.

Results
Positive affect decreased during sleep restriction+sleep deprivation and sleep restriction+circadian misalignment (p&lt;.05), regardless of chronotype. However, late chronotypes reported lower positive affect than early chronotypes across both sleep/circadian challenges (p&lt;.05), and this effect was accounted for by baseline positive affect. Negative affect was not consistently impacted by sleep/circadian challenges or chronotype, with or without considering baseline negative affect. In both studies, chronotype did not interact with sleep/circadian challenges.

Conclusion
These findings are consistent with prior work showing later chronotypes have lower positive affect. Chronotype and sleep loss/circadian misalignment may impact affect through independent mechanisms. Future work is needed to replicate these findings in larger samples with more extreme chronotypes.

Support (If Any)
Office of Naval Research MURI N00014-15-1-2809; CurAegis Technologies Inc. (formerly Torvec, Inc), NIH HL109706, NIH TR001082; Undergraduate Research Opportunities Grant University of Colorado Boulder.
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

Abstract

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

Abstract

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 &lt; 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 &lt; 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

Abstract

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&lt;0.01) and slow wave sleep (SWS, P&lt;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&lt;0.001) and REM sleep (P&lt;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

Abstract

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

Abstract

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 &gt; 250-milliseconds. With NRH &gt;5% of sleep-time and spindle-duration &lt;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&lt;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&lt;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&lt;0.05). Normal-NRH/abnormal-SpD occurred more often in AD (41%) than iRBD (5%) and PSP (0%)(both P&lt;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

Abstract

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 &gt;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&lt;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&lt;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&lt;0.0001) and PD=56% (P&lt;0.05), but not DLB/PDD=81% and iRBD=74%. Abnormal-NRH was significantly associated with the PSD group (P&lt;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

Abstract

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&lt;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

Abstract

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&lt;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