bluuebunny/crossref_metadata_2025_split huggingface dataset:
0169 Using serial awakenings to explore the spectral signature of sleep state misperception
Authors: Riedner Brady , Rumble Meredith , Dickson Daniel , Anna Castelnovo , Synder Ted , Jones Stephanie , Benca Ruth 
Published: May 2022

Abstract

Introduction
Sleep state misperception, or paradoxical insomnia, is a condition whereby an individual reports being awake even though polysomnographic evidence confirms they were asleep. Normally, an indication of sleep state misperception is determined by asking a patient to estimate the amount of wakefulness experienced after a full night of laboratory-monitored sleep. While clinically useful, this crude, post-hoc assessment does little to inform the neurobiological underpinnings of sleep state misperception. Here we used serial awakenings to exploit instances where a direct confirmation of sleep was followed by a subjective report of wakefulness.

Methods
256 channel EEG with EMG, EOG and ECG was recorded in 19 primary insomnia (PI) subjects and 19 age- and sex-matched good sleeping controls (GSC) after a baseline sleep night ruled out comorbid disorders. After periods of stable sleep, participants were probed every 30 seconds with increasing intensity tones until a full awakening was achieved. Subjects were then asked to report whether they were awake or asleep before hearing the sound before going back to sleep. EEG data prior to the awakening was examined using multi-taper spectral analysis.

Results
Out of 464 serial awakenings (average 12 per subject, range 4-16), roughly 10% resulted in subjective wake reports during sleep (35 in NREM, 11 in REM; 24 in PI, 22 in GSC). Many of these occurrences included obvious arousals or other signs of wakefulness prior to the awakening tone. Altogether, 8 clean wake reports (4 in PI), occurred during stage N2 or N3 that could be matched with similarly clean data when the same subject reporting being asleep. Interestingly, spectral analysis of the 10 seconds prior to the awakening revealed significantly more alpha activity (9.1-11.3Hz paired t-test, p &lt; .05) but no significant difference in slow wave activity. The alpha increase was localized to a mid-central region, similar to the alpha difference seen previously during deep sleep between PI and GSC groups, but also extended frontally.

Conclusion
Sleep state misperception may result from a localized increase in alpha activity while sleep persists. Serial awakenings are a useful tool for examining this paradoxical state.

Support (If Any)
Funded by the MERCK Sharp and Dohme Corporation.
0171 Parabrachial-CGRP neurons regulate awakenings to pain stimulus
Authors: Lynch Nicole , Thomas Renner , Saper Clifford , Kaur Satvinder 
Published: May 2022

Abstract

Introduction
The external lateral part of the PB (PBel), receives spinal afferents carrying pain-signals, which are then relayed to other brainstem and forebrain arousal areas. Many PBel neurons that express calcitonin gene-related peptide [CGRP; PBelCGRP] also receive spinal afferents carrying pain signals. Selective activation of PBelCGRP neurons, in CGRP-CreER mice, cause short latency cortical arousal, while inhibition of these neurons prevents waking to hypercapnia. Also, blocking CGRP receptors has a potential to reverse opiate tolerance in rodents, however, mechanism of action or the circuitry remains unknown.

Methods
To test if PBelCGRP is the critical relay node transmitting pain to induce cortical arousals, we conducted either genetic deletion or acute optogenetic inhibition of this node, in both inflammatory pain and opto-pain models. All mice were implanted for recording sleep.Inflammatory-pain model: CGRP-creER mice were bilaterally injected with AAV-Flex-DTA (n=10) to delete CGRP neurons in PBel or AAV-GFP (n=6; control). Both groups received a foot injection of either 5% formalin or saline (10 µl) and were recorded for the sleep.Opto-pain model: CGRP-ChR2 mice were injected in the PB with AAV-Flex-JAWS (n=5) and implanted with bilateral optical fibers directed to the PB, and miniature probes in the foot pad to facilitate stimulation of the nociceptors. We recorded sleep while stimulating nociceptors every 5 min with or without opto-inhibition of PBelCGRP.

Results
In mice with intact CGRP neurons, foot stimulation with formalin produced 100% wakefulness for the first three hours, while with deletion of PBCGRP neurons, pain induced sleep loss could be attenuated in both males (by 83%) and females(by 60%). This recovery of NREM sleep significantly correlated with loss of PBelCGRP. In the opto-pain model, opto-stimulation of nociceptors at 10Hz for 5 sec woke up mice in 100% of the trials with a short latency of 4.4 ± 0.78 sec, while opto-inhibition of PBelCGRP that expressed JAWS, by red laser that preceded the nociceptive stimulus by 20s, prevented stimulus-induced awakenings.

Conclusion
This suggests that PBelCGRP is the main relay node for awakening to pain. We are now investigating the terminal fields of the PBelCGRP neurons to assess which of them contribute to pain induced arousal.

Support (If Any)
NS112175
0176 Comparing Sleep and Homeostatic Sleep Drive Between Retired Night Shift Workers and Retired Day Workers
Authors: Lehrer H Matthew , Tracy Eunjin Lee , Chin Brian , Kimutis Sarah , Krafty Robert , Hall Martica , Buysse Daniel 
Published: May 2022

Abstract

Introduction
Retired night shift workers report poorer sleep quality compared to retired day workers, even after returning to a nocturnal sleep schedule, suggesting a potential “scarring” of night shift work on sleep. History of sleep deprivation and sleep at an unfavorable circadian phase may compromise sleep and homeostatic sleep regulation, potentially contributing to poor sleep quality in retired night shift workers. This study compared sleep efficiency and homeostatic sleep regulation in response to sleep deprivation (delta EEG power during NREM sleep, theta EEG power during wakefulness) between retired night shift workers and retired day workers.

Methods
Participants (N = 75, mean age: 68.3 +/-5.5 years, 51% females, 87% non-Hispanic White) were 35 retired night shift workers and 40 age-, sex-, and race-equated retired day workers. Participants completed a 60-hour laboratory study including one baseline night of sleep, followed by 36 hours of sleep deprivation, followed by one recovery night of sleep. Sleep efficiency and NREM delta EEG power were measured by polysomnography on both nights, and waking theta EEG power was measured every other hour during the 36-hour sleep deprivation period. We analyzed the effects of group (retired night shift workers vs. retired day workers), time (baseline vs. recovery night for sleep efficiency and delta EEG power, hour for theta EEG power), and their interaction on each outcome using linear mixed models.

Results
Groups did not differ in sleep efficiency averaged across nights (F=1.48, p&gt;0.05) or from baseline to recovery nights (F=0.05, p&gt;0.05). Delta EEG responses to sleep deprivation did not differ by group (F=0.33, p&gt;0.05). Compared to retired day workers, retired night shift workers showed greater overall waking EEG theta power during sleep deprivation (F=13.20, p&lt;0.001). The group by time interaction was not significant (F=0.36, p&gt;0.05), suggesting that group differences in theta EEG power were not due to increased sleep deprivation.

Conclusion
Sleep efficiency and homeostatic sleep regulation appeared to be preserved in retired night shift workers. Theta EEG power findings suggested greater sleep propensity during wakefulness in retired night shift workers. Interventions to improve sleep quality in retired night shift workers may leverage intact homeostatic sleep regulation mechanisms.

Support (If Any)
R01AG047139, T32HL082610, T32HL07560, T32MH019986
0178 Examining Rates and Change in Insomnia Severity among Veterans Enrolled in an Outpatient Exercise Program
Authors: Boyle Julia , Bamonti Patricia , Harris Rebekah , Moye Jennifer , Bean Jonathan 
Published: May 2022

Abstract

Introduction
Exercise moderately improves middle insomnia and sleep quality in older adults. GeroFit is a national structured exercise program for Veterans over age 60 that offers 14 virtual classes per month. Each 60-minute class has a combination of cardiovascular, resistance, flexibility, and balance training and is modified to accommodate the range of functional abilities. The purpose of this analysis was to characterize insomnia symptoms (using the Insomnia Severity Index [ISI]) among GeroFit participants across different time points and examine the impact of attendance on change in insomnia symptoms over time.

Methods
Veterans in the VA Boston GeroFit program (n=69; 60-93years; Meanage=74.3±8.3; 80.6%male; 80.6%White) were administered the ISI at baseline (n=32), 3-months (n=38), 6-months (n=23), and 12-months (n=21) after enrollment. Participants were categorized by ISI scores: no clinically significant insomnia (ISI=0-7), subthreshold insomnia (ISI=8-14), moderate clinical insomnia (ISI=15-21), and severe clinical insomnia (ISI=22-28). A repeated measures ANOVA was performed to assess for ISI score change over time by attendance rate.

Results
Veterans attended 64% of the 14 classes per month and exhibited a range of functional ability (Physical Function Subscale [SF-36] scores ranged from 11-29 at baseline). The rates of subthreshold and moderate insomnia were: baseline (15.6%;6.3%), 3-months (26.3%;13.2%), 6-months (30.4%;8.7%), and 12-months (38.1%;9.5%), respectively. Overall, ISI scores remained consistent over time as there were no significant score changes over the first 6 months (p=.121); however, participants with &lt;50% attendance demonstrated a significant increase in ISI scores from baseline to 3months (p=.002).

Conclusion
Of Veterans participating in the VA Boston GeroFit program, about 1 in 10 reported moderate insomnia and 1 in 4 had subthreshold insomnia. Increasing attendance rates is important for improving sleep quality and more research is needed to clarify the “dose” of exercise required to reap meaningful gains in insomnia symptoms, particularly among Veterans with more severe symptoms. Given that 1/3 of participants reported at least subthreshold insomnia, future studies are needed to better understand whether supplemental interventions (e.g., sleep psychoeducation, stimulus control) might be offered to GeroFit participants with clinically significant insomnia symptoms, to dually target sleep and physical functioning.

Support (If Any)
0186 Post-Birth Feeding Experiences are Associated with Actigraphy-Assessed Sleep Patterns among Newborns
Authors: Petrov Megan , Jiao Nana , Whisner Corrie 
Published: May 2022

Abstract

Introduction
Exclusively breastfed (EBF) newborns wake more often at night than partially breastfed, or exclusively formula fed (EFF) newborns. Contextual factors during the first weeks of life related to these associations are understudied. We examined relationships among post-birth experiences, objectively-estimated sleep-wake patterns, and feeding practices through three weeks post-delivery.

Methods
English or Spanish speaking mothers (n=20) and their full-term (≥37wk), singleton infants were recruited from Phoenix, Arizona. Mothers were 32.7±5.1y, 30.0% identified as Hispanic, 20.0% with &lt; high school degree, and 15.0% were enrolled in the federal Women, Infants, and Children program. Infants were born normal weight (2500-4000g) and without major complications. At three weeks post-delivery, infants wore a Micro Motionlogger (Ambulatory Monitoring Inc.) on their left ankle for five 24hr periods at three weeks of age. Mothers completed an accompanying sleep diary and an adapted Infant Feeding Practices Study-II questionnaire. Pearson correlations and t-tests examined relationships between nocturnal sleep-wake patterns and feeding practices at birth and 3-weeks post-delivery.

Results
At birth, all mothers attempted breastfeeding, 40.0% of infants received formula, and mean time for milk to come in was 2.7 days (range: 1-4). At three weeks, one mother was EFF, 55.5% (n=11) were EBF, and 40.0% (n=8) were mixed feeding. Infant sleep-wake patterns included midpoint of 2:40±1:01, long wake episode (≥5min) frequency of 5.8±2.3, longest sleep bout duration of 127.2±34.9min, WASO of 124.1±54.3min, and TST of 434.7±79.7min. Breastmilk feeding frequency was positively related to long wake episode frequency (r=.49, p=0.03) and WASO (r=.47, p=0.04), and negatively related to longest sleep bout (r=-.59, p=0.006). Formula feeding frequency was positively related to longest sleep bout (r=.58, p=0.007). Greater time for milk to come in was positively related to long wake episode frequency (r=.53, p=0.02) and WASO (r=.56, p=0.01), and negatively related to longest sleep bout (r=-.47, p=0.04). Receiving formula in the hospital was associated with later sleep midpoint (t[18]=3.2, p=0.005), regardless of current formula feeding.

Conclusion
Feeding experiences and ability to breastfeed during the first few days of life may play a role in the quality and patterning of actigraphy-estimated sleep among newborns. Future research should investigate whether these associations persist into later infancy.

Support (If Any)
National Institutes of Health / National Heart, Lung, and Blood Institute R01 HL147931
0190 Association of Sleep Spindle Activity with Cognition in Youth from the General Population
Authors: Ricci Anna , He Fan , Calhoun Susan , Fang Jidong , Vgontzas Alexandros , Liao Duanping , Bixler Edward , Younes Magdy , Fernandez-Mendoza Julio 
Published: May 2022

Abstract

Introduction
Sleep spindle activity has been increasingly studied as an underlying mechanism of cognition. In youth, it appears the relationship between spindle activity and cognition depends upon the spindle metric and cognitive domain examined. Prior research has been conducted primarily in highly selective experimental studies of typically developing youth. We aimed to clarify the relationship between spindle activity and lower and higher order cognitive functions in children and adolescents from the general population.

Methods
We studied 639 children aged 5-12y (median 9y) and 418 adolescents aged 12-23y (median 16y) from a population-based cohort. All subjects underwent a 9-hour, in-lab polysomnography. We calculated sleep spindle density (SSD), the total number of spindles per minute of stage 2 of non-rapid eye movement sleep, and peak spindle frequency (PSF) in the 10-16 Hz range at central, frontal and fronto-occipital derivations. Wechsler intelligence testing assessed verbal and non-verbal intelligence quotients (IQ), processing speed (coding) and working memory (digit span backward [DSB]). Multivariable-adjusted linear regression models with age, sex, race/ethnicity, body mass index, apnea/hypopnea index, and insomnia symptoms as covariates examined the association between SSD and PSF with cognitive outcomes.

Results
At ages 5-12, central SSD was positively associated with verbal IQ (p=0.04), non-verbal IQ (p=0.03), coding (p=0.01) and DSB (p&lt;0.01); additionally, frontal SSD was positively associated with coding and DSB (both p&lt;0.01) and fronto-occipital SSD with DSB (p&lt;0.01). Also, central (p&lt;0.01) and frontal (p=0.01) PSF was positively associated with DSB. At ages 12-23, fronto-occipital SSD was positively associated with non-verbal IQ (p=0.02), while no other statistically significant associations were observed for SSD or PSF with cognitive outcomes (all p≥0.08).

Conclusion
Spindle density is a strong correlate of general ability (both verbal and non-verbal IQ) in childhood, and it remains for non-verbal IQ in adolescence. Both increased spindle density and peak frequency are associated with better working memory in childhood, yet not in adolescence. These developmental differences may be due to cortical (e.g., synaptic pruning) and thalamocortical (e.g., increased myelination) maturational changes occurring during adolescence.

Support (If Any)
National Institutes of Health (R01MH118308, UL1TR000127)
0191 Characteristics of sleep spindles across development in males with Duchenne/Becker Muscular Dystrophy Disorder
Authors: Simon Katharine , Nakra Neal , Mednick Sara , Malerba Paola , Nagel Marni 
Published: May 2022

Abstract

Introduction
Sleep supports cognition, in particular, the consolidation of memories. Sleeping brain rhythms, such as slow oscillations (1hz) and spindles (9-15 Hz), play a key role in facilitating this consolidation. Our prior research reported age-associated declines in slow oscillations in Duchenne and Becker Muscular Dystrophy (DMD/BMD) (Simon et al., 2020). Here, we characterize age-associated changes in sleep spindle characteristics across development in this group.

Methods
Following our 2020 analysis, we retrospectively analyzed the clinical sleep studies of 28 DMD/BMD males (Age span: 4 to 20 years). We applied our spindle detection algorithm to six electrodes (F3, F4, C3, C4, 01, O2). We assessed spindle density, frequency, and amplitude based on age (child, early adolescent, and late adolescent).

Results
We conducted rmANOVAs to evaluate each spindle characteristics using within-factors (Stage and Electrode) and between-factor (Age). We found significantly more spindles with longer durations in N2 than N3; greater spindle density at frontal compared to occipital regions; and higher amplitudes at central compared to frontal sites. We found no age-associated changes in these spindle metrics. We did find an age-associated change in the frequency of spindles, with significantly greater average spindle amplitude increasing significantly with age.

Conclusion
In line with prior research, we found more spindles in N2 than N3 and greater spindle density at frontal compared to posterior electrodes. In contrast to our previous research demonstrating age-associated declines in slow oscillations, our current analyses show minimal age-associated changes in spindle characteristics from 4 to 20 years. Further analysis is required to assess for age-associated changes in spindle-slow oscillation coupling occur across development. Our findings have implications for functional changes in sleep-dependent cognition mechanisms across development in BMD/DMD.

Support (If Any)
0195 Integrated actigraphy-based biomarker for the risk of Alzheimer’s dementia
Authors: Yang Hui-Wen , Li Peng , Sun Haoqi , Maher Matthew , Lane Jacqueline , Lim Andrew , Bennett David , Yu Lei , Saxena Richa , Buchman Aron , Hu Kun 
Published: May 2022

Abstract

Introduction
Many physiological measures derived from actigraphy including physical activity, sleep, circadian/daily rhythm, and temporal correlations have been shown to predict Alzheimer’s dementia (AD). This study aimed to combine these actigraphy-based measures to develop an integrated actigraphy biomarker (IAB) for AD and to test its link to the genetic risk for AD.

Methods
We analyzed data of 1107 participants (age 80.9±7.3(mean±SD)) from the Rush Memory and Aging Project who were non-demented and had actigraphy (~10 days) at baseline, and had annual cognitive assessment during the follow-up (1-15 years). 270 developed AD (mean = 7.4 years). To construct the IAB for the AD’s risk, we trained a random forest survival model, in which time to incident AD was the outcome, and inputs included 10 features derived from actigraphy data: physical activity level, 3 features for sleep (sleep duration, sleep fragmentation, activity fragmentation), 4 features for circadian rhythmicity (amplitude, acrophase, interdaily stability, and intradaily variability of 24-hr rhythms), and 2 features for temporal correlations (at timescales between 1-90 min and 120-480 min). Polygenic risk score (PRS) was calculated using 457 independent SNPs strongly associated with Alzheimer’s disease (p&lt;0.001). Cox proportional hazard ratio models were performed with different combinations of IAB, PRS, age, sex, and education, and the concordance score (C-score) was used to evaluate model performance.

Results
The derived IAB was 0.6 SD larger in the AD group as compared with the controls. The IAB alone achieved a C-score = 0.61 in predicting AD, with a hazard ratio=1.5 for 1-SD increase in IAB. The IAB and PRS were not correlated (r2=0.0004, p=0.25), and both significantly contributed to the prediction (both p&lt;=0.0001) when included in one model, giving a C-score of 0.65. C-score was 0.7 in the model using only age, sex and educations yielded, and increased to 0.74 after including IAB and PRS (both effects remained significant p&lt;0.0001).

Conclusion
The integrated actigraphy biomarker may provide complementary information for early prediction and detection of AD, independent of the known demographic and genetic risk factors.

Support (If Any)
NIH (RF1AG064312, RF1AG059867, R01AG56352, R01AG17917, T32GM007592, and R03AG067985); The BrightFocus Foundation (A2020886S).
0196 Retinal responsivity is associated with circadian phase and circadian alignment but not sleep timing
Authors: Wescott Delainey , Klevens Alison , Hasler Brant , Franzenn Peter , Roecklein Kathryn 
Published: May 2022

Abstract

Introduction
Light entrains the central circadian clock, with projections from the retina to the SCN through melanopsin-containing retinal ganglion cells (ipRGCs). Altered responsivity to light reflects ipRGC functioning and may be a physiological vulnerability for disrupted photoentrainment. Understanding how retinal responsivity relates to sleep and circadian timing may inform who might most benefit from sleep and circadian interventions.

Methods
64 participants (85 observations) ages 20-66 years old were recruited during winter (n=35) and summer months (n=50), and included individuals with seasonal depression (n=33) and nonseasonal, never depressed controls (n=31). The post-illumination pupil response (PIPR) to red and blue light was used to measure the responsivity of ipRGCs (average 1:30pm; 10am-7pm). Circadian phase was assessed using Dim Light Melatonin Onset (DLMO), collected every 30-minutes on Friday evenings. Midsleep timing was measured using actigraphy (average number nights=4), and circadian alignment was calculated as the DLMO-midsleep phase angle. We performed a multilevel regression to determine the relationship between PIPR and markers of sleep and circadian timing, accounting for repeated seasonal assessments with a random intercept of participant. Covariates included age, gender, diagnostic group, and circadian time of PIPR assessments. We ran sensitivity analyses including photoperiod length on the day of PIPR assessment to account for potential light exposure on the PIPR.

Results
Greater retinal responsivity was associated with later DLMO (b=4.45; partially standardized b=0.28; SE=1.84; p=0.03), and shorter DLMO-midsleep phase angle (b= -7.33; partially standardized b= -0.32; SE=2.51; p=0.004), but not midsleep (b= -3.44; partially standardized b= -0.14; SE=2.35; p&gt;0.05). Individuals with later DLMO had PIPR assessments at earlier circadian times (b= -0.12; SE=0.04; p=0.01). Older participants (b= -0.04; SE=0.02; p=0.04) and controls (b= -0.95; SE=0.44; p=0.04) had earlier sleep midpoints, but covariates were not associated with circadian markers. The association between circadian timing and PIPR became nonsignificant (b=4.15; partially standardized b=0.26; SE=1.88; p=0.06) when including photoperiod.

Conclusion
Retinal responsivity was associated with circadian but not behavioral sleep timing, suggesting ipRGC functioning may have downstream effects on circadian entrainment. Assessing circadian variation of retinal responsivity remains a crucial next step prior to testing whether retinal responsivity impacts response to circadian-focused interventions.

Support (If Any)
NIMH K.A.R.MH103303