bluuebunny/crossref_metadata_2025_split huggingface dataset:
0126 Zona incerta Lhx6 neurons are most active during NREM and REM sleep and after prolonged waking
Authors: Blanco-Centurion Carlos , Vidal-Ortiz Aurelio , Shiromani Priyattam 
Published: May 2022

Abstract

Introduction
Emerging data shows that GABA neurons in the zona incerta (ZI) play a prominent role in regulating sleep. Transfer of the orexin gene into ZI neurons blocks cataplexy in narcoleptic orexin-knockout mice (Liu et al., JNeurosci, 2011) and vGAT GABA neurons in the ZI anticipate onset of NREM (Blanco-Centurion et al., SLEEP, 2021). To identify the subtype of GABA neurons regulating sleep, we examined the activity of Lhx6 neurons. This study tests the hypothesis that Lhx6 neurons show peak calcium fluorescence during sleep, and that the fluorescence is further increased after prolonged waking.

Methods
In Lhx6-cre mice (mice=4; all females; 4-5 mo), rAAV-DIO-GCaMP6s was delivered stereotaxically to the ZI (isofluorane anesthesia) and a GRIN lens, along with EEG and EMG electrodes were implanted. 21d later a miniscope (INSCOPIX) was attached, and after 3d of adaptation, sleep and fluorescence in individual Lhx6 neurons were recorded for 4h (baseline). On another day, the mice were kept awake for 6h (gentle handling; 9a-3p) and fluorescence in Lhx6 neurons was recorded for 2h during recovery sleep. The imaged data from the two recording periods (baseline and recovery sleep) was combined into a single data file and the change in fluorescence was determined against the mean image frame (F0). Previously, we and others found that the GCamP calcium fluorescence is a direct measure of action potentials and serves as a marker of activity.

Results
97 neurons were automatically extracted (PCA-ICA analysis; blinded without knowledge of sleep state). In 66 neurons (68%) the average fluorescence was significantly higher during REM, NREM or both, compared to waking (Mixed Model ANOVA; SPSS25; P&lt;0.01). In this population the fluorescence was significantly higher during recovery sleep compared to baseline (P&lt;0.001) indicating increased activity of the sleep-active neurons during recovery sleep. With ensuing sleep, the increase in fluorescence gradually returned to baseline levels, attesting to the fluorescence as a marker of homeostatic sleep pressure. In 14 neurons (14%), fluorescence was highest in waking as compared to the other states during baseline, and in these neurons, fluorescence did not increase after sleep loss. Interestingly, six neurons (6%) were most active in waking and NREM but silent in REM (REM-off).

Conclusion
This is the first study to measure fluorescence in individual neurons after sleep loss. We find that the fluorescence in two-thirds of ZI Lhx6 neurons is tightly linked to sleep, and that the average fluorescence is further increased after prolonged waking. Microendoscopy is superior to indirect measures such as c-FOS or photometry in gauging sleep pressure in individual neurons.

Support (If Any)
VA BX000798, 1K6BX004216.
0131 Theta oscillations during REM sleep synchronize behavior and neural activity in the developing motor system
Authors: Dooley James , Sokoloff Greta , Blumberg Mark 
Published: May 2022

Abstract

Introduction
Myoclonic twitches are abundantly produced during REM sleep in skeletal muscles across the body. In infant rats, movements are produced by the red nucleus (RN), with the RN both sending motor commands and receiving sensory feedback from twitches. The RN’s role in producing twitches contrasts with that of primary motor cortex (M1), which does not generate motor commands at early postnatal ages. Instead, M1 functions as a sensory structure, processing sensory feedback from self-generated movements, including twitches. By postnatal day (P) 12, the RN (but not M1) also begins to exhibit a continuous theta rhythm (~6 Hz) during REM sleep that promotes sensorimotor integration with other brain areas. Given that the RN and M1 collaborate to control movement in adult rats, we hypothesized that theta emerges in M1 after P12, at which time theta synchronizes M1 and RN activity.

Methods
To determine if and when theta synchronizes activity in the RN and M1, we recorded local field potentials and unit activity in the RN and the forelimb region of M1 in unanesthetized preweanling rats at P12 and P20. Rats were head-fixed but were able to locomote and cycle freely between sleep and wake.

Results
Neurons in the RN and M1 continued to respond to twitches through P20. Further, as predicted, we observed the developmental emergence of REM-associated theta oscillations in M1 by P20 that were coherent with theta in the RN. Additionally, neural activity was phase-locked to theta; surprisingly, twitches were also phase-locked to theta, with twitches being more likely during the troughs of the oscillation. Finally, the temporal relationship between twitch-related activity in the two structures depended on the phase of theta, with twitch-related activity in M1 lagging behind twitch-related activity in the RN in the rising phase of theta. However, in the falling phase of theta, twitch-related activity in the RN and M1 showed similar time courses.

Conclusion
These results show how theta during REM sleep promotes the developmental integration of behavior with neural activity in the RN and M1. Because synchronous activity strengthens synaptic connectivity, and theta synchronized twitch-related activity in the RN and M1, these results also implicate twitches and twitch-related activity in the development of somatotopically precise functional connectivity between the RN and M1.

Support (If Any)
R37-HD081168 to M.S.B. and SRSF Career Development Award to J.C.D.
0132 Loss of Neurons in the Intermediate Nucleus is Related to Perturbed Sleep-Wake Rhythms in Older Adults
Authors: Wagner Max , Li Peng , Lim Andrew , Gao Lei , Gao Chenlu , Yang Hui-Wen , Yu Lei , Fan Wenqing , Bennett David , Buchman Aron , Schneider Julie , Saper Clifford , Hu Kun 
Published: May 2022

Abstract

Introduction
The ventrolateral preoptic nucleus (VLPO) is composed of neurons that are maximally active during sleep. In animal studies, VLPO lesion decreased the amount of sleep but only marginally attenuated circadian rhythm. The human intermediate nucleus (IN) is believed to be the homologue of the VLPO. Neuronal loss in IN has found to be associated with increased sleep fragmentation in older adults. We investigated whether IN neuronal loss is also associated with perturbed sleep-wake rhythms in humans.

Methods
We studied 50 deceased participants [age at death: 88.9±6.1 (mean±SD; female: 33 (66%)] from the Rush Memory and Aging Project, who had actigraphy assessment 1.6±1.3 years (range: 0.1-5.1 years) before death. Post-mortem immunohistochemical and stereological analysis was performed to quantify the count of galanin-immunoreactive neurons (Gal+) in the IN of them. Actigraphy data were used to calculate amplitude, acrophase, interdaily stability, and intradaily variability of the 24-h activity rhythms. Linear regression models were used to determine the associations of the four measures of sleep-wake rhythms with the GAL+ neuron counts, adjusting for age at death and sex. Further covariates considered included sleep fragmentation (derived from actigraphy) and the time interval between actigraphy assessment and death.

Results
The number of Gal+ neurons in IN was positively associated with interdaily stability and amplitude, and negatively associated with intradaily variability. Specifically, for one-SD decrease in Gal+ neurons, interdaily stability decreased by 0.06±0.02 (mean±standard error; equivalent to 40% SD of interdaily stability; p=0.009), amplitude decreased by 5.8±2.3 (equivalent to 35% SD of amplitude; p=0.014), and intradaily variability increased by 0.12±0.04 (equivalent to 36% SD of intradaily variability; p=0.009). Longer time interval between actigraphy and death showed a trend to attenuate these associations although not statistically significant (all p&gt;0.1). These observations also remained statistically significant after adjusting for sleep fragmentation.

Conclusion
Neuronal loss in the IN was linked with perturbed sleep-wake rhythms in older adults. Further investigations are warranted to examine whether the observed associations are mediated by reduced sleep quantity or other aspects of sleep quality.

Support (If Any)
NIH RF1AG064312, RF1AG059867, R01AG017917, R01AG56352; and the BrightFocus Foundation A2020886S.
0133 Sleeping Well or Sleeping Poorly: Clues from Brain Neurochemistry
Authors: Killgore William , Grandner Michael , Dailey Natalie , Reign Deva , Silveri Marisa 
Published: May 2022

Abstract

Introduction
Sleep problems are prevalent throughout the population, but little is known about the brain mechanisms that differentiate good and poor sleepers. We studied the association between brain neurochemistry, as measured by proton magnetic resonance spectroscopy (1H-MRS), and sleep quality as measured by actigraphy. We hypothesized that better sleep quality would be predicted by brain metabolites indicative of greater neuronal health, neural inhibition, and reduced levels of excitatory neurotransmitters.

Methods
24 healthy adults (12 females25.4±5.6 years) wore an actigraph for seven consecutive days to collect Time in Bed (TIB), Total Sleep Time (TST), Sleep Efficiency (SE), Sleep Onset Latency (SOL), and Wake After Sleep Onset (WASO), and underwent 1H-MRS neuroimaging at 3T. Metabolite data from the medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (dlPFC), and medial parietal-occipital cortex (P-OCC) were entered stepwise into a series of multiple linear regression models to predict each actigraphic outcome.

Results
For SE, the regression analysis yielded a significant three predictor model (adjusted R2=.59), p=.0001, including mPFC choline (Cho; β=-.60), P-OCC N-Acetylaspartate (NAA ; β=.56), and P-OCC glutamate+glutamine (Glx; β=-.33). Better SE was associated with a combination of decreased Cho within the mPFC, and increased NAA and decreased Glx within the P-OCC. SOL was predicted by mPFC Cho alone (β =.60; adjusted R2 = .33), p=.002. This suggests that greater Cho within the mPFC was associated with a longer latency to fall asleep. Finally, for WASO, the regression analysis yielded a significant two predictor model, (adjusted R2 = .39), p=.002, including mPFC Cho (β = .56), P-OCC NAA (β = -.41). This suggests that a combination of greater Cho within the mPFC and decreased NAA in the P-OCC was associated with more minutes of wake after sleep onset.

Conclusion
Sleep quality was predicted from brain metabolites within the medial default mode network (DMN), an interconnected system of cortical regions that is normally deactivated during effortful cognitive processing. Sleep quality was predicted by a combined pattern of metabolites consistent with greater neuronal integrity, reduced cellular turnover, and lower excitatory neurotransmitters. Findings suggest potential metabolic and neuroanatomic targets for enhancing brain health to facilitate sleep quality.

Support (If Any)
0150 Afternoon Napping Does Not Impact Autonomic Function in Healthy Adults
Authors: Nicevski Jennifer , Migliaccio Gianna , Bigalke Jeremy , Kerkering Emma , Greenlund Ian , Tikkanen Anne , Carter Jason 
Published: May 2022

Abstract

Introduction
Proper overnight sleep is important for autonomic nervous system function. However, less is known about the effects of daytime napping on wake autonomic regulation. In the present study, we assessed autonomic function following a daytime nap. We hypothesized that a 90-minute afternoon nap would significantly improve wake heart rate variability (HRV) and blood pressure (BP).

Methods
Fourteen participants (7 female, 24±1 years, 24 ±1 kg/m2) took part in the study. Subjects completed an autonomic function test after no nap (control condition) or a 90-minute nap opportunity (nap condition) on separate days using a randomized, crossover design. During the autonomic test, participants were fitted with three-lead electrocardiography (ECG), continuous beat-to-beat blood pressure (Finapres NOVA, Netherlands), and respiratory monitoring (pneumobelt). The autonomic function test consisted of 5-minutes of spontaneous breathing, 5-minutes of controlled breathing (15 breaths/min), and a 2-minute cold pressor test (CPT). Frequency-domain HRV in the low (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.4 Hz) components were determined via Fast Fourier transformation. Time-domain HRV was quantified using RMSSD and pNN50. Paired sample t-tests were completed between the control and nap sessions.

Results
Mean total sleep time (TST) for the nap session was 74±5 minutes. Contrary to our hypothesis, an afternoon nap did not change wake heart rate (HR, Control: 70±3 vs. Nap: 68±3 bpm, p = .31) or mean arterial pressure (MAP, Control: 77±3 vs. Nap: 83±3 mmHg, p = 0.70). Similarly, no differences were observed in HF (Control: 2632±628 vs. Nap: 2150±494 ms2, p = .33), LF (Control: 1702±373 vs. Nap: 1345±257 ms2, p = .20), or LF/HF (Control: 92±16 vs. Nap: 92±17%, p = .97) between conditions. RMSSD (Control: 82±12 vs. Nap: 79±11 ms, p = .723) and pNN50 (Control: 43±6 vs. Nap: 47±6%, p = .30) were not impacted by a daytime nap. Lastly, changes in HR (Control: ∆14±3 vs Nap: ∆18±3 bpm, p = .114) and MAP (Control: ∆23±4 vs. ∆Nap: 27±4 mmHg, p = .28) during CPT were not different between conditions.

Conclusion
An afternoon nap does not appear to significantly influence autonomic function at rest or during CPT in young healthy adults.

Support (If Any)
0151 Subjective sleep onset latency is influenced by the sleep structure and body heat loss in human subjects
Authors: Iijima Ryusei , Kadooka Akari , Sugawara Kairi , Fushimi Momo , Hosoe Mizuki , Aritake-Okada Sayaka 
Published: May 2022

Abstract

Introduction
Humans can estimate the time that has elapsed during sleep (time estimation ability; TEA). Although research on the TEA during sleep has advanced in the field of sleep research, few studies have focused on the relationship between the subjective sleep onset latency (SOL), which is an indicator of TEA, and objective sleep structures, body heat loss, and body temperature. This paper investigates the association of the subjective SOL with sleep structures such as the objective SOL, duration of each sleep stage, subjective sleep parameters, and body heat loss in healthy young participants.

Methods
Twenty six participants (7 men and 19 women, mean age of 21.5 ± 0.5 years) having no sleep problems participated in a 1-hour polysomnographic recording that obtained objective sleep parameters during the daytime while temperatures of the skin (i.e., dorsum of the hand and foot, forehead, and subclavian) and eardrum were recorded at intervals of 1 min. The distal–proximal skin temperature gradient (DPG), which is a good predictor of body heat loss and sleepiness, was calculated. Subjective parameters, such as the subjective SOL, sleep time, sleep depth, sleepiness, and mood, were evaluated before and after sleep. We examined the association of the subjective SOL with objective sleep parameters, DPG, and other subjective parameters.

Results
Most participants estimated their sleep latency to be longer than their actual SOL (mean objective SOL of 7.6 min vs. subjective SOL of 13.7 min). The objective SOL was significantly correlated with each sleep stage parameter whereas the subjective SOL was negatively correlated with the stage N2 sleep duration (Rho = −0.454, p = 0.020) and correlated with the stage N2 sleep latency (Rho = 0.402, p = 0.051). Participants who estimated a shorter subjective SOL had a higher DPG before sleep periods than that after sleep onset (Rho = −0.692, p &lt; 0.001). Additionally, the subjective SOL was correlated with the subjective sleep depth, subjective wake after sleep onset, and restorative sleep.

Conclusion
The subjective sleep onset latency in the healthy young participants was affected by the degree of body heat loss before sleep onset and stable shallow nonrapid-eye-movement sleep.

Support (If Any)
0152 A functional role for global slow oscillations in major depressive disorder with hypersomnia
Authors: Malerba Paola , Dave Abhishek , Cook Jesse , Mednick Sara , Plante David 
Published: May 2022

Abstract

Introduction
Sleep slow oscillations (SOs, 0.5-1.5Hz) during stages N2 and N3 sleep facilitate cortical communication and are important to the restorative properties of sleep. Spatiotemporal clustering analysis of SOs on the electrode manifold has identified 3 topographically distinct patterns of SOs: Frontal, Local, and Global. Global SOs are spatially widespread cortical events implicated in anterior-posterior long-range communication. However, their precise functional significance is not fully understood. Patients experiencing Major Depressive Disorder (MDD) with comorbid hypersomnia show local deficits in parieto-central slow wave activity, suggesting that frontally-initiated SOs are not propagating to parietal-central regions. Hypersomnolence in MDD may therefore be connected to insufficiently restorative sleep. Here, we retrospectively examine associations between Global SOs in N2 and N3 sleep and hypersomnia severity in healthy controls and MDD patients.

Methods
MDD patients with (n=22) and without (n=22) hypersomnia, and age-gender balanced healthy controls (n=22) underwent overnight polysomnography studies with 256-channel hdEEG. After detection of SOs, our previously developed classification method was applied retrospectively to all SOs in this dataset, including leveraging a k-means clustering algorithm naïve to the MDD/Hypersomnia label. Fractions of global SOs during stages N2 and N3 were compared across healthy controls and MDD patients. Finally, the fraction of global SOs occurring during the night was correlated against all subjects’ individual scores on the Hypersomnia Severity Index (HSI).

Results
Analysis of EEG data revealed pronounced, but not statistically significant deficits in global SOs during N3 sleep in MDD patients with comorbid hypersomnia. These deficits were significantly correlated with HSI when examining MDD patients together (Pearson’s r = -0.397, p&lt;0.01).

Conclusion
Our findings suggest that MDD patients with higher hypersomnia severity experience more pronounced deficits in Global SOs. Given the importance of SOs for the restorative properties of sleep, it is possible that MDD patients with hypersomnia might incur an enhanced sleep need driven by the homeostatic cost of a deficit in Global SOs.. Future studies are necessary to investigate causal mechanisms underlying these findings.

Support (If Any)
American Sleep Medicine Foundation (76-JF-12), Brain and Behavior Research Foundation (19193), and NIMH (K23MH099234) to DTP.
0158 Risk perception, outcome expectancy, and treatment self-efficacy among women and men with obstructive sleep apnea (OSA)
Authors: Sharma Akanksha , Byrne Sean , Deng Annan , Chu Jen-hwa , Sands Scott , Wellman Andrew , Redeke Nancy , Yaggi Henry , Zinchuk Andrey 
Published: May 2022

Abstract

Introduction
Continuous positive airway pressure (CPAP) is the first-line therapy for OSA. CPAP improves OSA severity, sleep architecture, and daytime symptoms. The effectiveness of CPAP, however, is limited to poor adherence. Individual's risk perception, outcome expectancy, and treatment self-efficacy predict CPAP adherence. CPAP adherence also differs by sex. However, it is unknown if predictors of CPAP use are different for women and men. We thus assessed sex differences in risk perception, outcome expectancy, and treatment self-efficacy among those with OSA.

Methods
Individuals enrolled to date (target n=267) in the NICEPAP study (NCT05067088), a prospective, observational cohort examining predictors of CPAP adherence, were included. Adults newly diagnosed with OSA prescribed CPAP therapy were included, while those with a need for non-CPAP therapy or unstable medical conditions (e.g., cancer receiving chemotherapy, severe lung, heart, or mental health disorders) were excluded. The exposure was sex. Co-primary outcomes were sub-scale scores from the Self-Efficacy Measure for Sleep Apnea (SEMSA) tool: Perceived Risk, Outcome Expectancies, and Treatment Self-Efficacy before starting CPAP. In addition, we assessed a comprehensive set of established psycho-social and biomedical CPAP adherence predictors using validated measures. SEMSA sub-scale scores for males and females were compared using Kruskal-Wallis statistics.

Results
We analyzed data for 33 females and 19 males. Females and males were 52 (41.0, 60.5) and 52 (35.0, 58) years old respectively (median [Q1, Q3]). Ten of 33 females and 4 of 19 males were Black with majority of others being White. The apnea-hypopnea index was 17.0 (9.1, 27.0) and 19.0 (13.3, 38.4), Epworth sleepiness scale and insomnia severity index scores were 9.0 (5.0, 12.0) & 15.0 (11.0, 18.0) and 6.0 (4.0, 9.0) & 17.0 (8.0, 19.5) for females and males respectively. There were no statistical differences in scores of Perceived Risk 2.4 (1.6, 2.9) vs 2.1 (1.8, 2.5) (p=0.717), Outcome Expectancies 2.8 (2.3, 3.4) vs 3.3 (2.4, 3.5) (p=0.371) or Treatment Self-Efficacy 3.1 (2.3, 3.7) vs 3.1 (2.0, 3.5) (p=0.977) for females vs. males.

Conclusion
We found no statistically significant differences in determinants of self-efficacy between women and men. Our findings may reflect a small sample size recruited to date or that self-efficacy of CPAP therapy is independent of sex.

Support (If Any)
This work was supported by Parker B. Francis Foundation and National Heart, Lung, and Blood Institute/NIH (1K23HL159259-01).