bluuebunny/crossref_metadata_2025_split huggingface dataset:
0437 Characterizing the Impact of EEG Referencing on Sleep Spindle and Slow Oscillation Analyses
Authors: He M , Prerau M J , Dimitrov T S 
Published: May 2020

Abstract

Introduction
The impact of EEG referencing on sleep oscillations, such as spindles and slow oscillations, is largely overlooked across studies. While it is recognized that a topographic head plot of EEG activity does not reflect the true location of the underlying cortical activity, spatial distributions, as well as spectral properties and morphology of EEG oscillations can change dramatically as a function of referencing scheme. It is therefore vital to understand the impact of referencing when drawing inferences about the nature of EEG sleep oscillations. In this study, we use MRI structural data to construct subject-specific forward models of EEG signals. Using these models, we can simulate cortical activity and observe its true representation on the scalp. In particular, we simulate spindles and slow wave oscillations and examine how referencing affects topography, spectral power, and phase of oscillations.

Methods
High-density EEG (Brain Vision, 64-channel) polysomnography was performed on 9 healthy young subjects. 3T structural MRI scans were acquired and forward models were built in MNE-Python using 3-shell Boundary Element Models (BEM) based on individual anatomical details processed with Freesurfer. Simulations of various sleep spindle and slow oscillation dynamics were projected to the sensor space. Different referencing schemes (common average, Laplacian, linked-mastoid) were then applied to the experimental and simulated data and analyzed for effects on time-frequency characteristics of sleep oscillations.

Results
Analyses of experimental data showed distinct reference-based differences in topographical distribution of spectral power and phase of oscillations. Simulated data revealed many scenarios in which the spatial distribution of activity the EEG sensor space poorly represented the true location of the underlying source activity. Moreover, there were alterations to the spatial spread and envelope form of sleep spindle events under different referencing schemes despite from identical source activities.

Conclusion
This study shows that spindle and slow oscillation activity is highly variable across referencing schemes and that EEG topographical plots on the scalp may poorly represent cortical activity locations. It is thus vital to consider the choice of referencing when quantifying characteristics of sleep EEG oscillations.

Support
This work was supported by R01 NS-096177.
0441 An Automatic Sleep Scoring System Based on Ensemble Convolutional Neural Network and Spectrogram of Sleep Physiological Signal
Authors: Kuo C , Chen G 
Published: May 2020

Abstract

Introduction
Manual sleep stage scoring is time consuming and subjective. Therefore, several studies focused on developing automated sleep scoring algorithms. The previously reported the automatic sleep scoring have been develop usually using small dataset, which less than 100 subjects. In this study, an automatic sleep scoring system based on ensemble convolutional neural network (ensemble-CNN) and spectrogram of sleep physiological signal was proposed and evaluated using a large dataset with sleep disorder.

Methods
The spectrograms were computed from each 30-s EEG and EOG of 994 subjects from PhysioNet 2018 challenge dataset, using the continuous wavelet transform, which were fed into an ensemble-CNN classification for training. The ensemble-CNN contained five pretrained models, ResNet-101, Inception-v4, DenseNet-201, Xception, and NASNet models, because these models’ architectures are different which can learn different features from the spectrograms to obtain high accuracy. The probabilities of five models were averaged to decide the sleep stage for each spectrogram. After classifying sleep stage, a smoothing process was used for sleep continuity. Moreover, the total 80% data from PhysioNet dataset were randomly assigned to the training set, and the remaining data were assigned to the testing set.

Results
To validate the robustness of the proposed system, the validation procedure was repeated five times. The performance measures were averaged over the five runs. The overall agreement and kappa coefficient of the proposed method are 82% and 0.73, respectively. The sensitivity of the sleep stages of Wake, N1, N2, N3, and REM are 90.0%, 48.6%, 84.9%, 84.2%, and 81.9%, respectively.

Conclusion
The performance of the proposed method was achieved expert level, and it was noted that the ensemble-CNN is a promising solution for automatic sleep stage scoring. This method can assist clinical staff in reducing the time required for sleep stage scoring in the future.

Support
This work was supported by the Ministry of Science and Technology, Taiwan. (MOST 106-2218-E-035-013-MY2, 108-2221-E-035-064, and 108-2634-F-006-012).
0445 A Novel Algorithm for the Estimation of Sleep States Based on Breathing and Movement
Authors: Dietz-Terjung S , Martin A , Schöbel C 
Published: May 2020

Abstract

Introduction
We tested the diagnostic accuracy of the novel Nox BodySleep™ algorithm (Nox Medical, Iceland) for the estimation of sleep states from polygraphy (PG) sleep recordings based on features extracted from actigraphy and respiratory inductance plethysmography (RIP) belts. The algorithm automatically classifies epochs into three states, Wake, REM sleep and NonREM sleep. Validation was performed against polysomnography (PSG) in a sleep laboratory collective including patients with sleep disordered breathing (SBAS) and sleep related movements disorders.

Methods
Patients received PSG according to clinical routine. The recording was evaluated by the novel algorithm and the results were evaluated by descriptive statistics methods (IBM SPSS Statistics 25.0).

Results
We found a good Spearman correlation (r=0.8) and a bias of 11 minutes for the estimation of Total Sleep Time. Sleep Efficiency was also valued with a good Spearman correlation (r=0.7) and a bias of 1.6%. Wake phases were estimated with a F1 score of 0.64 while REM and Non-REM phases were evaluated with a F1 score of 0.73 and 0.82, respectively. Additionally, an overall accuracy of 0.8 and a Cohens kappa of 0.7 were found. Patients with sleep related movement disorders showed a slighly weaker correlation as patients with SBAS.

Conclusion
The algorithm shows a good diagnostic accuracy for the estimation of sleep states and significant sleep parameters. After validation on a larger patient collective, it could be used in the ambulatory and telemedical field to allow investigations comparable to the accuracy of a PSG.

Support
No support.
0454 Sleep Disruptive Cognitions in Deployment-Related Insomnia
Authors: Howell M , Mellman T 
Published: May 2020

Abstract

Introduction
Sleep disturbance is common following military deployment, and insomnia is associated with many adverse psychiatric and medical outcomes. Deployment to a threatening environment can engender nocturnal vigilance, which may be a salient feature of sleep disturbance in formerly deployed Veterans. Cognitive behavioral therapy for insomnia (CBTI) is an effective treatment; however, CBTI emphasizes targeting dysfunctional beliefs about sleep (DBAS) and generalized worries rather than vigilance. The goal of the present study was to investigate the role of vigilance, in relation to other potential types of sleep-interfering cognitions in formerly deployed Veterans with sleep disturbance.

Methods
Thirty-nine formerly deployed Veterans with disturbed sleep completed measures prior to an intervention. Insomnia was measured with the Insomnia Severity Index (ISI) and measures derived from actigraphy and morning sleep diaries administered for one week. Measures for sleep interfering cognitions included Dysfunctional Beliefs about Sleep (DBAS), the Penn State Worry Questionnaire (PSWQ), a measure of generalized worry, and the Fear of Loss of Vigilance (FLV) subscale of the Fear of Sleep Inventory (FOSI).

Results
All of the measures of sleep-interfering cognitions were significantly associated with ISI score. Generalized worries (PSWQ scores) were strongly and significantly correlated with both FLV and DBAS, which were not significantly correlated with each other. FOSI FLV explained 7.1% more variance in ISI score than DBAS alone (p = .04) while DBAS explained 23.1% additional variance in ISI score over FOSI FLV alone (p &lt; .001).

Conclusion
It may be important to target both nocturnal vigilance and dysfunctional beliefs about sleep in the treatment of insomnia in formerly deployed Veterans.

Support
Supported by W81XWH-14-1-0066 from the Congressionally Directed Peer-Reviewed Medical Research Program of the Department of Defense.
0461 Blunted Baroreflex Sensitivity and Reduced Morning Parasympathetic Activity in Sleep-Onset Insomnia
Authors: Tsai H , Kuo T , Yang C 
Published: May 2020

Abstract

Introduction
Insomnia is a risk factor for hypertension and cardiovascular events, and this association is strongest for sleep-onset insomnia. However, little is known about insomnia on cardiovascular modulation, especially soon after morning awakening, the peak period of time for cardiovascular incidents. This study explored morning cardiovascular function in individuals with sleep-onset insomnia by analysing heart rate variability, blood pressure variability, and baroreflex sensitivity.

Methods
Sleep structure of the participants (15 good sleepers and 13 individuals with sleep-onset insomnia) was measured by laboratory polysomnography, followed by continuous recordings of the participant’s blood pressure and heart rate for 10 min in the morning.

Results
When compared to the good sleepers, the insomnia group showed significant reductions in total sleep time, a longer sleep-onset latency, and reduced sleep efficiency. The sleep structure, including durations of sleep stages, numbers of awakenings and arousal index did not differ between the groups. After morning awakening (averaged time: 12.33 ± 10.48 min), the shorter R-R intervals, lower total power, and lower high-frequency power of heart rate variability were observed among individuals with sleep-onset insomnia, compared with good sleepers. Elevated slopes of systolic and diastolic blood pressure, as well as lower baroreflex sensitivity, were also shown in the insomnia group. Indices of sympathetic activity, including low-frequency percentage of heart rate variability or low-frequency power of blood pressure variability, did not differ between the groups.

Conclusion
Weak vagal activity and blunted baroreflex sensitivity were evident among sleep-onset insomnia. These findings indicate difficulty in initiating sleep, without significant sleep fragmentation, can independently affect morning cardiovascular function. This study provides a possible link between sleep-onset insomnia and risk of cardiovascular events.

Support
N/A
0464 Sleep Continuity by Neighborhood: Are There Differences?
Authors: Giller J , Muench A , Grandner M A , D’Antonio B , Perlis M L 
Published: May 2020

Abstract

Introduction
To our knowledge, no prior work has been conducted on whether sleep continuity disturbance (e.g., SL; WASO; EMA, etc.) varies by neighborhood. While differences on these metrics have been found by, e.g., race and socioeconomic status, it may also be that sleep continuity disturbance varies relative to where one lives and works. Accordingly, an analysis was undertaken to assess whether regional differences exist with respect to sleep continuity disturbance (SCD).

Methods
The study utilized a cross-sectional group design in an archival/community dataset that was collected in the Philadelphia area (www.sleeplessinphilly.com). This dataset (n = 2840) was comprised of adults between 18 and 89 years of age with self-reported sleep complaints (63.4% female; 36.6% male; average age 38). Study subjects who endorsed &gt;30 minutes on &gt;3 days/week on SL, WASO & EMA were categorized by zip code and into four regional groups: Center City (n=258); South Philadelphia (n=103); North & Northeast Philadelphia (n=400) and West Philadelphia (n=345). Contingency analyses and ANOVAS were used to assess for regional group differences.

Results
It was found that SCD rates significantly differed by region. Differences in percent endorsement by region were as follows, SL:, 64.1% (Northeast/North), 63.5 (South), 56.3% (West Philadelphia), & 48.7% (Center City); WASO: 45% (Northeast/North), 40% (South), 36.5% (West Philly), & 32.4% (Center City); EMA: 46.4% (South); 43.7 (Northeast/North); 43.7 (West Philly); 43.1 (Center City).

Conclusion
The Northeast/North region of Philadelphia had the highest rates, and center city had the lowest rates of SCD for the early part of the night (SL & WASO). Early morning SCD was most common for “South Philly and least common for Center City. Analyses are on-going in relation to other regional differences (demographic, income, crime stats, etc.) and those found to vary by region will be assessed for their predictive value.

Support
No support was provided for this abstract
0467 Benefits of CBT-I for Women Veterans with and without PTSD
Authors: Carlson G C , Kelly M R , Josephson K , Mitchell M , Fiorentino L , McGowan S , Culver N , Kay M , Alessi C , Washington D L , Yano E , Martin J L 
Published: May 2020

Abstract

Introduction
A quarter of women Veterans (WVs) receiving VA healthcare meet diagnostic criteria for both insomnia disorder and posttraumatic stress disorder (PTSD). Cognitive Behavioral Therapy for Insomnia (CBT-I) is effective at improving sleep among individuals with comorbid psychiatric conditions; however, no studies have examined the impact of CBT-I in women with insomnia plus PTSD. The current analyses examined changes in sleep symptoms, quality of life (QoL), and mental health symptoms from pre- to post-CBT-I in WVs with and without PTSD.

Methods
This was a secondary analysis of 75 WVs with insomnia (32 with probable PTSD), who received CBT-I within a behavioral sleep intervention study (NCT02076165). Measures completed at baseline, posttreatment, and 3-month follow-up included: insomnia severity (Insomnia Severity Index, ISI), sleep quality (Pittsburgh Sleep Quality Index, PSQI), PTSD symptoms (PTSD Checklist-5, PCL-5; probable PTSD=total score ≥33), depressive symptoms (Patient Health Qestionnaire-9, PHQ-9), and mental and physical quality of life (Short Form Health Survey, SF-12). One sample T-tests examined changes in ISI, PSQI, PHQ-9, PCL-5, and SF-12 from baseline to posttreatment and baseline to follow-up. Two samples T-tests compared change scores in ISI, PSQI, PHQ-9, and SF-12 between participants with and without PTSD.

Results
There were significant improvements in ISI (p≤.001), PSQI (p≤.001), PHQ-9 (p≤.001), PCL-5 (p=.001), and SF-12 mental (p≤.001) and physical (p=.03) from baseline to posttreatment and 3-month follow-up (p≤.001-.01). There were no significant change score differences between WVs with and without PTSD from baseline to posttreatment (p=.06-.98) or 3-month follow-up (p=.09-.93).

Conclusion
CBT-I appears to be an effective treatment to improve insomnia symptoms among WVs with and without PTSD, and may reduce psychiatric symptoms as well. These findings suggest WVs with comorbid insomnia and PTSD benefit from CBT-I. The appropriate sequencing of CBT-I and PTSD treatments remains potentially important, but unstudied.

Support
VA/HSR&D IIR-HX002300; NIH/NHLBI K24HL14305; VA Office of Academic Affiliations through the Advanced Fellowship Programs in HSR&D and Women’s Health
0472 Do the Subjective Effects of Hypnotic Medications Result in Unblinding of Treatment Assignment in Hypnotic Randomized Clinical Trials?
Authors: McCall W V , Benca R M , Rumble M , Krystal A D 
Published: May 2020

Abstract

Introduction
Some hypnotic medications have obvious subjective effects, including therapeutic effects (i.e., anti-insomnia effects), and side effects (i.e., feelings of impairment/intoxication). Information is lacking regarding whether the subjective effects of hypnotics result in unblinding of treatment assignment (active drug versus placebo) in hypnotic randomized clinic trials (RCTs), thus undermining internal validity of study results. In response, we now report the ‘best guesses’ of clinical trial participants, versus study coordinators, versus study physicians in the study Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT).

Methods
Eighty-nine of the 103 participants in the REST-IT study completed their ‘best guess’ regarding which randomized treatment they had been assigned. REST-IT was a blinded RCT, comparing zolpidem controlled release (CR) versus placebo at bedtime given over 8 weeks in adults with major depressive disorder who also had insomnia and suicidal ideation, and who also received open label fluoxetine. At the conclusion of study participation, the study participants, the study coordinators and the study physician each independently recorded their ‘best guess’ regarding which treatment arm the patient had been assigned. The study physicians and the study coordinators had access to the participants’ Insomnia Severity Index scores when the ‘best guess’ was made.

Results
Patients guessed correctly 58.4% of the time, coordinators 53.9% of the time, and physicians 49.4% of the time. The percentage guessed correctly did not differ significantly between groups. Physicians most often guessed placebo (56.2%) while study coordinators most often guessed zolpidem-CR (55.1%). Agreement between pairs of study participants with the study coordinators and the study physician was moderately high, with all kappa values 0.49- 0.57, and all kappa differences between zolpidem and placebo with p-values &gt;0.8.

Conclusion
The blind was maintained in this RCT of zolpidem-CR versus placebo, especially for the physicians. Our results may not apply to other hypnotics or other RCT designs.

Support
NIMH MH095776, MH095780, MH95778
0473 Effectiveness and Safety of Lemborexant in Subjects Previously Treated with Placebo for 6 Months in SUNRISE-2
Authors: Yardley J , Inoue Y , Pinner K , Perdomo C , Filippov G , Kubota N , Moline M 
Published: May 2020

Abstract

Introduction
In SUNRISE-2 (NCT02952820; E2006-G000-303), while lemborexant (LEM) provided significant benefit versus placebo (PBO) on sleep-diary measurements over 6mo, some improvement was noted in PBO subjects. We report outcomes from PBO subjects rerandomized to LEM during the last 6mo of SUNRISE-2.

Methods
SUNRISE-2 was a randomized, double-blind, global phase 3 study in adults (≥18y) with insomnia disorder. Subjects received PBO or LEM (5mg [LEM5]; 10mg [LEM10]) for 6mo. PBO subjects were rerandomized to LEM for another 6mo; LEM subjects continued assigned treatment. Changes from 6mo baseline (calculated after PBO completion) in subjective sleep onset latency (sSOL), subjective sleep efficiency (sSE), and subjective wake after sleep onset (sWASO) are reported for rerandomized subjects.

Results
At study baseline for PBO subjects (n=318), median sSOL (min) was 55.9, mean (SD) sSE (%) and sWASO (min) were 61.3 (17.8) and 132.5 (80.2), respectively. The 6mo baseline values for rerandomized PBO-LEM5 (n=133) and PBO-LEM10 (n=125) subjects, respectively, were: median sSOL, 31.2, 34.3; mean (SD) sSE, 70.5 (20.2), 71.1 (18.0); mean (SD) sWASO, 105.1 (80.6), 100.1 (84.6). Median sSOL decreased from the 6mo baseline after 1mo (PBO-LEM5, −3.2; PBO-LEM10, −2.9) and 6mo (PBO-LEM5, −2.7; PBO-LEM10, −5.0). Mean (SD) sSE increased from the 6mo baseline after 1mo (PBO-LEM5, 3.9 [12.1]; PBO-LEM10, 3.5 [8.1]) and 6mo (PBO-LEM5, 3.9 [13.6]; PBO-LEM10, 4.5 [13.0]). Mean (SD) sWASO decreased after 1mo (PBO-LEM5, −8.5 [49.4]; PBO-LEM10, −5.7 [36.1]) and 6mo (PBO-LEM5, −8.2 [49.0]; PBO-LEM10, −10.0 [58.8]). Treatment-emergent adverse events incidence was similar during PBO (62.7%) and LEM treatment (PBO-LEM5, 54.9%; PBO-LEM10, 57.7%). Adverse events were consistent with those seen in the initial 6mo of treatment for patients originally randomized to LEM.

Conclusion
Rerandomization to LEM was associated with additional improvement in sleep outcomes following the PBO-related response. LEM benefit was evident after 1mo and was sustained throughout treatment. LEM was well tolerated.

Support
Eisai Inc.
0479 Sleep Onset and Sleep Maintenance Responder Profiles Over 12 Months of Treatment with Lemborexant: Results from SUNRISE-2
Authors: Zammit G , Yardley J , Pinner K , Moline M 
Published: May 2020

Abstract

Introduction
In addition to analyzing treatment response by comparing change from baseline (CFB) between active treatment and placebo (PBO), it is also informative to evaluate the percent of patients with a given magnitude of response. This can help establish the expected degree of improvement for patients, thereby helping to determine treatment success.

Methods
SUNRISE-2 (NCT02952820; E2006-G000-303) was a randomized, double-blind, global phase 3 study of lemborexant (LEM) in adults (≥18y) with insomnia disorder. Subjects received PBO or LEM (5mg [LEM5]; 10mg [LEM10]) for 6mo. LEM subjects continued their original dose, while PBO subjects were rerandomized to LEM for another 6mo (not reported here). Responder profiles were constructed separately for patient-reported, sleep diary-based subjective sleep onset and sleep maintenance based on the cumulative proportion of subjects with CFBs in 10-minute increments for subjective sleep onset latency (sSOL) or subjective wake after sleep onset (sWASO), respectively. The proportion was based on number of subjects with baseline data (denominator) and data available at time of visit; study dropouts were considered nonresponders.

Results
Baseline values were similar (median sSOL [min]: PBO, 55.9; LEM5, 53.6; LEM10, 55.7; mean[SD] sWASO [min]: PBO, 132.5[80.2]; LEM5, 132.8[82.5]; LEM10, 136.8[87.4]). At 6mo, a higher percentage of subjects with CFB of ≥20min in sSOL was observed with LEM versus PBO (PBO, 30.4%; LEM5, 45.5%; LEM10, 44.9%). At 12mo, a similar percentage of responders with a ≥20min CFB in sSOL was observed for LEM (LEM5, 40.4%; LEM10, 43.3%). A higher percentage of subjects with a CFB in sWASO of ≥60min was observed for LEM versus PBO at 6mo (PBO, 24.2%; LEM5, 27.8%: LEM10, 30.2%); similar percentages were observed at 12mo with LEM (LEM5, 27.8%; LEM10, 27.7%). The majority of treatment-emergent adverse events were mild/moderate.

Conclusion
LEM treatment provided important levels of sustained efficacy over the long term. LEM was well tolerated.

Support
Eisai Inc.