bluuebunny/crossref_metadata_2025_split huggingface dataset:
0431 Transcranial Electrical Stimulation with a Wearable Device Dramatically Reduces Sleep Onset Latency in Insomnia
Authors: Simons Stephen , Provo Maria , Shimizu Renee 
Published: April 2024

Abstract

Introduction
The normal transition to sleep is characterized by a reduction in higher frequency activity and an increase in lower frequency activity in frontal brain regions. In sleep onset insomnia these changes in activity are weaker and may prolong the transition to sleep. We performed a translational study to investigate the impact of a new wearable neurotechnology using 0.75 Hz transcranial electrical stimulation (tES) to improve sleep outcomes in a population displaying symptoms of sleep onset insomnia.

Methods
Participants were enrolled based on a qualifying insomnia severity index score of greater than 7 and an average sleep onset latency of greater than 30 minutes during baseline monitoring. Using a wearable device we compared 30 minutes of 0.75 Hz tES prior to going to bed with an active control at 25 Hz in the same individuals. Sleep behaviors were tracked in the home using a FitBit inspire wrist worn actigraphy device. Sleep onset latency (SOL), time asleep, and wake after sleep onset were measured during one-week baselines and then again over the two, one-week periods of use with the wearable device. Neurophysiological responses to both stimulation frequencies were observed using electroencephalography within the wearable device and correlated with observed differences in sleep behaviors. All outcome measures were compared against pre-stimulation baselines within subjects and then averaged across subjects.

Results
Treatment with 0.75 Hz consistently reduced SOL by 54% when compared with pre-treatment baselines (p&lt;&lt; 0.001). Stimulation with 25 Hz reduced SOL by 28% (p&lt; 0.05) but displayed order effects suggesting the possibility of placebo. The reduction in SOL with 0.75 Hz treatment was linearly proportional to an individual’s baseline with those individuals with the greatest severity realizing the greatest benefit (r^2 = 0.62, p&lt;&lt; 0.001). Changes in SOL were correlated with left/right coherence around the stimulation frequency of 0.75 Hz (r^2 = 0.33, p&lt; 0.01) providing a possible mechanism. Time asleep was increased by 20 minutes with 0.75 Hz treatment (p&lt; 0.05), and -1 minute with 25 Hz (N.S.).

Conclusion
Our study provides translational evidence for an exciting new treatment for sleep onset insomnia that is safe, effective and can be delivered in the home.

Support (if any)
0432 Neuromodulation of REM Sleep: Age-Associated Effects of Transcranial Magnetic Stimulation
Authors: Yakpogoro Nekabari , Desai Shivani , Huskey Alisa , Henderson-Arredondo Kymberly , Jankowski Samantha , Patel Salma , Hildebrand Lindsey , Trapani Christopher , Franca Gabriela , Reich-Fuehrer Melissa Melissa , Grandner Michael A , Chen Yu-Chin (Allison) , Chou Ying-Hui , Dailey Natalie , Killgore William 
Published: April 2024

Abstract

Introduction
We recently reported findings from a project that used a form of repetitive transcranial magnetic stimulation (rTMS) known as continuous theta burst stimulation (cTBS) to modulate connectivity within the brain’s Default Mode Network (DMN) as a potential treatment for insomnia. Continuous theta-burst stimulation(cTBS) was used to reduce cortical excitability within the DMN. Our prior analyses showed that the approach significantly improved total sleep time, sleep efficiency, N3 latency, and the arousal index, but rapid eye-movement (REM) did not appear affected. Based on growing evidence that REM sleep may show changes in the third decade and beyond, and that the effects of rTMS may be, at least partially, influenced by age, we further explored the potential effect of age in this dataset.

Methods
cTBS was administered to a total of 20 participants with self-reported insomnia symptoms (Mage=26.90, SD=6.56). Each participant underwent one round of sham stimulation and one round of active cTBS in a randomized order with one week in between. Participants were monitored with polysomnography (PSG) during a 7-hour sleep window. We first examined the association between age and REM sleep at each visit. A repeated measures ANOVA was employed, incorporating age as a covariate to assess potential age-dependent effects on cTBS effects.

Results
REM duration was positively correlated with age for the active cTBS visits (r=0.506, p=0.023) but not for the sham (r=-0.059, p= .806). With age as a covariate, the ANOVA revealed a significant effect of TMS treatment on REM sleep duration, F(1,18)=7.507, p=0.013. Participants in the TMS treatment group experienced an increase in REM sleep duration compared to the sham group when age was controlled in the analysis.

Conclusion
Age significantly influenced the effect of cTBS on REM sleep outcomes. The finding that older individuals demonstrated a greater effect of stimulation on REM duration suggests potential implications for clinical application in individuals with insomnia. Future work may focus on refining therapeutic strategies for sleep modulation, advocating for a personalized and age-aware approach.

Support (if any)
US Army Medical Research Acquisition Activity Grant: W81XWH2010173
0433 Suppression of the Default Mode Network Affects the Arousal and Reduces Time in Non-Restorative Sleep
Authors: Franca Gabriela , Negelspach David , Reich-Fuehrer Melissa Melissa , Franz Daniel , Wellman Camryn , Grabner Palmer , Huskey Alisa , Henderson-Arredondo Kymberly , Jankowski Samantha , Patel Salma , Trapani Christopher , Chen Yu-Chin (Allison) , Chou Ying-Hui , Dailey Natalie , Killgore William 
Published: April 2024

Abstract

Introduction
We recently demonstrated that continuous theta burst stimulation (cTBS), a form of suppressive transcranial magnetic stimulation (TMS), was effective at improving total sleep time, sleep efficiency and arousal index scores in people with symptoms of insomnia (Killgore, 2023, zsad077.0332). We now present additional analyses on the effects of this stimulation on functional brain activation during a complex cognitive task (multi-source interference task; MSIT) that targets the cingulo-frontal-parietal cognitive/attention network and its correlations with overnight polysomnography (PSG).

Methods
Nineteen people (11 females) with moderately severe symptoms of insomnia (age=27.2 SD=6.6), underwent active or sham cTBS followed by an overnight PSG monitored sleep study on two counterbalanced occasions separated by at least a week. Immediately before and after each cTBS/sham stimulation, participants completed functional MRI scans that included the MSIT. Contrasts were created between the more difficult interference condition and the simple control condition and task activation changes were compared across time and treatment condition using paired t-tests, repeated measures ANOVA, and within-condition Pearson’s correlations.

Results
A paired t-test of the primary task contrast (interference&gt;control) maps showed a significant decline from pre- to post-treatment in a region of the supplementary motor area (SMA) for the active cTBS (p&lt; 0.001, FWE corrected), but no change for the sham condition, as evidenced by a significant time x treatment interaction (p=.004). Moreover, for the sham condition, activation of this region was correlated with more time in wake/non-restorative sleep (i.e., wake, N1, N2, awakenings, and arousal index, all p-values&lt;.05), while for the active cTBS, changes in activation within this region were no longer associated with indices of poor sleep.

Conclusion
Building on our previously reported finding that cTBS reduced arousal and improved sleep time, this analysis suggests that activity within the SMA may play a role in mediating the insomnia-related symptoms with respect to arousal. Under sham conditions, increased activity of the SMA was associated with increased awakenings and arousal index. This disruptive effect appears to be eliminated by cTBS to the DMN. This result raises the possibility that insomnia symptoms may be partially mediated through the interactions between DMN and cognitive-attention networks.

Support (if any)
USAMRAA: W81XWH2010173
0437 The Effects of a 6-week Single-blind Online CBT-I Program on Daily Subjective and Objective Sleep Parameters
Authors: Topalidis Pavlos , Eigl Esther-Sevil , Hinterberger Alexandra , Schabus Manuel 
Published: April 2024

Abstract

Introduction
Insomnia exerts a substantial impact on a considerable portion of the population, resulting in significant detriments to health, workplace safety, and overall quality of life. Digital treatment programs have currently made effective and easily accessible treatment options possible. In our current study, we examine the impact of a 6-week single-blind digital CBT-I program by daily tracking sleep quality, duration, and fragmentation, subjectively and objectively. Tracking sleep objectively was made possible using an innovative sleep staging method founded on heartbeat variability and machine learning, enabling access to daily sleep macrostructure (i.e., a hypnogram).

Methods
Fifty-six participants with self-reported sleep problems were randomly assigned to either a control or an experimental group. Both groups used a mobile smartphone application daily to provide subjective reports and track their sleep using a heart-rate wearable (H10, POLAR®) over the course of 6 consecutive weeks. Only the experimental group completed the sleep training program (e.g., included educational videos, relaxation exercises, and cognitive training). We examined changes in subjective and objective sleep parameters using mixed Analysis of Variance with the factors Group (Control, Experimental) and Time (Beginning, End). We also analysed significant interactions with paired samples t-tests. Spearman correlations were used to examine the changes in daily sleep parameters over time.

Results
Only the experimental group showed higher subjective sleep quality (t=-3.8, p&lt;.001) and shorter sleep onset latency (t=3.1, p=.006) at the end of the program. Among the objective sleep parameters, we found a small but statistically significant increase in the amount of deep sleep (t(25)=-2.93, p=.007), while the number of awakenings (t(25)=2.21, p=.03) and the number of sleep stages (t(25)=2.17, p=.04) showed a significant decrease from the beginning to the end of the sleep training.

Conclusion
The results reported in the current study indicate significant improvements in subjective sleep parameters and objective sleep parameters throughout a digital CBT-I sleep training program. When assessing the effects of digital interventions, it is important to consider daily and long-term objective sleep-related parameters.

Support (if any)
We would like to express our gratitude to the Doctoral College 'Imaging the Mind' for their financial support (FWF, Austrian Science Fund: W 1233-B).
0442 A Qualitative Assessment of Digital Cognitive Behavioral Therapy for Insomnia in Heavy Drinkers with Insomnia
Authors: Moloney Mairead , Verlinden Justin , Weafer Jessica 
Published: April 2024

Abstract

Introduction
Insomnia, a public health problem impacting approximately 10-30% of the population, is both a risk factor for Alcohol Use Disorder and a common comorbid condition. Evidence suggests that intervening on sleep problems could serve as a novel and efficacious means of simultaneously improving sleep and problematic drinking. This study qualitatively and quantitatively assessed a well-validated, interactive version of digital cognitive behavioral therapy for insomnia (dCBTI) in heavy drinkers with insomnia. We report on qualitative themes related to beliefs about alcohol’s impact on sleep, self-reported positive outcomes of the dCBTI program, and aspects of the program that participants found most helpful.

Methods
Heavy drinking men (n = 28) and women (n = 42) with insomnia were randomly assigned to complete either the dCBTI program or a control patient education program. Semi-structured qualitative interviews were conducted at baseline and after program completion. Interviews were digitally recorded, professionally transcribed, and lasted approximately 45 minutes on average. The first and second authors conducted and coded the interviews using a multi-stage, inductive process aided by NVIVO software. Here we report on data from pre-intervention interviews with all 70 subjects and post-intervention interviews with the dCBTI subjects (n=40).

Results
At baseline most participants did not associate their heavy drinking habits with their difficulties in falling or staying asleep. Some participants reported using alcohol to help them fall asleep more quickly or “pass out.” Participants who participated in the dCBTI program reported improved ease in falling asleep, fewer nighttime awakenings, and the ability to fall more readily back asleep if they experienced early or nighttime awakenings. These participants also reported a new or increased understanding of the ways in which alcohol use impacted their sleep. Participants reported that having to track their daily number of drinks, and learning to stop drinking several hours before bedtime were the most helpful components of the dCBTI program.

Conclusion
Heavy drinkers with insomnia may lack awareness of how alcohol use impacts their sleep or believe that alcohol helps them sleep. Using a well-validated version of dCBTI may be an accessible, efficacious means of improving two burgeoning public health problems.

Support (if any)
NIAAA R21 AA029201, T32 AA027488
0443 Change in Sleep-Cognitions After Digital or Therapist-Led Cognitive Behavioral Therapy for Insomnia in Older Adults
Authors: Burda Kristen , Gumport Nicole , Tully Isabelle , Simpson Norah , Manber Rachel 
Published: April 2024

Abstract

Introduction
Traditional therapist-led cognitive behavioral therapy for insomnia (CBTI) is associated with a shift to more adaptive cognitions about sleep, as measured by the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS). To address unhelpful beliefs about sleep, CBTI uses cognitive therapy strategies. This study sought to assess the degree to which changes in DBAS differ between patients receiving digital CBTI (dCBTI) and those receiving therapist-led CBTI after two months of treatment access.

Methods
The RCT of the Effectiveness of Stepped-Care Sleep Therapy in General Practice (RESTING) study evaluated a triaged stepped-care framework for delivering dCBTI and therapist-led CBTI. Based on a study-developed checklist, 137 (M age=63.26 years [SD=7.79], 69% female) participants were identified as candidates who would likely benefit from higher intensity CBTI. However, these candidates were randomly assigned to one of two study arms: online only (n=68) or stepped care (n=69). Those in the online only arm received dCBTI, and those in the stepped care arm received therapist-led CBTI. Both arms included the same CBTI components, but therapist-led CBTI additionally included a module on supporting reduction in sleep medications. Participants completed the 16-item DBAS at baseline and two months post randomization. Multilevel modeling was used to examine changes in DBAS scores and subscale scores, including Expectations, Worry/Helplessness, Consequences, and Medication subscales.

Results
There were no significant differences in DBAS scores between participants receiving dCBTI and those receiving therapist-led CBTI (Beta=-0.05, SE=0.21, p=.82). At the level of subscale scores, compared to dCBTI, therapist-led CBTI was associated with greater reduction in dysfunctional beliefs in the 3-item Medication subscale (Beta=-1.10, SE=0.34, p=.001).

Conclusion
Whereas there was no differential impact of delivery mode on overall DBAS scores, therapist-led treatment resulted in greater change in DBAS Medication subscale scores for participants pre-identified as those who would benefit from higher intensity treatment. Specifically, therapist-led interventions might be especially effective for changing beliefs that insomnia has a biochemical etiology and that sleep medications are necessary for better sleep. Changing such beliefs may be an important element in supporting sustained improvement and potentially reducing sleep medication use.

Support (if any)
R01AG057500
0448 Upper Airway Collapsibility Is Associated with Fluid Shifts in Patients with Sleep Apnea and Diastolic Dysfunction
Authors: Tolbert Thomas , Lerakis Stamatios , Zhao Wenli , Valencia Daphne , Licona Diego Quintana , Hadley Michael , Correa Ashish , Parekh Ankit , Ayappa Indu , Rapoport David 
Published: April 2024

Abstract

Introduction
Left ventricular systolic dysfunction contributes to sleep-disordered breathing (SDB) pathophysiology through overnight rostral fluid shifts leading to fluid accumulation in the neck (increasing upper airway collapsibility) and pulmonary vasculature (increasing ventilatory control instability). In contrast to systolic dysfunction, the relationship of left ventricular diastolic dysfunction (LVDD) to overnight fluid shifts and SDB pathophysiology is less well characterized. In an ongoing prospective clinical study of patients with risk factors for or established LVDD and untreated SDB, we are using Phenotyping Using Polysomnography (PUP) analysis to investigate the relationship of overnight fluid shifts to upper airway collapsibility and ventilatory control instability.

Methods
Patients are enrolled in the presence of known LVDD or ≥1 risk factor (age ≥55 years, hypertension, diabetes, coronary artery disease, or amyloidosis) and known or suspected SDB with an apnea-hypopnea index (AHI3A) of ≥15 events/hr. Exclusion criteria include ejection fraction (EF) &lt; 40% or factors suspected to interfere with LVDD indices or PUP estimates (e.g. ventricular dyssynchrony, severe lung disease). LVDD is confirmed on transthoracic echocardiography. Patients undergo in-lab polysomnography (PSG) with pre- and post-sleep circumference measurements of the neck and calves (averaged from both calves). PUP estimates of upper airway collapsibility (Vpassive) and ventilatory control instability (loop gain, LG1) are determined for the first and second half of sleep.

Results
14 patients have been enrolled. Complete PSG data is available for 8 patients (age 52.6±10.7 years, 50% female, BMI 36.2±5.0 kg/m^2, AHI3A 28.7±18.4 events/hr, EF 63.0±7.0%). While neck circumference did not significantly change, calf circumference significantly decreased overnight (pre- vs post-sleep median [IQR] 39.4 [37.3-40.5] cm vs 38.6 [25.8-40.2] cm, p = 0.047). Overnight change in Vpassive was inversely correlated with overnight change in neck circumference (R = -0.82, p = 0.023) and positively correlated with overnight change in calf circumference (R = 0.76, p = 0.049). Correlations of overnight changes in LG1 with neck and calf circumferences were not significant.

Conclusion
PUP analysis suggests overnight rostral fluid shift in patients with LVDD contributes to upper airway collapsibility. This preliminary trend will be more fully investigated on reaching the enrollment goal of 30 patients.

Support (if any)
AASM PSTA. NIH T32HL160511.
0451 Different Roles of Homocysteine Metabolism in Hypertension Among Normal-weight and Obese Patients with OSA
Authors: Chen Baixin , Chen Le , Dai Yanyuan , Vgontzas Alexandros , Li Yun 
Published: April 2024

Abstract

Introduction
Obstructive sleep apnea (OSA) is causally associated with hypertension. However, the differential mechanisms underlying OSA related hypertension between normal-weight vs. obese patients is limited.

Methods
We studied 92 consecutive patients with OSA. Blood pressure (BP) was measured twice during awake and continuously monitored during nighttime sleep. Obesity and normal weight were defined as body mass index ≥ and &lt; 28 kg/m2. Serum metabolite levels were assessed by metabolomics.

Results
Among 59 normal-weight and 33 obese patients, 639 and 174 metabolites showed differences between hypertension and normotension or were associated with systolic and diastolic BP (SBP, DBP) after controlling for confounders. These metabolites were significantly involved in 16 and 12 Kyoto Encyclopedia of Genes and Genomes enrichment pathways in normal-weight and obese patients, whereas 6 pathways overlapped between these two phenotypes. Among these 6 overlapping pathways, 4 pathways were related to homocysteine metabolism and the other two were non-specific pathways. In homocysteine metabolism pathway, 13 metabolites were identified by metabolomics. Interestingly, the change trends of 7 metabolites associated with SBP (all interaction-p≤0.081) and 8 metabolites associated with DBP (all interaction-p≤0.034) were opposite between normal-weight and obese patients. Specifically, in normal-weight patients increased BP was associated with down-regulated folate-dependent remethylation and accelerated transsulfuration whereas in obese patients increased BP was associated with enhanced betaine-dependent remethylation and reduced transsulfuration. Similar findings were observed in ambulatory BP during sleep.

Conclusion
Mechanisms in OSA related hypertension differ between normal-weight and obese patients, which can be primarily explained by the different systematic changes in homocysteine metabolism. Assessing the metabolites in homocysteine metabolism pathway may benefit personalized treatments for hypertension in these two OSA phenotypes.

Support (if any)
This study was supported by the National Natural Science Foundation of China (81970087, 82270105, 82300117), 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant (2020LKSFG05B) and China Postdoctoral Science Foundation (2022M712010).