bluuebunny/crossref_metadata_2025 huggingface dataset:
Genicular Nerve Radiofrequency Ablation for Chronic Knee Pain Using a Three-Tined Electrode: A Technical Description and Case Series
Authors: Koshi Edvin , Cheney Cole W , Sperry Beau P , Conger Aaron , McCormick Zachary L
Published: May 2020

Background

Genicular nerve radiofrequency ablation (RFA) for the treatment of chronic knee pain has traditionally targeted the superomedial, superolateral, and inferomedial genicular nerves. However, recent cadaveric studies of knee neuroanatomy demonstrate varied locations of these specific nerves as well as additional articular nerves. This work suggests that traditional genicular nerve RFA lesion locations may be inadequate.

Objective

1) To describe a novel protocol utilizing a three-tined RFA electrode to target the superomedial (SMGN), superolateral (SLGN), and inferomedial genicular nerves (IMGN), as well as the terminal articular branches of the nerves to the vastus medialis (NVM), intermedius (NVI), and lateralis (NVL). 2) To assess the ability of this technique to reduce chronic knee pain.

Methods

Case series of consecutive patients with six or more months of refractory knee pain who underwent genicular nerve RFA according to the novel protocol described. Seven discrete RFA lesions were placed to target the SMGN, NVM, NVI, NVL, SLGN, and IGMN.

Results

Eleven patients underwent RFA, nine with knee osteoarthritis and two postarthroplasty. At one month, 91% (95% CI = 59–100%), 82% (95% CI = 48–98%), and 9% (95% CI = 2–41%), of patients reported ≥50%, ≥80%, and 100% improvement in knee pain on the numeric rating scale, respectively. These results were sustained at six months. There were no complications.

Discussion/Conclusions

These preliminary data suggest the feasibility and possible effectiveness of genicular nerve RFA using the described novel protocol including a three-tined electrode. Larger-scale studies with comparative groups are warranted.
0008 SUVN-G3031, A Histamine H3 Receptor Inverse Agonist Produces Robust Wake Promoting and Anticataplectic Activity in Orexin Knockout Mice
Authors: Benade V , Daripelli S , Petlu S , Subramanian R , Bhyrapuneni G , Shinde A , Rasheed M , Jayarajan P , Choudakari P , Nirogi R
Published: May 2020

Introduction

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, sleep paralysis, hallucinations, and in some cases episodes of cataplexy. Results from animal studies indicate the involvement of deficient orexin transmission in narcolepsy which can be circumvented by the activation of histaminergic neurons. SUVN-G3031 is a potent and selective histamine H3 receptor inverse agonist with hKi of 8.7 nM and shows less than 50% inhibition at 1 µM against 70 other targets. SUVN-G3031 exhibited excellent pharmacokinetic properties and brain penetration in preclinical species. Oral administration of SUVN-G3031 produces significant increase in histamine, dopamine and norepinephrine levels in the rat cortex. Long-term safety studies in animals have been successfully completed without any concern for further development of SUVN-G3031. In the present study, the effects of SUVN-G3031 were evaluated in orexin knockout mice, a reliable animal model of narcolepsy as a proof-of-concept study for the treatment of narcolepsy with and without cataplexy.

Methods

Male orexin knockout mice (10 - 15 weeks old, 25 - 35 g at the time of surgery) were implanted with telemetric device for simultaneous monitoring of electroencephalography (EEG) and electromyography. Animals were allowed surgical recovery of 3 weeks prior to EEG recording. Effects of SUVN-G3031 (3 and 10 mg/kg, p.o.) were evaluated during active period of animals.

Results

SUVN-G3031 produced significant increase in wakefulness with concomitant decrease in non-rapid eye movement sleep in orexin knockout mice. SUVN-G3031 also significantly decreased the number of cataplectic episodes in orexin knockout mice.

Conclusion

Results from the current preclinical study provide a strong basis for the utility of SUVN-G3031 for the treatment of narcolepsy with and without cataplexy. SUVN-G3031 is currently being evaluated in a Phase 2 study as monotherapy for the treatment of narcolepsy with and without cataplexy (ClinicalTrials.gov Identifier: NCT04072380).

Support

None
0011 The Influence of Obstructive Sleep Apnea Severity and Sex on Cerebral Perfusion
Authors: Turner A D , Bubu O M , Rapoport D M , Varga A W , Ayappa I , de Leon M , Rusinek H , Glodzik L , Jean-Louis G , Osorio R
Published: May 2020

Introduction

Obstructive Sleep Apnea (OSA) has been shown to initiate a pathological cascade negatively affecting the cardiovascular system, including cerebral circulation. There is limited data on OSA effects on regional brain function, though reduced global cerebral blood flow (CBF) has been observed among patients with OSA. However, there are few precise assessments. We hypothesized that regional CBF values are altered in OSA, and that sex influences the hypothesized relationship.

Methods

Participants from the NYU Center for Brain Health cohort (n=68; 57.4% female; mean age=66.32±6.84), representing cognitively healthy volunteers with OSA (AHI4% > 5/hr) and without, from several NIA-supported studies, completed evaluations including clinical, structural & functional high-resolution arterial spin labeling 3 tesla MRI scans. Hippocampal and temporal cortex CBF was assessed at baseline and after CO2 challenge using a rebreathing protocol. Analyses were completed using one-way ANCOVA controlling for age and BMI.

Results

More men had OSA (82.8% vs 56.4%). Men without OSA showed a larger change in CBF after challenge in left (t=2.6, p=0.014) and right (t=2.4, p=0.021) hippocampus. Although the main analyses by severity level only boarded significance, pairwise comparisons indicated men with severe OSA (AHI4%>30/hr) exhibited a larger change in CBF after challenge in the hippocampus overall compared to those with mild OSA (AHI4%5–15/hr; p=0.015) and without OSA (p=0.017). Women with severe OSA showed a reduced change in CBF after challenge in the right hippocampus compared to those with mild (p=0.016), moderate (AHI4%16–29/hr; p=0.008), and without OSA (p=0.015).

Conclusion

This study suggests a possible differential effect of OSA severity and sex on regional CBF in response to a CO2 challenge, specifically in the hippocampus. Further studies will examine cognitive consequences of these sex-specific hippocampal perfusion abnormalities in OSA.

Support

NIH/NIA (1R01HL118624) Osorio, RS 07/01/13-04/30/17 Sleep Disordered Breathing in normal elderly and risk for Alzheimer’s disease (AD).NIH/NIA (R01AG056031S1) Osorio, RS 8/01/2019-7/31/2020 Sleep Aging and Risk for Alzheimer’s disease - Research Supplement to Promote Diversity in Health-Related Research
0016 Genetic Basis of Daytime Napping and Consequence on Cardiometabolic Health
Authors: Dashti H S , Daghlas I , Lane J , Udler M , Garaulet M , Saxena R
Published: May 2020

Introduction

Although daytime napping is a common, evolutionarily conserved behavior, its genetic basis is unknown. Elucidating its genetic basis may clarify relevant underlying biological pathways and determine causal links with cardiometabolic health.

Methods

We performed a genome-wide association study of self-reported daytime napping using linear regression in adults of European ancestry in the UK Biobank (n=452,633) and assessed robustness of signals with accelerometer-derived daytime inactivity duration (n=84,671). Next, we conducted a phenome-wide association study in a hospital-based clinical biobank (n=30,683) using napping genome-wide polygenic score (GPS), and Mendelian randomization (MR) with cardiometabolic traits. To deconstruct the napping genetic variants, we applied a novel “soft clustering” Bayesian nonnegative matrix factorization method and generated partitioned cluster-specific polygenic risk scores (PRS).

Results

We identified 121 distinct genome-wide significant loci for daytime napping, with lead signals at or near genes KSR2 (kinase-suppressor of ras 2), HCRTR1/HCRTR2 (hypocretin-receptor 1/2), SKOR2 (SKI family transcriptional-corepressor 2), and MAPT (microtubule-associated protein tau), among others. The loci associated with accelerometer-derived daytime inactivity duration. Gene enrichment analyses pointed to pathways involved in neurogenesis and others including nervous system development and opioid signaling. Genetic overlaps were evident in a clinical biobank where highest, compared to lowest, decile of napping GPS associated with 30%, 40%, and 50% higher odds for essential hypertension, obesity, and nonalcoholic liver disease, respectively (P<0.0001). In MR, potential causal links were identified with higher diastolic blood pressure (2.67 mmHg per napping category-increase, 95% CI 1.62–3.23, P=6.80e-07), systolic blood pressure (3.65mmHg, 1.86–5.44, P=6.40e-05), and waist circumference (0.28 SD-units, 0.11–0.45, P=0.0015). The clustering of variants identified 3 robust clusters (cluster-1: “higher sleep propensity”; cluster-2: “more fragmented/inefficient night sleep”; cluster-3: “early sleep timing”). Only clusters 2 and 3 PRSs were associated with worse cardiometabolic health outcomes, including higher BMI, waist circumference, CRP, and triglycerides (all P<0.05).

Conclusion

These findings expand our understanding of the genetic architecture of napping implicating multiple biological pathways, indicating possible genetic overlap and causal links to cardiometabolic traits, and suggesting distinct nap-promoting mechanisms with differential associations with health outcomes.

Support

This work is supported by grants NIH-F32DK102323, NIH-4T32HL007901, NIH-R01DK107859, NIH-R35HL135818, and MGH Research Scholar Fund.
0027 Alternations in Contractility, Calcium Signaling and Nuclear Factor Kappa B Activation in Stem Cells Derived Cardiomyocytes Following Exposure to Obstructive Sleep Apnea Children’s Serum, and Intermittent Hypoxia
Authors: Goldbart A , Haddad H , Etzion S , Gopas J
Published: May 2020

Introduction

There are cardiovascular morbid effects of OSA in adults and children. We have previously reported over-expression of Nuclear-Factor-κappa B in tonsils of children with OSA, and NF-κB activation after exposure to sera of children with OSA. In order to investigate NF-kB activation and the physiology of cardiomyocytes of human origin (CM’s), we have established an ex-vivo model where CM’s derived from human embryonic stem cells H-9.1 clone (hES) and from Induced pluripotent stem cells (iPSC) are either incubated with human sera, or exposed to intermittent hypoxia(IH) or room air (RA).

Methods

Serum samples were drawn following overnight polysomnography (PSG) from children with OSA (AHI>5) or control (AHI<1). Differentiated human cardiomyocytes were incubated with 5% OSA sera or control. Average cell beating/min was determined and NF-kB p50 and p65 cytoplasmic or nuclear localization were detected by immunofluorescence (operetta). CM’s were exposed to either RA or to IH (21% alternating with 1% O2, 6 cycles/h, 24 h) in a chamber (BioSpherix Instruments, Redfield, NY)Intracellular calcium transient signal (ionoptix) and mechanical contraction of CM (Musclemotion) were assessed.

Results

1. Cell beating/min was reduced in cells incubated with OSA (n=10) as compared to control (n=10);(p<0.01), and following IH exposure vs RA (p<0.01),). 2. There is an over-expression of NF-κB p50, p65 subunits as a result of exposing CMs to OSA sera, and following IH exposure 3. a rapid decrease (up to 100%) was measured in calcium transient amplitude as well as contraction amplitude (p<0.05) after adding OSA sera, that was completely restored after washing.

Conclusion

We revealed human cardiomyocytes NF-kB activation and decreased contractility following exposure to OSA sera and to IH. The rapid decrease in calcium signaling and contractility infer the presence of factors that reversibly affects CMs contraction. This ex-vivo model enables the study of functional and molecular alterations in human CM

Support

Israel science Foundation (ISF) 1344/15
0039 The Clinical Utility of Dim Light Melatonin Onset in Treatment of Delayed Sleep-Wake Phase Disorder: Preliminary Findings
Authors: Swanson L , Arnedt J , DuBuc K , de Sibour T , Burgess H
Published: May 2020

Introduction

Delayed sleep-wake phase disorder (DSWPD) is common, debilitating, and challenging to treat. In an ongoing randomized trial, we are comparing exogenous melatonin treatment outcomes in DSWPD participants for whom dim light melatonin onset (DLMO) is measured objectively vs. estimated.

Methods

Thus far, 13 participants (27±6 years old, 67% female) have completed a randomized, controlled, double-blind 4-week trial of 0.5 mg of exogenous melatonin timed to either 3 h before measured DLMO (M-DLMO, n = 6) or 3 h before DLMO estimated at 2 h before average sleep onset time based on at least 7 days of wrist actigraphy and sleep diary (E-DLMO, n = 7). All participants met International Classification of Sleep Disorders-3 diagnostic criteria for DSWPD and were otherwise healthy. Participants completed 4 weekly treatment sessions with a blinded psychologist; time of melatonin administration and bed-rise schedule were advanced up to 1 h/week. A validated home saliva collection kit measured DLMO in all participants. Between-group t-tests and Hedges’ g effect sizes (ES) were calculated at post-treatment for the following outcomes: DLMO; Pittsburgh Sleep Quality Index (PSQI) global score; Morningness-Eveningness Questionnaire (MEQ); and the actigraphy parameters sleep efficiency (SE) and clock time of sleep onset and offset. A paired-sample t-test compared the measured vs. estimated DLMO at baseline.

Results

The M-DLMO group had a 65±88 mins DLMO advance vs. 27±30 mins in the E-DLMO group (ES=0.51 p=.381). PSQI scores were similar between groups (M-DLMO=6.67±2.06, E-DLMO=7.1± 1.57, ES=-0.24, p=.646), as were MEQ scores (M-DLMO=43±4.98, E-DLMO=48±12.72, ES=-0.47, p=.387). Sleep onset time (M-DLMO=0:32±1:02, E-DLMO=0:31±1:38, ES=0.01, p=.98) and offset time (M-DLMO=8:05±1:03, E-DLMO=8:08±2:14, ES=-0.02, p=.968) were similar between the groups, although sleep was more efficient in M-DLMO vs. E-DLMO (84%±3% vs. 76%±10%, ES=0.94, p=.096). On average, baseline measured DLMO occurred 123±83 mins earlier than estimated DLMO (p=.001).

Conclusion

We are continuing to enroll participants in this trial. Preliminary results suggest some potential benefit of measuring the DLMO, but results will need to be clarified in a larger sample.

Support

American Sleep Medicine Foundation Strategic Research Award
0053 Effect of Changes in Intracellular Adhesion Molecule-1 on Measures of Sleepiness and 24-hour Ambulatory Blood Pressure After 4 Months of Continuous Positive Airway Pressure
Authors: Pak V M , Maislin D , Keenan B T , Townsend R , Dunbar S B , Pack A I , Gislason T , Kuna S T
Published: May 2020

Introduction

Previous studies have shown that continuous positive airway pressure (CPAP) therapy of adults with obstructive sleep apnea (OSA) reduces circulating levels of intercellular adhesion molecule 1 (ICAM-1). ICAM-1 levels may affect daytime sleepiness and elevated blood pressure associated with OSA. Our goals were to explore associations between changes in ICAM-1 and objective and subjective measures of sleepiness, as well as 24-hour ambulatory blood pressure monitor (ABPM) parameters in adults with OSA following 4 months of CPAP treatment.

Methods

We identified 140 adults with newly diagnosed OSA in the Penn Icelandic Sleep Apnea (PISA) Study, with a mean (±SD) body mass index (BMI) of 31.5±4.2 kg/m2 and apnea-hypopnea index (AHI) of 36.8±15.3 events/hour; 83.3% were males. Plasma ICAM-1 levels, 24-hour ABPM, Epworth Sleepiness Scale (ESS), and Psychomotor Vigilance Task (PVT) measures were obtained at baseline and after 4 months of CPAP treatment. Associations between changes in natural log ICAM-1 and both sleepiness and 24-hour mean arterial blood pressure (MAP) were assessed using multivariate regression models, controlling for a priori baseline covariates of age, sex, BMI, race, site, smoking status, physical activity, use of anti-hypertensive medications, AHI and hours/night of CPAP usage.

Results

Overall, there was no significant change in ICAM-1 from baseline to follow-up among all participants after 4 months (0.027 ng/ml, p=0.52). There were no statistically significant associations between the change in ICAM-1 and change in sleepiness measures (all p>0.05) or 24-hour MAP (1.124 mm Hg, p=0.07). A nominal association between increased ICAM-1 and increased daytime MAP after 4 months was observed (1.39 mm Hg, p=0.033), although this result was not significant after correction for multiple comparisons.

Conclusion

Our results do not support changes in ICAM-1 as the biological pathway linking changes in sleepiness or ABPM following CPAP treatment of adults with OSA.

Support

P01-HL094307 (NHLBI, PI: Pack AI)
0054 Metabolite Profiles of Obstructive Sleep Apnea Distinguishes Cases from Controls and Improve With CPAP
Authors: Sengupta A , Lim D C , Keenan B T , Keele L , Pack A , Weljie A
Published: May 2020

Introduction

Obstructive sleep apnea (OSA) is a common sleep breathing disorder with significant public health consequences. Despite this, no clinically available objective molecular biomarkers to diagnose, risk stratify and quantify treatment efficiency exist. To this end, high-throughput metabolomics data could serve as a valuable quantitative tool.

Methods

We designed a pilot study to investigate the metabolomic effects of OSA and CPAP treatment. Blood serum samples were collected from OSA patients and healthy controls matched with respect to age (±5 years), BMI (±2.5 kg/m2) and gender (N = 20/group). Samples from OSA patients were obtained before and after continuous positive airway pressure (CPAP) treatment. Polar metabolites were analyzed using a targeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabolomics technique.

Results

Supervised multivariate analysis using serum metabolic values of OSA patients and healthy controls showed a significantly different overall metabolic profile between the two groups (orthogonal partial least squares discriminant analysis [OPLS-DA] Q2=0.25, p=0.04). Acetylornithine, choline, cytidine, dodecenoylcarnitine, methionine sulfoxide and 3-indoxylsulfate were among the most perturbed metabolites. Major metabolic pathways altered in the OSA patients were methionine and phospholipid metabolism, as well as gut microbial co-metabolism. Lysophosphatidylcholine (16:0), a phospholipid metabolite, demonstrated significant linear association with improved oxygen saturation nadir post CPAP treatment (R2 = 0.57), suggesting the metabolic features may be used as prognostic clinical biomarkers.

Conclusion

These results suggest that OSA significantly impacts blood metabolites, which could potentially be used to establish OSA biomarkers. Moreover, specific metabolic features are associated with post CPAP improvement, such as phospholipids, suggesting a functional association of these metabolites that may help us understand the heterogeneity of OSA. Overall, these results demonstrate the potential of metabolic profiling to develop quantitative molecular markers of OSA. Further studies are underway to validate these findings and investigate the utility of metabolic profiles to objectively measure CPAP efficacy.

Support

The work was supported by the program project grant P01 HL094307.
0064 Heightened Neural Responses to Negative Words in Shift Workers Using the Stroop Task
Authors: Lee K , Lee H , Jeon J , Jeon S , Kim N , Oh S , Lee M , Kim S , Lee Y
Published: May 2020

Introduction

Shift work is known to have a negative impact on a wide range of health problems such as sleep disturbance, cognitive impairment, and emotional disorders (e.g., anxiety and depression). It is important to understand underlying mechanisms for negative impact of shift work on health problems. This study aimed to investigate psychological and neural mechanisms associated with shift work.

Methods

Thirty six shift workers (28 females, age = 29.9 ± 7.4) and 35 non-shift workers (20 females, age = 30.5 ± 5.5) participated in this study. They were performing the word Stroop task during fMRI scanning. This task included sleep-related words and negative words to investigate neural substrates associated with sleep-related information and emotional information processing. Neutral words were included as control stimuli. The participants also completed questionnaires assessing sleep-related problems such as Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale, and emotion-related problems such as Beck Depression Inventory and Beck Anxiety Inventory. Two-sample t-tests were conducted to find group differences in self-report measures and neural response to sleep-related words and negative words compared to neutral words.

Results

Relative to non-shift workers, shift workers showed greater sleep disturbance (i.e., higher PSQI), but they did not show any evidence of emotion-related problems. Shift workers also demonstrated greater neural response to negative words (vs. neutral words) in several prefrontal regions (e.g., dorsal anterior cingulate cortex and dorsolateral prefrontal cortex), anterior insula and caudate compared to non-shift workers. However, shift workers did not show significantly different neural response to sleep-related words (vs. neutral words) compared to non-shift workers.

Conclusion

The result from this study provides supporting evidence that shift work is associated with subjective sleep disturbance. Shift workers’ heightened neural response to negative information may reflect their increased sensitivity to negative information, that may contribute to sleep disturbance.

Support

Brain Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (Study No.: 2016M3C7A1904338 and NRF-2018R1D1A1B07049704).
0081 Habitual Sleep Duration is Negatively Correlated with Emotional Reactivity within the Rostral Anterior Cingulate Cortex in Individuals with PTSD
Authors: King R , Jecmen D , Mitchell J , Ralston K , Gould J , Burns A , Bullock A , Grandner M A , Alkozei A , Killgore W D
Published: May 2020

Introduction

Sleep difficulties, such as insomnia, are highly prevalent in individuals with Post-Traumatic Stress Disorder (PTSD). However, sleep deprivation can also increase emotional reactivity to positive (as well as negative) stimuli. While the effects of sleep loss on emotional perception healthy individuals has been documented, it remains unclear how lack of sleep in individuals with PTSD may affect their emotional reactivity to positive stimuli. We hypothesized that lower habitual sleep duration would be associated with greater functional brain activation changes in response to subliminally presented happy faces in brain areas of the reward network, such as the rostral anterior cingulate cortex (rACC).

Methods

Thirty-nine individuals with DSM-5 confirmed PTSD were administered the Pittsburgh Sleep Quality Index (PSQI) as a measure of their average nightly sleep duration over the past month. Participants then underwent fMRI imagining while viewing subliminal presentations of faces displaying happiness, using a backward masked facial affect paradigm to minimize conscious awareness of the expressed emotion. Brain activation to masked happy expressions was regressed against sleep duration in SPM12.

Results

There was a negative correlation between habitual sleep duration and activation within the rACC in response to the masked happy faces (x=14,y=40,z=0; k=102, pFWE-corr= 0.008).

Conclusion

Individuals with PTSD who average less sleep at night showed greater emotional reactivity, as indexed by greater functional brain activation changes within an area of the reward network, than individuals who obtained more sleep per night. Future research involving actual sleep duration manipulation will be necessary to determine whether this finding reflects the well-known antidepressant effect of sleep deprivation or a form of greater emotional expression error monitoring among traumatized patients when lacking sleep. Regardless, these findings suggest that insufficient sleep could affect unconsciously perceived emotion in faces and potentially affect social and emotional responses among individuals with PTSD.

Support

US Army Medical Research and Materiel Command: W81XWH-14-1-0570
0085 Vulnerability to Sleep Restriction is Associated with Decreased Working Memory Performance
Authors: Mathew G M , Strayer S M , Ness K , Buxton O M , Chang A
Published: May 2020

Introduction

We investigated whether individuals with more lapses on the psychomotor vigilance task (PVT) after sleep restriction (SR) demonstrated poorer working memory compared to those with fewer PVT lapses.

Methods

Fifteen healthy men (22.3±2.8 years) participated in a 10-night inpatient protocol with three nights of 10-hour baseline time in bed (TIB), five nights of SR (5-hour TIB), then two recovery (10-hour TIB) nights. Participants completed the Visual Object Learning Task (VOLT) and Fractal 2-Back (F2B; visual n-back) measuring working memory and the PVT (Joggle Research® battery) approximately every two hours during wake. During the VOLT, participants indicated whether presented images had been shown previously. Outcomes included number of misses and false alarms. During the F2B, participants tapped the screen when an image appeared that had been shown 2 images previously. Outcomes included sensitivity and specificity. Median split of mean PVT lapses after the last night of SR was used to categorize participants into “vulnerable” (n=8) versus “resistant” (n=7) groups. Outcomes were analyzed in mixed models with the predictor day*vulnerability, excluding the first three baseline days to preclude practice effects.

Results

There was a significant interaction between day and attentional vulnerability for VOLT misses (p<.001); misses increased linearly across days in vulnerable (b=.18, p<.001) but not resistant (p=.956) participants. There was no interaction between day and vulnerability for VOLT false alarms, which did not change across days. There was a significant interaction between day and attentional vulnerability for F2B sensitivity (p=.002); sensitivity increased linearly across days in resistant (b=.02, p<.001) but not in vulnerable (p=.273) participants. There was no interaction between day and vulnerability for F2B specificity, which did not change across days.

Conclusion

Performance on the VOLT decreased in vulnerable participants only; performance on the F2B improved in resistant participants likely due to practice effects not seen in vulnerable participants. Findings indicate vulnerability to attentional lapses after SR is a marker of vulnerability to working memory decrements.

Support

This study was funded by grant UL1TR000127 from the Clinical and Translational Science Institute (Chang PI) and the College of Health and Human Development at the Pennsylvania State University.
0086 Daytime Napping and Memory Consolidation of Novel Word Learning in Children and Adults
Authors: van Rijn E , Walker S A , Knowland V C , Cairney S A , Gouws A D , Gaskell M , Henderson L
Published: May 2020

Introduction

Memory for novel words benefits from sleep, particularly non-rapid eye movement (NREM) sleep and its features, such as sleep spindles and slow oscillations. This is consistent with systems consolidation models, in which sleep supports transfer from hippocampal to neocortical memory networks. Larger amounts of slow wave sleep in children has been proposed to account for enhanced consolidation effects, but such studies have typically focused on nocturnal sleep. We examined whether daytime naps benefit word retention in adults and children aged 10–12 years, and whether this relationship in children is affected by differences in white matter pathway microstructure. We hypothesized that the link between memory consolidation and structural brain connectivity will be mediated by the degree of sleep spindles during the nap.

Methods

Adults (N = 31; mean age = 20.91, SD = 1.55) and children (N = 38; mean age = 11.95, SD = 0.88) learned spoken novel words, followed by a 90-minute nap opportunity monitored with polysomnography. Memory for the words was tested pre- and post-nap. Children’s structural brain connectivity was measured using diffusion tensor imaging (DTI).

Results

Word memory was preserved following sleep in adults, while an adult wake control condition showed deterioration. Similarly, in children memory performance was stable over the nap, with wake control data currently being collected. Analyses relating behavioral changes over the nap to NREM sleep features and structural brain connectivity will be presented.

Conclusion

In line with sleep-dependent memory consolidation models, daytime naps protect novel words from forgetting in adults and children. Examining potential relationships between nap-based consolidation and structural integrity has important theoretical implications, given the increase in brain connectivity in language areas during childhood, as well as white matter alterations in developmental populations.

Support

This research was supported by the UK Economic and Social Research Council, grant no. ES/N009924/1.
0088 Gravity Dreams Following a Virtual Reality Flight Simulation
Authors: Picard-Deland C , Pastor M , Solomonova E , Paquette T , Nielsen T
Published: May 2020

Introduction

Flying is a prevalent but infrequent experience in dreams. Despite a broad interest in such unique dream experiences, there is still no experimental procedure for reliably inducing them. Our study aimed 1) to induce flying dreams in the laboratory using virtual reality (VR), 2) to examine phenomenological correlates of flying dreams, such as lucidity and emotions and 3) to investigate the dynamics of dreamed gravity imagery in relation to participant state and trait factors.

Methods

A total of 137 healthy participants (24.01±4.03 y.o.; 85 F; 52 M) took part in a custom-built immersive VR task in which they learn how to ‘fly’ as precisely and quickly as possible, engaging vestibular, motor and visuo-spatial systems. Dreams were collected a) from home dream journals for 5 days before and 10 days after the laboratory VR task and b) after a 90-min morning nap in laboratory. Dream reports were scored by 2 independent judges for flying and other gravity-related imagery. Linear mixed models statistics were used to compare dreams from this cohort with a separate control cohort (N=52) that followed a similar protocol in the same lab but did not undertake a virtual flying task.

Results

The VR task successfully increased the likelihood of experiencing flying in dreams from both the laboratory nap (7.1%) and the following night (10.6%) compared to baseline (1.3%) and the control cohort on those days (Lab: 2.4%; following night: 0%). In contrast, the occurrence of other gravity imagery showed no differences. Flying dreams were altered qualitatively, exhibiting higher levels of lucid-control and emotional intensity after VR exposure. Moreover, various factors such as sex, prior dream experiences and sensory immersion in VR differentially modulated flying dream induction.

Conclusion

Our findings provide both quantitative and qualitative insights into flying dreams that may facilitate understanding of these typical dream experiences and future developments in dream flight-induction technologies.

Support

Natural Sciences and Engineering Research Council of Canada
0091 Sleep as a Mediator of the Relationship Between Exercise and Self-Reported Cognitive Function
Authors: Chappel-Farley M G , Nan B , Grill J D , Mander B A , Yassa M A , Benca R M
Published: May 2020

Introduction

Insufficient sleep and sedentary behavior are associated with cognitive decline. How sleep and physical activity interact to influence cognition is not fully understood. This study sought to examine whether self-reported sleep and exercise impact subjective cognitive complaints across adulthood.

Methods

Self-report questionnaire data from 2,744 adults (μ=56.18 yrs/old; 63.8% F; μ=16.36 yrs/edu) in the University of California Irvine Consent-to-Contact Registry were analyzed. Multiple regression models, analysis of covariance, and ordinary least squares path analysis were conducted to investigate relationships among the Cognitive Function Instrument (CFI), Medical Outcome Study Sleep Scale (MOS-SS) Subscales, and exercise frequency. All models adjusted for education, sex, age, BMI, medical comorbidities, depression, cancer diagnosis, and antidepressant usage. Individuals taking medications known to affect sleep or with a diagnosis major psychiatric illness were excluded from analyses.

Results

All MOS-SS Subscales significantly predicted CFI score (all p<0.001). Individuals who exercise >3times/week had significantly lower scores on the CFI (p<0.05), Sleep Problems Index I & II (both p<0.05), Somnolence Subscale (p<0.01), and higher scores on the Sleep Adequacy Subscale (p=0.001). Mediation analyses revealed that all subscales, aside from the Sleep Disturbance Subscale, mediated the relationship between exercise frequency and CFI Score (Bootstrapped CI’s did not include zero).

Conclusion

More self-reported sleep disturbance and greater daytime sleepiness are associated with more subjective cognitive complaints. Individuals who exercise more frequently report lower daytime sleepiness and higher quality sleep. The effects of exercise frequency on cognitive complaints appear to be mediated by the impact of exercise on sleep. These results suggest that sleep health may be a crucial consideration when evaluating outcomes of exercise-based therapies aimed at delaying the onset of cognitive impairment.

Support

The C2C registry was made possible by a donation from HCP, Inc. and is supported by NIA AG016573 and NCATS UL1 TR001414.
0094 The Effect of Zolpidem on Sleep-Dependent Declarative Memory Consolidation
Authors: Zhang J , Mednick S
Published: May 2020

Introduction

Sleep plays a critical role in memory consolidation. At the same time, about 20% of population in the U.S. suffer from sleep disorders or deprivation, and about 16% of them reported using sleep aids (CDC, 2015). However, the effect of sleep aids on sleep-dependent memory consolidation remains unclear. Previous studies have observed an improvement in sleep-dependent declarative memory consolidation with zolpidem over a daytime nap (Mednick et al., 2013). The current study investigates the effect of zolpidem on declarative memory consolidation over a night of sleep and over 24 hours.

Methods

This study employed a double-blind, placebo-controlled, within-subject design, in which every subject (N=26, 12 females) experienced both zolpidem and placebo. All subjects were healthy, college-aged adults without sleep disorder. A 32-channel electroencephalogram cap was used to record brain activity during sleep. Word paired-associates task was used to evaluate memory performance. Participants reported to the laboratory in the evening, performed word paired-associates task (test1), then ingested either zolpidem or placebo before sleep. They were tested on the task in the following morning (test2) as well as in the following evening (test3). Paired-sample t-tests for retrieval difference scores between placebo and zolpidem conditions were conducted.

Results

Participants showed similar baseline performance on the word paired-associates task (test 1, p=0.45). Zolpidem condition showed higher memory retention compared to placebo 24hr after drug ingestion (test3-test1, t₂ 5=2.09, p<0.05). The improvement in performance for zolpidem condition occurred across the following day (test3-test2, t₂ 5=2.22, p<0.05), as no difference was observed between conditions after sleep (test2-test1, t₂ 5=0.34, p=0.74)

Conclusion

Consistent with previous studies, participants showed better memory performance after taking zolpidem compared to placebo. However, the current study showed that the improvement in memory occurred across a day of wakefulness after nighttime drug ingestion, while other studies observed improvements shortly after sleep, indicating a potential delayed benefit of zolpidem on memory consolidation.

Support

This work was supported by the Office of Naval Research grant N00014-14-1-0513
0095 Sleep Boosts Schema-Related Memory Consolidation and Inference
Authors: Golkashani H A , Chee M W
Published: May 2020

Introduction

A schema is a previously learned framework of information that helps the learning and retention of new, but related material. We examined how sleep, compared to staying awake following the acquisition of a schema, and thereafter novel material, affects the consolidation of new memoranda that were either embedded or not into the learned schema. We also tested if sleep affects the inference of hierarchy within these memoranda.

Methods

54 adolescents (mean age 16.6 years; 26 males) learned the age hierarchy of 7 galaxies by viewing adjacent pairs, one at a time e.g. A-B, D-E, and making transitive inferences (If B>C and C>D then B>D). Once this schema was learned to criterion, participants learned two new sets of galaxies: one set comprised 5 galaxies from the schema and 4 new, intercalated galaxies; the other contained 9 unfamiliar galaxies (schema & no-schema conditions). Memory for galaxy ordering was tested immediately after learning and again after 12-hours. One group(n=25) was kept awake in the day, while the other group (n=29) slept overnight for 8-h. Memory was tested for galaxies that were directly adjacent e.g. A-B, as well as for ‘inference pairs’ that were two apart: e.g.:(B-D, C-E).

Results

Change in memory following the respective 12-hour intervals was analyzed using a mixed ANOVA with schema (schema, no-schema) and pair-type (adjacent, inference) as within-subject factors and sleep group (sleep/awake) as the between-subjects factor. There were significant main effects of sleep and pair type as well as a significant interaction, where schema-related memory was better preserved in the sleep group. This group also had higher performance for inference pairs embedded within the original schema.

Conclusion

Sleep benefitted the consolidation of new memoranda embedded in a schema. This benefit was stronger for non-adjacent inference pairs suggesting that sleep boosts insight into non-explicitly declared, hierarchically organized information.

Support

Supported by NMRC/STaR/0015/2013 and NRF2016-SOL002-001
0098 The Role of Sleep in Novel Category Learning in Infancy
Authors: Sucevic J , Plunkett K
Published: May 2020

Introduction

A growing body of research suggests that sleep has an important role in consolidating newly learnt information and generalising this knowledge to novel instances (e.g. Djonlagic et al., 2009). The effects of sleep on early categorisation abilities haven’t been investigated so far and thus the aim of this study is to examine the role of sleep in formation of category representations. Two experiments were conducted. Experiment 1 set out to determine 4-months-old infants’ ability to form novel visual categories when category formation test immediately followed learning. Experiment 2 investigated the impact of sleep on category consolidation by testing category formation after a 2 hours delay.

Methods

Both experiments employed eye-tracking familiarisation-novelty-preference paradigm. In Experiment 1, infants were familiarised with a set of exemplars from a novel category. Immediately after the familiarisation phase, infants’ category formation was tested and their looking references were used as an index of category learning. Experiment 2 tested consolidation of the newly acquired categories by introducing a delay between the familiarisation and the test phase. Half of the participants took a nap during the delay, whereas the other half remained awake. Polysomnography was recorded using a standard PSG protocol. Sleep stages were scored according to the AASM guidelines, and sleep spindles were detected using an adapted algorithm for children.

Results

Results of the Experiment 1 revealed that infants were able to learn novel visual categories when category formation was tested immediately after learning suggesting therefore that infants are able to extract relevant information and generalise to novel instances. Preliminary results of Experiment 2 (data analysis ongoing) suggested that infants who napped performed better than infants who stayed awake.

Conclusion

The present study suggests that infants are able to rapidly form novel categories, and that consolidation of this knowledge is shaped by the activity following learning.

Support

N/A
0100 Effect of Naps on Preschoolers’ Consolidation of an Emotional Storybook
Authors: Holmes J F , Deighan M K , Miranda N W , Mason G M , Spencer R M
Published: May 2020

Introduction

Naps are known to benefit emotional memory consolidation in preschoolers, though improvement is not evident until the following day. The mechanisms by which naps aid emotional memory, and how they differ from those facilitating more neutral declarative memory consolidation, are currently unknown. In this study, we used an emotional storybook task to assess change in memory for emotionally salient vs. neutral events across a nap and overnight sleep. PSG was included to explore sleep physiology correlates.

Methods

Preschool children (n = 9; Mage= 43.2 months) were read a novel storybook featuring negative and neutral events. Memory of story events was probed through sets of multiple-choice questions and assessed at three time points: immediately following the story, following a nap or equivalent wake period (within-subject; counterbalanced; separated by ~1 week), and 24h post-encoding. PSG was recorded during the nap period and both subsequent overnight sleep bouts.

Results

Memory performance across time points was assessed via change scores. Recall of story events did not differ between conditions from immediate to post-nap/wake assessment. When probed the following morning, children better remembered events when a nap took place the day prior (F(1,7) = 8.848, p=.021). This delayed nap benefit correlated with time spent in NREM2 during the nap (r=.91, p=.017). No differences were found between recall of negative vs. neutral events at any time point or between conditions.

Conclusion

Our results show a delayed benefit of napping on recall of a storybook, though at present no preference for emotional events is seen. Time spent in NREM2 during the nap was strongly associated with our finding, likely reflecting the declarative memory benefits conferred from this stage. Further analyses will include overnight sleep physiology to explore differential enhancement between event types, and possible interactions with nap microstructure.

Support

This work was supported by NIH R01 HL111695.
1017 An Integrated Behavioral Therapy for Positive Airway Pressure Adherence and Insomnia Reduces Nocturia Frequency
Authors: Fung C H , Martin J L , Dzierzewski J M , Fiorentino L , Stepnowsky C , Song Y , Zeidler M , Mitchell M , Vaughan E C , Huang A , Markland A , Josephson K , Alessi C
Published: May 2020

Introduction

Nocturia is common among patients with both insomnia disorder and obstructive sleep apnea (OSA) and adversely affects quality of life. Within a randomized controlled trial testing an integrated behavioral therapy for positive airway pressure (PAP) adherence and insomnia for patients with coexisting OSA and insomnia disorder, we examined the impact of the integrated therapy on nocturia frequency.

Methods

Patients aged > 50 years with untreated OSA (apnea hypopnea index > 15) and chronic insomnia disorder were recruited from a VA medical center and randomized to 5 weekly individual integrated behavioral treatment sessions versus control (general sleep education). Nocturia frequency (self-reported average number of nocturia events per night) was assessed at baseline, 3 months, and 6 months. Linear regression models were used to examine relationships between objective PAP adherence (# nights used > 4hrs over the last 30 days) and Insomnia Severity Index (ISI) score (0 [none] - 28 [severe]) and nocturia frequency (0 - 5+/night), and change in nocturia frequency associated with integrated therapy.

Results

Nocturia data were available for 112 participants (treatment=56, control=56; mean age 63 [SD 7], 95% male). Mean nocturia frequency (episodes/night) was 2.1 (SD 1.3; baseline), 1.6 (SD 1.1; 3 months), and 1.7 (SD 1.2; 6 months). Overall, higher PAP adherence (B=.029, p=.008) and ISI score improvement (B=0.05, p=.004) were associated with decreased nocturia frequency at 3-month follow-up. No differences were observed in nocturia frequency between treatment and control participants at baseline (p=.429). Integrated therapy reduced nocturia frequency at 3 months (B=-0.56, p=.020) but not at 6 months follow-up (B=-0.4, p=.081) compared to control.

Conclusion

Nocturia frequency improved with integrated behavioral therapy for PAP adherence and insomnia in veterans (primarily male) with co-existing OSA and insomnia. Additional studies are needed to examine the mechanisms underlying the relationship between the behavioral therapy for PAP adherence and insomnia and nocturia.

Support

VA HSR&D; NIA; VA GRECC
1023 Oncologists’ Beliefs About Medical Marijuana’s Effectiveness for Sleep in Cancer Patients: A Nationally Representative Survey
Authors: Zhou E S , Nayak M M , Braun I M
Published: May 2020

Introduction

Cancer is a qualifying condition for medical marijuana (MM) access in almost every state which has legalized medical use. Over 20% of patients report recent cannabis use to manage cancer treatment side effects, including poor sleep. However, there have been no clinical trials of MM for sleep in oncology populations. This study explores oncologists’ characteristics associated with their views on MM for sleep.

Methods

N=237 medical oncologists completed a mailed survey querying demographics, training history and current practice, and their knowledge and views on MM. In these analyses, we compared oncologists who viewed MM as being equally or more effective than standard treatment approaches to manage poor sleep with those who viewed MM as less effective.

Results

Sixty-four percent of oncologists believed MM to be equally or more effective than standard treatments for poor sleep. They were significantly less likely than peers to have a medical school faculty appointment (53% vs 72%) or self-report sufficient knowledge about MM to make clinical recommendations (42% vs 57%). Oncologists who viewed MM favorably compared to standard treatments for poor sleep were more likely to have recommended its use and to view it as beneficial during end of life care. We identified no differences between groups by age, sex, ethnicity, US vs foreign medical training, patient volume, or whether the state where they practiced had legalized MM.

Conclusion

Oncologists affiliated with a medical school report less knowledge about MM and are more cautious in their views of its effectiveness for treating poor sleep. This may be due to their institutions’ reluctance to draft MM policies for fear of losing federal licensure or their awareness of the limitations of existing data. There are important practice implications related to the likelihood of an oncologist recommending MM for poor sleep.

Support

Hans and Mavis Lopater Foundation.