bluuebunny/crossref_metadata_2025_split huggingface dataset:
035 Activating the concept of “relaxation” during sleep using relaxation-related words
Authors: Beck Jonas , Loretz Erna , Rasch Björn 
Published: May 2021

Abstract

Introduction
Cognitive processes (e.g., rumination, perception of an unfamiliar sleeping environment, relaxation techniques) alter our sleep, but the underlying mechanisms are still unknown. Theories of embodied or grounded cognition assume that semantic meaning is stored in multimodal neuronal networks. We therefore assume that cognitive concepts are closely linked to related bodily functions. We propose that mental processes are active to a greater or lesser extent during sleep and that this degree of activation affects our sleep depth.

Methods
We examined this notion by activating the concept of “relaxation” during sleep using relaxation-related words in 50 healthy participants. After an adaption night, subjects slept in the sleep laboratory for two experimental nights according to a within-subject cross-over design. During one experimental night, relaxing words (e.g., “sea”, “relax”) were presented to promote sleep depth. During the other experimental night, control words were presented (e.g., “produce”, “materials”). As the amount of SWS peaks within the first sleep cycle, words were presented during NREM sleep starting with the second sleep cycle (at the latest 120 min after sleep onset). In addition, a mood and a subjective sleep quality questionnaire was conducted.

Results
In support of our hypothesis, playing relaxing words during non-rapid eye movement sleep extended the time spent in slow-wave sleep during the period, when words were presented. Furthermore, power in the slow-wave activity band was increased several seconds after the cue for relaxing compared with control words. The increased sleep depth by means of relaxing words was accompanied by a reduced interhemispheric asymmetry of SWA and slow-wave density in the during-cueing period. The changes observed in objective sleep translated to the subjective level with an increase in subjective sleep quality and alertness ratings.

Conclusion
The present study showed that the semantic meaning of words presented during NREM sleep is capable of affecting sleep physiology, SWS maintenance and the subjective evaluation of sleep quality. Our results support the notion that the activation of mental concepts during sleep can influence sleep depth and provide a basis for interventions using targeted activations to promote sleep depth and sleep quality to foster well-being and health.
Support (if any):
038 Sleep and Hippocampal Function during an Associative Memory Task are Influenced by Surgical Menopause at Midlife
Authors: Brown Alana , Gervais Nicole , Gravelsins Laura , Nicoll Gina , Rieck Jenny , Almey Anne , Sun Dorothy Leqi , Ge Jennifer Xiangning , Laird Kaz , Reuben Rebekah , Karkaby Laurice , Perovic Mateja , Grady Cheryl , Einstein Gillian 
Published: May 2021

Abstract

Introduction
17β-estradiol loss is related to Alzheimer’s disease (AD) risk factors, including disordered sleep and associative memory decrements. Women have higher risk for AD than men, and those with mid-life 17β-estradiol loss due to surgical menopause, including bilateral salpingo-oophorectomy (BSO) before age 48, have even higher risk. We wondered whether sleep and associative memory in women with BSO (mean age 44–46) would be comparable to those with spontaneous/natural menopause (SM; mean age 57), and whether 17β-estradiol-based hormone therapy (ET) might mitigate these effects.

Methods
We assessed sleep using the average of three nights of portable polysomnography (Temec) in women with BSO either taking ET (BSO+ET; n=16), or not (BSO; n=18), and in older spontaneously menopausal women (SM; n=14). Using EEG (Fp1-Fp2), we obtained sleep staging automatically (Neurobit Technologies). Participants also completed a face-name associative memory task during functional magnetic resonance imaging. Recognition accuracy and brain activation during encoding were measured.

Results
BSO exhibited reduced sleep efficiency compared to BSO+ET. For BSO, there was no relationship between percent of total sleep time in N3 and hippocampal activation during associative encoding, even though percent of total sleep time in N3 was negatively associated with hippocampal activation during associative encoding in BSO+ET. For all groups, including BSO, lower latency to consolidated N3 correlated with better associative memory accuracy. There were no group differences in associative memory accuracy. In contrast to BSO, SM showed significantly longer latency to consolidated N3 than BSO+ET.

Conclusion
Younger women with BSO have comparable sleep to older women in SM. In younger women with BSO, ET improves sleep efficiency. Further, while associative memory may be disrupted by increased latency to consolidated N3 in all women, BSO and BSO+ET showed similar associative memory accuracy and latency to consolidated N3. Only BSO+ET exhibited a significant correlation between hippocampal activity during associative encoding and time spent in N3, indicating that ET may support the negative relationship between N3 and hippocampal function. Overall, ET in younger women with BSO potentially ameliorates poor sleep and associative memory decrements.

Support (if any)
Alzheimer’s Association/Brain Canada Foundation: AARF-17-504715; Wilfred and Joyce Posluns Chair in Women’s Brain Health and Aging
039 Sleep Preferentially Supports Problem-Solving Skills via Greater Functional Connectivity Between the Caudate and Cerebral Cortex
Authors: van den Berg Nicholas , Smith Dylan , Fang Lydia , Fogel Stuart 
Published: May 2021

Abstract

Introduction
Sleep consolidates memory, including newly acquired procedural skills. One putative systems-level mechanism for this function of sleep is via sleep-dependent strengthening of functional connectivity between the putamen and the cortico-hippocampal-striatal-cerebellar network, which supports procedural motor skills. For procedural motor skills that also require problem solving and rule-learning, sleep preferentially benefits the cognitively complex aspects over the motor skills required to execute the solution itself. The caudate is implicated in higher-order cognitive components of skill learning, which include error monitoring and automizing new information. In the current study, we investigated how sleep alters functional connectivity in higher-order learning networks that support problem solving and rule learning-related procedural skills.

Methods
Participants (n = 38) were trained on a procedural skills task; the Tower of Hanoi (ToH), that requires the acquisition of a novel cognitive strategy (e.g., recursive logic), while undergoing functional magnetic resonance imaging (fMRI). After either a full night of sleep (n=19) or a full day of wakefulness (n=19), participants were retested on the same task in the fMRI. Resting state activity was acquired before (R1) and after the training session (R2), and before the retest session (R3).

Results
Behavioral performance on the ToH improved following sleep compared to wake (reduced number of errors: t(38)=2.92, p=0.006, d=1.24). Regions associated with higher-order learning and cognitive complexity (i.e., the caudate) and regions typically implicated in sequence learning (i.e., the putamen, hippocampus, cerebellum) were selected as regions of interest (ROI). Increased functional connectivity across the retention interval (R3-R2) was observed in the sleep vs. wake condition between the caudate and the motor cortex (t(36)=3.32, p=0.042, FWE). By contrast, changes in functional connectivity were not observed between the putamen and other ROIs.

Conclusion
These results suggest that sleep supports improved consolidation of motor skills that involve the acquisition of a novel cognitive strategy. Sleep enhanced functional connectivity in brain areas associated with higher-order cognitive skills (i.e., the caudate), but not regions typically associated with motor skills (i.e., the putamen) that are required to execute the solution to the cognitive procedural skill.

Support (if any)
Natural Science and Engineering Research Council of Canada
042 A look at sex differences on sleep’s impact on working memory improvement
Authors: Zhang Jing , Whitehurst Lauren , Mednick Sara 
Published: May 2021

Abstract

Introduction
Studies have shown that sleep affects working memory (WM) improvement, but specific electrophysiological features are unclear (Sattari et al., 2019; MacDonald et al., 2018). In addition, sex differences have been found in both sleep and working memory (Mong, 2016; Harness, 2008). The goal of this study is to identify sex differences in EEG correlates of working memory over a night of sleep.

Methods
Sixty-three healthy (33 females), college-aged adults without sleep disorder were enrolled. A 32-channel electroencephalogram (EEG) cap was used to record brain activity during sleep. Operation span (OS) task was used to evaluate WM performance. Participants reported to the laboratory in the evening, performed OS before sleep (test1) and after sleep (test2). Trials were divided into easy and hard trials based on the number of letters subjects had to recall. A repeated-measure analysis of variance was conducted to examine the effects of time and trial difficulty. Paired-sample t-tests between test 1 and test 2 were conducted for males and females. Pearson’s correlations were examined between WM performance at test 1 and the difference score between test 1 and test 2 and EEG frequency bands. The Benjamini–Hochberg method was used to control for multiple comparisons.

Results
There was an increase in performance across the night in WM hard trials across all subjects (F(1,62)=4.86, p=0.03), no effect for easy trials (p&gt;0.05). Females, but not males, showed a significant decrease in easy trials (t62= 2.40, p=0.02), while both males and females showed improvement in hard trials across the night. Females showed a positive correlation between test 1 hard trials and slow sigma, delta, slow oscillation in stage 3, this correlation is not seen in males. No correlations between overnight improvement and EEG bands were found.

Conclusion
Consistent with previous studies, participants showed better memory performance over a night of sleep, and the WM performance was associated with slow wave activity in females. Slow sigma also plays a role in the WM performance for females, indicating a possible role of sleep spindles. These associations were not shown in males, suggesting sex hormones mediate sleep’s impact on WM performance.
Support (if any):
045 Associations of Actigraphic Sleep and Circadian Rest/Activity Rhythms with Cognition in the Early Phase of Alzheimer’s Disease
Authors: Alfini Alfonso , Albert Marilyn , Faria Andreia , Soldan Anja , Pettigrew Corinne , Wanigatunga Sarah , Zipunnikov Vadim , Spira Adam 
Published: May 2021

Abstract

Introduction
Alterations in sleep and circadian rhythms are common in persons with Alzheimer’s disease (AD) dementia, but the nature of such changes in the early phases of AD remains unclear. This study compared sleep and circadian rest/activity rhythms (RARs), measured by standard and novel actigraphic indices, between participants with normal cognition or mild cognitive impairment (MCI), and examined cross-sectional associations between these measures and cognition.

Methods
Actigraphy data were collected in 179 individuals (mean age=72.6 years, gender=64.8% female) with normal cognition (n=153) or MCI (n=26) from the Biomarkers for Older Controls at Risk of Dementia (BIOCARD) study. Standard sleep parameters (i.e., total sleep time [TST], sleep efficiency [SE], wake after sleep onset [WASO], average wake bout length [WBL]), and standard non-parametric RAR metrics (i.e., relative amplitude [RA], intradaily variability [IV], interdaily stability [IS]) were generated. Functional principal component (fPC) methods were used to generate three novel RAR indices (fPC1, fPC2, fPC3) representing 69% of the total variance. Cognitive test scores were used to generate composite measures reflecting the domains of episodic memory and executive function using factor analysis. Regression models were used to compare sleep and circadian RAR parameters between the diagnostic groups and to evaluate their associations with cognitive performance.

Results
After adjustment for age, sex, education, and APOE-4 genotype, compared to normal controls, MCI subjects had significantly lower SE, lower RA, and lower scores on the novel RAR measure fPC3, which reflects a later rhythm phase, lower amplitude, and lower activity both at night and early in the day. In analyses combining data from participants with MCI and controls, several standard RAR parameters (e.g., higher RA and IS) and higher fPC3 scores were associated with both better episodic memory and executive function. Additionally, several standard measures (e.g., lower WASO and IV) and lower fPC1 scores (reflecting higher rhythm amplitude and greater activity throughout daytime hours) were linked with better executive function.

Conclusion
MCI participants have sleep and circadian alterations, which are significantly associated with cognitive performance. A novel RAR measure, fPC3, showed differences in rhythm patterns that extended from the night into the daytime.

Support (if any)
Funding-support NIA (U19-AG033655, T32-AG027668, R01-AG050507) and AASMF (#223-BS-19).
047 Fear-Potentiated Startle and Sleep in Trauma-Exposed Men and Women with and without PTSD
Authors: Richards Anne , Inslicht Sabra , Huie J Russell , Yack Leslie , Straus Laura , Felmingham Kim , Woodward Steve , Neylan Thomas 
Published: May 2021

Abstract

Introduction
Animal and human studies indicate that fear conditioning disrupts subsequent sleep, including REM sleep (REMS). REMS is thought to be central to fear information processing. We utilized an afternoon nap protocol to examine the effects of fear-potentiated startle (FPS), a variant of fear conditioning, on subsequent sleep integrity and REMS in trauma-exposed participants with varying levels of PTSD. We also examined the effects of changes in sleep integrity and REMS on subsequent retention and extinction of pre-sleep learning.

Methods
Participants (N=47) participated in 3 nap visits. The first was an adaptation nap. The second and third nap visits were counterbalanced: a stress-condition nap, during which participants underwent FPS procedures prior to a nap and assessment of retention of fear and safety signal learning and fear extinction after the nap, and a control visit during which participants had a nap opportunity without stressful procedures. Canonical correlation analysis assessed the relationship between FPS responses and change in subsequent sleep relative to a control nap, as well as the relationship between change in sleep from control to stress condition and both subsequent fear and safety learning retention, and subsequent extinction.

Results
Results demonstrated a relationship between fear learning and change in sleep and supported a relationship between safety signal learning and subsequent REMS, as well as differential conditioning and wake after sleep onset. Sleep did not predict measures of fear retention or extinction. PTSD symptoms did not predict fear learning or sleep measures.

Conclusion
These findings replicate prior work showing a relationship between safety learning and REMS, suggesting that this is a core mechanism through which stress impacts fear processing. Further research is critical to further understand this effect, and to examine how different aspects of fear learning impact different components of sleep. This study also demonstrates that nap studies can be a valuable approach for studying the stress-sleep relationship.

Support (if any)
VA Career Development Award to Dr. Richards (5IK2CX000871-05)
052 APOE-ε4 is associated with impaired sleep-dependent memory consolidation in healthy carriers
Authors: Djonlagic Ina , Guo Mengshuang , Igue Moroke , Kishore Divya , Marshall Lisa , Malhotra Atul , Stickgold Robert 
Published: May 2021

Abstract

Introduction
The Apolipoprotein E (APOE)-ε4 genotype is a marker of susceptibility for late-onset Alzheimer’s disease (AD). Sleep disturbances may accelerate the aging process and increase the risk for future development of cognitive impairment and dementia. Given that the pathophysiological process of AD can predate its clinical manifestations by years or even decades, the aim of this study was to assess the role of the APOε4 allele on sleep-dependent memory consolidation in cognitively healthy adults.

Methods
16 healthy APOE-ε4 carriers (mean age=49.9±13.7) and 32 healthy non-carriers (age=45.7±12.9) were included in the main analysis. Baseline screening included the Epworth Sleepiness Scale, Morningness-Eveningness scale, Wechsler Adult Intelligence Scale (WAIS) and Beck Depression Inventory (BDI), as well as a baseline polysomnogram (PSG), which also served as an adaptation night. Participants subsequently underwent an overnight testing session, which included computer sessions of the Psychomotor Vigilance Task (PVT) and the declarative Verbal Paired-Associates Task (VPA) in the evening followed by a full night PSG and repeat PVT and VPA sessions in the morning. For further reference, we added an age matched group of 16 non-carriers with newly diagnosed obstructive sleep apnea (OSA, age=48.1±15.1), who underwent the same study procedures.

Results
APOE-ε4 carriers had higher BDI (p=0.04) and ESS (p=0.01) scores than non-carriers. There were no significant group differences for sleep macrostructure. Evening VPA performance was similar for both groups (p=0.77). The following morning, APOE-ε4 carriers improved by 7.5±6.4 % from the evening before, compared to 13.5±7.0% for the healthy non-carriers (p=0.005). OSA subjects improved by 5.0± 8.1%, which was similar to APOE-ε4 carriers (p=0.34).

Conclusion
To our knowledge, this is the first study to reveal that healthy APOE-ε4 carriers while showing similar initial learning (encoding) on a declarative memory task compared to healthy controls, exhibit a deficit in sleep-dependent memory consolidation, similar to patients with obstructive sleep apnea. Consequently, this study provides evidence that impaired sleep-related memory processes could be an important harbinger in otherwise healthy individuals, who are at high risk for AD.

Support (if any)
NIH grant # K23HL103850 (Ina Djonlagic) and American Sleep Medicine Foundation grant #54-JF-10 (Ina Djonlagic)
053 REM Sleep Apnea Severity Contributes to Poor Verbal Memory in Cognitively Asymptomatic Older Adults
Authors: Lui Kitty , Sprecher Kate , Dave Abhishek , Heston Margo , Chappel-Farley Miranda , Chen Ivy , Riedner Brady , Bendlin Barbara , Mander Bryce , Benca Ruth 
Published: May 2021

Abstract

Introduction
The prevalence of obstructive sleep apnea (OSA) rises with age, leading to increased dementia risk and memory decline. However, it remains unclear which OSA features drive this relationship. Here, we examine associations between verbal memory and multiple OSA features in healthy older adults.

Methods
58 cognitively asymptomatic adults (61.4±6.3 years; 38 females) underwent polysomnography (PSG) and the Rey Auditory Verbal Learning Test (RAVLT; 0.2±0.5 years between assessments). OSA measures included apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and desaturation index in both NREM and REM sleep. RAVLT measures included total learning (sum of trials 1–5), short-delayed recall, and long-delayed recall. Pearson correlations with FDR correction were calculated between OSA-related measures and RAVLT. Multiple regression was then used to adjust for OSA features in other sleep stages (i.e., REM versus NREM), age, sex, time between PSG and neuropsychological assessments, years of education, and APOE4 status. We also explored whether age moderated these relationships.

Results
REM RDI is negatively associated with RAVLT total learning (r=-0.31, p&lt;0.01 with age moderating the effect at 1SD above mean: B=-0.22, t(49)=-2.88, p=0.01) and RAVLT long-delayed recall (r=-0.36, p&lt;0.001; with age moderating the effect at mean: B=-0.05, t(49)=-2.38, p=0.02; and moderating at 1SD above mean: B=-0.09, t(49)=-3.91, p&lt;0.01). REM desaturation index was also associated with RAVLT total learning (r=-0.21, p&lt;0.01) and RAVLT long-delayed recall (r=-0.34, p&lt;0.01). REM AHI was negatively correlated to RAVLT long-delayed recall (r=-0.34, p&lt;0.01; with age significantly moderating the effect at the mean: B=-0.06, t(49)=-2.87, p=0.01; and moderating at 1SD above the mean: B=-0.11, t(49)=-4.23, p&lt;0.01). Of note, NREM OSA features were not significantly correlated to RAVLT measures when REM OSA features were included in the model.

Conclusion
These findings demonstrate that REM OSA features in particular contribute to poor verbal memory encoding and retrieval, especially at older ages. Verbal memory decline has been predictive of conversion to Alzheimer’s disease (AD). Future studies including brain imaging, AD biomarkers, REM sleep oscillations, and comprehensive neuropsychological testing may elucidate the underlying mechanisms linking REM OSA features to memory decline and dementia risk.

Support (if any)
This research was supported by R56 AG052698 and P50AG033514.
054 Characterization of Sleep Phenotypes and Sleep-Dependent Memory Consolidation in a Mouse Model of Fragile X Syndrome
Authors: Martinez Jessy , Popke Donald , Donnelly Marcus , Torres Daniel , Clawson Brittany , Jiang Sha , Aton Sara 
Published: May 2021

Abstract

Introduction
Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by disruption of Fmr1 gene function, leading to intellectual disability. FXS individuals report increased incidence of sleep disruptions such as loss of NREM sleep, irregular sleep/wake cycles, and circadian rhythm disturbances that warrant pharmacological intervention. Since sleep has critical roles in the promotion of memory consolidation, it is unknown whether disrupted cognitive function in FXS is exacerbated by abnormal sleep. We characterized the link between sleep loss phenotypes and cognition in FXS mice (Fmr1 KO). We hypothesized that normalizing sleep in Fmr1 KO mice could improve sleep-dependent cognitive function. Because direct activation of G-protein inward rectifying potassium (GIRK) channels by ML297 has been found to promote NREM sleep, we tested how ML297 affected sleep and memory consolidation phenotypes in Fmr1 KO mice.

Methods
Wild type (WT) and Fmr1 KO were implanted with electrodes for electroencephalogram/electromyogram (EEG/EMG) recording of wakefulness, NREM and REM sleep. Sleep-dependent memory consolidation was measured using single-trial contextual fear conditioning (CFC). ML297 or vehicle was administered after CFC training to measure the effects on sleep and fear memory consolidation.

Results
Fmr1 KO mice showed reduced sleep in the hours following CFC learning compared to wild type littermates, and reduced contextual fear memory consolidation. Post-CFC sleep deprivation disrupted memory consolidation in wild type littermates, but not Fmr1 KO mice. Both NREM sleep time and NREM bout length were reduced in Fmr1 KO mice, and preliminary data suggest reduced NREM delta (0.5–4 Hz) power in the prefrontal cortex. These deficits were present at baseline and also following CFC. Post-CFC training administration of ML297 rescued NREM sleep and contextual fear memory deficits in Fmr1 KO mice.

Conclusion
Our study showed a strong link between NREM sleep loss and cognitive deficits in Fmr1 KO mice. Critically, normalization of NREM sleep through direct activation of GIRK channels rescues cognitive deficits seen in Fmr1 KO mice, suggesting a new therapeutic approach to treating cognitive deficits associated with FXS.

Support (if any)
This work was supported by a Rackham Merit Fellowship to JDM.