bluuebunny/crossref_metadata_2025 huggingface dataset:
0049 Orexin 2 receptor agonist activates pre-Bötzinger complex neurons, phrenic motoneurons and the diaphragm in rodents
Authors: Kimura Haruhide , Yamada Ryuji
Published: May 2023

Introduction

Neurons in the pre-Bötzinger complex are critical for the generation of inspiratory rhythm and regulation of activity of phrenic motoneurons, which control the activity of the diaphragm. Dysregulation of this neuronal network and resulting dysfunction of the diaphragm is associated with central sleep apnea (CSA). Orexins by stimulating both orexin 1 receptor (OX1R) and/or orexin 2 receptor (OX2R) can activate these neurons and the diaphragm. In this study, we assessed effects of OX2R-selective agonists on the activity of neurons in the pre-Bötzinger complex, phrenic motoneurons, and the diaphragm.

Methods

OX2R-selective agonists danavorexton (TAK-925) and OX-201 (a tool compound with longer plasma half-life than danavorexton in rodents) were used. OX2R and OX1R agonistic activities were examined by calcium mobilization assay in hOX2R/CHO-K1 cells and hOX1R/CHO-K1 cells, respectively. Activity of neurons in the pre-Bötzinger complex and phrenic motoneurons was investigated by electrophysiological recording in rat tissues. Activity of the diaphragm was evaluated by electromyogram recording in anesthetized rats. Respiratory activity was evaluated by whole-body plethysmography recording in mice.

Results

Danavorexton and OX-201 showed potent OX2R agonistic activity with 50% effective concentration (EC50) values of 5.5 nM and 8.0 nM, respectively. Danavorexton and OX-201 had >5,000-fold and 1,000-fold OX2R selectivity over OX1R, respectively. In in vitro electrophysiological analyses, danavorexton and OX-201 increased the burst frequency of neurons in the pre-Bötzinger complex (EC50: 300 nM and 760 nM, respectively) and phrenic motoneurons (EC50: 1.6 µM and not determined, respectively). Intravenous administration of OX-201 at 1 and 3 mg/kg increased burst frequency of the diaphragm in anesthetized rats and oral administration at 3 mg/kg increased respiratory activity in conscious mice.

Conclusion

OX2R-selective agonists may enhance respiratory function via activation of the diaphragm through stimulation of neurons in the pre-Bötzinger complex and phrenic motoneurons. OX2R agonists may have therapeutic potential in patients with CSA if enhancement of respiratory function by OX2R agonists can be observed at non-arousal concentrations. Further preclinical and clinical studies are worth conducting in patients with CSA.

Support (if any)

This work was conducted by Takeda Pharmaceutical Company Limited.
0053 Circadian Regulation in the Social Brain: How Sleep Deprivation Compromises Empathy
Authors: Turnbull Mark , Malby Connor , Jensen Emily , Sharif Fatima , Donninger Jenna , Goodall Stuart , Ansdell Paul , Santhi Nayantara
Published: May 2023

Introduction

The interaction between the circadian clock and sleep drive generates a rhythm of deterioration and recovery in cognition over wake and sleep, respectively. In modern society, our sleep is often disrupted due to long and unsociable work hours. Emerging evidence suggests that this negatively impacts our social interactions, but the physiological mechanisms remain unclear. Our perceptions of other people’s mental states dominate interpersonal interactions, and profoundly impact our lives. This study examined how sleep deprivation impacts our perceptions of another’s mental state (a cognitive domain known as Theory of Mind: ToM).

Methods

21 young healthy adults completed the study (11 females: mean age +/-SD =22.09 +/- 3.59, 10 males: mean age +/- SD =23 + 4.13). Over a 12-hour overnight wakefulness period, we examined changes in ToM every two hours with the Reading in the Mind’s Eye (RMIE) task. It consists of 36 images, each a pair of eyes representing an emotion, categorized as Easy or Difficult and as positive, negative, and neutral (valence). We measured accuracy based on a 4-forced alternative response. Subjective sleepiness was measured every two hours with the Karolinska Sleepiness Scale (KSS).

Results

Our analysis revealed a significant effect of wakefulness on accuracy (p < 0.0001), such that it declined precipitously 4 hours into the protocol (coinciding with midnight). Accuracy was significantly better (p< 0.01) for Easy stimuli than on Difficult stimuli, but accuracy on both declined significantly with wakefulness. A similar result was seen with valence (p< 0.0001), with Positive stimuli (74.5% +/- 1.8%) showing a better accuracy (mean +/- 1SE) than negative (57.4% +/- 1.9%) and neutral (58.2% +/- 1.7%) ones. But accuracy on all three declined with wakefulness (Positive: 84% -72.4%; Negative:61.2% - 58.5; Neutral: 64.2% - 59.9%). Sleepiness increased significantly overnight (p< 0.0001). Furthermore, there was a significant correlation (correlation: 0.5; Fisher’s z test: p = 0.03) between the change sleepiness and RMIE task accuracy.

Conclusion

These findings are one of first descriptions of the circadian and sleep regulation in Theory of Mind, our ability to empathize. They have significant scientific and clinical implications.

Support (if any)

British Academy/Leverhume Small Research Grant to Nayantara Santhi.
0056 Sleep Characteristics Predict Metacognitive Functioning Above-and-Beyond Age, Education, and Mood
Authors: Nielson Spencer , Dautovich Natalie , Dzierzewski Joseph
Published: May 2023

Introduction

Metacognition, also-known-as subjective cognitive functioning, is an important predictor of cognitive decline and previous work has identified age, education, and mental health symptoms as important predictors. Sleep is essential for optimal neurocognitive functioning; as such, sleep may also play an important role in determining estimates of metacognition. However, it is currently unknown if sleep is associated with metacognition above-and-beyond known predictors. This study aimed to investigate whether sleep characteristics, including insomnia symptoms, global sleep health, and sleep regularity, were associated with metacognitive functioning above-and-beyond know predictors of age, education, and mood.

Methods

Participants (N=3284) included adults (Mage=42.7 years,48.5% female) who completed an online study investigating sleep and health across the lifespan. Participants self-reported their age and education and completed various questionnaires including the 6-item PROMIS Cognitive Function questionnaire, the Patient Health Questionnaire-4 (PHQ-4), the Insomnia Severity Index (ISI), the RU-SATED sleep health questionnaire, and the Sleep Regularity Questionnaire (SRQ). Stepwise regression models were used to investigate whether ISI, RU-SATED, and SRQ scores predicted PROMIS Cognitive Function scores after accounting for age, education, and PHQ-4 scores.

Results

In Step 1 of the model, age and education significantly predicted metacognitive functioning (β=.146, t=8.44, p<.001; β=.086, t=4.97, p<.012). In Step 2, PHQ-4 scores and education were significant while age was no longer significant (β=-.589, t=-40.56, p<.001; β=.03, t=2.10, p=.036). In Step 3, age, education, and RU-SATED scores were not significant predictors while scores on the PHQ-4, ISI, and SRQ were significant predictors of metacognitive functioning (β=-.346, t=-21.93, p<.001; β=-.38, t=-20.20, p<.001; β=.052, t=3.20, p=.001). Step 3 accounted for a significant increase in variance explained (∆R2=.121, F=497.07, p<.001).

Conclusion

Sleep characteristics, including insomnia symptoms and sleep regularity, are associated with metacognition above-and-beyond known predictors including age, education, and mood. Sleep characteristics may be an important part of estimates of metacognition. Moreover, because sleep is a modifiable risk factor with effective treatments, it may have potential as a treatment target for cognitive decline. Further research is needed to investigate whether the sleep-metacognitive functioning differs between common demographic groups and whether sleep disturbances predate declines in metacognitive functioning or vice versa.

Support (if any)

National Institute on Aging: Award K23AG049955 (PI: Dzierzewski).
0057 The Impact of Cortical Oxygenation During Sleep-Disordered Breathing on Cognition
Authors: Kawai Makoto , O'hara Ruth
Published: May 2023

Introduction

Untreated sleep-disordered breathing (SDB) has been reported as a common risk for dementia. However, the association between current SDB parameters (i.e., AHI) and cognition is not straightforward. To examine the impact of cortical oxygenation during SDB on cognition in older adults, we measured the coherence of oxyHb and SpO2 during SDB, in which a higher level can represent less protection against systemic hypoxia, is associated with cognition in older adults.

Methods

Thirty-eight community-dwelling, healthy older adults without dementia (20 women) were recruited. The mean and standard deviation (SD) of age was 72.6±6.4years. All participants underwent comprehensive neuropsychiatric evaluation of short and long-term verbal memory(Wechsler Memory Scale & Rey Auditory Verbal Learning Test), Executive Functioning (Delis-Kaplan Executive Function System), verbal naming abilities (Boston Naming Test), and visuo-spatial ability (Judgment of Line Orientation). We performed a simultaneous PSG and NIRS recording overnight at the participants’ houses. We measured the mean max coherence of oxyHb and SpO2 and analyzed its correlation to cognition.

Results

The mean and SD of total sleep time, N1, N2, N3, and REM were 392.8±71.8 min, 65.5±60.3min, 210.7±68.5min, 53.1±30.9min, and 63.5±25.4 min. The mean and SD of AHI were 21±17.4 events/hour. The mean and SD of the max coherence ratio were 0.78±0.10. Linear regression analysis found higher coherence of oxyHb and SpO2 to be significantly correlated, after Bonferroni Correction, with a poorer score on the age-corrected BNT score (t = -3.174, p = .003), covaried for gender and education.

Conclusion

Higher coherence of oxyHb and SpO2 during SDB may predict poorer verbal naming abilities in older adult

Support (if any)

National Instutite on Aging
0059 Acoustic enhancement of sleep slow oscillations nested to spindles relative to delta waves improves memory consolidation
Authors: Grimaldi Daniela , Mikutta Christian , Reid Kathryn , Papalambros Nelly , Malkani Roneil , Abbott Sabra , Paller Ken , Zee Phyllis
Published: May 2023

Introduction

The nesting of electroencephalographic (EEG) sleep slow oscillations (SOs) to spindles has been shown to be important for sleep-dependent memory consolidation. However, recent evidence indicates that a higher proportion of SOs nested to spindles, relative to δ waves, might be even more critical for sleep-dependent memory consolidation. Acoustic stimulation during slow wave sleep has been shown to be effective in improving memory consolidation. Here, we examined the contribution of SOs nested to spindles relative to δ waves on sleep-dependent declarative memory consolidation associated with acoustic stimulation.

Methods

Twenty subjects (18-35 years, 75% females) participated in a randomized cross-over study. At each visit participants received either stimulation (stim) or sham following an adaption night. Stim occurred in blocks of 5 pulses (ON intervals) followed by a period of equal length with no stimulation (OFF intervals). Participants learned 40 Arabic-English word pairs and were tested before sleep and after sleep in the morning and again in the afternoon. Detection of SOs (< 2 Hz), δ waves (2-4 Hz), spindles (11-16Hz), and the ratio (%) of spindles nested to SO over δ waves (SO/δ Nesting Index) were calculated during ON intervals for stim and sham conditions.

Results

Overnight mean (SD) percentage change in word recall between conditions was similar in the morning (stim 6(3)%, sham 4(6)%, p=0.68), but was higher in the afternoon in stim compared to the sham condition (stim 10(4)%, sham 4(6)%, p=0.02). The SO/δ Nesting Index was higher in stim compared to the sham condition (stim 21(13)%, sham 13(10%), p=0.004). Within-subject improvement from sham to stim condition in afternoon memory was associated with a greater change in SO/δ Nesting Index (R=0.63, p=0.03), this association was not observed for spindles nested to SOs (R=0.33, p=0.202) or spindles nested to δ waves (R=-0.18, p=0.811).

Conclusion

Enhancement of memory consolidation with acoustic stimulation may be dependent on its ability to increase SOs nested to spindles relative to δ waves. Dynamic changes in the relationships between SOs, δ waves and spindles can help inform novel EEG-derived markers and targets to enhance sleep-dependent memory consolidation.

Support (if any)

DARPA award W911NF-16- 2-0021
0063 Slow-wave Sleep Onset Latency Mediates Improvements in Attention and Processing Speed Following Continuous Theta-Burst (cTBS) TMS
Authors: Huskey Alisa , Jankowski Samantha , Henderson-Arredondo Kymberly , Hildebrand Lindsey , Trapani Christopher , Elledge Heidi , Lucas Daniel , Suckow Emmett , Reich-Fuhrer Melissa , Franca Gabriela , Reign Deva , Chen Yu-Chin , Chou Ying-Hui , Dailey Natalie , Killgore William
Published: May 2023

Introduction

Insomnia causes substantial health-care cost burden and is a risk factor for neurocognitive impairment. Increased DMN activity has been implicated in the hyperarousal theory of insomnia. In this pilot clinical trial, DMN was targeted via the left inferior parietal lobe using a brief 40 second cTBS Transcranial Magnetic Stimulation (rTMS). We hypothesized that neurocognitive improvements due to cTBS would be mediated by polysomnographic (PSG) parameters of slow wave sleep.

Methods

Twenty participants (12 female; age=26.9, SD=6.6 years) meeting criteria for insomnia completed a counterbalanced sham-controlled crossover design in which they served as their own controls on two separate nights of in-laboratory assessments. Sessions for both conditions included neurocognitive assessments at baseline, after stimulation (cTBS/sham) before bed, and the following morning. After stimulation, participants were allowed an 8-hour sleep opportunity from 2300 to 0700 monitored with PSG. The symbol coding and digit span subtests of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) exam are the main assessments in the current investigation.

Results

Improvements in attention and processing speed were observed after a night of sleep following both active TMS (cTBS; B = 11.05, p < .001) and sham TMS conditions (B = 8.10, p = .002) the prior day. In the cTBS condition only, these improvements in attention were mediated by latency to slow wave sleep (N3), such that shorter latencies were related to greater improvements on a simple attention task (RBANS digit span; B = -0.75, p < .001). This effect of night to morning improvement in attention and processing speed was also found in the sham condition for the coding task (B = 60.81, p < .001), but not for digit span. No effects of slow wave sleep duration on RBANS coding or digit span were observed in either condition.

Conclusion

Improvements in simple attention performance in response to cTBS may be, in part, due to slow wave sleep parameters. Moreover, results suggest that simple attention may have been more sensitive to the effects of cTBS, whereas processing speed may have been a factor of lower slow wave sleep onset latency.

Support (if any)

DoD PRMRPD W81XWH2010173
0064 Trading sleep for learning time improves next-day recall, but with poorer retention of items learned during sleep deprivation
Authors: Kalaivanan Kastoori , Yeo Sing Chen , Gooley Joshua
Published: May 2023

Introduction

Sleep is important for learning and memory retention. However, students often cram for examinations by staying awake late to study. We tested the hypothesis that trading sleep for learning time leads to better next-day recall, but items learned during sleep deprivation will be more poorly retained.

Methods

Seventy healthy adults (18–24 years; 32 males) participated in an overnight laboratory study and were tasked with learning the meanings of 120 pseudowords using digital flashcards. Half of participants were randomly assigned to 8 h of TIB for sleep (23:00 to 07:00) and the other half to 4 h of TIB for sleep with a later bedtime (03:00 to 07:00). The 8-h TIB group was given 3 learning sessions (17:50, 19:50, and 21:50) with each flashcard shown twice per session. The 4-h sleep group was given an additional 2 learning sessions that occurred during the night (23:50 and 01:50). Cued-recall performance was tracked during pre-sleep learning, and participants were tested the following morning (09:30) on 60 randomly selected flashcards.

Results

Prior to sleep, the 4-h TIB group learned more items than the 8-h TIB group (Mean score ± SD: 4-h TIB, 85.31% ± 20.92%; 8-h TIB, 63.76% ± 24.22%) because they successfully encoded new items during their additional nocturnal learning sessions. On the following morning, the 4-h TIB group had significantly higher scores on the cued-recall test compared with the 8-h TIB group (Mean score ± SD: 4-h TIB, 83.71% ± 23.50%; 8-h TIB, 70.10% ± 24.18%; Mann-Whitney U test, p< 0.001). However, items learned during the final learning session before sleep were retained significantly better in the 8-h TIB group compared with the 4-h TIB group (4-h TIB, 76.64%; 8-h TIB, 91.35%, Chi-squared = 20.43, p< 0.001).

Conclusion

There was a trade-off of exchanging sleep for additional learning time. More learning time at the expense of sleep resulted in better next-day test scores but recall performance was poorer for items newly learned during partial sleep deprivation. Our findings help to explain why students often sacrifice sleep for short-term gains in test performance despite poorer memory retention.

Support (if any)

National Research Foundation, Singapore (NRF2016-SOL002-001)
0066 Continuous Theta Burst Transcranial Magnetic Stimulation for Insomnia and its Effects on Verbal Recall Performance
Authors: Hildebrand Lindsey , Jankowski Samantha , Henderson-Arredondo Kymberly , Patel Salma , Chen Yu-Chin , Chou Ying-Hui , Dailey Natalie , Killgore William
Published: May 2023

Introduction

In this project, we studied the efficacy of focused inhibitory stimulation using continuous theta burst stimulation (cTBS) repetitive transcranial magnetic stimulation (rTMS) on an easily accessible region of the default mode network (DMN). As reported elsewhere, we found that cTBS improved brain connectivity and objectively measured sleep. However, there is little known about the side effects of rTMS in the treatment of insomnia, so here we evaluated the effects on verbal memory recall.

Methods

Twenty adults with clinical insomnia completed this study (Mage=26.90, SD=6.56). Participants conducted two overnight visits during the study; one where they received active cTBS and one where they received a sham cTBS prior to sleep. Participants completed the California Verbal Learning Test (CVLT) before stimulation and again completed the recall portion following a night of laboratory monitored sleep. We analyzed CVLT recall performance with a repeated measures ANOVA with factors of condition (active cTBS vs. sham cTBS) and session (Short Recall, Long Recall, Cued Recall, and Recognition).

Results

Contrary to our hypothesis, our analyses indicate there was no significant effects on recall performance due to active cTBS. There was no main effect of condition on recall scores post-TMS administration (F(1, 18)=1.162, p=.220, ηp2 = 0.082). There was no interaction effect of active or sham cTBS on recall performance (F(4, 15)=.828, p=.528, ηp2=0.181). Posthoc pairwise comparisons demonstrated that there was no significant difference post-TMS administration between active cTBS and sham cTBS conditions on long recall, cued recall, or recognition (p>.05). There was no significant difference post-TMS administration on short-term recall performance. Participants scored lower on short term recall after receiving active cTBS (M=12.632; SD=2.910) than after sham cTBS administration (M=13.42 ;SD=2.545) (p=.048).

Conclusion

Compared to sham, active cTBS was not associated with any significant difference in long-term recall performance after TMS administration. While the results demonstrate there are short term effects to recall after administration, recall scores bounce back shortly after. While participants didn’t necessarily improve with active cTBS, it is beneficial to know there are no long-term harmful effects of active cTBS on recall as side effect of insomnia treatment.

Support (if any)

W81XWH2010173
0069 Effects of Depression and Anxiety Symptoms on Sleep-Dependent Consolidation of Emotional Memory in College Students
Authors: Banik Nandita , Harrington Ciara , Baran Bengi , Kapucu Aycan , Ersoy Pinar Kurdoglu , Arpaci Hazal
Published: May 2023

Introduction

Depression and anxiety have been associated with emotional memory biases, disturbed sleep, and cognitive deficits. The goal of the present study is to investigate the effects of elevated levels of depressive and anxiety symptoms on sleep physiology and sleep-dependent consolidation of emotional memory and reactivity over a mid-day nap in young college students.

Methods

Data collection is ongoing, preliminary analyses are based on 34 participants (26F, 7M, 1 non-binary, 18-27 yrs). Based on well-validated depression and anxiety scales, participants were classified into high (n=10) vs low (n=24) symptom groups. Participants studied negative and neutral picture stimuli and rated them on the dimensions of valence and arousal. Recognition memory was tested after a 5 hr interval which included a high-density EEG monitored 90 min nap.

Results

We do not observe any group differences in memory accuracy (d’) or in selectivity for emotional stimuli. In the entire sample, depressive symptoms correlate with decision criterion (C) for negative stimuli (r = -0.357, p=.04), such that individuals with higher depressive symptoms have a more liberal responding bias for negative stimuli. Napping is associated with a decrease in arousal ratings across all participants (F(1,32)=5.43, p=.03), and the high mood symptom group rate stimuli as more arousing (F(1,32)=13.96, p<.001). Further, high levels of trait anxiety is associated with more negative valence ratings post-nap (r = -0.350, p=.03).

Conclusion

The effects of a mid-day nap on memory consolidation and reactivity for emotional stimuli are similar between individuals with high vs low levels of mood symptoms, but heightened levels of depression and anxiety are associated with altered response bias and higher emotional reactivity. Future plans involve comparisons of NREM oscillations between groups and investigation of their relations with task performance.

Support (if any)

Iowa Neuroscience Institute “2021 Ideas Lab” Award (Baran)
0070 Fatigue state does not impact attention to learnable information in 17-month-old infants but affects retention
Authors: Simon Katharine , Lara Hatty , Sweeney Lucia , Gerken LouAnn , Gomez Rebecca
Published: May 2023

Introduction

Sleep restriction and fatigue negatively impacts learning in adults, but the effect of fatigue on learning in infants remains unexplored. During their first two years infants frequently cycle through periods of wakefulness and sleep. Thus, infants often encounter new information in an unrested state. How might mild fatigue impact their attention and learning? Given that infants devote more attention to new learnable than new unlearnable patterns (Gerken et al, 2011) how might their physiological state impact the cognitive resources required to attend to and learn new information?

Methods

We randomly assigned 80 17-month-old infants (Mage=17.06m, SD=1.85, Female=38) to a rested or unrested condition corresponding to their participation just after or before their typical nap. Within conditions, we randomly assigned infants to a learnable or unlearnable artificial language. We measured time to habituate over blocks of 4 trials that ended when total looking time over a fixed window of four trials reduced to less than 50% of total looking time across the prior four trials. We tested retention after a 5-minute delay in the learnable condition by measuring mean looking time for 8 trials with new grammatical stimuli vs. 8 trials with ungrammatical stimuli. Thus, we evaluated whether physiological state impacted 1) habituation during initial language exposure and 2) discrimination of grammatical vs. ungrammatical language structure, or learning.

Results

First, does state of fatigue impact infants’ attention to learnable vs. unlearnable stimuli? Infants attended longer to learnable than unlearnable stimuli regardless of physiological state (t(78)=2.043, p=.044, ML=175.77, MU=140.51). Second, does state affect learning? Fatigued infants discriminated grammatical from ungrammatical stimuli at test (MG=6.81s, MUG=8.24s; t(17)=-2.26, p=.037), but rested infants did not (MG=6.69s, MUG=6.59s, t(13)=.26, p=.80).

Conclusion

Fatigue does not appear to impact infants’ ability to detect learnable information but may impact their ability to learn and retain that information. All infants eventually acquire their native language, but mild fatigue, whether reflecting an enhanced physiological or cognitive learning state, appears to contribute to more rapid learning.

Support (if any)
0073 Investigating the epigenetic mechanisms underlying memory consolidation during sleep
Authors: Chen Xinyue , Park Hyunjin , Peng Yueqing , Liu Shawn
Published: May 2023

Introduction

It has been established that sleep after learning something (“post-learning sleep”) actively consolidates what was learned. Yet, the underlying cellular and molecular mechanisms are undergoing active investigation. The fear conditioning (FC) memory paradigm, in which an animal learns to associate an environmental cue to an aversive foot shock, has been widely used for memory investigation. While amygdala and hippocampus are two critical sites for processing and storing the FC memory, how the amygdala consolidate this memory during sleep, from both cellular and molecular perspectives, has been little understood, compared to the hippocampus. Moreover, one potential molecular substrate of memory, DNA methylation, has been studied in the hippocampus for its role in learning and memory. Yet it is little known for its memory role in the BLA.

Methods

Here, we used fiber photometry, miniscope calcium imaging, EEG recording, optogenetic manipulation, and whole genome bisulfite sequencing to study the neural mechanisms underlying memory consolidation in the basolateral amygdala (BLA) during sleep.

Results

(1) We found that the BLA neurons display increased activity during REM sleep, compared to that in non-REM (NREM) sleep. (2) Using closed-loop optogenetic strategy, our preliminary results showed that silencing BLA activity during REM sleep leads to memory impairment in contextual fear conditioning task. (3) We compared DNA methylation of BLA neurons at a whole genome level between mice with and without sleep after FC learning and identified differentially methylated regions between them.

Conclusion

Together, our data suggests that the BLA activity during REM sleep is required for consolidation of fear memory, and DNA methylation might mediate this process.

Support (if any)
0075 Melatonin impairs morning cognition in healthy young adults without any benefit to sleep
Authors: Wernette Elle , Altmann Erik , Fenn Kimberly
Published: May 2023

Introduction

Exogenous melatonin has been shown to improve sleep in individuals with sleep disorders, such as insomnia and delayed sleep phase disorder. However, research on the effect of exogenous melatonin on sleep in healthy young adults is limited. Additionally, there is some evidence that melatonin can negatively affect cognitive processes, such as long-term memory, working memory, and attention. Therefore, we assessed the effect of melatonin supplementation on nocturnal sleep and morning cognition in healthy undergraduates.

Methods

In the evening, participants (N = 120) completed three cognitive tasks: the Psychomotor Vigilance Task (PVT; a measure of attention), UNRAVEL (a measure of procedural placekeeping), and the Paired Associates Learning (PAL) test (a measure of long-term memory). We then asked participants to take a pill under double-blind conditions that contained either melatonin or placebo. Afterwards, participants received an 8-hour sleep opportunity monitored with polysomnography (PSG). One hour after waking, participants completed PAL, UNRAVEL, and PVT again.

Results

We compared morning cognitive performance across the melatonin and placebo conditions, with evening performance as a covariate. Interestingly, melatonin participants had more placekeeping errors than placebo. However, melatonin did not affect PVT or PAL performance. We found no significant differences between the melatonin and sleep groups on any of our sleep measures.

Conclusion

The results suggest that negative performance effects of exogenous melatonin may outweigh any benefits for healthy young adults, particularly when cognitive performance is measured shortly after the sleep opportunity. Our results also suggest that sleep factors captured by PSG may not accurately predict next-day cognitive performance, and that researchers should consider additional factors, such as melatonin concentration, when assessing the relationship between sleep and performance.

Support (if any)

This work was funded by the Office of Naval Research (N00014-20-1-2739).
0078 Subjective but not objective sleep predicts morning motivation to complete more difficult tasks
Authors: Zendels Philip , Gaultney Jane
Published: May 2023

Introduction

Sleep deprivation impairs many facets of behavior, including performance at tasks. People may perform less efficiently at tasks due to impairments to cognitive processes like working memory following sleep deprivation. However, research shows that compensatory activity occurs when participants are sleep deprived and are faced with difficult tasks (Horne & Pettitt, 1985). This study explored participants’ capability and motivation of completing tasks of varying difficulties.

Methods

These data come from a larger study investigating bedroom environment, sleep, and cognition. In this study participants were given an actigraph wgt3x and were told to sleep as they normally would for three-day period. Each morning, participants took a brief survey and cognitive battery shortly after waking. In the survey, participants self-reported their sleep quality from the previous night using a modified version of the sleep disturbance subscale from the Medical Outcomes Survey (Hays et al., 2005). Additionally, a modified version of the Math Effort Task (MET; Engle Friedman et al., 2003) was used. Participants chose a difficulty and completed six simple addition problems without aid of a calculator or scratch paper. Data were cleaned and analyzed using generalized linear mixed effect modeling in SPSS 28.

Results

Two models were run to examine performance (accuracy) and difficulty choice on the MET. In our model predicting performance there were no significant predictors. In our model predicting the choice of difficulty, participants of more socially advantaged populations and those who reported better subjective sleep quality chose to complete harder problems (b = -.05, p = .01). No significant findings were observed between objective measures of sleep such as sleep efficiency and duration with difficulty chosen or performance.

Conclusion

Motivation to complete more difficult tasks may be related to the quality of sleep one receives during the previous night. The observed lack of difference in performance based on sleep suggest that when given simple problems, sleep deprivation does not impair cognitive performance or that people can compensate for poor sleep when the task is easy. Future studies should continue to explore the relationship between sleep and motivation.

Support (if any)

I/O small grant department funding, university research funding, and travel funding.
0079 Subjective-Objective Sleep Discrepancy in Older Adults: Does Cognitive Functioning Matter?
Authors: Musich Madison , Liu Karina , Costa Amy , McCrae Christina , Beversdorf David , Curtis Ashley
Published: May 2023

Introduction

Differences between subjective and objective sleep [subjective-objective sleep discrepancy (SOSD)] is prevalent in insomnia and older adults. Despite associations between cognition and sleep parameters, the impact of cognitive functioning on SOSD is unclear. We examined associations between various cognitive domains and SOSD in older adults and whether insomnia status moderates these associations.

Methods

Older adults with (N=47, Mage=68.85, 66% women) and without (N=32, Mage=67.41, 78% women) insomnia [met DSM-5 criteria plus reported >30 mins sleep onset latency (SOL) and/or wake time after sleep onset (WASO) on 3+nights/7] completed measures of subjective sleep (7-days of sleep diaries), objective sleep (one-night polysomnography, PSG), and objective cognitive tasks: Dimensional Change Card Sort (executive functioning, EF), List Sorting (working memory, WM), Auditory Verbal Learning Test (episodic memory), Flanker (inhibitory control), Pattern Comparison (processing speed). SOSD direction (average sleep diary variable – PSG variable) was computed. Moderated regressions determined independent and interactive (with insomnia status) associations between cognitive performance and SOSD for SOL, WASO, total sleep time (TST) and sleep efficiency, controlling for age, sex, apnea-hypopnea index, and sleep medication usage.

Results

For insomnia, longer self-reported than PSG TST was associated with better WM (b=27.90, SE=9.05, p=.003, episodic memory (b=12.83, SE=2.77, p=.01), processing speed (b=9.50, SE=2.00, p<.01), and inhibitory control (b=118.40, SE=54.09, p=.03). Similarly for insomnia, better self-reported than PSG sleep efficiency was associated with better WM (b=5.58, SE=2.12, p=.01), episodic memory (b=2.66, SE=1.08, p=.02), and processing speed (b=2.11, SE=0.47, p<.01). For non-insomnia, reports of SOSD were not associated with cognitive functioning (ps>.05).

Conclusion

Better diffuse cognitive functioning may be a contributing SOSD mechanism in older adults with insomnia. We speculate that better cognitive functioning may suppress cognitive arousal symptoms that are prevalent in insomnia patients, leading to better self-reported sleep relative to what is objectively measured. Prospective studies examining independent and interactive associations between cognition functioning and arousal, and insomnia on SOSD may inform underlying mechanisms of poor sleep health and the temporal impact on cognition.

Support (if any)

This research project was made possible by awards (PI: Curtis) from the American Academy of Sleep Medicine Foundation, a foundation of the American Academy of Sleep Medicine.
0080 TBI Time Since Injury: A Comparison Model Between Sleep Efficiency and Neurocognitive Performance
Authors: Reign Deva , Grandner Michael , Hildebrand Lindsey , Dailey Natalie , Killgore William
Published: May 2023

Introduction

MTBI remains on one of the most prevalently reported brain injuries. Previous studies have shown an association between sleep efficiency, performance, and neurocognitive outcome. Reported time-since-injury (TSI) has also shown an association with neurocognitive outcome measures, with some evidence suggesting neurocognitive status is significantly worse at 2 weeks post-injury. Here, we examined differences in self-reported sleep efficiency at various time points since injury among individuals who had sustained an mTBI in the preceding year.

Methods

190 Participants [71 male, 119 female], age M=24.48, SD=6.80 (HC, n=39) and five mild TBI groups based on time post-injury, 2-weeks (2W, n=12), 1-month (1M, n=30), 3-months (3M, n=34), 6-months (6M, n=33), and 12-months (12M, n=40) post-injury. Participants completed a cross-sectional study at specific post-injury time points ranging from (2W, 1M, 3M, 6M, 12M). Participants completed comprehensive Repeatable Battery for Neuropsychological Status (RBANS) and were administered the Pittsburg Sleep Quality Index (PSQI) at the time of assessment. Here we analyzed the sleep efficiency subscale of the PSQI. Separate correlation analysis examined the association between sleep efficiency and the attention index for each TSI group.

Results

The ANOVA showed a main effect of TSI group, F(5,182) = 2.83, p=.017. Post Hoc comparisons with the LSD test showed that the 12M group had worse sleep ­efficiency than HC and 2W, 1M, and 3M but did not differ from 6M (p<.05). Separate correlations between sleep efficiency and the attention index of the RBANS for each TSI group showed a marginally significant association at 2W (r(10)=-.467, p=.063, one tailed), and statistically significant at 12M (r(38)=-.266, p=.049, one tailed), suggesting that worse sleep efficiency was associated with worse attention performance at those time points.

Conclusion

Sleep efficiency differs across the first year of recovery from mTBI. Notably, individuals in the 12M TSI group appear to have worse sleep efficiency than any other TSI group but did not differ from the 6M group. Sleep efficiency appears to be associated with attentional capacity at 2W and 12M timeframes. This suggests that interventions that focus on enhancing sleep in patients with mTBI may prove promising for facilitating recovery.

Support (if any)

W81XWH-12-1-0386
0087 Associations between AHA’s Life’s Essential 8 and cognition in a sample of diverse midlife adults
Authors: Shen Yuqi , Master Lindsay , Baydoun May , Zonderman Alan , Buxton Orfeu , Gamaldo Alyssa , Evans Michele
Published: May 2023

Introduction

Life’s Simple 7 (LS7), originally proposed as the seven most important predictors of heart health, is associated with negative cognitive outcomes. Recently an updated Life’s Essential 8 (LE8) added sleep as the new eighth component. However, limited research has investigated LE8 and cognitive outcomes. We hypothesize that a higher composite LE8 score will be associated with better cognitive performance.

Methods

Cross-sectional analyses were conducted including 1498 adults (36-76 years old, 41% male, 61% African American) from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study who completed all LE8 and global cognition measurements in wave 4 data collection (2013-2017). Blood pressure, glucose, cholesterol, BMI, diet, physical activity, and smoking were calculated based on available wave 4 data per LE8 scoring guidance. The sleep component was scored based on the sleep duration question from the Pittsburgh Sleep Quality Index (“During the past month, how many hours of actual sleep did you get at night?”). LE8 score was calculated by averaging the scores from the eight components. Cognitive performance was measured from a Joggle battery to calculate a total global cognition score and individual domains (memory, attention, visual orientation, executive function, speed). A set of linear regression analyses were performed. Covariates included biological age, sex, race, poverty status, sleep apnea, education attainment (high school), reading literacy, and depression (CES-D).

Results

Higher scores on LE8 were significantly associated with better global cognitive performance, even after adjusting for covariates (b=0.024, p = .014). Among all cognitive domains, higher LE8 scores were significantly associated with better memory (b = 0.011, p < .001), attention (b=0.012, p = .007), but not visual orientation, executive function, or speed.

Conclusion

Better cardiovascular health, as indicated by a higher LE8 composite score, is associated with better cognitive performance among U.S. middle-aged and older adults. Future studies may further explore this relationship using longitudinal data and explore the predictive power of each LE8 component.

Support (if any)

UF1AG072619 (PI: Gamaldo)
0088 Bidirectional Pathways Linking Daily Partner Interactions to Sleep Quality in Older Adult Couples
Authors: Xie Yuxi , Feeney Brooke
Published: May 2023

Introduction

Decreasing sleep quality is a challenge for older adults over age 65. Researchers have found significant associations between romantic relationships and sleep quality. However, most existing studies are cross-sectional; few have focused on the aging population who experience the most sleep problems; few have considered mechanisms linking close relationships and sleep quality; few have considered the specific effects of social interactions on sleep quality; and few have considered bidirectional relationships. To address these gaps in the literature, this study investigated the bidirectional pathways linking daily partner interactions to sleep quality in older adult couples. This study also tested daily negative affect, positive affect, and perceived partner responsiveness as three possible mediators explaining recursive associations between daily partner interactions and sleep quality.

Methods

This study recruited 238 older adult couples to complete baseline questionnaires including assessments of attachment orientation and demographics. Couple members also completed daily diaries for 7 consecutive days, reporting on their daily relationship, emotional, and sleep experiences.

Results

Results supported the predicted bidirectional relationship between daily partner interactions and sleep quality via three hypothesized pathways (i.e., negative affect, positive affect, and perceived partner responsiveness). Specifically, older adults who reported higher than average negative partner interactions during the day reported increases in negative affect, and decreases in positive affect and perceived partner responsiveness on the same day, which in turn were associated with worse sleep quality that night. The opposite was true for positive partner interactions. Bidirectionally, older adults who reported higher than average sleep quality on one night reported decreases in negative affect and increases in positive affect and perceived partner responsiveness the next day, which in turn were associated with fewer negative partner interactions and more positive partner interactions that day. Results also revealed moderating effects of attachment orientation and gender.

Conclusion

In conclusion, this study contributes to a sparse literature assessing the bidirectional relationship between daily partner interactions and sleep quality in the aging population. This research adds to our knowledge of the mechanisms underlying the recursive relationship and informs us of potential avenues for relationship-based interventions aimed at improving sleep quality.

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0089 Chronic sleep disruption increases amyloid beta deposition and gliosis in the 5xFAD mouse model
Authors: Pedersen Taylor , Agarwal Sanjana , Sevao Mathew , Braun Molly , Keil Samantha , Iliff Jeffrey
Published: May 2023

Introduction

Recent studies have found that mid-life sleep disruption is associated with the development of Alzheimer’s disease-related neuropathology, including the deposition of amyloid beta. Yet, the mechanism connecting sleep disruption, particularly over chronic timescales, and downstream Alzheimer’s pathology remains unclear.

Methods

In this study, we evaluated the impact chronic sleep disruption has on the development of neuroinflammation and amyloid beta plaques in the 5xFAD amyloidosis mouse model. Chronic sleep disruption in male and female C57BL/6 and 5xFAD+ mice was performed in Lafayette sleep fragmentation cages from 10-18 weeks of age. Glymphatic function was assessed by measuring the influx of fluorescent cerebrospinal fluid tracers into brain tissue. Aquaporin-4 localization, amyloid-beta plaque deposition, and markers of astroglial and microglial activation were assessed by immunofluorescence.

Results

We observed that chronic sleep disruption increased neuropathological outcomes in 5xFAD+ and littermate controls. This was evident in significantly increased amyloid-beta plaque deposition and significantly increased gliosis, indicated by increases in both astrocyte (GFAP) and microglial (Iba1) expression. The impact on glymphatic function, evaluated through both cerebrospinal fluid tracer distribution and assessment of aquaporin-4 mislocalization, was assessed in parallel and correlated with neuropathological outcomes.

Conclusion

These findings highlight the critical association between dysfunctional sleep and the development of Alzheimer’s-related amyloid beta pathology. They indicate that there is an interaction between chronic sleep disruption, neuroinflammation, and amyloid □ deposition.

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0091 The Association Between Sleep Health Facets and Inflammatory Markers: Results from the Einstein Aging Study
Authors: Ji Linying , Shen Yuqi , Harrington Erin , Van Bogart Karina , Engeland Christopher , Graham-Engeland Jennifer , Bertisch Suzanne , Derby Carol , Buxton Orfeu
Published: May 2023

Introduction

Prior research assessing self-reported or nocturnal sleep suggested that specific sleep traits (sleep restriction in the laboratory; poor sleep quality, sleep disorders) are associated with both pro and anti-inflammatory cytokine and C-Reactive Protein (CRP) levels. To extend prior research, we investigated associations between multiple dimensions of objectively assessed sleep health with both circulating and stimulated inflammatory markers in a diverse sample of older adults.

Methods

Participants in the Einstein Aging Study (EAS) were included (N=218, Mage=77.5 years, 6% female; 46% White, 38% Black, 14% Hispanic/other). A confirmatory factor analysis using wrist actigraphy sleep variables over 16 days yielded 6-component multi-dimensional sleep health facets: Regularity, Alertness/Sleepiness (daytime), Timing, Efficiency, Duration, and Rhythmicity. Inflammatory markers collected in the morning included CRP and both circulating markers reflecting current systemic inflammation, and lipopolysaccharide (LPS)-stimulated levels of (IL-1β, IL-4, IL-6, IL-8, IL-10, TNF𝛼), which reflect responses to an inflammatory challenge, an index of immune reactivity. Associations between each inflammatory marker and each sleep health facet were examined using linear regression, controlling for BMI, gender, age, education, ethnicity/race, number of health conditions, nocturnal hypoxemia, Oxygen Desaturation Index (ODI)≥15.

Results

Participants with more daytime sleepiness (i.e., higher number and longer duration of naps and lower activity level) had higher circulating IL-6 and CRP levels. Lower sleep efficiency was associated with lower levels of the anti-inflammatory circulating cytokine IL-4 and higher levels of stimulated IL-8 and TNF𝛼. Longer sleep duration was associated with higher levels of circulating IL-1β and CRP. Less rhythmicity across days was associated with higher levels of circulating IL-6. Nocturnal hypoxemia was associated with higher levels of CRP and stimulated IL-4, IL-8, and TNFα. We found no association between sleep timing and regularity and any inflammatory marker.

Conclusion

We observed that various sleep health facets are related to markers of inflammation and immune reactivity in older adults. This research also demonstrates the value of using 24-hour, device-based estimates of different sleep health facets relevant for immune function. Associations between 24-h sleep and inflammation are particularly important for older adults, who evidence more daytime sleepiness and less rhythmic sleep/active patterns in daily life.

Support (if any)

R01AG062622, P01AG003949, RF1AG056331-04