bluuebunny/crossref_metadata_2025 huggingface dataset:
0032 ADA Functional Polymorphism Modulates REM Sleep Following Total Sleep Deprivation
Authors: Fluke Sofia , Hansen Devon , Satterfield Brieann , Van Dongen Hans
Published: May 2023

Introduction

Adenosine Deaminase (ADA) regulates extracellular levels of adenosine, a brain correlate of sleep homeostasis. A single nucleotide polymorphism (SNP) of the ADA gene (rs73598374) is known to be associated with increased homeostatic pressure for NREM sleep after total sleep deprivation (TSD). Whether this genotype effect also impacts REM sleep after TSD has not been systematically investigated. The limit cycle reciprocal interaction model posits that NREM/REM cycles are regulated by cholinergic and GABAergic neurotransmitter systems. While NREM/REM regulation is also thought to be mediated by sleep homeostatic state, evidence of an association with adenosine levels has not been reported. Here we investigate the influence of ADA on REM sleep at baseline and following TSD.

Methods

N=48 healthy, normal sleepers (ages 27.7 + 5.3, 23 females) participated in one of three in-laboratory TSD studies. Following 10h baseline sleep (22:00–08:00), participants underwent 38h TSD, with subsequent 10h recovery sleep (22:00–08:00). Sleep periods were recorded polysomnographically and scored visually according to AASM criteria. Genomic DNA was extracted from whole blood, and the ADA SNP was assayed using real-time PCR. Sleep stages were analyzed using mixed-effect ANOVA with fixed effects of ADA genotype, night (baseline vs. recovery), and their interaction, controlling for study, with a random effect over subject on the intercept.

Results

The frequency of genotypes (G/G: 42, A/G: 6) did not vary from Hardy-Weinberg equilibrium. There was no genotype effect on total sleep time and no genotype by night interaction (p>0.7). However, A allele carriers spent more time in REM during baseline and less during recovery compared to G/G homozygotes (genotype by night interaction: F[1,46]=8.13, p=0.007). Conversely, while not statistically significant (p>0.1), A allele carriers spent less time in NREM during baseline and more during recovery compared to G/G homozygotes.

Conclusion

ADA genotype was associated with a shift in balance between REM and NREM at baseline, as well as changes therein after TSD, without concomitant effect on total sleep time. This suggests a role for adenosine in mediating REM sleep regulation, possibly through a sleep homeostatic effect on the reciprocal interaction between NREM and REM.

Support (if any)

CDMRP W81XWH-05-1-0099; ONR N00014-13-C-0063; NIH R21CA16769; ARO W911NF2210223.
0035 Melanopsin genetic variants and delayed sleep phenotype – whole genome sequencing analysis
Authors: Smieszek Sandra
Published: May 2023

Introduction

Melanopsin (OPN4) is a blue light-sensitive opsin-type G-protein coupled receptor. It is highly expressed in photosensitive retinal ganglion cells which mediate responses to light, including regulation of sleep, circadian photoentrainment, and pupillary light response. Mutations in OPN4 were shown to affect responses to light, ultimately affecting the regulation of circadian rhythms and sleep. Previously, we describe a male carrier of the OPN4 missense variant diagnosed with delayed sleep-wake phase disorder (DSWPD), with a consistent recurrent pattern of delayed sleep onset The rs143641898 [NM_033282.4:c.502C>T p.(Arg168Cys)] variant in the OPN4 gene that was shown in a functional study to render the OPN4 protein non-functional.

Methods

The analysis was conducted on whole genome sequencing samples obtained from patients with a clinical diagnosis of DSWPD. Age and sex-matched samples were used as controls.

Results

Here we report an enrichment of OPN4 rare coding variants, MAF< 1, in a set of 117 DSWPD samples as compared to 315 healthy controls. This significant enrichment likely implies that other rare pLOFs can similarly contribute to the delayed sleep phenotype. Moreover, we report a significant association of rs rs1079610, a common variant in OPN4 – with delayed bedtime in DSWPD patients. This variant has been previously reported in association with altered pupillary responses. This effect is not seen in a large set of healthy controls without DSWPD diagnosis.

Conclusion

The OPN4 discussed rare OPN4 variants likely increase the risk of DSWPD via its direct effect on the pathophysiology along the melanopsin axis. This study offers useful insights for the differential diagnosis and ultimately treatment of DSWPD risk in which patients carry pathogenic variants in the OPN4 gene.

Support (if any)
0038 Genioglossus muscle (GG) activity evoked by pharmacological stimulation of alpha1-adrenoceptors in pre-hypoglossal region (PHR)
Authors: Reis Leonardo Frasson , Xu Kelly , Rukhadze Irma , Fenik Victor
Published: May 2023

Introduction

The sleep-related withdrawal of noradrenergic excitation and increased cholinergic inhibition of hypoglossal motoneurons (HM), which control the tone of the GG, the largest protruder muscle of the tongue, play a critical role in obstructive sleep apnea pathophysiology. In an animal model of REM sleep, antagonism of alpha1 noradrenergic signaling by microinjections of prazosin into the hypoglossal nucleus (HN) strongly decreased hypoglossal nerve activity. However, a significant delay of this decrease prompted a hypothesis that prazosin must diffuse outside the HN to block alpha1-adrenoceptors that are located on interneurons, which mediate noradrenergic drive to HM. Here, we aimed to map the PHR by microinjecting alpha1 drugs for possible location of these interneurons.

Methods

Adult C57bl/6J mice (n=28) of both sexes were anesthetized with either ketamine/xylazine (120/20 mg/kg, i.p.) or 1.5-2.0% isoflurane inhaled through a nose mask. Electromyogram electrodes were implanted into GG and diaphragm to record their activity. We microinjected phenylephrine (alpha1-adrenoceptor agonist, 5-10 nl, 1 mM) in both ketamine/xylazine- and isoflurane-anesthetized mice, while prazosin (10 nl, 0.2 mM) was injected only in mice under isoflurane anesthesia. The injection sites were marked with Pontamine Skye Blue. After the completion of experiments, all animals were perfused, and brains removed for histological analysis.

Results

The activity of GG showed spontaneous phasic inspiratory modulation with minimal tonic component under both anesthesia conditions although its amplitude was markedly lager in animals anesthetized by isoflurane. Effective microinjections of phenylephrine elicited short-lasting (approximately 15 minutes) excitatory GG responses. When injected into the HN, phenylephrine strongly excited GG as compared to injections to the PHR in ketamine/xylazine-anesthetized mice. However, in isoflurane-anesthetized animals, microinjections of phenylephrine into the PHR induced greater activation of GG than injections onto the HN. Microinjections of prazosin in isoflurane-anesthetized mice produced long-lasting disfacilitation of GG activity. However, prazosin injections into the PHR elicited responses with the shortest latencies (0-120 s).

Conclusion

These results suggest that the putative interneurons that mediate noradrenergic drive to HM are located in the PHR. This finding is important for deciphering the neuronal network that controls the state-dependent activity of GG, which may provide new therapeutic targets for OSA treatment.

Support (if any)

NIHR01HL133847, NIAR01AG065233.
0039 Investigating the role of striatal dopamine in sleep and narcolepsy-cataplexy
Authors: Toth Brandon , Burgess Christian , Chang Katie
Published: May 2023

Introduction

Dopamine release in the striatum is known to govern reward, motor, and sleep behaviors. There also exists a link between pharmacological manipulation of dopamine receptors and cataplexy occurrence, yet the precise spatial and temporal dynamics of dopamine release in relation to cataplexy onset are not understood. In the present study, we evaluate dopamine release dynamics in orexin knockout (OX KO) mice during cataplexy and physiological behaviors.

Methods

OX KO mice were implanted with EEG/EMG electrodes, and dLight1.1 was expressed in the nucleus accumbens core (NAcc), shell (NAcSh), and dorsolateral striatum (DLS) to perform in vivo fiber photometry of dopamine release in freely-moving animals. In NAcc and NAcSh mice, ChrimsonR was retrogradely expressed in the ventral tegmental area (VTA), to allow for precise optogenetic control of midbrain dopamine projections to different regions of the striatum. We also expressed dLight1.1 in the NAcc of wildtype (WT) mice as a control. Three different stimulation parameters were used in independent recordings: phasic 20 Hz stimulation, phasic 10-40 Hz variable stimulation, and tonic 2 Hz stimulation.

Results

First, we show that while dopamine release in response to rewarding behaviors is muted in OX KO animals, there is no difference in dopamine release across sleep state transitions between OX KO and WT animals. Second, we demonstrate that there is a striking increase in dopamine release in both the NAcc and NAcSh, but not in the DLS, at the onset of cataplexy. This increase occurs independently of the behaviors that the animals were engaged in immediately prior to cataplexy, suggesting that the increase is characteristic of all cataplexy episodes. Finally, we find that while high frequency phasic stimulation did not affect cataplexy frequency, low frequency, tonic stimulation reduced both cataplexy and REM occurrence.

Conclusion

We show that there are differences in dopamine release in response to rewarding events, but not changes in sleep states, in OX KO and WT animals. We also identify dopamine release in the ventral striatum as a key node in cataplexy regulation, which helps to further our understanding of the limbic circuitry that underlies narcolepsy symptoms.

Support (if any)

University of Michigan Gilmore Award and Rackham Graduate Research Award.
0040 Leptin Signaling in the Dorsomedial Hypothalamus Couples Metabolism and Breathing in Obesity
Authors: Amorim Mateus , Wang Xin , Aung O , Bevans-Fonti Shannon , Anokye-Danso Frederick , Escobar Joan , Freire Carla , Pho Huy , Dergacheva Olga , Branco Luiz , Mendelowitz David , Polotsky Vsevolod
Published: May 2023

Introduction

Individuals with obesity hypoventilation syndrome (OHS) are unable to increase ventilation to match increased CO2 production (VCO2). Obstructive sleep apnea (OSA), defined by the closure of the upper airway during sleep, is present in 90% of OHS patients. Leptin, an adipocyte-produced hormone, acts in leptin receptor (LEPRb) positive neurons and was implicated in the pathophysiology of OSA and OHS. Diet-induced obese (DIO) C57BL/6J mice shows features of OHS and OSA. Leptin-mediated neural pathways may link metabolism and breathing in obesity. We hypothesized that LEPRb-positive neurons in the dorsomedial hypothalamus (DMH) are necessary and sufficient to match control of breathing to VCO2 and that the stimulation of these neurons relieves OHS in DIO mice.

Methods

We expressed designer receptors exclusively activated by designer drugs (DREADDs) in DMH of DIO Leprb-Cre mice and measured breathing during sleep, the hypercapnic ventilatory response (HCVR), VCO2, and O2 consumption (VO2).

Results

Activation of LEPRb-positive DMH neurons increased inspiratory flow and minute ventilation during REM sleep, without affecting sleep architecture. The effect was pronounced during inspiratory flow limitation, suggeting that upper airway obstruction during REM sleep was relieved. Activation of these neurons increased the HCVR and this response was blunted by a serotonin receptor antagonist, methysergide. Activation of these neurons augmented VCO2, VO2, and VE/VCO2, suggesting that breathing was stimulated out of proportion to increases in metabolism. In vitro experiments revealed that LEPRb-positive DMH neurons project to 5-HT neurons in the dorsal raphe (DR) and that optogenetic stimulation of these neurons evoked excitatory postsynaptic currents in 5-HT neurons of the DR. Administration of retrograde Cre-dependent AAV harboring caspase to the DR in Leprb-Cre mice deleted LEPRb-positive DMH neurons and abolished respiratory and metabolic effects of chemogenetic stimulation. Apoptosis of LEPRb-positive DMH neurons projecting to the DR also prevented the increase in ventilation during REM sleep induced by intranasal leptin.

Conclusion

Leptin increases the HCVR, improves upper airway patency during sleep, and increases VCO2 acting on LEPRb-positive DMH neurons projecting to the DR. We conclude that LEPRb-positive DMH neurons projecting to the DR couple metabolism and breathing in obesity.

Support (if any)

NIH (R01 HL128970, R01 HL133100, and R01 HL138932), AHA (#915167).
0044 Thalamocortical functional connectivity increases during REM sleep sawtooth waves
Authors: Peter-Derex Laure , Avigdor Tamir , Rheims Sylvain , Guénot Marc , von Ellenrieder Nicolas , Gotman Jean , Frauscher Birgit
Published: May 2023

Introduction

Whereas sawtooth waves have been described as phasic bursts of slow oscillations in the scalp EEG during rapid-eye-movement (REM) sleep sixty years ago, little is known about their generators and functional role. Stereo-electroencephalography recordings (SEEG) performed for presurgical evaluation in drug-resistant focal epilepsy have allowed to demonstrate a peculiar slow activity in the thalamic medial pulvinar nucleus during REM sleep, contrasting with the fast desynchronized cortical activity. However, the link between this slow thalamic activity and sawtooth waves remains unexplored. Here, we used combined polysomnography and SEEG to investigate the dynamics of thalamic activity and thalamocortical functional connectivity at the time of scalp EEG sawtooth waves.

Methods

Night sleep recordings from six patients investigated with SEEG including thalamic recording in the Epilepsy Department of Lyon University Hospital were analyzed. Sawtooth waves were visually detected in the scalp EEG and compared with control segments selected in REM sleep. Thalamic SEEG and cortical EEG spectral power as well as thalamo-cortical functional connectivity assessed by the phase locking value were compared between sawtooth waves and control segments using paired t-tests. The effect size was assessed with Cohen’s d.

Results

A significant increase in the delta-theta (2-5 Hz, p< 0.003, d=0.31) and gamma (30-100 Hz, p< 0.003, d=0.31) power bands was found in posterior nuclei of the thalamus at the time of scalp-detected sawtooth waves. Functional thalamocortical connectivity in the 2-5 Hz band was enhanced during sawtooth waves as compared to control segments, with the thalamus driving the cortex (p< 0.001; d=0.84, average +/- SD time lag: 23 +/- 22 ms).

Conclusion

Our results provide evidence that sawtooth waves involve not only cortical areas but also the thalamus, suggesting a relation with ponto-geniculo-occipital waves. They may hence represent phasic brainstem-triggered short windows of an increased thalamocortical dialogue during REM sleep.

Support (if any)

B.F was supported by the Natural Sciences and Engineering Research Council of Canada RGPIN2020-04127 and RGPAS-2020-00021, and by the Fonds de Recherche du Québec–Santé 2021-2025 Salary Award “Chercheur-boursier clinicien Senior”. T.A. was supported by the “Healthy Brains, Healthy Lives initiative at McGill University” from the Canada First Research Excellence Fund and Fonds de recherche du Québec 2021-2022.
0045 Characterization of a novel narcolepsy mouse model with conditional ablation of the orexin neurons
Authors: Kurimoto Emi , Ishikawa Takashi , Joyal Adam A , Scammell Thomas E
Published: May 2023

Introduction

Narcolepsy type 1 (NT1) is caused by selective loss of orexinergic neurons. Although narcolepsy typically begins in childhood or adolescence, most mouse models induce loss of the orexin peptides or orexin neurons from birth. To generate a mouse model that reflects the acquired loss of orexinergic neurons in human NT1, we produced recombinant mice expressing the human diphtheria toxin receptor (DTR) driven by the prepro-orexin promoter (orexinDTR mice). We examined whether administration of diphtheria toxin (DTX) to orexinDTR mice caused selective loss of orexinergic neurons and induced narcolepsy symptoms such as sleep-wake fragmentation and cataplexy. In addition, we investigated the effects of an orexin 2 receptor (OX2R)-selective agonist OX-201 on narcolepsy symptoms in DTX-treated orexinDTR mice.

Methods

We produced orexinDTR mice with the human DTR knocked into the prepro-orexin locus. To induce loss of orexinergic neurons, we intramuscularly injected DTX into heterozygous orexinDTR mice, and later counted orexin-A (OX-A) immunoreactive neurons. Moreover, we collected functional data of EEG/EMG recordings during the dark period in orexinDTR mice. Finally, we evaluated the effects of OX-201 on narcolepsy symptoms, including sleepiness and cataplexy, 6 weeks after DTX injection.

Results

Within 1 week after injection of DTX, the number of OX-A immunoreactive neurons was reduced to 1% of normal with no change in the number of neurons making melanin-concentrating hormone. Furthermore, orexinDTR mice treated with DTX developed severe sleep-wake fragmentation within 1 week, and very frequent cataplexy (~100 episodes/night) in the subsequent weeks. These symptoms were substantially and dose-dependently improved by administration of OX-201.

Conclusion

OrexinDTR mice are a useful and simple model for understanding the neurobiology of narcolepsy and evaluating new drugs to treat narcolepsy symptoms. As only one allele of the orexin-DTR is required, these mice are also convenient for crossing with other lines, enabling a variety of methods to study the orexinergic neurons. OX-201 markedly reduced narcolepsy symptoms. Although it is a tool compound unlikely to be used in patients, it further demonstrates the potential of high efficacy of OX2R agonists in treating narcolepsy.

Support (if any)

This work was funded by Takeda Pharmaceutical Company Limited.
0048 Orexin 2 receptor agonist activates pre-Bötzinger complex neurons, hypoglossal motoneurons and the genioglossus muscle in rodents
Authors: Yamada Ryuji , Kimura Haruhide
Published: May 2023

Introduction

Neurons in the pre-Bötzinger complex are critical for the generation of inspiratory rhythm and control the activity of the genioglossus muscle via activation of hypoglossal motoneurons. Activation of the genioglossus muscle causes anterior movement of the tongue and widens the upper airway. As obstructive sleep apnea (OSA) is associated with obstruction of the upper airway, activation of this neuronal pathway may be a novel therapeutic approach. Orexins have been shown to activate these neurons by stimulation of both orexin 1 receptor (OX1R) and/or orexin 2 receptor (OX2R). In this study, we assessed effects of OX2R-selective agonists on activity of neurons in the pre-Bötzinger complex, hypoglossal motoneurons, and the genioglossus muscle.

Methods

OX2R-selective agonists danavorexton (TAK-925) and OX-201 (a tool compound with longer plasma half-life than danavorexton in rodents) were used. Arousal effects were investigated by electroencephalogram/electromyogram recording in C57BL/6J mice and OX2R knockout mice. Activity of neurons in the pre-Bötzinger complex and hypoglossal motoneurons was investigated by electrophysiological recording in rat tissues. Activity of the genioglossus muscle was evaluated by electromyogram recording in anesthetized rats.

Results

Oral administration of OX-201 increased wakefulness time during sleep phase in C57BL6J mice but not in OX2R knockout mice. 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 hypoglossal motoneurons (EC50: 610 nM and 260 nM, respectively). Intravenous administration of OX-201 at 1 mg/kg increased burst amplitude of the genioglossus muscle in anesthetized rats.

Conclusion

OX2R-selective agonists may enhance the respiratory function via activation of the genioglossus muscle through stimulation of neurons in the pre-Bötzinger complex and hypoglossal motoneurons. OX2R agonists may have therapeutic potential in patients with OSA 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 OSA.

Support (if any)

This work was conducted by Takeda Pharmaceutical Company Limited.
0050 Pediatric OSA and neurodevelopment
Authors: Chandrakantan Arvind , Okoro Joy
Published: May 2023

Introduction

Pediatric OSA and its associated sleep disorders occur in up to 7% of children. Whereas the sequelae of the disease are well characterized, the underpinnings of its phenotypes are poorly understood. This is mainly because of a lack of comprehensive model of the disease in the young. Here I present the neurobehavioral phenotype of pediatric OSA utilizing a preclinical murine model.

Methods

This proposal represents a departure from prior models and is embedded in the sculpting of the IH model. 1) Human polysomnographic data: We studied human data in children with OSA 2) Murine oximetry data: we create murine oximetry curves 3) Cross Species Curve Fitting: We cross fit those across species 4) Optimization of hypoxic gas throughputs: We then optimized this for the hypoxia chamber we are using

Results

We examined 4 behavioral tasks over a number of time periods to establish the temporality needed for hippocampal task ablation, as the hippocampus is the center of learning and memory in mammals. 2 tasks were hippocampal dependent: a) Novel object recognition b) Object place recognition. 2 tasks were hippocampal independent: 1) Hot plate: 2) OFA. We utilized 3 time periods initially: exposure from p14 to p23 (9 days acute), to p35 (21 days intermediate), and p70 (56 days, chronic). There was no deterioration in hippocampal tasks from p14 to p35, however at p70 we noted task ablation. We therefore systematically worked backwards, until we discovered the 'tipping point' where hippocampal task ablation is observed is p49 (35 days of exposure). Prior to this, we note no task ablation, however after this time point, hippocampal task ablation is preserved.

Conclusion

We have demonstrated a tractable, temporal model for pediatric OSA over a systematic set of time points to show when hippocampal deficits from the OSA stimulus manifest phenotypically. We have further isolated these deficits to the hippocampus of developing mice, which is the mammalian center of learning, memory, and retrieval.

Support (if any)

Arvind has previously received support from AASM and BCM OOR. He is currently supported by 1K08HL161263-01 from NHLBI.
0054 Does the Early Bird Get the Worm? Associations of Waketime Variability and Metacognition in College Students
Authors: Costa Amy , McGovney Kevin , Rzeppa Chloe , McCrae Christina , Curtis Ashley
Published: May 2023

Introduction

Deviation in sleep patterns have been associated with cognitive functioning in college students, but little research has examined how deviation in bed and waketime impact next-day metacognition. Given college students have high daily variability with their bedtime and waketime, these are understudied parameter of interest in this population. Considering metacognition has been associated with academic outcomes (e.g., GPA), it is important to understand how daily bedtime and waketime patterns might impact metacognition. The present study examined how daily deviation from bedtime and waketime are associated with metacognitive ratings in college students.

Methods

College students (N=81, Mage=18.8, SD = 1.1, 64 females) completed seven days of sleep diaries reporting bedtime, sleep duration, and waketime. Students also provided morning metacognitive ratings regarding the perceived quality of mental functioning from very poor (0) to very good (100). Multilevel modeling analyses tested whether intraindividual patterns of associations between daily bedtime and daily waketime and daily morning metacognitive ratings, after controlling for intraindividual daily anxiety severity, interindividual levels of bed/wake time variability and sleep duration, as well as age, sex, and daily sleep medication usage.

Results

Daily waketime was associated with same morning metacognitive ratings (B=.02, p=0.03), in that those who woke up earlier than their typical average reported worse cognitive function. Findings did not reveal an association between bedtime variability and metacognition.

Conclusion

Findings suggest that regardless of how long one has slept, waking up earlier than typical may negatively impact perceptions of cognitive functioning in college students. Similar patterns are not observed at the average/interindividual level. Given younger adults typically have a delayed circadian preference, findings may reflect acute circadian disruption and associated “brain fog” in college students when waking up earlier than typical. Future studies should examine associations between daily waketime and objective cognition to better understand how regularity impacts daytime functioning. Similar to findings in adolescent populations, such evaluations could inform recommendations regarding college class start times.

Support (if any)
0058 The sleepy eyewitness: Self-reported sleep predicts eyewitness memory
Authors: Carlson Maria , Carlson Curt , Fitzsimmons Corinne
Published: May 2023

Introduction

Sleep is critical for memory, but research indicates that eyewitness identification may be an exception. We conducted three experiments to assess the effect of self-reported sleep duration and quality, and current sleepiness on eyewitness recall for a mock crime and suspect identification. Experiments 1 and 2 looked at pre-encoding sleep on lineups and showups, respectively. Experiment 3 investigated lineups across two days to assess retrieval effects.

Methods

Participants viewed a mock crime video then answered sleep questions as well as central and peripheral recall questions over the crime. Participants were then randomly assigned to view a fair 6-person target-present (TP) or target-absent (TA) lineup for experiments 1 and 3, or a TP or TA showup for experiment 2. In experiment 3, the recall questions and lineups occurred on day 2, but the sleep questions were asked both days. Decision confidence was provided after the identification procedure.

Results

Sleep quality predicted central recall for experiment 1 [F(1, 3834)=12.96, p<.001] whereas sleep quantity predicted central recall for experiment 2, F(1, 2712)=36.22, p< .001. Choosing rate for pre-encoding sleep was higher for low quality [X2(1)=29.10, p<.001] and low duration [X2(1)=20.15, p<.001], but false IDs were lower for high duration [X2(1)=29.76, p<.001] and high quality, X2(1)=35.47, p<.001. High quality self-reported sleep increased discriminability for lineups, G=2.14, p=.016. False IDs for showups were lower for high duration [X2(1)=5.27, p=.024] and all three sleep questions predicted discriminability for showups: more sleep (G=2.85, p=.002), better sleep (G=2.60, p=.005), and less sleepiness, G=2.44, p=.007. Showups had greater accuracy (p=.038) and a stronger confidence-accuracy relationship (p<.001) for the average of the “good sleep” conditions than the average of the three “bad sleep” conditions, p=.022. In experiment 3, involving post-encoding self-reported sleep, there were still effects on recall but minimal effects on eyewitness identification (and no effects on discriminability).

Conclusion

Self-reported sleep for the night prior to the crime could be an important individual difference variable for eyewitness memory, affecting encoding more than post-encoding processes.

Support (if any)

This project was supported by Grant 2018-R2-CX-0027 awarded by the National Institute of Justice, Office of Justice Programs, and U.S. Department of Justice.
0060 A Classification Based Generative Approach to Selective Targeting of Global Slow Oscillations during Sleep
Authors: Alipour Mahmoud , Seok SangCheol , Mednick Sara , Malerba Paola
Published: May 2023

Introduction

Interacting with sleep slow oscillations (0.5,15 Hz) is essential to understanding the mechanisms underlying their role in sleep functions, including homeostasis, synaptic reorganization, and memory consolidation. Current approaches to SO-based non-invasive closed loop alternate current stimulation (cl-tACs) focus on timing, and do not differentiate among oscillations based on their space-time profiles. In this study, we leverage machine learning and global optimization to introduce a generative model of brain stimulation protocols targeting Global SOs.

Methods

We identify a stimulation protocol that matches a Global SO in two stages: first focusing on the electrode montage, and then on the stimulation waveform. Using the sleep night of 22 volunteers acquired in the lab with high density EEG (175 electrodes), we labeled the SOs as Global/non-Global SOs based on their co-detection on the scalp at a small delay (0.4s). We used the current density (CSD) profile of each SO in cortical and subcortical regions to develop a well-trained classifier (based on weighted k-nearest neighbors). We identify as optimal the electrode montage that resulted in CSDs labeled as Global with highest likelihood by the classifier. We then parameterized a sinusoidal waveform and identified optimum parameters with a genetic algorithm that used feature ranking to establish a weighted distance metric to target Global SO profile built from sleep data. We repeat this approach focusing on Global SO dynamics at a slow time scale and a faster time scale (200ms vs 20ms resolution).

Results

We identified optimal stimulation profiles matching Global SOs at both time scales. At slow time scale, montage selection relied only on CSD near the SO trough and in the reward network and the brainstem. Linear waveforms over-performed sinusoidal waveforms for fit at low time scales. At fast time scale, CSD at both trough and 500ms before the trough were strongly selective for Global vs. non-Global SO.

Conclusion

Global SOs are a gating mechanism for large-scale neural communication, a necessary substrate for systems consolidation and long-term memory formation. This data-driven method builds on natural sleep data to shape a stimulation protocol that imitates Global SO dynamics and is generalizable to other SO types.

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0061 Background Context but not Sleep Facilitates Visual Episodic Memory for Objects
Authors: Madden Emily , Cairney Scott , Evans Karla
Published: May 2023

Introduction

Context serves as a retrieval aid and supports accurate recollection of elements within an episodic event. Associative links between elements of the episode can be weakened via decontextualization. Memory traces are considered to be decontextualized when they have undergone a process that makes them less context-dependent and more gist-like. Furthermore, sleep has been shown to facilitate consolidation of newly formed verbal memories, particularly when sleep occurs shortly after learning. The current study sought to better understand what supports accurate retrieval of visual episodic memories and whether they are modulated by sleep. We examined changes in memory accuracy following either a daytime nap or an equivalent period of quiet wakefulness when background context was changed or reinstated at retrieval.

Methods

Participants were presented with target objects that either appeared in the same scene across multiple trials or in changing scenes during encoding. Memory for target objects was tested using a two-alternative-forced-choice task before and after a 90-min daytime nap (or equivalent period of quiet wakefulness). During testing, the targets either appeared in the same scene context or in a new scene.

Results

Preliminary behavioural results suggest that recognition accuracy significantly decreased from Test 1 to Test 2. However, there was no difference in recognition scores after a nap compared to a period of quite wakefulness. Recognition was highest, at both tests, when the encoding context was reinstated. There was no difference in recognition between when the context was continually changing and when there was one context change between study and test.

Conclusion

When it comes to visual episodic memory, context plays a predominant role in accurate retrieval of the elements within the scene. The present results suggest that reinforcing the target object with consistent reinstatement of background context facilitates accurate object retrieval. Context reinstatement strengthened the object-to-scene binding, improving recognition accuracy. This effect remains robust regardless of whether learning was followed by a period of sleep or quite wakefulness, suggesting that context rather than consolidation during sleep plays a key role in visual episodic memory retrieval.

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0067 Dreams and Personality Influence Creativity
Authors: Price Michael , Chavez Ray , Perrotte Jessica , Westerberg Carmen
Published: May 2023

Introduction

Theoretically, during dreaming, weak associations are explored, and information is combined in novel ways, which could lead to increased creativity during waking. However, little research has explored direct relationships between dreaming and objective measures of creativity and the ability to creatively solve problems. Furthermore, personality influences dream recall frequency (DRF) and other aspects of dreaming, suggesting that the relationship between dreaming and creativity may vary based on personality. The goal of the current experiment was to determine if DRF is related to creativity and creative problem-solving, and if these relationships are influenced by personality traits.

Methods

Seventy-six participants completed questionnaires about dreaming and the Big 5 personality traits (neuroticism, conscientiousness, openness, extraversion, agreeableness) and completed creativity and creative problem-solving tasks. Two tasks measured creativity. In one task, participants generated as many possible uses for an object as they could in one minute. In the other, they generated novel captions for five cartoons. Creative problem-solving was measured using two classic insight problem sets: the matchstick and compound remote associates tasks. Correlations were conducted to determine if DRF is related to any personality traits and multiple regressions were conducted to determine whether DRF or any personality traits predict creativity or creative problem-solving.

Results

DRF was negatively correlated with agreeableness, such that individuals higher in agreeableness recalled fewer dreams. The multiple regression analyses revealed that both DRF and conscientiousness are significant predictors of divergent thinking. Neither DRF nor any personality traits predicted creative problem-solving.

Conclusion

These results indicate that agreeableness reduces the frequency of dream recall, perhaps because agreeable individuals try to find problem solutions immediately while awake so they do not worry about them later. Consistent with current theories, frequently recalling dreams increased creativity, suggesting that the exploration of weak or novel relationships during dreaming increases creativity while awake. Conscientiousness also predicted creativity, suggesting that self-sufficient people tend to be more creative. However, frequently recalling dreams did not increase the ability to creatively solve problems. Collectively, these results suggest that personality influences dreaming behaviors and that frequent dreaming and conscientiousness promote creativity.

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0076 Resilience to Acute Sleep Loss When Learning Organic Chemistry
Authors: Suarez Andrea Castillo , Barley Blake , Nickel Allison , Gao Chenlu , Scullin Michael
Published: May 2023

Introduction

Short sleep is often associated with worse academic outcomes, but it remains unknown whether this relationship is causal. In addition, many students perceive that cutting back on sleep is necessary for successful performance in rigorous and intimidating courses, such as organic chemistry. In the current work, we experimentally tested whether acute sleep restriction affected organic chemistry learning outcomes.

Methods

Participants were 60 undergraduate students who had not previously taken organic chemistry. They maintained a sleep diary for seven days and then completed an overnight session that included polysomnography (PSG) monitoring. Participants were randomly assigned to go to bed at either 10:30pm (normal sleep) or 1:30am (sleep restriction). The next morning, all participants were woken up at approximately 7am and completed a virtual lecture on organic chemistry. In one segment, the lecture was self-paced; in the other segment, the lecture was set to advance automatically at a speeded pace. Following the lecture, participants completed a 50-item test over the studied material.

Results

The conditions were similar in age, gender, race/ethnicity, chemistry intimidation, chronotype, prior sleep, and fluid intelligence (ps > .30). The bedtime manipulation successfully decreased total sleep time from 454.10 (47.90) minutes to 300.93 (37.23) minutes (p<.001), by decreasing time spent in REM and N2 (ps<.01; no changes to N1 or N3, ps>.05). Sleep restriction significantly altered stress levels during the test (p<.05), but not test performance (p>.10). Organic chemistry test performance was lower after a speeded lecture than a self-paced lecture, F(1, 57) = 15.649, p < .001, though this pattern did not interact with sleep condition (ps>.10). Students who were more intimidated by chemistry (at baseline) performed more poorly on the speeded section (r=-.36, p<.01), but just as well on the self-paced section (r=-.09, p=.51), and these patterns were not moderated by sleep duration.

Conclusion

Students who are intimidated by organic chemistry learning can overcome these barriers via self-paced learning, even when they have been acutely sleep restricted.

Support (if any)

This work was supported by the National Science Foundation (1943323 and 1920730).
0077 Sleep and Imagination: Poor Sleep Quality is Associated with More Complex and More Goal-Directed Imaginations
Authors: Barley Blake , Clay John , Vargas Ivan , Scullin Michael , Zabelina Darya
Published: May 2023

Introduction

The relationship between sleep and creativity is complex. Typically, better sleep quality and greater sleep quantity is associated with better cognitive functioning. Despite this general rule, people who demonstrate higher than average levels of creativity are more likely to report worse sleep quality and more insomnia symptoms. The current work investigated sleep health in relation to precursors to creativity: imagination frequency, emotion, complexity, and goal-directedness.

Methods

Two hundred and thirty-seven undergraduate student participants completed demographic questionnaires and self-report measures of imagination (Four-Factor Imagination Scale), sleep (Pittsburgh Sleep Quality Index), and insomnia symptoms (Insomnia Severity Index; Ford Insomnia Response to Stress Test).

Results

Individuals with low sleep quality/quantity, higher insomnia severity, and higher levels of sleep reactivity were those with the most complex imaginations (i.e., imaginations that are rich in details). These associations were generally stronger in female participants than male participants. Furthermore, individuals with higher sleep reactivity also demonstrated more goal-directed imagination (e.g., daydreams have clear goals/outcomes, involve planning the future). Frequency and emotional valence of imaginations were unrelated to sleep measures.

Conclusion

Individuals, and particularly females, with more complex and goal-directed imaginations were more likely to experience worse sleep quality. These findings aligned with the theoretical view that diminished inhibitory control (resulting from poor sleep) can benefit some aspects of creative thinking. Experimental work is needed to determine the causal direction of sleep—imagination associations.

Support (if any)

National Science Foundation (1920730).
0081 The impact of sleep deficiency on spatial working and long-term memory in different rat models of sleep deprivation
Authors: Guzeev Mikhail , Chernyshev Mikhail , Ekimova Irina
Published: May 2023

Introduction

A pressing issue in modern society, lack of sleep has detrimental health consequences, among which cognitive dysfunctions attract great attention. Although there is consensus about the harmful effects of insufficient sleep on vigilance and attention, there is still a debate about memory susceptibility to acute and chronic sleep deprivation. Which types of memory are more vulnerable remains unclear. We studied the susceptibility of spatial working and long-term memory to acute and chronic sleep deprivation in rats.

Methods

Male Wistar rats were deprived of sleep (SD) by placing cages on an orbital shaker. Animals were subjected to three patterns of SD: 1) acute SD (ASD) — continuous SD for 18 hours; 2) short sleep restriction (SSR) —cycles of 3-hour SD followed by 1 hour of sleep opportunity over 24 hours, with a total SD duration of 18 hours; 3) chronic sleep restriction (CSR) — SSR for 5 consecutive days. For each SD protocol, working spatial memory was assessed with the spontaneous alternation test in the Y-maze. Learning and long-term spatial memory were assessed in the Barnes maze test.

Results

ASD impaired spatial working memory, as assessed by spontaneous alternations in the Y-maze test, and decreased the level of locomotion/exploration (assessed by the number of arm entries). However, in SSR and CSR, 1-hour alternating sleep opportunities allowed for preventing working memory loss. The Barnes maze test demonstrated no changes in learning or spatial long-term memory under any tested SD conditions.

Conclusion

The results suggest that spatial working memory is the most vulnerable to continuous sleep loss. Even under a 5-day chronic sleep restriction, the negative effect disappears if rats are allowed to sleep during intermittent 1-hour intervals. It indicates the great importance of short sleep intervals that protect memory against sustained sleep restriction. The resilience of long-term memory to any of the tested sleep deprivation conditions implies that short-term and long-term memory systems diverge in their susceptibility to sleep deficiency.

Support (if any)

State assignment to the Institute of Evolutionary Physiology and Biochemistry; theme reg. no. АААА-А18-118012290427-7.
0082 The Role of Sleep Duration and Daytime Sleepiness on Neurocognitive Functioning
Authors: Soto Pablo , Peck Edward
Published: May 2023

Introduction

Studies examining the impact of sleep on neurocognitive functioning have broadly found that poor sleep and daytime sleepiness manifest in poorer performance on tasks involving attention, concentration, memory, reasoning and thinking. Given the expansive nature of neurocognition, the current study assessed the role of sleep duration and daytime sleepiness broadly on overall neurocognitive functioning as well as more specifically on executive functioning when controlling for age and gender identity. We hypothesized that both sleep duration and reported daytime sleepiness would be associated with a lower neurocognitive status and poorer executive functioning as observed through computerized assessment.

Methods

Participants included 148 (50.7% male; µage=34.58) patients who presented to a Neuropsychological practice for the assessment of ADHD through a structured assessment battery. All patients completed a multi-component computerized assessment of overall neurocognitive status (CNS Vital Signs) and pen-and-paper questionnaires targeting the subjective reporting of sleep duration (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale). Two separate multiple regressions were run to determine the association of sleep duration and daytime sleepiness to overall neurocognitive status and executive functioning abilities when controlling for age and gender identity of patients.

Results

The full model demonstrated that when considered together sleep duration and daytime sleepiness significantly aided in the prediction of neurocognitive status, F(4,143)=3.81, p=.006, R2 =.096, and executive functioning abilities, F(4,143)=3.90, p=.005, R2 =.098, of patients when controlling for age and gender identity. Of note, only daytime sleepiness was a statistically significant sleep predictor of both neurocognitive status (β=-.172, p=.035) and executive function (β=-.197, p=.016).

Conclusion

Broadly, these findings suggest that sleep is an important predictor of neurocognitive functioning. Within the clinical field, these results support the inclusion of sleep measurement, whether objective or subjective, during the assessment of neurocognitive functioning to better account for the role played by sleep on patient performance. To this end, it would be beneficial to assess a greater range of sleep factors and how they may be associated with the various neurocognitive domains.

Support (if any)
0085 Peripheral glucose metabolism bidirectionally modulates sleep in a model of Alzheimer's disease
Authors: Carroll Caitlin , Constantino Nicholas , Irmen Riley , Snipes J Andy , Benca Ruth , Macauley Shannon
Published: May 2023

Introduction

Metabolic impairments and sleep disruptions are both recognized as modifiable risk factors in the development of Alzheimer’s disease (AD). A bidirectional relationship exists between sleep and AD where pathology can disrupt sleep, but sleep disturbances can also increase AD-related pathology. This results in a feed-forward cycle of disease progression and further sleep impairments. Sleep fragmentation and poor sleep quality can also cause glucose intolerance and insulin resistance. However, it remains unclear if peripheral metabolic dysfunction alone can impair sleep, particularly in the context of AD-related pathology. Therefore, the goal of this study was to establish mechanisms connecting peripheral metabolic and sleep disruptions and identify potential therapeutic targets for mitigating AD risk.

Methods

We implanted biosensors measuring interstitial fluid (ISF) levels of glucose and lactate, biomarkers of cerebral metabolism and neuronal activity, respectively, directly into the hippocampus of wildtype and APP/PS1 mice, a model of amyloid-beta (Aβ) overexpression. Biosensors were paired with cortical EEG and EMG recordings for simultaneous sleep/wake analysis. To understand the relationship between metabolic dysfunction and sleep, we altered the peripheral metabolic environment using two paradigms: an acute high-fat, high-sugar diet (HF/HSD) and a pharmacological metabolic rescue.

Results

We found short-term HF/HSD exposure was sufficient to disrupt ISF glucose and lactate diurnal rhythms, independent of changes to pathology burden. Moreover, we found significant sleep disruptions, particularly decreased delta power, indicating slow wave sleep impairments. These findings were exacerbated in mice with Aβ pathology who have disrupted metabolic and sleep functioning at baseline. Conversely, we found normalizing peripheral glucose tolerance in mice with Aβ pathology was sufficient to rescue impaired ISF glucose and lactate rhythms. We also saw a restoration of normal sleep-wake patterns, specifically within slow wave activity.

Conclusion

We found modulating peripheral glucose metabolism can bidirectionally alter sleep, particularly slow wave sleep, independent of changes in Aβ burden. This indicates sleep as a mediator in the relationship between metabolic impairments and AD pathophysiology. While impaired sleep increases AD risk, improved sleep slows pathology accumulation. Therefore, this study demonstrates targeting peripheral glucose regulation is a potential avenue for early AD intervention and risk mitigation.

Support (if any)

F31-AG066302, R01-AG068330, P30-AG072947