bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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&lt; 0.003, d=0.31) and gamma (30-100 Hz, p&lt; 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&lt; 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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&lt;.001] whereas sleep quantity predicted central recall for experiment 2, F(1, 2712)=36.22, p&lt; .001. Choosing rate for pre-encoding sleep was higher for low quality [X2(1)=29.10, p&lt;.001] and low duration [X2(1)=20.15, p&lt;.001], but false IDs were lower for high duration [X2(1)=29.76, p&lt;.001] and high quality, X2(1)=35.47, p&lt;.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&lt;.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

Abstract

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.

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

Abstract

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.

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

Abstract

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.

Support (if any)