bluuebunny/crossref_metadata_2025_split huggingface dataset:
0030 Gene Expression and Attention Lapses with a Countermeasure for Sleep Loss
Authors: Uyhelji Hilary , Munster Susan , White Vicky , Nicholson Scott 
Published: April 2024

Abstract

Introduction
Few studies have investigated the association between genetic and neurobehavioral performance changes during sleep loss, or how that relationship may be impacted by wakefulness promoting agents. We hypothesized that we could associate gene expression with impairment during sleep deprivation, both with and without use of the countermeasure modafinil.

Methods
Healthy young adults (N=19) were exposed to total sleep deprivation for ~36 hours on each of two separate study runs. On one night, each participant received 200 mg of modafinil, and during the other night, they were given a placebo. Objective performance was assayed with the Psychomotor Vigilance Test (PVT), Delayed Match to Sample, and Rapid Decision Making Test, along with self-reported fatigue on the Profile of Mood States questionnaire. Whole transcriptome sequencing data of blood samples drawn every 4 hours (N=8 times per subject) were analyzed with generalized linear modeling for associations of gene expression with neurobehavioral metrics.

Results
Performance was impaired during sleep loss, with maximum values of PVT lapses reaching over 10 attention lapses in ~90% of subjects. Modafinil served to mitigate the impairment. In models including circadian rhythms, we discovered 232 genes significantly associated with PVT lapses in the placebo run, but zero genes in the run with administration of modafinil. Limited overlap was found between biomarker genes associated with PVT, and genes related to other neurobehavioral assays.

Conclusion
Genetic findings include potential molecular biomarkers for neurobehavioral effects of sleep loss, and reproducible findings of select genes in prior work reveals strong candidate gene biomarkers for attention impairment during sleep loss. Differences in molecular associations across neurobehavioral tests suggests the potential to develop tailored genetic panels for specific types of neurobehavioral changes. However, the use of modafinil greatly diminished not only attention lapses but also the association of gene expression with attention impairment. These findings demonstrate the importance of considering background countermeasure use in development of biomarker panels.

Support (if any)
Blood draws and genetics analyses were supported by FAA awards DTFAAC-17-X-00001 and 6973GH-18-D-00110.
0033 Proteomic Profiling of Plasma Biomarkers in Men and Women with Diagnosed Insomnia
Authors: Mithani Sara , Brock Matthew , Pruiksma Kristi , Li Xueying , Gerwell Kelsi , Momin Arees , Powell Tyler , Straud Casey , Young-McCaughan Stacey , Peterson Alan , Mysliwiec Vincent 
Published: April 2024

Abstract

Introduction
Chronic insomnia disorder affects approximately 10% of the U.S. population and is linked to various adverse health consequences. Despite advancements in pharmacological interventions, many individuals continue to experience recurrent symptoms. A comprehensive understanding of the molecular mechanisms underlying insomnia is crucial for developing innovative and effective treatments. This study aimed to profile plasma proteins using an unbiased high-throughput assay to identify potential biomarkers for insomnia, with a specific focus on discerning any differential responses between men and women.

Methods
This prospective, observational study (n=60; 40 insomnia, 20 control; 58.3% females) was part of a larger study completed at Joint Base San Antonio-Lackland. Participants completed an overnight in-lab diagnostic polysomnogram, blood collection and clinical evaluation. We applied an unbiased high multiplexed proteomic discovery technique using DNA aptamers to target 7,000 proteins in plasma samples. Chi-square test and Mann–Whitney U-test were performed to determine the group differences. Adjusted p-values were calculated by using Benjamini–Hochberg's false discovery rate (FDR). Dysregulated proteins were uploaded into the Ingenuity Pathway Analysis software (Qiagen IPA) to explore the mechanistic networks most significantly associated with the study outcome. Significance level was set at 0.05 in all tests.

Results
We identified 54 significantly dysregulated plasma proteins (29 upregulated, 25 downregulated) when comparing individuals with diagnosed insomnia, stratified by gender. The top three upregulated proteins were T cell surface antigen CD2, Leptin (LEP), and N-terminal pro-BNP (NPPB); the top three downregulated proteins were Kunitz-type protease inhibitor 3 (SPINT3), Beta-defensin 104 (DEFB104A), and Benign Prostate-specific Antigen (KLK3). Pathway analysis revealed associations with proinflammatory cascades and metabolic signaling pathways.

Conclusion
Our findings highlight the feasibility of multiplex proteomic profiling in identifying blood-based biomarkers for understanding the pathophysiological mechanisms of insomnia disorder. Further research is warranted to ascertain the clinical utility of these candidate proteins.

Support (if any)
This research was supported by grants from the American Academy of Sleep Medicine Foundation (supported by Eisai, Inc.), the Defense Health Agency, Defense Medical Research and Development Program, Clinical Research Intramural Initiative for Military Women’s Health (DM170708; Mysliwiec), and the US Air Force Air Force Materiel Command (AFMC), Wright-Patterson Air Force Base, Ohio (FA8650-18-2-6953; Peterson).
0040 Metabolic Effects of Superimposed Sustained and Intermittent Hypoxia in Hepatocyte-Derived Spheroids
Authors: Hackbarth Megan , Olvera Kristine , Brewster Katie , Moya Esteban , Ganguly Souradipta , Dhar Debanjan , Mesarwi Omar 
Published: April 2024

Abstract

Introduction
Chronic obstructive pulmonary disease/obstructive sleep apnea (COPD/OSA) overlap syndrome is characterized by chronic sustained hypoxemia due to COPD and superimposed intermittent hypoxemia due to OSA, and is associated with poor clinical outcomes related to the severity of hypoxemia. Overlap hypoxia (OH) combining sustained hypoxia and intermittent hypoxia (IH) causes an elevation in serum LDL cholesterol (LDL-C) and hepatic malondialdehyde, a marker of oxidative stress. The use of liver organoids (spheroids) cultured in hypoxia preserves liver-specific variability in tissue oxygenation. We aimed to determine how malondialdehyde and LDL-C uptake were impacted by OH in liver spheroids.

Methods
HepG2 cells were seeded into wells of round-bottom ultra-low attachment microplates to encourage spheroid formation. Media was changed 1:1 every other day for a total of 8 days. The spheroids were then pipetted into microplates with gas-permeable membranes. In a subset of wells, half the media was replaced by reconstituted LDL-DyLight 550, a conjugated human LDL-C which fluoresces upon endocytosis. Then, the spheroids were placed into one of three hypoxic environments using an OxyCycler C42 Dynamic O2 and CO2 controller: normoxia (16% O2 and 5% CO2), IH (O2 cycling between 16% and 2.5% every 3 min, constant 5% CO2), or OH (O2 cycling between 11.5% and 2.5% every 3 min, constant 5% CO2). After 4 hours, media and spheroids were collected for quantification of malondialdehyde (n=4 pooled samples/group), and spheroids with LDL-DyLight 550 were examined for fluorescence (n=24 spheroids/group).

Results
There were no morphologic differences among the groups after hypoxic or normoxic exposures. Malondialdehyde was increased in both hypoxic spheroid groups, though more in OH (RA: 2.9±1.4 µM; IH: 7.4±3.7 µM, p=0.005 vs RA; OH: 9.6±4.8 µM, p&lt; 0.001 vs RA). LDL-C uptake was reduced by 28.4% in OH relative to RA (p=0.003). No effect was noted in IH (p=0.863).

Conclusion
Culture of hepatocyte-derived spheroids in hypoxic environments is feasible. OH in spheroid culture increases an important marker of oxidative stress, and reduces LDL-C uptake. These results echo previous animal-based data. Future experiments are intended to understand underlying mechanisms.

Support (if any)
This project was supported by grants NIH K08HL143140 and UCSD RG104448.
0050 Glossopharyngeal Nerve Discharge Patterns in Neuromuscular Control of Breathing
Authors: Nakamura Eriko , Kola Gjinovefa , Dewald Denise , Dick Thomas , Dutschmann Mathias , Strohl Kingman , Curado Thomaz Fleury 
Published: April 2024

Abstract

Introduction
The glossopharyngeal nerve is important for gas exchange in fish, but in mammals concentration is focused on the hypoglossal nerve (Dewald et al, 2018). In the present study, we hypothesize the discharge pattern of glossopharyngeal nerve activity (GPNA) will relate to the 3-phase respiratory motor pattern apparent in the vagal, hypoglossal, and phrenic nerves in mammals.

Methods
We recorded GPNA from in situ arterially perfused brainstem preparations of juvenile rats (n=10) and compared these data to simultaneously recorded phrenic (PNA), vagal (VNA), and hypoglossal (HNA) nerve activities. We report the timing of GPNA relative to onset and duration of PNA, HNA, and VNA for at least 32 respiratory cycles in each preparation.

Results
Preparations had a eupnea-like 3-phase respiratory motor pattern (Dutschmann et al 2009). The average respiratory cycle length was 4.30s ± 0.61 (Mean±SD). The inspiratory discharge duration analyzed from PNA was 0.73s ± 0.15; the postinspiratory discharge duration analyzed from VNA, 2.85s ± 0.69; and a late expiratory phase duration, 0.87s ± 0.46. The GPNA started significantly before the onset of PNA with a pre-inspiratory discharge duration of 0.53s ± 0.23 (ANOVA p=0.0001). Overall the pre-inspiratory discharge of GPNA was similar compared to pre-inspiratory discharge of HNA (0.36s ± 0.21), postinspiratory discharge duration of GPNA (0.53s ± 0.12) was also comparable to HNA (0.59s ± 0.26), but significantly shorter compared to VNA (2.85s ± 0.69; p=0.0001).

Conclusion
Both GPNA and HNA displayed robust, characteristic pre-inspiratory/inspiratory discharge patterns in every preparation. Clinically, the activation pattern of the GPNA may be as crucial as that of the HNA, for maintaining a healthy, patent upper airway for breathing during sleep.

Support (if any)
The Japanese Respiratory Society Fellowship Grants, NIH/NHLBI
0058 Neural Differentiation of Competing Memory Representations After a Prediction Error Depends on REM Sleep
Authors: McDevitt Elizabeth , Kim Ghootae , Turk-Browne Nicholas , Norman Kenneth 
Published: April 2024

Abstract

Introduction
When we retrieve a memory, competing memories can come to mind. One way the brain might resolve this competition is by pushing the interfering memory representations away from one another (neural differentiation). Previous work found that, when an item predicted in a particular context (A predicts B) failed to appear and was later restudied in a different context, the A and B representations became less similar in the hippocampus. We used fMRI to test the preregistered hypothesis that rapid eye movement (REM) sleep (occurring post-prediction-error) is required to observe this effect.

Methods
In the morning, we first obtained pre-learning fMRI “snapshots” of each item’s neural representation by extracting the spatial pattern of BOLD activity corresponding to each item. Next, participants viewed a continuous stream of scenes that, unbeknownst to them, followed a pair structure. Each pair had one scene as the first item (scene A) and a different scene as the second item (scene B). Each pair was shown together three times, inserted in the stream continuously amongst the other pairs, creating the expectation that B will follow A. For a subset of pairs, this expectation was then violated on trials where B failed to follow A; the B item was subsequently restudied on its own (i.e., not preceded by its pairmate A). Participants were then randomly assigned to remain awake, take a nap containing non-REM sleep only, or take a nap with both non-REM and REM sleep. Later the same day, we obtained post-learning fMRI snapshots of each item’s neural representation.

Results
We used pattern similarity analysis to compare the pre- and post-learning snapshots and found evidence of neural differentiation of the A and B items in the right CA2/3/DG subfield of the hippocampus, but only in the group whose nap contained REM sleep.

Conclusion
This result provides the first evidence linking REM sleep to changes in the hippocampal representations of specific memories in humans, and - more generally - suggests that REM helps to restructure neural representations in response to competition that occurs during wake.

Support (if any)
R01 MH06945 (K.A.N and N.T.-B.) K99 MH126154 (E.A.M.)
0061 Pulling an All-Nighter Impairs Organic Chemistry Learning: An At-Home, Zoom-Based Sleep Deprivation Experiment
Authors: Barley Blake , Tran David , Fitzsimmons Corinne , Suarez Andrea Castillo , Pua Kay Chi , Scullin Michael 
Published: April 2024

Abstract

Introduction
College students often believe that cutting back on sleep is necessary to have success in rigorous gateway courses like organic chemistry. At the same time, experimental sleep deprivation is known to impair laboratory tests of cognitive functioning. We bridged these naturalistic-laboratory approaches by testing whether a single night of total sleep deprivation impacted at-home learning and retention of an ecologically-valid organic chemistry lecture.

Methods
Undergraduate students (N=36; Mage = 19.22; 68.8% female; 59.4% non-white) who had not taken organic chemistry and were not chemistry pre-majors completed a 5-day study. At baseline, participants visited the laboratory to complete questionnaires, computerized tasks, and receive wristband actigraphy and an Oura ring. The following night, participants joined an online Zoom session and were randomly assigned to go to bed at 10:30pm or to undergo a night of total sleep deprivation. Caffeine and other substances were not allowed overnight. At 7:30am, all participants completed a virtual organic chemistry lecture and a 50-item test. After a two-day washout period, participants returned to the laboratory for a second organic chemistry test to assess retention.

Results
Most participants (n=32) completed all study phases, and only one withdrew due to sleep deprivation. Actigraphy and ring monitoring confirmed that participants in the normal sleep condition slept on the experimental night (actigraphy M=7.37 hours, ring M=7.64 hours), whereas participants in the sleep deprivation condition did not sleep [actigraphy M=0.08 hours, ring M=0.08 hours; ts&gt;35, ps&lt;.001, cohen's ds &gt; 12]. Sleep deprivation altered perceived stress and metacognitive outcomes [t(30) = 2.11, p = .043, d = .75 and t(30) = 3.27, p = .003, d = 1.16) and significantly impaired morning organic chemistry learning (M=47.4%) compared to normal sleep [M=60.8%; t(30) = 2.11, p = .044, d = .75]. Similar trends were observed at the two-day retention test (Sleep deprivation: 46.4%; Normal sleep: 57.1%, p&gt;.05, d = .55).

Conclusion
Pulling an all-nighter was sufficient to compromise complex educational learning. Sleep deprivation experiments can be feasibly conducted in participants’ homes so long as they are video-monitored by research staff and wakefulness is confirmed by wearable sleep trackers.

Support (if any)
National Science Foundation (1943323) and Baylor URSA (#2412).
0070 The Effect of Post-Learning Rest on False Memory in the Deese-Roediger-McDermott Paradigm
Authors: Livingston William , Putnam Adam , Wamsley Erin 
Published: April 2024

Abstract

Introduction
Although sleep has long been known to benefit memory consolidation, recent studies demonstrate that even a brief period of eyes-closed waking rest can similarly benefit a wide variety of memory types, including declarative, procedural and spatial. But sleep is argued to not only quantitatively strengthen memory traces, but also qualitatively transform them over time. The present study tested whether post-encoding waking rest affects the formation of false memories in the Deese-Roediger-McDermott (DRM) false memory paradigm, which are thought to arise from a “gist extraction” transformation of memory. We hypothesized that rest would increase false memory as measured by recall, but decrease false memory as measured by recognition.

Methods
In a within-subjects, counter-balanced design, N=51 participants auditorily encoded 8 DRM word lists. Each list consisted of 15 semantically-related words, all of which were derived from a central “critical lure” not heard by participants. After encoding, participants either sat quietly with their eyes closed for 15 minutes or spent an equivalent period of time completing a distractor task. Afterwards, participants were tested on their memory via both recall and recognition. False memory was defined as the false recall or recognition of “critical lure” words that had not been included on the list. Scores on the recall test were adjusted for incorrect responses, by subtracting the number of words incorrectly recalled (not including the lure words) from the number of words correctly recalled.

Results
Paired samples t-tests revealed that there was no significant effect of rest on false memory using either recall (t(50)=.26, p = .796) or recognition (t(50)=1.20, p = .237) tests. There was also no significant effect of rest on memory for studied words (recall: t(50)=1.32, p = .194; recognition: t(50)=0.51, p = .612).

Conclusion
This study indicates the possibility that waking rest does not affect certain types of qualitative memory transformation thought to occur during sleep. This includes the gist-extraction type processes underlying false memory. Potentially, rather than acting independently of each other, waking rest and sleep may act in coordination, each with distinct roles in the consolidation process.

Support (if any)
Intramural funding from Furman University.
0075 Individual Differences in Habitual Sleep Discontinuity Predict Memory Consolidation and Supporting Neural Activity
Authors: Nyan Chuu , Chhabra Isha , Ram Sahana , Mirjalili Soroush , Duarte Audrey 
Published: April 2024

Abstract

Introduction
Numerous studies manipulating sleep (i.e., deprivation, intervening naps between encoding and retrieval) have shown that sleep facilitates episodic memory consolidation in young, healthy adults. The relationship in older adults is more mixed, though generally supportive of age-related attenuations in sleep-dependent memory consolidation. However, studies using manipulations of sleep or a single night of sleep architecture may omit potentially important information about individual differences in one’s habitual sleep patterns that may contribute to the episodic memory performance across age. There is great interest in determining if well-known age-related impairments in sleep quality are related to those in episodic memory consolidation and the neural activity supporting memory.

Methods
As part of an ongoing study, we recruited samples of cognitively unimpaired younger and older adults and measured their habitual sleep using a wrist-worn accelerometer for 1 week. Principle component analysis (PCA) was used to reduce data dimensionality and identify sleep components. We recorded their electroencephalography (EEG) as they performed an object-scene associative memory task with immediate and delayed (48 hours) retrieval assessments. Participants were asked during both retrieval phases if object-scene pairs were new, matched or did not match pairs that were presented during encoding. Memory retention (delayed-immediate d’) was used as the index of consolidation, correcting for each participant’s learning level.

Results
Across age groups, higher levels of habitual sleep discontinuity, which were elevated in older adults, were associated with reduced memory retention/consolidation estimates (t(11) = -2.74, p = 0.02, d = 0.81) and neural activity during delayed retrieval associated with successful recovery of retained memories (rho = 0.499, rho-value = 0.015).

Conclusion
These results support the idea that age-related increases in habitual sleep discontinuity may contribute to age-related reductions in sleep-dependent episodic memory consolidation, and the neural mechanisms supporting successful recovery of consolidated memories.

Support (if any)
This work was supported by the NIA # R21AG064309.
0077 TITLE: Test Format Influences the Effectiveness of Wakeful Rest for Memory Consolidation
Authors: Gonsalez Daniel , Knife Yordanos , Biggs-Rodriguez Omalys , Kowe Favour , Westerberg Carmen 
Published: April 2024

Abstract

Introduction
New memories are stabilized and strengthened during memory consolidation, which is facilitated during sleep. Recent research suggests that wakeful rest (WR), i,e., a period in which attention and other cognitive demands are reduced, May also facilitate memory consolidation. However other studies have failed to find such benefits of WR. Complicating matters, several methodological differences across successful and unsuccessful WR studies exist, including differences in learning material and test format. This experiment examined how test format may influence the effects of WR on memory consolidation.

Methods
Participants completed two consecutive sessions. In each session, they watched a 15-min video and then took an immediate memory test followed by a 15-min break while electroencephalography (EEG) was recorded. During the break, participants engaged in WR by sitting quietly in a comfortable chair in one session and completed a computer game distractor test in the other. Next, participants took a delayed memory test for the video and then completed a mind wandering questionnaire. For 16 participants, the memory test were multiple-choice and for 15 participants, the memory test were free recall.

Results
For participants who took multiple-choice test, let’s forgetting occururred from the immediate to the delayed memory test when participants engaged in WR compared to a distractor task during the break, and this difference was larger for participants who engaged in WR during the first session. For participants who took free recall test, although memory improved from the immediate to the delayed test during both sessions, there was no difference in size the improvement when participants engaged in WR compared to a distractor task during the break.

Conclusion
The efficacy of WR or memory consolidation depends on the format in which memory is tested. In the current experiment, WR during the break was more effective than a distractor task for preserving memories when tests were in multiple-choice but not free-call format. Additionally, when using a within-participants design, the order in which WR and the distractor task are completed is also relevant. EEG and mind-wandering data may be useful in understanding context in which WR may be most effective for memory consolidation.

Support (if any)