bluuebunny/crossref_metadata_2025_split huggingface dataset:
0045 Lateral Hypothalamic Neurotensin Neurons Are Necessary for Wake Maintenance
Authors: Khanday Mudasir , Naganuma Fumito , Hasan Whidul , Bandaru Sathyajit , Ibrahim Nazifa , Nandigam Shaili , Vetrivelan Ramalingam 
Published: April 2024

Abstract

Introduction
The lateral Hypothalamic area (LH) has been established as a critical site for regulating wakefulness. However, the exact neural elements within this region that promote and stabilize wakefulness are not completely understood. While the orexin neurons in the LH are well-known, other subpopulations within this area may also contribute to arousal control. In this regard, we have recently identified a subset of LH neurons expressing neurotensin (Nts) promoting wakefulness. Optogenetic activation of LH-Nts neurons rapidly induces arousal from non-rapid eye movement (NREM) sleep, while chemoactivation induces up to five hours of uninterrupted wakefulness. However, the precise role of these neurons in initiating and maintaining spontaneous wakefulness remains unknown. To address this question, we investigated 1) the activity dynamics of LH-Nts neurons across sleep-wake behavior and 2) the impact of their ablation on sleep-wake amounts and architecture.

Methods
Experiment 1 – LH-Nts neuron activity dynamics: Nts-Cre mice (expressing Cre recombinase specifically in Nts neurons) were injected with an adeno-associated viral (AAV) vector coding for a Cre-dependent GCaMPS (genetically encoded calcium sensors) into the LH. They were also implanted with optical fibers targeting 50µm above the injection site and EEG/EMG electrodes to assess sleep-wake. After three weeks, fiber photometry with concurrent sleep-wake recordings was performed for two hours during the light period in all mice. Experiment 2 – sleep-wake effects of LH-Nts neuron ablation: Nts-Cre mice were injected with an AAV coding for diphtheria toxin-A subunit (AAV-flex-DTA) or a control AAV coding for a red fluorescent protein (AAV-flex-mCherry) into the LH and were implanted with transmitters for the telemetric recording of EEG/EMG. Sleep-wake recordings were performed 24 hours at four weeks after surgery. All mice were then perfused, and injection/lesion sites were verified histologically.

Results
LH-Nts neurons were more active during Wakefulness and REM sleep when compared to NREM sleep. The loss of these neurons reduced the total amounts of Wake and the average duration of Wake bouts but increased the 0.5-4 Hz delta power in Wake EEG.

Conclusion
LH-Nts neurons are necessary for maintaining spontaneous wakefulness, and their loss leads to chronic sleepiness in mice.

Support (if any)
NIH R01-NS119223 (to R.V)
0046 A Mechanism by Which Estradiol (E2) Regulates Adenosinergic Signaling in the Median Preoptic Nucleus (MnPO)
Authors: Kruk Katie , Mong Jessica , Viechweg Shaun , Byrd Carissa 
Published: April 2024

Abstract

Introduction
Women report more sleep difficulties than men, particularly during times of hormonal fluctuations. This indicates that sex hormones likely play a role in a woman’s sleep-wake cycle, but the mechanism by which they do so is largely unknown. We have previously shown that estradiol (E2) increases wake and decreases NREM sleep in female rats, and that E2 action in the median preoptic nucleus (MnPO), a major sleep center in the brain, is necessary and sufficient to induce wakefulness. Additionally, in the MnPO, E2 increases extracellular adenosine, which is known to induce NREM sleep via activation of the A2A adenosine receptor (A2AR). Our previous work demonstrated that an A2AR agonist infused in the MnPO is not able to mediate its pro-sleep effects in the presence of E2, and the current work investigates a mechanism for this finding. Our preliminary data shows that E2 upregulates the mRNA of an orphan receptor, GPR37, in the MnPO; GPR37 has been shown to form heteromers with A2AR and reduce the expression and function of A2AR in the striatum. We hypothesize that E2-induced upregulation of GPR37 leads to inhibition of A2AR in the MnPO, thus preventing its pro-sleep effects.

Methods
To examine mRNA and protein expression, ovariectomized female rats were treated with subcutaneous injections of E2 or oil for two days and sacrificed on the third day, where their brains were collected. To examine if GPR37 knockdown in the MnPO affects E2’s ability to induce wakefulness, a GPR37 shRNA virus or scramble virus control was injected into the MnPO of female rats; they were also ovariectomized and had telemeters implanted to measure sleep-wake states in the presence of oil and E2.

Results
We found that E2 increases GPR37 mRNA and protein expression while decreasing A2AR mRNA expression in the MnPO. Furthermore, we found that knockdown of GPR37 in the MnPO significantly attenuates the effects of E2 on wakefulness, NREM sleep, and REM sleep in the dark phase but not the light phase.

Conclusion
E2 appears to have an effect on the sleep/wake phenotype through adenosinergic signaling and expression in the MnPO through E2-induced upregulation of GPR37.

Support (if any)
0047 Intracranial EEG Reveals Human Cerebral Cortical Regions That Are Spared from Alpha-delta Sleep
Authors: Liu Junjie , Asgarli Aygun , Banks Matthew , Nourski Kirill 
Published: April 2024

Abstract

Introduction
Alpha-delta sleep, also known as alpha wave intrusion during sleep, is an electroencephalography (EEG) pattern often observed in clinical settings, and is associated with unrefreshing sleep and chronic fatigue or pain. The neural basis of alpha-delta sleep is poorly understood, and the extent of the cerebral cortex’s involvement is unknown. Here we use overnight intracranial and scalp EEG in adult humans to explore the cortical neural mechanisms of alpha-delta sleep.

Methods
We studied neurosurgical epilepsy patients who underwent longitudinal intracranial EEG (iEEG) monitoring. In each patient, data were simultaneously recorded overnight from iEEG electrodes and electrodes placed on scalp for polysomnography. To focus on local neural activity, we derived each iEEG channel as the signal difference between two adjacent recording sites separated by 5 mm within the cerebral cortex. For each 30-second epoch, we calculated EEG power in delta (1-4 Hz), theta (4-8 Hz), and alpha (8-15 Hz) frequency bands for all iEEG channels, and for sleep-scoring scalp EEG channels (e.g. C3-A2). Other bands were studied to rule out the effects of sleep spindles. For each night (comprising around 1000 epochs), we calculated the Spearman’s rank correlation coefficients of the EEG power values across epochs between the delta-band and the alpha-band power in each channel.

Results
All scalp EEG and most iEEG channels showed large increases of delta-band power during non-REM sleep compared to awake. Many (&gt; 75%) of these channels also showed significant increases of alpha-band power, and positive correlations across overnight epochs between delta-band and alpha-band power, indicating involvement of alpha-delta sleep. However, a minority (&lt; 25%) of iEEG channels, often located in the temporal lobe, showed significant decreases of alpha-band power during non-REM sleep compared to awake, and negative correlations between delta-band and alpha-band power, therefore appearing to be not involved in alpha-delta sleep.

Conclusion
Our iEEG study showed for the first time that alpha-delta sleep is not homogeneous across the cerebral cortex. Instead, the cortical distribution of alpha waves is more spatially restricted than the distribution of delta waves during non-REM sleep. This finding sheds new light on the neural basis of alpha-delta sleep.

Support (if any)
NIH R01-GM109086 (to M.I.B, K.V.N.)
0051 The Melanocortin and Endorphin Neuropeptides in Patients with Restless Legs Syndrome
Authors: Koo Brian , Abdelfattah Ahmed , Eysa Athar , Lu Lingeng 
Published: April 2024

Abstract

Introduction
Based upon similarities between the urge to move and sensory discomfort of restless legs syndrome (RLS) and properties of melanocortin hormones, like their incitement of movement and hyperalgesia, we assessed plasma and cerebrospinal fluid (CSF) α-melanocyte stimulating hormone (α-MSH) and β-endorphin in RLS patients and controls.

Methods
Forty-two untreated moderate-to-severe RLS patients and 44 matched controls underwent venipuncture at 19:00PM, 20:30PM, and 22:00PM; 37 RLS and 36 controls had lumbar puncture at 21:30PM. CSF and plasma were analyzed for pro-opiomelanocortin (POMC), adrenocorticotropin hormone (ACTH), α-MSH, β-MSH, and β-endorphin by immunoassay. RLS severity was assessed by International RLS Study Group Severity Scale.

Results
RLS participants were 52.7±12.0 years; 61.9% women; 21.4% painful RLS; RLS severity 24.8±9.0. Controls had similar age and sex. Plasma ACTH, α-MSH, and β-endorphin were similar between groups. Plasma POMC was significantly greater in RLS than controls (17.0±11.5 vs. 12.7±6.1 fmol/mL; p=0.048). CSF ACTH was similar between groups. CSF β-MSH was significantly higher in painful than non-painful RLS or controls (48.2±24.8 vs. 32.1±14.8 vs. 32.6±15.2 pg/mL; ANOVA p=0.03). CSF α-MSH was higher in RLS than controls (34.2±40.9 vs. 20.3±11.0 pg/mL; p=0.062). CSF β-EDP was lowest in painful RLS, intermediate in non-painful RLS, and highest in controls (8.0±3.4 vs. 10.8±3.1 vs. 12.3±5.0 pg/mL; ANOVA p=0.049). The ratio of the sum of CSF α- and β-MSH to CSF β-endorphin was highest, intermediate, and lowest in painful, non-painful RLS, and controls (p=0.007).

Conclusion
CSF α- and β-MSH are increased and CSF β-endorphin decreased in RLS patients, particularly for painful RLS.

Support (if any)
This work was supported by a Department of Defense Discovery Award grant, part of the Peer Reviewed Medical Research Program and the Congressionally Directed Medical Research Program (CRMRP). The grant was entitled Restless Legs Syndrome and the Melanocortin System; grant number W81XWH2010003.
0053 The Temporal Dynamics of Emotional Memory and Reactivity in Patients with Insomnia Disorder
Authors: Zeng Shengzi , Sit Hao Fong , Bottary Ryan , Pace-Schott Edward , Cunningham Tony , Li Shirley Xin , Hu Xiaoqing 
Published: April 2024

Abstract

Introduction
Insomnia is commonly linked with mood and anxiety-related disorders characterized by disrupted emotional memory processing. However, much remains unknown about the neurocognitive mechanisms underlying emotional memory processing among patients with insomnia. The current study seeks to examine the temporal dynamics of emotional memory processing among both patients with insomnia and healthy sleepers.

Methods
Thirty-four patients with DSM-5 insomnia disorder (23 females; Mage = 24.94) and 35 healthy sleepers (23 females; Mage = 23.91) encoded 48 pairs of pseudo-words and negative/neutral scene pictures in the evening, followed by overnight EEG-recorded sleep. All participants completed cued-recall memory tasks and affective ratings at pre-sleep, post-sleep, and 7-day delayed sessions.

Results
From the post-sleep to 7-day delayed sessions, patients with insomnia showed greater preservation of pictorial memory (ps &lt; 0.001) and less dissipation of affective tone compared to the healthy sleepers (ps &lt; 0.016). Moreover, among healthy sleepers, the product of post-encoding slow wave sleep (SWS) and rapid eye movement (REM) sleep duration predicted greater over-time negative memory decay (b = -0.001, p = 0.035), whereas REM duration predicted the dissipation of negative arousal ratings over time (b = -0.03, p = 0.041). Notably, these associations were not observed in the insomnia group.

Conclusion
These findings provide insight into the fundamental irregularities in emotional memory processing among patients with insomnia. For healthy sleepers, the results suggest a joint engagement of SWS and REM in promoting negative memory decay, and an adaptive role of REM sleep in facilitating the attenuation of affective arousal over time.

Support (if any)
0056 Overnight Memory Consolidation in Adolescents: Effects of Change in DLMO Phase After Sleep Restriction
Authors: Stager Lindsay , Gredvig-Ardito Caroline , Carskadon Mary , Saletin Jared 
Published: April 2024

Abstract

Introduction
Sleep aids learning and memory. Limited studies have examined how circadian rhythms moderate this process, particularly in adolescents who experience developmental changes in circadian biology. Here we examine how sleep restriction, memory consolidation, and circadian biology interact in youth with distinct circadian phase preferences.

Methods
Adolescents were recruited based on circadian phase preference on the Morningness/Eveningness (M/E; Carskadon et al., 1993) scale. Sixteen participants entered the current analysis (6F, 2 Non-White; age 10-15, mean±sd:12.69±1.76 years; M/E 22-40; mean±sd: 33.38±5.78; 1 Evening-Type [M/E≤23]; 4 Neither Type [23&gt;M/E&lt; 34]; 11 Morning type]). All completed 19 nights of stabilization on a self-selected 9-hour in bed schedule followed by 7 nights of sleep restriction (6.5 hours in bed; bedtime delayed and rise time advanced equally). In-lab dim-light-melatonin-onset (DLMO) assessment occurred on the final nights of stabilization and restriction. Overnight memory consolidation was indexed on the motor sequence task (MST; Walker et al., 2006) across the final night of sleep restriction. Memory outcomes included speed (# correct sequences), # of errors, and precision (speed-error trade-off). We examined overnight improvement (morning-evening) in MST performance and associations between improvement, phase preference score, stabilized DLMO phase, and the DLMO phase change after restriction (negative numbers indicate phase delay). Regressions controlled for age where statistically justified.

Results
MST speed improved (t(15)=-3.44, p&lt;.01, d=0.86) for the morning (12.94±6.89) test session compared to evening (10.81±5.69). There were no overnight changes in errors or precision (d’s&lt;.14, p’s&gt;.34). Overnight improvement was not related to M/E phase preference (Adj. R2’s&lt; 0.17; p’s&gt;.05); however, there was a significant association between the change in DLMO phase (mean±sd: 10.34±41.69 minutes) and memory consolidation for both speed (Adj. R2=0.54, F(2,13)=9.79, p&lt;.01) and errors (Adj. R2=0.21, F(1,15)=4.94, p&lt;.05). Specifically, children with a greater delay in DLMO phase demonstrated greater overnight improvement on the MST.

Conclusion
These data indicate a potential link between circadian biology and the cognitive benefits of sleep during adolescence. These findings are significant given the shifts in circadian rhythms occurring across adolescence. Understanding the influence of circadian rhythms in sleep-dependent memory may inform discussions of how sleep loss affects learning in school-aged youth.

Support (if any)
R01NR08381 and P20GM139743
0057 Functional Network Architecture Supports Memory Consolidation via NREM Sleep Oscillation Expression and Coupling
Authors: Chappel-Farley Miranda G , Adams Jenna , Sattari Negin , Berisha Destiny , Meza Novelle , Janecek John , Betzel Richard , Niknazar Hamid , Kim Soyun , Dave Abhishek , Chen Ivy Y , Lui Kitty K , Benca Ruth , Yassa Michael , Mander Bryce 
Published: April 2024

Abstract

Introduction
Memory consolidation is facilitated by trace reactivation during non-rapid eye movement slow wave sleep (SWS), involving reinstatement of a hippocampal index driving integration of activity patterns stored in cortical modules. Slow oscillation (SO) and sleep spindle (SP) coupling reflects this process. Here, we used a novel graph theory approach to examine whether network modularity (Q) and the relative import of the hippocampus and amygdala in network function, measured by eigenvector centrality (EC) and betweenness centrality (BC), are associated with SWS expression, SO-SP coupling, and emotional memory consolidation.

Methods
Thirty-six cognitively intact older adults (μ=72.9±5.6 years, 23 Females) completed structural and resting-state functional magnetic resonance imaging (MRI) at 3T, an overnight polysomnography with electroencephalography, and, prior to and following sleep, performed the Emotional Mnemonic Discrimination Task, with the Lure Discrimination Index quantifying memory. MRI data were preprocessed with the CONN toolbox. Network nodes were defined using the Brainnetome atlas. Graph metrics were computed using the Brain Connectivity Toolbox. In a subset, p-welch derived SO power (N=18) and mean vector length computed phase-amplitude SO-SP coupling (N=16) were derived.

Results
Q was associated with diminished emotional memory retention (B=-1.394, p=0.042) and greater SWS percentage (B=48.476, p=0.023), which was also associated with emotional memory retention (B=0.013, p=0.020). An inconsistent mediation effect of SWS in the Q-emotional memory retention relationship was found (95% CIs: 0.015, 0.345). Hippocampal EC (B=36.845, p=0.008) and amygdala EC (B=47.277, p=0.022) were associated with emotional memory retention. Hippocampal BC was associated with immediate test performance (B=19.859, p=0.027), whereas amygdala BC was associated with delayed test (B=1.823, SE=0.745, p=0.020) and emotional memory retention (B=1.699, p=0.047). Hippocampal EC (B=0.475, p=0.047) and BC (B=0.426, p=0.086) were associated with frontal SO expression, which was associated with delayed test performance (B=0.492, p=0.038). Hippocampal EC (B=0.649, p=0.006) and amygdala BC (B=0.545, p=0.029) were associated with frontal SO-SP coupling.

Conclusion
These findings suggest that greater network integration supports SWS-dependent emotional memory consolidation during sleep. A more topologically influential hippocampus aids in memory acquisition and retention, whereas a more influential amygdala supports emotional memory consolidation.

Support (if any)
This research was supported by NIA grants F31AG074703, F32AG074621, R21AG07955, R01AG053555, K01AG058353, and AASM Foundation SRA-1818.
0060 A Meta-Analytic Investigation of the Effect of Sleep Deprivation on Inhibitory Control
Authors: Choong Sze Yinn , Byrne Jamie E M , Lum Jarrad A G , Staiger Petra K , Jones Andrew , Rispoli-Yovanovic Maris , Drummond Sean P A 
Published: April 2024

Abstract

Introduction
Research has suggested that varying degrees of sleep deprivation have a detrimental effect on inhibitory control (a collection of neural processes evoked to suppress a prepotent response). This is the first meta-analysis to assess the impact of sleep deprivation on inhibitory control in controlled studies.

Methods
The review was performed following PRISMA guidelines. Four electronic databases, APAPsycINFO, Medline, CINAHL and Embase, were systematically searched from inception to November 2023. Selection criteria included studies that conducted experimentally induced sleep disruption (sleep deprivation protocols) in healthy adults (aged above 18 years, no sleep-related/mental disorders/cognitive impairments) and reported inhibitory control performance defined by the Go/No-Go and/or Stop-Signal Task paradigms. Quality appraisal was assessed using the revised Cochrane Risk-of-Bias Tool for Randomised Trials (RoB 2) and Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I). Effect sizes (Hedge’s g) examining the impact of sleep deprivation on inhibitory control were pooled using random-effects meta-analysis.

Results
Twenty-four studies (n = 712 participants) were included. Sleep deprivation protocols included total sleep deprivation (N= 21 studies), partial sleep deprivation (N= 2) and both (N= 1). Seventeen studies used the Go/No-Go Task, and seven studies used the Stop Signal Task. The meta-analysis showed sleep deprivation negatively affected inhibitory control as measured by the Go/No-Go and Stop-Signal (Hedge’s g = 0.481, [95% CI: 0.361 to 0.600], p &lt; .001, I2 = 43%). Sleep deprivation effects were similar across Go/No-Go (Hedge’s g = 0.475, [95% CI: 0.346 to 0.604], p &lt; .001, I2 =34%) and Stop-Signal performance (Hedge’s g = 0.482, [95% CI: 0.190 to 0.773], p &lt; .001, I2 =63%).

Conclusion
Our findings demonstrate that sleep deprivation has a significant negative impact on inhibitory control as measured by Go/No-Go and Stop-Signal. These results have important implications regarding the impacts of sleep deprivation on the ability to suppress prepotent responses. Resultant impaired decision-making, higher levels of risk-taking behaviours and difficulties in stopping and modifying planned actions may have real-world consequences for workplace or vehicular safety.

Support (if any)
Deakin University Postgraduate Research Scholarship (DUPRS)
0062 Memory for Text Meaning Is Maintained During 24 Hours of Continuous Wakefulness
Authors: Kurinec Courtney , Whitney Paul , Hinson John , Van Dongen Hans 
Published: April 2024

Abstract

Introduction
Total sleep deprivation (TSD) has been shown to impair associative memory, but little is known about the effects of TSD on memory for naturalistic text. Naturalistic text has different levels of representation: memory for surface form (verbatim text), which is short-lived; memory for textbase (ideas expressed in the text); and event model (representation of the situation described in the text). We investigated whether TSD differentially impacts memory by level of representation.

Methods
N=10 female active-duty dayshift (DS; n=5) and nightshift (NS; n=5) workers (ages 35.1±8.1y) matched by age participated in a 36h laboratory study. After waking at their habitual wake time (DS: 05:57±64min; NS: 12:52±62min) and working their normal shift, participants arrived at the laboratory at 08:00 (DS) or 20:00 (NS). Following a 2h acclimation period, participants completed a 24h constant routine protocol with continuous wakefulness, followed by recovery sleep 1h later. 1h into the constant routine, participants read three narrative texts (self-paced). Memory for text was tested immediately (3h awake), 1h later (4h awake), and 24h later (27h awake). Participants saw 64 recognition probes per text, which varied by whether they required memory for surface form, textbase, or event model. Discriminability indices were calculated for each level of representation.

Results
Mixed-effects ANOVA with fixed effects of test bout (0h, 1h, 24h after reading), level of representation, and their interaction, covariates for shift and age, and a random intercept over participants showed a significant effect for level of representation (F=32.17, p&lt; 0.001). Memory for surface form, which was near chance levels, was worse (p&lt; 0.05) than that for textbase and event model, which did not differ from each other (p=0.271). There was no significant effect for test bout (p&gt;0.1).

Conclusion
Memory for naturalistic text was not significantly impaired by 24h TSD. Memory for surface form was at chance level throughout, as expected since it is known to be short-lived. However, memory for textbase and event model, which reflect text meaning, was retained despite the anticipated impact of TSD on associative memory. The widespread associations in texts may provide more cues to facilitate retrieval and maintain memory performance during TSD.

Support (if any)
CARE Fund FY22-POP-02; HSSA