Sleep Onset REM Research Articles

Sleep schedules and MSLT-based diagnosis of narcolepsy type 2 and idiopathic hypersomnia: Exploring potential associations in a large clinical sample.

Differential diagnosis of narcolepsy type 2 and idiopathic hypersomnia relies on the frequency of sleep-onset rapid eye movement periods observed on the Multiple Sleep Latency Test. This study investigated whether variations in sleep schedules, particularly delayed sleep-wake patterns, contribute to the diagnostic distinction between narcolepsy type 2 and idiopathic hypersomnia. The study included 871 patients aged 18-39 years (316 with narcolepsy type 2, 555 with idiopathic hypersomnia). These patients were diagnosed based on MSLT results following polysomnography from November 2013 to November 2017. Patients' sleep habits, including bedtime and wake-up times on weekdays and weekends during the 2 weeks preceding the polysomnography/Multiple Sleep Latency Test, were assessed using self-reported sleep logs. A multivariate logistic regression analysis was conducted to identify factors associated with narcolepsy type 2 diagnosis. The analysis revealed that being male (p < 0.001), younger age (p < 0.001), shorter weekday sleep duration (p < 0.05), and a delayed weekday sleep midpoint time (p < 0.01) were significantly associated with a diagnosis of narcolepsy type 2. The study suggests that the conventionally fixed schedule of polysomnography and Multiple Sleep Latency Test administration may have contributed to the increased occurrence of sleep-onset rapid eye movement periods particularly in individuals with a delayed sleep-wake schedule.

The Lehigh Valley Health Network narcolepsy cohort: clinical and polysomnographic analysis of 304 cases.

We aimed to characterize clinical features, comorbidities and polysomnographic characteristics of a large cohort of patients with narcolepsy. We undertook a retrospective chart and polysomnographic review of all patients with a diagnosis of narcolepsy type 1 (NT1) or narcolepsy type 2 (NT2) seen within the Lehigh Valley Health Network between 2000 and 2022. We found 304 cases with a diagnosis of narcolepsy (52 NT1, 252 NT2), based on International Classification of Sleep Disorders, third edition criteria. Compared to NT2, patients with NT1 had younger diagnosis age (24.5 versus 27.4 years, p=0.03), shorter diagnostic gap (3.0 versus 4.6 years, p=0.002), more frequent sleep paralysis (55.8% versus 19.4%, p<0.0001) and hypnagogic hallucinations (46.2% versus 25.4%, p=0.003), and higher Epworth Sleepiness Scale (ESS) scores (17.8 versus 16.7, p=0.02). The most common comorbid sleep disorders were breathing disorders (17.4%) and insomnia (15.5%). Migraine was the most common neurological disorder. Depression was more common in NT2 than NT1 [12 (23.1%) versus 94 (37.3%), p=0.05]. On the Multiple Sleep Latency Test, patients with NT1 had more sleep onset REM periods (SOREMPs) than patients with NT2 (≥3 SOREMPs in 59.2% versus 26.9%, p<0.0001). Only in NT2, hypnagogic hallucinations and higher ESS scores were associated with higher numbers of SOREMPs (p=0.0277 and p=0.0179 respectively). This is one of the largest monocentric studies to date of patients with narcolepsy and confirms the frequent comorbidities of narcolepsy. Specific clinical characteristics and comorbidities may help differentiate NT1 from NT2.

Wakefulness Induced by TAAR1 Partial Agonism in Mice Is Mediated Through Dopaminergic Neurotransmission.

Trace amine-associated receptor 1 (TAAR1) is a negative regulator of dopamine (DA) release. The partial TAAR1 agonist RO5263397 promotes wakefulness and suppresses NREM and REM sleep in rodents and non-human primates. We tested the hypothesis that the TAAR1-mediated effects on sleep/wake regulation were due, in part, to DA release. Male C57BL6/J mice (n = 8) were intraperitoneally administered the D1R antagonist SCH23390, the D2R antagonist eticlopride, a combination of D1R + D2R antagonists, or saline at ZT5.5, followed 30 min later by RO5263397 or vehicle per os. EEG, EMG, subcutaneous temperature, and activity were recorded across the 8 treatments and sleep architecture was analyzed for 6 h post-dosing. As described previously, RO5263397 increased wakefulness and delayed NREM and REM sleep onset. D1, D2, and D1 + D2 pretreatment reduced RO5263397-induced wakefulness for 1-2 h after dosing but only the D1 antagonist significantly reduced the TAAR1-mediated increase in NREM latency. Neither the D1 nor the D2 antagonist affected the TAAR1-mediated suppression of REM sleep. These results suggest that, whereas the TAAR1 effects on wakefulness are mediated, in part, through the D2R, D1R activation plays a role in reversing the TAAR1-mediated increase in NREM sleep latency. In contrast, the TAAR1-mediated suppression of REM sleep appears not to involve D1R or D2R mechanisms.

Fluoxetine, but not paroxetine, alters the jaw-closing muscle activity during non-rapid eye movement sleep in mice

Sleep bruxism is an involuntary, exaggerated jaw-closing activity during sleep. Selective serotonin reuptake inhibitor (SSRI) use is a risk factor for bruxism. However, the effect of various SSRIs on masseter (jaw-closing) muscle activity remains unclear. Here, we examined the effects of long-term administration of two SSRIs, fluoxetine (FLX) and paroxetine (PRX), for 14 days on masseter muscle activity during wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep for 24 h in mice. Vigilance states were scored based on electroencephalographic, electrooculography and neck electromyographic (EMG) activities. The EMG activity of the masseter muscle was quantified in 6 h periods. FLX and PRX did not affect the duration of the three vigilance states. Both drugs significantly prolonged the REM sleep episode duration while decreasing the number of episodes. FLX significantly increased REM sleep onset latency. Neither FLX nor PRX affected the mean masseter EMG activity during wakefulness. FLX significantly increased the relative time of masseter muscle activity in NREM sleep during 02:00–08:00 and 08:00–14:00, while PRX did not affect three vigilance states. Overall, FLX had a limited but significant effect on masseter muscle activity in NREM sleep during specific periods.

Narcolepsy and Idiopathic Daytime Hypersomnia: A Study of Cohort in the Chilean Population

Introduction: Central disorders with hypersomnolence (CDH) are a group of sleep disorders characterized by excessive daytime sleepiness (EDS) that can be related to REM-sleep dissociative symptoms. They have a low prevalence in the population and may not be explained by other medical conditions. Materials and methods: A cohort of 59 Chilean patients with the most common types of CDH were studied. Clinical data, and results of polysomnography (PSG) plus multiple sleep latency tests (MSLT) were analyzed.. Results: The median age of the cohort was 35.26 ± 13.23 years (69.5% female). Diagnosis of narcolepsy Type 1, narcolepsy Type 2, and idiopathic daytime hypersomnia, were determined in 54.2%, 23.7% and 22% of patients respectively. All patients reported EDS, while 57.6%, 81.4% and 78% reported cataplexy, sleep paralysis and hypnagogic/hypnopompic hallucinations respectively. Polysomnographic studies showed non relevant alterations in the majority of patients. The MLTS was abnormal in all patients, 78% of them with 2 or more sleep onset REM periods (SOREMP). In 52.5% of cases, the delay in final diagnosis was more than 5 years. About a third of patients had another sleep disorder that could not explain the severity of EDS. We observed a comorbidity with an immunological disorder in 30.5% of patients. Conclusion: The EDS is the main symptom in CDH. Related REM-sleep symptoms and MSLT alterations were the second most important features to establish final diagnosis. However, we observed a significant delay in CDH diagnosis in the majority of patients.

Association between human leukocyte antigen class II-DR-DQ and narcolepsy: a case control study.

Narcolepsy is a neurologic disorder characterized by irresistible sleep attacks. Although its etiology is unknown, it is strongly associated with genetic variances in the human leukocyte antigen (HLA) complex. We investigated the association of HLA class II-DR-DQ alleles in a sample of patients with narcolepsy-cataplexy (narcolepsy type 1; NT1) and patients with narcolepsy without cataplexy (narcolepsy type 2; NT2) with a control group. Additionally, we compared demographic, clinical, and laboratory characteristics of patients with narcolepsy with or without the DQB1*06:02 allele. This case control study included 21 patients with NT1 (56.8%), 16 patients with NT2 (43.2%), and 100 controls. Sequence-based typing identified HLA-DRB1 alleles, and HLA-DQB1 typing was done using PCR-Sequence-Specific Oligonucleotide. Allele and haplotype frequencies were calculated by direct counting. Nocturnal polysomnography and Multiple Sleep Latency Test were performed in all participants. In the NT1 group, only one allele had a significantly higher frequency than in the NT2 group: DQB1*06:02 (61.9% vs. 18.8%;). Compared to controls, DQB1*06:02 (61.9% vs. 18.0% in controls) and DRB1*15:01(47.6% vs. 8.0%), had higher frequencies in patients with NT1. Multiple analyses showed that patients with NT1 had an increased chance of being HLA-DQB1*06:02 positive. HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype is associated with NT1 in our Brazilian patients. PSG was identified in DQB1*06:02 positive subgroup REM sleep latency (REML) ≤ 15 minutes, and all patients had two or more sleep-onset REM periods (SOREMPs) at MSLT. This study showed a strong association between HLA DQB1*06:02 and the haplotype HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 in patients with NT1. Patients with DQB1*0602 allele showed shorter REMLs at PSG. These results reinforce the suggestion of DQB1 genotyping as relevant to narcolepsy screening.

Quantitative EEG in Parkinson's disease: when REM sleep behavior disorder onset really matters.

Parkinson's Disease (PD) body-first subtype is characterized by prodromal autonomic symptoms and REM sleep behavior disorder (RBD), symmetric dopaminergic degeneration, and increased risk of dementia. On the other hand, the PD brain-first subtype has fewer non-motor symptoms and a milder motor phenotype. The temporal relationship between RBD onset and motor symptoms onset may differentiate these two subtypes. We aimed to investigate electrocortical differences between brain-first and body-first PD patients. PD patients with an available routinely collected EEG were retrospectively selected. RBD was diagnosed using the RBD screening questionnaire (≥ 6). According to the onset of RBD patients were classified into PD-RBDpre (RBD onset before motor symptoms) and PD-RBDpost (RBD onset after motor symptoms). Patients without RBD were classified as PD-RBD-. Presence of Mild Cognitive Impairment (MCI) was diagnosed according to the MDS criteria. EEG Spectral analysis was performed in resting state by computing the Power Spectral Density (PSD) of site-specific signal epochs for the common frequency bands (delta, theta, alpha, beta). Thirty-eight PD-RBD-, 14 PD-RBDpre and 31 PD-RBDpost patients were recruited. Comparing both global and site-specific absolute values, we found a significant trend toward beta band reduction going from PD-RBD-, PD-RBDpost and PD-RBDpre. No significant differences were found between PD-RBDpost and PD-RBD- patients. PD-RBDpre patients may represent a different subset of patients as compared to patients without RBD, while patients with later onset have intermediate EEG spectral features. Quantitative EEG may provide new hints in PD subtyping.

Narcolepsy and rapid eye movement sleep.

Since the first description of narcolepsy at the end of the 19th Century, great progress has been made. The disease is nowadays distinguished as narcolepsy type 1 and type 2. In the 1960s, the discovery of rapid eye movement sleep at sleep onset led to improved understanding of core sleep-related disease symptoms of the disease (excessive daytime sleepiness with early occurrence of rapid eye movement sleep, sleep-related hallucinations, sleep paralysis, rapid eye movement parasomnia), as possible dysregulation of rapid eye movement sleep, and cataplexy resembling an intrusion of rapid eye movement atonia during wake. The relevance of non-sleep-related symptoms, such as obesity, precocious puberty, psychiatric and cardiovascular morbidities, has subsequently been recognized. The diagnostic tools have been improved, but sleep-onset rapid eye movement periods on polysomnography and Multiple Sleep Latency Test remain key criteria. The pathogenic mechanisms of narcolepsy type 1 have been partly elucidated after the discovery of strong HLA class II association and orexin/hypocretin deficiency, a neurotransmitter that is involved in altered rapid eye movement sleep regulation. Conversely, the causes of narcolepsy type 2, where cataplexy and orexin deficiency are absent, remain unknown. Symptomatic medications to treat patients with narcolepsy have been developed, and management has been codified with guidelines, until the recent promising orexin-receptor agonists. The present review retraces the steps of the research on narcolepsy that linked the features of the disease with rapid eye movement sleep abnormality, and those that do not appear associated with rapid eye movement sleep.

The effects of daylight duration on the multiple sleep latency test (MSLT) results: A pilot study

ObjectiveMSLT results are known to be affected by multiple factors including sleep time, frequency of nighttime arousals, and medications intake. Although being the main synchronizer of sleep and wakefulness, daylight duration effects on MSLT have not been examined. Burlington, Vermont, USA experiences great variations in daylight duration, ranging from 8 h 50 min to 15 h 33 min of daylight. The aim of this study was to test the hypothesis that there would be photoperiod duration effects on MSLTs performed during short daylight (short daylight studies, SDS) vs. long daylight (long daylight studies, LDS) from 2013 to 2023 in our sleep laboratory. methodsWe identified and analyzed 37 SDS (daylight 530–560 min) and 36 LDS (daylight 903–933 min) from our database. Groups of SDS and LDS results were compared using non-paired student T test, Chi-Square and non-parametric Mann Whitney U Test. ResultsAverage daylight duration was 15 h 18 ± 14.6 min for LDS and 8 h 57 ± 18 min for SDS. Two groups did not differ in terms of the age, gender, BMI and race of patients studied. Mean total sleep time and sleep efficiency during PSG preceding MSLT, and MSLT mean sleep onset latency did not significantly differ for the two groups. However, SDS MSLT naps had significantly more sleep onset REM periods (SOREMP), and distribution of the number of SOREMP captured during MSLT was different for SDS and LDS groups. Differences of SDS and LDS results did not relate to sleep architecture of the overnight PSG as analysis of sleep and REM latency and relative percentages of N1, N2, REM, and N3 was not significantly different between SDS and LDS. The two groups showed difference in arousal indexes during N1 and REM sleep. ConclusionsDaylight duration may impact MSLT results and should probably be accounted for in MSLT interpretation. Attention to photoperiod could be considered in MSLT guidelines, if our results are replicated in larger samples.

Identifying time-resolved features of nocturnal sleep characteristics of narcolepsy using machine learning.

The differential diagnosis of narcolepsy type 1, a rare, chronic, central disorder of hypersomnolence, is challenging due to overlapping symptoms with other hypersomnolence disorders. While recent years have seen significant growth in our understanding of nocturnal polysomnography narcolepsy type 1 features, there remains a need for improving methods to differentiate narcolepsy type 1 nighttime sleep features from those of individuals without narcolepsy type 1. We aimed to develop a machine learning framework for identifying sleep features to discriminate narcolepsy type 1 from clinical controls, narcolepsy type 2 and idiopathic hypersomnia. The population included polysomnography data from 350 drug-free individuals (114 narcolepsy type 1, 90 narcolepsy type 2, 105 idiopathic hypersomnia, and 41 clinical controls) collected at the National Reference Centers for Narcolepsy in Montpelier, France. Several sets of nocturnal sleep features were explored, as well as the value of time-resolving sleep architecture by analysing sleep per quarter-night. Several patterns of nighttime sleep evolution emerged that differed between narcolepsy type 1, clinical controls, narcolepsy type 2 and idiopathic hypersomnia, with increased nighttime instability observed in patients with narcolepsy type 1. Using machine learning models, we identified rapid eye movement sleep onset as the best single polysomnography feature to distinguish narcolepsy type 1 from controls, narcolepsy type 2 and idiopathic hypersomnia. By combining multiple feature sets capturing different aspects of sleep across quarter-night periods, we were able to further improve between-group discrimination and could identify the most discriminative sleep features. Our results highlight salient polysomnography features and the relevance of assessing their time-dependent changes during sleep that could aid diagnosis and measure the impact of novel therapeutics in future clinical trials.

Exploring sleep characteristics in Chinese patients with narcolepsy: insights from the nocturnal sleep onset rapid eye movement period (nSOREMP).

This study aimed to investigate the unique characteristics and clinical significance of the nocturnal sleep onset rapid eye movement period (nSOREMP) in the Chinese population with narcolepsy, enhancing our understanding and management of the disorder globally. This retrospective analysis investigated narcolepsy in Chinese patients from six hospitals, using the International Classification of Sleep Disorders. A parallel retrospective analysis of the Chinese Clinical Sleep Database focused on polysomnography records was conducted to evaluate nSOREMP prevalence in other sleep disorders. The study found a 2.51% nSOREMP prevalence in other sleep disorders in the Chinese Clinical Sleep Database. Significant differences in age, N2 and rapid eye movement percentages, rapid eye movement latency, and various indexes were noted among patients with narcolepsy with or without nSOREMP and other sleep disorders with nSOREMP in the Chinese Clinical Sleep Database. nSOREMP prevalence in narcolepsy type 1 was 33.33% and in narcolepsy type 2 was 28.30%. Noteworthy disparities in narcolepsy type 1 included N2 percentages, rapid eye movement latency, and SOREMPs on Multiple Sleep Latency Test. In narcolepsy type 2, differences were significant for age, sleep latency, N2 and rapid eye movement latencies, arousal index, mean sleep latency on the Multiple Sleep Latency Test, and Multiple Sleep Latency Test SOREMPs. This study highlights the distinct characteristics of nSOREMP in the Chinese population. Patients exhibiting symptoms suggestive of the onset of narcolepsy are advised to undergo a Multiple Sleep Latency Test, irrespective of the occurrence of SOREMP during nocturnal polysomnography. Zeng S, Feng F, Li W, etal. Exploring sleep characteristics in Chinese patients with narcolepsy: insights from the nocturnal sleep onset rapid eye movement period (nSOREMP). J Clin Sleep Med. 2024;20(8):1349-1355.

0669 Oxidative Stress in Hypersomnia Patients: Correlation with Sleep Onset REM Period

0669 Oxidative Stress in Hypersomnia Patients: Correlation with Sleep Onset REM Period

Exploring the Intersection of Narcolepsy and Attention Deficit Hyperactivity Disorder: Similarities, Differences, and Clinical Implications

Narcolepsy and attention deficit hyperactivity disorder (ADHD) are distinct neurobiological conditions characterized by overlapping symptoms, including excessive daytime sleepiness and cognitive dysfunction. Despite their differences in etiology and pathophysiology, recent studies have highlighted a potential association between the two disorders, with a significant prevalence of ADHD symptoms observed in narcolepsy patients. This narrative review explores the similarities and differences between narcolepsy and ADHD, focusing on their shared symptomatology, neurobiological mechanisms, challenges in diagnosis, and treatment implications. While both disorders exhibit disruptions in dopaminergic and noradrenergic neurotransmitter systems, differential diagnosis remains challenging due to overlapping clinical presentations. Polysomnography findings, such as appearance of sleep onset rapid eye movements in narcolepsy patients, provide important distinctions that enable accurate diagnosis. Treatment strategies often involve stimulant medications for symptom management; however, nonpharmacological interventions, such as cognitive behavioral therapy, have been shown to have the potential to improve patient outcomes. Clinicians must consider the possibility of coexisting narcolepsy in ADHD patients and vice versa to ensure appropriate treatment selection and optimal patient care. Further research is needed to refine diagnostic criteria, elucidate the complex interplay between the two disorders, and develop personalized therapeutic approaches. A multidisciplinary approach involving sleep specialists, neurologists, psychiatrists, and psychologists is essential to address the diverse biopsychosocial needs of patients with concurrent narcolepsy and ADHD.

Sleep architecture of elite soccer players surrounding match days as measured by WHOOP straps

ABSTRACT This study aimed to quantify and compare sleep architecture before and after home and away matches in elite soccer players from the English Premier League. Across two seasons, 6 male players (age 28 ± 5 y; body mass 85.1 ± 9.5 kg; height 1.86 ± 0.09 m) wore WHOOP straps to monitor sleep across 13 matches that kicked off before 17:00 h. For each, sleep was recorded the night before (MD−1), after (MD) and following the match (MD +1). Across these 3 days total sleep time (TST), sleep efficiency (SE), sleep disturbances, wake time, light sleep, deep sleep, REM sleep, sleep and wake onsets, alongside external load, were compared. TST was reduced after MD versus MD +1 (392.9 ± 76.4 vs 459.1 ± 66.7 min, p = 0.003) but no differences existed in any other sleep variables between days (p > 0.05). TST did not differ after home (386.9 ± 75.7 min) vs. away matches (401.0 ± 78.3 min) (p = 0.475), nor did other sleep variables (p > 0.05). GPS-derived external load peaked on MD (p < 0.05). In conclusion, despite reduced TST on MD, sleep architecture was unaffected after matches played before 17:00 h, suggesting sleep quality was not significantly compromised.

Aging and sex are associated with multiple sleep latency test findings and their relationship with self-reported sleepiness.

The aim of this study was to assess age- and sex-related differences in multiple sleep latency test (MSLT) results and in the performance of the Epworth Sleepiness Scale (ESS) at classifying objective hypersomnia (mean sleep latency (MSL) ≤ 8min). We studied 480 consecutive adults (39.3 ± 15.3years old [18-93], 67.7% female) who underwent hypersomnia evaluation. We fit linear regression models to investigate associations between age and sex and sleep latencies (mean and for every nap), after adjusting for total sleep time and sleep efficiency (on polysomnography), and REM-suppressing antidepressant effect. A logistic regression was performed to assess whether age and sex were associated with sleep-onset REM period (SOREMP) occurrence. ROC analysis assessed the diagnostic performance of ESS scores to identify a MSL ≤ 8min in different age/sex groups. For every 10years of age, there was 0.41 (95% CI 0.11-0.72, p = 0.008)min reduction in MSL. Objectively (MSL ≤ 8min) sleepy patients had shortening of latencies in naps 4 and 5 with aging. Female sex was associated with a higher MSL only in patients with MSL > 8min. A 2.4% reduction in the odds of SOREMP occurrence was observed for every year of age in objectively sleepy patients (p = 0.045). ESS scores had a better diagnostic performance in older (≥ 50years old) men than younger (< 50years old) women (p < 0.05). Older patients with objectively confirmed hypersomnia may be sleepier in later naps, possibly due to less restorative naps and/or circadian rhythm factors. Self-reported sleepiness is more predictive of objective sleepiness in older men than younger women.

A narcolepsy detection paradigm: automated nocturnal detection and notification of sleep onset rapid eye movement periods

A narcolepsy detection paradigm: automated nocturnal detection and notification of sleep onset rapid eye movement periods

Sleepy Kids: are the current diagnostic criteria for multiple sleep latency tests enough?

Excessive daytime sleepiness (EDS) is common in childhood and is currently quantified using adult criteria on a multiple sleep latency test (MSLT). This study aimed to describe paediatric MSLT results, particularly focussing on a previously proposed alternative mean sleep latency (MSL) threshold for children of 12 min, and assess the impact of a 5th nap. We performed a retrospective analysis of MSLTs at a single paediatric centre from 2004 to 2021. Narcolepsy was defined as a mean sleep latency (MSL) ≤8min with ≥2 sleep onset REM (SOREM) periods. Idiopathic Hypersomnia (IH) was defined as a MSL ≤8min with <2 SOREMs. An ambiguous MSLT result was defined as a MSL 8–12min and/or ≥2 SOREM periods. Of 214 MSLTs [50 % female, median age 14.0y (range 3.3–20.1y)], narcolepsy was diagnosed in 48 (22 %), IH in 22 (10 %) and the result was ambiguous in 44 (21 %). Those with ambiguous MSLT results were older (15.6 vs 13.4y, p = 0.006) with a higher proportion of females (61 % vs 35 %, p = 0.01) in comparison to the narcolepsy group. A 5th nap was performed in 60 (28 %) of MSLTs and only changed the outcome in one case. In conclusion, MSLT results are borderline in 21 % of paediatric cases, suggesting that current adult diagnostic criteria may miss narcolepsy and IH in children. A 5th nap usually makes no difference or increases the MSL, suggesting that a four nap MSLT protocol could be used apart from rare cases where the result is borderline after the 4th nap.

Orexin Neurons to Sublaterodorsal Tegmental Nucleus Pathway Prevents Sleep Onset REM Sleep-Like Behavior by Relieving the REM Sleep Pressure.

Proper timing of vigilance states serves fundamental brain functions. Although disturbance of sleep onset rapid eye movement (SOREM) sleep is frequently reported after orexin deficiency, their causal relationship still remains elusive. Here, we further study a specific subgroup of orexin neurons with convergent projection to the REM sleep promoting sublaterodorsal tegmental nucleus (OXSLD neurons). Intriguingly, although OXSLD and other projection-labeled orexin neurons exhibit similar activity dynamics during REM sleep, only the activation level of OXSLD neurons exhibits a significant positive correlation with the post-inter-REM sleep interval duration, revealing an essential role for the orexin-sublaterodorsal tegmental nucleus (SLD) neural pathway in relieving REM sleep pressure. Monosynaptic tracing reveals that multiple inputs may help shape this REM sleep-related dynamics of OXSLD neurons. Genetic ablation further shows that the homeostatic architecture of sleep/wakefulness cycles, especially avoidance of SOREM sleep-like transition, is dependent on this activity. A positive correlation between the SOREM sleep occurrence probability and depression states of narcoleptic patients further demonstrates the possible significance of the orexin-SLD pathway on REM sleep homeostasis.

Sleep Stage Transition of Sleep Onset Rapid Eye Movement Periods Suggesting REM Dysregulation in Narcolepsy

Objectives: Narcolepsy diagnosis is often complicated, using relatively simple criteria that rely on sleep onset rapid eye movement periods (SOREMP) and average sleep latency in the multiple sleep latency test (MSLT). Therefore, the main goal of this study was to gain a new perspective on narcolepsy diagnosis and explore the role of rapid eye movement (REM) dysregulation by examining the progression of sleep stage transitions leading to SOREMP.Methods: From 2008 to 2022, 109 patients diagnosed with narcolepsy who underwent polysomnography and MSLT were included. Comprehensive data on clinical features, polysomnography, and MSLT findings were collected. For the MSLT, we not only considered SOREMP and mean sleep latency but also the sleep stage transition preceding SOREMP, the presence of N3, and the average SOREMP duration.Results: Among the 109 patients enrolled in the study, 59 were diagnosed with narcolepsy type 1 (NT1) and 50 with narcolepsy type 2 (NT2). We observed a high frequency of transitions in the MSLT of waking to REM (W-R) in patients with NT1. Moreover, the occurrence of W-R was associated with a higher number of SOREMPs. The temporal distribution of the MSLT results revealed a significant correlation; W-R occurrences were more frequent during the third nap.Conclusions: W-R occurrence was frequent in patients with NT1, indicating more pronounced REM dysregulation than in patients with NT2.

A Meta-Analysis of the Effectiveness of Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation as Therapy of Insomnia

Objective: Insomnia serves as the most common sleep disorder. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are amongst most popular treatment for insomnia. This research aimed to determine the comparative effectiveness of TMS and tDCS as therapies for insomnia.Methods: PubMed/MEDLINE, ScienceDirect, Google Scholar, ResearchGate, Wiley Library Online, and Neurona were used to search for randomized controlled trials (RCTs) comparing TMS/tDCS with sham group in insomnia. Meta-analysis was done to determine the effectiveness of TMS and tDCS as a therapy for insomnia. Weighted mean difference were computed and reported with its 95% CI. Heterogeneity was reported with I&lt;sup&gt;2&lt;/sup&gt;. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Subjective pooled-analysis was done using Mann-Whitney U test with p&lt;0.05.Results: From a total 1,000 publications, 15 studies were included, revealing varying types of insomnia as follows: 26.7% comorbid depression, 13.3% comorbid pain, 13.3% involving athletes, 13.3% primary insomnia, 6.7% due to medication, 6.7% comorbid polio, 6.7% comorbid Sjogren’s syndrome, 6.7% comorbid stroke, and 6.7% comorbid Parkinson’s disease. From 15 studies, four homogenous articles were made for pooled-analyses, which included two studies on TMS and two studies on tDCS in insomnia comorbid depression. tDCS improved sleep onset latency, N2, and REM latency better than sham. TMS (2.29, 95% CI: 1.82–2.76) was superior to sham in improving the subjective quality of sleep, and tDCS (1.05, 0.68–1.43) with p=0.121.Conclusion: No significant differences were found between TMS and tDCS as therapies for insomnia. Most RCTs studying TMS/tDCS in insomnia reported high comorbidity with depression.