The heritable trait of non-rapid eye movement (NREM) parasomnias is well known, but differences between sporadic and familial phenotypes have not been studied. The aim of our study was to evaluate, in a clinical series of adults with NREM parasomnias, clinical and sleep differences between familial versus sporadic forms, and between childhood versus adolescent versus adult-onset forms. We prospectively collected clinical features, family history, questionnaires (Epworth Sleepiness Score and Paris Arousal Disorders Severity Scale (PADSS)), and video-polysomnography measures from patients with NREM parasomnias confirmed by video-polysomnography, admitted over a 12-year period. Familial NREM parasomnia was defined as having at least one relative of the index case with NREM parasomnia. Of the 625 consecutive adults with NREM parasomnias, 50% had a family history of NREM parasomnia (most commonly parents, followed by siblings, then children). Compared to those with sporadic NREM parasomnias, participants with familial NREM parasomnias had an earlier age of onset and greater severity of NREM parasomnias (according to the PADSS). They were more likely to report sleepwalking, sleep terrors, and a combination of parasomniac manifestations (but no more confusional arousals or sleep-related eating disorders), and were less likely to report sexsomnia. In contrast, monthly episode frequency, sleepiness score, sleep structure, and EEG and behavioral markers of NREM parasomnias did not differ between groups. Familial NREM parasomnias have a typical phenotype with an earlier age of onset and a more severe clinical course. This phenotyping may guide medical care and future genetic studies.

To examine the pattern of sedative-hypnotic prescriptions associated with the risk of suicidal behavior among older adults with and without insomnia. The study included 8319 suicide cases and age- and sex-matched controls from the population-wide National Health Insurance Research Database. Suicide methods and insomnia were defined using diagnostic codes. The sedative-hypnotic use pattern was categorized by half-life, prescription volume measured in defined daily doses (DDDs), and its temporal relationship with suicide. Odds ratios were employed to assess the risk of insomnia and the prescription patterns of sedative-hypnotics on suicide. Additionally, we compared suicide methods between sedative-hypnotic users and nonusers. Insomnia was mildly associated with suicide behavior after adjusting for mental illnesses (adjusted relative risk [RR] = 1.82, OR = 1.86, 95% confidence interval [CI] = 1.76 to 1.97), but the prescription of sedative-hypnotics was associated with 5-fold suicide risk (adjusted RR = 5.22, OR = 5.90, 95% CI = 5.11 to 6.82). Among patients with insomnia, a prescription volume of ≥31 DDDs per year and a prescription within 90 days of the suicide index date were associated with increased suicide risk. Individuals prescribed sedative-hypnotics were more likely to commit suicide by methods involving sedative-hypnotic poisoning (21% vs. 0%). Among older adults, sedative-hypnotic prescription is associated with increased suicide risk and suicide by self-poisoning using such medications. Non-pharmacological treatment for insomnia, such as cognitive-behavioral therapy, is essential for suicide prevention.

Although rapid eye movement (REM) sleep is often thought of as a singular state, it consists of two substates, phasic and tonic REM, defined by the presence (respectively absence) of bursts of rapid eye movements. These two substates have distinct EEG signatures and functional properties. However, whether they exhibit regional specificities remains unknown. Using intracranial EEG recordings from 31 patients, we analyzed expert-labeled segments from tonic and phasic REM and contrasted them with wakefulness segments. We assessed the spectral and connectivity content of these segments using Welch’s method to estimate power spectral density and the phase locking value to assess functional connectivity. Overall, we found a widespread power gradient between low and high frequencies (p < 0.05, Cohen’s d = 0.17 ± 0.20), with tonic REM being dominated by lower frequencies (p < 0.01, d = 0.18 ± 0.08), and phasic REM by higher frequencies (p < 0.01, d = 0.18 ± 0.19). However, some regions, such as the occipito-temporal areas as well as medial frontal regions, exhibit opposite trends. Connectivity was overall higher in all bands except in the low and high ripple frequency bands in most networks during tonic REM (p < 0.01, d = 0.08 ± 0.09) compared to phasic REM. Yet, functional connections involving the visual network were always stronger during phasic REM when compared to tonic REM. These findings highlight the spatiotemporal heterogeneity of REM sleep which is consistent with the concept of focal sleep in humans.

Abstract Introduction Sleep loss vulnerability refers to individual differences in susceptibility to performance impairments in responding to sleeplessness. The Iowa Resistance to Sleeplessness Test (iREST) is designed to assess this trait by rating negative consequences in affective, cognitive, and somatic dimensions due to sleep loss. It has been shown to correlate with dysfunctional beliefs, sleep quality and sleepiness in young normal sleepers, suggesting the possibility that sleep loss vulnerability may play a role in the pathology of insomnia. This study evaluates the reliability and validity of the Chinese version of iREST (iREST-C) among patients with insomnia in order to serve as a tool for future study. Methods A total of 119 insomnia patients (F:M = 31:68, age = 33.38 ± 8.41) completed the iREST-C, ISI, and the Ford Insomnia Response to Stress Test (FIRST), with 79 participants retested 1.5 months later. Exploratory Factor Analysis (EFA) was conducted to identify factor structure and Chronbach’s alpha to assess internal consistency. Pearson correlations were used to evaluate test-retest reliability and correlations with the FIRST and ISI. Results EFA revealed that the IREST-C comprises three dimensions: affective, cognitive, and somatic (KMO = 0.895; Bartlett’s test: χ² = 1508.109, p &amp;lt;.001). The items included were the same as the original scale, except that item 13 changed from somatic to affective dimension with a low factor loading (0.410). After excluding item 13, Cronbach’s α coefficient showed good internal consistency (affective: 0.924; cognitive: 0.933; somatic: 0.818). Test-retest reliability showed significant correlations for all subscales (affective: r = 0.475; cognitive: r = 0.477; somatic: r = 0.493) and the total iREST score (r = 0.579, p &amp;lt;.001). Significant correlations were found between the FIRST score and the cognitive (r = -.201, p &amp;lt;.05) and somatic (r =.229, p &amp;lt;.05) subscales of iREST-C, but not the affective subscale. No correlations were obtained between the ISI and iREST-C scores. Conclusion The iREST-C demonstrates good construct validity and test-retest reliability in insomnia patients. Vulnerability to sleep loss is associated with stress-related sleep reactivity but not with insomnia severity, indicating that it may be associated with arousal but not with insomnia directly. Support (if any)

Abstract Introduction Narcolepsy is a chronic neurological disorder that causes debilitating daytime sleepiness among other symptoms. This study compared clinical and humanistic outcomes between those with and without narcolepsy to characterize the extent of disease burden. Methods This study was a retrospective, cross-sectional analysis of 2021/2023 US National Health and Wellness Survey data. The narcolepsy cohort included those who reported a physician diagnosis of narcolepsy. Propensity-score matching (1:3) adjusted for demographic/health characteristics between those with and without narcolepsy (controls). Chi-square tests and t-tests compared comorbidities, symptoms of depression and anxiety, and health-related quality of life (HRQoL) between groups. Results Before matching, respondents with narcolepsy (n=335; female=56%; mean age, 45.5 years; White=68%) and without narcolepsy (n=141,072; female=55%; mean age, 47.8 years; White=72%) were included. Additionally, the narcolepsy cohort had higher mean [SD] body mass index (30.1 [8.4] vs 27.6 [7.1], p&amp;lt;.001) and were more likely to have obesity (44% vs 28%, p&amp;lt;.001) and be current smokers (25% vs 17%, p&amp;lt;.001) than those without narcolepsy. After matching, the narcolepsy cohort reported more frequent physician-diagnosed psychiatric comorbidities vs controls, including depression (58% vs 32%, p&amp;lt;.001), anxiety (54% vs 33%, p&amp;lt;.001), and ADHD (20% vs 6%, p&amp;lt;.001). The narcolepsy cohort had higher reporting of moderate-to-severe depression symptoms via Patient Health Questionnaire-9 (52% vs 33%, p&amp;lt;.001) and moderate-to-severe anxiety via Generalized Anxiety Disorder Questionnaire-7 (41% vs 26%, p&amp;lt;.001). On the Brief Resilience Scale, more respondents with narcolepsy reported low resiliency scale score vs controls (43% vs 28%, p&amp;lt;.001). Compared with controls, the narcolepsy cohort scored lower on HRQoL measures, including mean [SD] mental health composite (32.8 [11.3] vs 40.6 [12.6], p&amp;lt;.001) and physical health composite (35.7 [11.4] vs 42.9 [11.6], p&amp;lt;.001) scores of the RAND 36-Item Health Survey. The narcolepsy cohort reported greater impairment of daily activities vs controls (51% vs 34%, p&amp;lt;.001). Conclusion Narcolepsy is associated with broad clinical and humanistic burden. Those with narcolepsy had more frequent psychiatric comorbidities, more severe depression and anxiety symptoms, less self-reported resiliency, and lower HRQoL. Future strategies should focus on comprehensive management that prioritizes mental health, while investigating new treatments that may improve HRQoL for narcolepsy patients. Support (if any) Alkermes, Inc.

Abstract Introduction Somatization is the manifestation of physical symptoms such as, pain or weakness, and is linked to impaired daytime functioning from poor sleep quality. Pre-injury somatization has been linked to higher concussion symptom scores and prolonged recovery, with worse effects in females. We hypothesized that somatization would be associated with sleep-related daytime dysfunction in women, but not men. Methods Participants included healthy adults (n=30) and individuals with mild traumatic brain injury (mTBI; n=150). Measures were collected from 113 adults (72 females; M age=23.79, SD=6.90, and 41 males; M age=26.88, SD=8.51) at five timepoints following injury (2-weeks, 1-month, 3-months, 6-months, 12-months). Daytime dysfunction was measured using a subscale of the Pittsburgh Sleep Quality Index (higher scores indicated greater sleep-related dysfunction). Somatization was assessed using the Personality Assessment Inventory. Multivariate regression and Pearson correlation analyses were used to examine the relationship between somatization and daytime dysfunction for the group and separately for males and females, controlling for age and time since injury. Results Somatization accounted for 62.3% of the variance in sleep-related daytime dysfunction at two-weeks (R2=0.62,F(2,7)=8.42) post-injury. When evaluated separately by sex, somatization predicted sleep-related daytime dysfunction in females (β=1.11, p=0.04) but not males (β=0.31, p=0.51). At one-month, somatization accounted for 21.9% of the variance in daytime dysfunction (R2=0.219,F(2,18)=3.80). After Bonferroni correction (p=0.042), males trended toward significance (β=1.041, p=0.083) but not females (β=0.57, p=0.33). There were no significant correlations at three-months. At six-months, somatization accounted for 49.5% of the variance in daytime dysfunction (R2=0.495,F(2,17)=10.30). Somatization predicted daytime dysfunction for both females (β=1.540, p&amp;lt; 0.001) and males (β=1.686, p&amp;lt; 0.001). There were no significant correlations at twelve-months post-injury. Conclusion Somatization was strongly associated with sleep-related daytime dysfunction, with notable sex differences at various points following injury. Early post-injury, females with somatization experienced greater sleep-related daytime dysfunction while males demonstrated stronger correlations over time. These findings suggest that females may show the strongest association between sleep-related dysfunction and somatization early in the course of injury, but these effects may be more apparent later in men. Support (if any) W81XWH-12-1-0386

Abstract Introduction Transcranial alternating electrical stimulation (tACS) is non-invasive brain stimulation technique that delivers alternating microcurrent via electrodes. This study aimed to evaluate whether tACS could effectively improve symptoms of insomnia. Methods Participants with insomnia symptoms without meeting the criteria of insomnia disorder were recruited and randomized to 0.5 Hz, 100 Hz, or a sham group. In order to maximize the delivery of intracranial stimulation, a frequency of 10 kHz was used as the carrier frequency. Participants were required to use the device for 30 minutes, twice a day for 6 weeks. The Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index, sleep diary, and actigraphy were administered before and after the intervention. Results Eighty-seven participants (74 females, mean age = 54.15 ± 0.73 years) were randomized and finished the trial. The PSQI score showed significant improvement across all three groups without significant difference between groups (Sham: 9.93 to 6.72, p &amp;lt; 0.001; 0.5 Hz: 9.24 to 6.62, p &amp;lt; 0.001; 100 Hz: 9.34 to 6.93, p = 0.001). In the average sleep diary over four days, sleep latency (SL) and wake after sleep onset (WASO) decreased in all three groups (sham, 0.5 Hz, 100 Hz) without significant group by visit interaction (SL: -5.74 min, -8.94 min, and -16.53 min, respectively, p = 0.345; WASO: -10.74 min, -23.62 min, and -16.73 min, respectively, p = 0.431). No significant improvement in objective sleep measurements was observed in any group. Conclusion The tACS was not more effective than the sham treatment in reducing insomnia symptoms. Future study design should consider the strong placebo effect on sleep and the possibility that high carrier frequencies may confound the original frequencies. Support (if any)

Abstract Introduction Decreased attention is common in pediatric Narcolepsy Type 1 (NT1). However, objective data assessing attention dysfunction in this population are limited. The psychomotor vigilance task (PVT) has been used to measure attention in adults with central disorders of hypersomnolence but understudied in pediatric NT1. In this study, we compare PVT metrics between pediatric NT1 patients and healthy controls (HC) in the evening and morning with a between interval of nocturnal sleep measured by in-lab polysomnography (PSG). We hypothesized that attention dysfunction would be worse in NT1 vs HC in evening and morning and both sessions would be associated with self-reported sleepiness. Methods 28 pediatric NT1 participants (mean age 15.9) and 27 healthy controls (mean age 13.6) completed 3-minute PVT testing in the evening before PSG and upon awakening in the morning. Before each PVT, participants rated their sleepiness on 3-item visual analog scale. We compared PVT metrics between NT1 and HC, adjusting for age (including non-linear effects) and gender. Outcomes included mean 1/reaction time (RT), lapses (RT ≥ 500 ms), lapses355 (RT ≥ 355 ms), and slowest 10% 1/RT. Results NT1 participants showed reduced attention across various PVT metrics vs. HC. In the evening, mean 1/RT was significantly worse in NT1 participants (p =.008) but we found no significant group differences in lapses, lapses355, or slowest 10% 1/RT. In the morning, NT1 participants performed significantly worse than controls on mean 1/RT (p =.002), lapses355 (p &amp;lt;.001), and slowest 10% 1/RT (p =.004). Age but not gender significantly predicted all PVT measures (p &amp;lt;.01). Contrary to our hypothesis, none of the PVT measures were associated with self-reported sleepiness. Conclusion Pediatric NT1 participants exhibit objective and significantly impaired objective attention vs HC. Slower mean reactions times were evident in evening and morning but lapses and slowest reactions times were more evident in the morning. Given that self-reported sleepiness did not predict PVT outcomes, it is possible other narcolepsy features such as disrupted nighttime sleep play contributing roles. Overall, the PVT could be useful for assessing attention in children/adolescents with NT1 in clinical and school based settings. Support (if any) NIH K23 NS104267 (Maski)

Abstract Introduction Obstructive sleep apnea (OSA) is a sleep disorder characterized by recurrent episodes of airway obstruction during sleep. Hypoglossal nerve stimulation (HGNS) is an emerging treatment option for patients who are intolerant to continuous positive airway pressure (CPAP) therapy. Report of case A 62-year-old male with history of generalized anxiety disorder presented to the sleep clinic seeking alternative treatments for OSA. He reported daytime sleepiness, loud snoring, and bruxism. He had previously been intolerant to CPAP due to anxiety and discomfort. A drug-induced sleep endoscopy was performed, confirming the patient as a suitable candidate for HGNS. His initial polysomnography (PSG) revealed an AHI of 50 events per hour, indicating severe OSA. The patient underwent HGNS implantation. Following activation of the device, he reported a significant improvement in sleep quality and increased daytime alertness. A follow-up PSG indicated a reduction in AHI from 50/hr to 11/hr, demonstrating the substantial effectiveness of HGNS therapy. Despite the improvement in AHI, which was now in the mild range, the patient continued to experience persistent snoring and bruxism. An oral examination revealed considerable tooth attrition. The dental team was consulted, leading to the removal of all maxillary teeth. A plan was established to restore the edentulous maxilla with a complete denture. Given the anticipated delay in denture fabrication and persistent bruxism injuring the gums, a custom-fabricated mandibular advancement device (EVO) was created. This unusual approach involved anchoring the device to the maxillary arch, accommodating the patient’s edentulous status. A home sleep apnea test was conducted with the hypoglossal nerve stimulator activated and the oral appliance in place. The result was a reduction in both AHI to 2/hr and bruxism therefore limiting the damage to the upper gums. The combination of HGNS therapy and the custom mandibular advancement device proved effective in managing the patient’s OSA and bruxism. Conclusion HGNS was successfully used in this case to treat severe OSA in a patient who was intolerant to CPAP. The addition of a custom mandibular advancement device in an edentulous patient underscores the adaptability of treatment strategies. The combination therapy emphasizes the importance of personalized and multidisciplinary approaches to treating OSA. Support (if any)

Abstract