SLEEP

ObjectivesChronic insomnia (INS) is particularly prevalent in older adults and females. Sex-and age-related differences in neurophysiological markers of sleep quality (sleep spindles and slow-wave activity [SWA]) may underlie differential vulnerability to INS. This study investigated the effects of sex and insomnia on spindle and SWA beyond aging, to better understand the mechanistic differences contributing to the higher prevalence of INS in females. MethodsAfter a habituation night, one night of sleep assessed with polysomnography was analyzed in 222 adults (aged 18-82) including 119 INS (71% female) and 103 healthy sleepers (HS; 61% female). Spindle density, slow oscillation (SO) density, relative sigma power and SWA were derived during NREM sleep. Age, group, sex, and group-by-sex interactions were examined, with age as a covariate. ResultsAge, insomnia, and sex each contributed uniquely to NREM oscillatory activity. INS primarily reduced spindle and SO density, while sex accounted for differences in SWA. While SWA was higher in females overall, sex differences were not significant within the INS or HS groups. Female INS reported highest rates of insomnia severity as well as lower sigma power than males in the INS group. Spindle and SO density deficits were also present in female INS relative to female HS, as well as male INS relative to male HS. ConclusionsThe combination of reduced sigma power in females with insomnia relative to their male counterparts, as well as less spindle and SO density compared to female healthy sleepers may contribute to greater insomnia severity in females. Statement of SignificanceInsomnia is a growing public health concern that is more commonly reported in females, yet the neural mechanisms underlying this sex difference remain poorly understood. Our findings suggest that specific markers of sleep quality are disproportionately disrupted in females with insomnia, potentially contributing to greater vulnerability and symptom severity. These results provide new insight into how sex influences the neurophysiology of insomnia disorder and identify oscillatory markers that could serve as targets for personalized interventions. Future research should investigate whether these alterations represent persistent dysfunction or reversible changes, which could advance understanding of the biological basis of insomnia and inform strategies to improve sleep health in at-risk populations.

Study ObjectivesAutomated sleep staging underpins clinical sleep assessment and translational neuroscience, yet most data analyses work addresses human and animal data separately. We tested whether a seizure-oriented machine learning framework can be repurposed for three-state sleep staging in humans and rats, and whether models trained solely on rodent data can be applied directly to human recordings using an explicit cross-species montage. MethodsWe used the PySeizure, a standardised EEG preprocessing and seizure-detection framework, together with TinySleepNet as the core classifier. Models were trained and evaluated on the Sleep-EDF expanded Sleep Cassette subset (three classes: wake, non-rapid eye movement sleep, rapid eye movement sleep), then applied without fine-tuning to the Sleep Telemetry subset. The same pipeline was used on a SYNGAP1 rat dataset with analogous three-state labels. A novel human-rat electroencephalography montage mapped rat electrodes to putative human scalp homologues, enabling direct application of rat-trained models to Sleep Cassette. ResultsWithin Sleep Cassette, the accuracy in three-stage sleep classification was 0.95. Applying this model directly to Sleep Telemetry yielded an accuracy of 0.89. On the rodent dataset, accuracy was 0.78. When the rat-trained model was applied directly to Sleep Cassette, accuracy was 0.68. ConclusionsA single deep learning pipeline can support robust three-state sleep staging in humans and rodents and retains meaningful performance under both human cross-subset and rat-to-human transfer without any retraining or fine-tuning. The rat-trained models above-chance performance on human data, achieved without human training samples, shows that rodent-derived representations can contribute directly to human sleep staging when constrained by an anatomically informed montage, linking preclinical rodent recordings and clinical human sleep studies.

INTRODUCTIONLocus coeruleus and glymphatic dysfunction are linked both to Alzheimers disease (AD) and, recently, to infraslow oscillation in sleep spindle (sigma) activity (ISO). Here we hypothesise ISO integrity is a critical link between sleep and AD. METHODSWe analyzed non-rapid eye movement sleep EEG from AD and controls, extracting ISO peak amplitude, intrinsic frequency, and bandwidth from the sigma-power time course. We assessed group differences and correlations with plasma biomarkers (A{beta}42/40, pTau181 and 217, NfL, GFAP). RESULTSISO peak amplitude was significantly reduced in AD, while intrinsic frequency and bandwidth were preserved. ISO peak amplitude positively correlated with A{beta}42/40 ratio, and ISO bandwidth correlated with GFAP and NfL levels, and with lower verbal memory retention. DISCUSSIONSuch selective weakening of ISO in AD is consistent with LC dysfunction and impaired glymphatic cycling. ISO may be a novel mechanism and electrophysiological marker linking sleep microarchitecture to AD pathology.

INTRODUCTIONSleep disturbance is common across the Alzheimers disease (AD) spectrum, yet the structural substrates linking sleep disruption and cognitive decline remain unclear. The hypothalamus regulates sleep-wake function and is affected by AD pathology, but its role across clinical stages is poorly defined. METHODS672 older adults classified as subjective cognitive decline, single- and multi-domain mild cognitive impairment, or probable AD underwent structural MRI. Subjective insomnia measures were available for the full cohort, and 209 underwent polysomnography. Associations between hypothalamic volume, sleep architecture, and cognition were examined. RESULTSHypothalamic volume declined progressively from SCD to MD-MCI and AD, with the greatest reductions in anterior subregions. Smaller hypothalamic volume associated with diminished slow-wave sleep, lower REM sleep in SD-MCI, poorer neuropsychological functions, and moderated the association between hippocampal volume and memory. CONCLUSIONHypothalamic atrophy emerges along the AD continuum, and relates to specific alterations in sleep quality and cognition.

INTRODUCTIONAgitation is a common and burdensome neuropsychiatric symptom in dementia that fluctuates from day to day, but objective tools for short-term risk stratification are limited. We examined whether nocturnal physiological signals from unobtrusive under-mattress sensors predict next-day daytime agitation and whether associations differ for agitation occurrence versus severity. METHODSWe extracted cardiorespiratory, movement, and sleep-proxy features from two long-term care cohorts (N=55; 333 nights) and one external home-monitoring cohort (N=18; 803 nights). A two-part mixed-effects framework was used to model next-day agitation episodes. RESULTSLower nocturnal respiratory rate and greater activity instability independently predicted higher odds of next-day agitation occurrence. Associations were stronger for motor than verbal agitation. Respiration-related predictors were validated externally. Conversely, no nocturnal features significantly predicted agitation severity. DISCUSSIONPassive sleep monitoring identified reproducible, physiologically interpretable markers of next-day agitation occurrence, supporting the potential of under-mattress sensing for short-term risk stratification and more proactive dementia care.

Motor memory retention is impaired in Parkinson's disease (PD), affecting long-term rehabilitation outcomes. It appears that NREM sleep could be beneficial for consolidation processes in PD, and could be leveraged with non-invasive sleep interventions. This study examined the effect of auditory targeted memory reactivation (TMR) during NREM sleep on the retention of a motor sequence learning finger tapping task in 20 PD and 20 healthy older adults (HOA). TMR was applied during a 2-hour nap and its effect on motor retention was post-nap, after 24-hours and with a dual-task. The impact of TMR on sleep electrophysiology was also evaluated. Results showed no effect of TMR on motor retention or dual-tasking, with no difference between the groups. However, the TMR intervention did increase slow-wave density and decreased spindle density in both groups, and slow-wave amplitude during the presentation of the auditory cues was positively associated with performance in HOA. In conclusion, TMR applied during a 2 hour nap did not enhance motor retention, but the changes in sleep physiological features could be linked to a possible underlying effect on memory processing that warrants further investigation.

IntroductionSleep spindles are electroencephalographic elements characteristic of non-rapid eye movement sleep generated by thalamo-cortical interactions. Spindles have been linked to some of the cognitive benefits afforded by sleep and high spindle activity is associated with increased arousal threshold. Here, we demonstrate that targeting the thalamus with Transcranial Electrical Stimulation with Temporal Interference (TES-TI) can enhance spindle activity. Methods46 participants (24 {+/-} 9.5 years; 58.7% F) underwent thalamic TES-TI stimulation during daytime naps. Three stimulation protocols with 15kHz carrier frequency were tested during stage 2 of non-rapid eye movement sleep (N2): fixed difference frequency of 10 Hz (TES15kHz-TI10Hz), difference frequency matched to individual spindle peak (TES15kHz-TIPeak), and no difference frequency (TES15kHz). Spectral power in the spindle (sigma) band and integrated spindle activity (ISA) were compared before and during the stimulation, and across stimulation protocols. ResultsTES15kHz-TI10Hz stimulation was associated with a significant increase in sigma band power ({Delta}[x]STIM-PRE = 0.46 log10{micro}V2, p = 0.0042) and ISA ({Delta}[x]STIM-PRE = 4.064 {micro}V/s, p = 0.030). Cluster-based analysis localized the increase in sigma power across the entire scalp (p = 0.008). Linear mixed effects models showed that both sigma band power and ISA during stimulation increased significantly more in TES15kHz-TI10Hz compared to the other experimental condition. ConclusionsThis study provides evidence supporting the successful use of TES-TI targeting the thalamus to enhance sleep spindle activity. Stimulation at a fixed difference frequency of 10 Hz increased sigma band power and ISA, whereas neither stimulation matched to individual sigma band peak nor TES alone produced comparable effects. These promising results warrant further investigations into the cognitive and clinical impact of TES-TI, a non-invasive neuromodulation tool that can reach deep brain regions. Statement of significanceThis study provides evidence that thalamo-cortical networks, which are central to many physiological and pathological brain activities, can be modulated non-invasively in humans. More specifically, the findings show that transcranial electrical stimulation with temporal interference targeting the thalamus can selectively enhance sleep spindle activity. This work introduces a new strategy for precisely targeting sleep-generating mechanisms regulated by deep brain circuits without surgery or medication. Key next steps include determining whether this increase in spindle activity can positively impact cognition and assessing the translational potential of this approach for clinical populations.

The brain continuously integrates information from the external environment (exteroception) and the internal bodily milieu (interoception). How the balance between these two processing streams shifts across vigilance states with differing levels of environmental responsiveness, however, remains poorly understood. Here, we examined neural responses to external auditory and internal cardiac signals across wakefulness and REM sleep microstates - tonic and phasic REM - which are characterized by progressively reduced responsiveness to external stimulation. High-density EEG was recorded in healthy participants (n=25). Auditory evoked potentials (AEPs) and heartbeat evoked potentials (HEPs) served as indices of exteroception and interoception, respectively, and were compared across vigilance states. AEPs progressively decreased from wakefulness to tonic REM and were most attenuated during phasic REM. In contrast, HEPs were preserved across REM microstates and were enhanced relative to wakefulness, indicating sustained - and even amplified - processing of cardiac signals during REM sleep. To quantify the relative weighting of external and internal signals, we introduce an exteroceptive-interoceptive index, defined as the ratio of auditory to cardiac neural responses. This index decreased systematically across vigilance states, revealing a graded shift from externally oriented processing during wakefulness to internally oriented processing during phasic REM, with tonic REM occupying an intermediate position. Together, these findings demonstrate that while responsiveness to external stimuli diminishes during phasic REM, the brain continues to prioritize physiologically relevant internal signals. The exteroceptive-interoceptive balance may thus provide a novel, mechanistically grounded marker of altered consciousness, particularly informative in contexts where behavioural responsiveness cannot be assessed. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/712081v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@1e46a9borg.highwire.dtl.DTLVardef@112f050org.highwire.dtl.DTLVardef@5f5249org.highwire.dtl.DTLVardef@135cc4_HPS_FORMAT_FIGEXP M_FIG C_FIG

Type 1 narcolepsy (NT1), a disorder caused by the loss of hypocretin/orexin transmission, is characterized by daytime sleepiness and symptoms where Rapid Eye Movement (REM) sleep, a state normally occurring from middle to late in the night, can intermingle with wakefulness. This results in cataplexy and sleep paralysis, episodes of muscle paralysis when awake, or in the generation of dream-like hallucinations and vivid dreaming, periods of visual imagery or sensory experiences that occur while awake, notably when falling asleep (hypnagogic hallucinations) or lingering dreams with over-realistic recall. Using deep learning of nocturnal sleep polysomnography (PSG) signals (EEG, EMG and EOG) applied to sleep stage scoring, we found that NT1 shows abnormally short wake to REM sleep transitions and occurrences of abnormal sleep stages probabilities of wake, REM sleep and N1 (very light NREM) sleep abnormally co-occurs (sleep stage mixing). Interestingly, although presence of these during sleep enables NT1 diagnosis with performances similar to gold standard diagnostic procedure, the multiple sleep latency test (MSLT), the cortical localization of these dissociations remains unclear. In this work, we used electrode specific predictions of sleep stages to explore if these are global or observed at the local cortical level. Surprisingly, although sleep stage mixing was preeminent between REM sleep, N1 and wake across all electrodes, it was found to fluctuate across locations, with stronger fluctuations found in frontal and central locations, notably in the dominant (left) hemisphere. The strongest single discriminator for NT1 was N1-REM stage mixing across central electrodes (C3-C4), showing 4.3-fold higher dissociation in NT1 patients (Cohens d = 0.61). Analysis of sleep stage dissociations across varying time scales revealed that windows lasting several minutes were most predictive of NT1 status, aligning with the duration of clinically reported symptoms of dissociated REM sleep in narcolepsy. Local N1-W-REM sleep dissociations correlated with CSF orexin/hypocretin levels and severity as measured using MSLT. The predominance of stage mixing in frontal and central regions, areas typically associated with executive and motor control, may contribute to the partial preservation of awareness during dissociated REM phenomena. Further, self-reports of hypnagogic hallucinations correlated best with dissociations involving occipital locations, in agreement with its usual visual content. Coherence analysis was also conducted but did not reveal additional insight. These results suggest that orexin deficiency destabilizes REM sleep organization across cortical projection area contributing both to REM sleep dissociation and to abnormal state transitions observed in NT1.

The transition from wake to stable sleep is characterized by multiple neural, physiological, and behavioral changes. How these changes may differ in individuals with difficulties falling asleep such as children with neurodevelopmental conditions is poorly understood. Here, we studied sleep initiation in >2000 nights recorded from 186 children who participated in the Simons Sleep Project (SSP). Data included simultaneous, synchronized recordings of actigraphy, electroencephalography (EEG), photoplethysmography (PPG), and skin temperature. We extracted multiple neural, physiological, and behavioral measures that are known to increase/decrease during the sleep initiation period including EEG delta (1-4Hz) power, movement counts, heart rate (HR), and skin temperature. Transitions from 20 minutes before sleep onset to 40 minutes after sleep onset were modeled with a sigmoid function enabling the quantification of transition timing, speed, and magnitude per measure. Individuals with longer sleep onset latencies (SOL) exhibited smaller increases in EEG delta power and skin temperature as well as smaller decreases in HR and activity counts. These findings indicate that difficulties falling asleep are associated with multiple forms of cortical, physiological, and behavioral hyperarousal that can be measured at home with wearable devices. Importantly, transition magnitudes were key to explaining differences in SOL across participants (26% explained variance) in contrast to transition speed or timing within the sleep initiation period (<13% explained variance). Longer SOL and weaker transitions were particularly prominent in children diagnosed with autism and/or attention deficit hyperactivity disorder (ADHD).

BackgroundInsomnia disorder is a common sleep disturbance characterized by adverse daytime cognitive and emotional impairments, such as repetitive negative thinking and increased psychological distress. Memory control, a key self-regulatory ability to control or inhibit unwanted thoughts and memories, plays an essential role in supporting cognitive functions and emotional well-being. Here, we delineate the neurocognitive mechanisms underlying memory control among individuals with insomnia. Methods41 participants meeting DSM-5 criteria for insomnia disorder and 40 healthy sleepers completed an emotional Think/No-Think task, during which participants either retrieved (Think) or suppressed the retrieval (No-Think) of aversive memories in response to memory cues while electroencephalograms were recorded. ResultsLinear mixed model analyses with age and depression scores as covariates showed that participants with insomnia exhibited impaired memory control abilities, as evidenced by reduced suppression-induced forgetting in memory recall when compared to healthy sleepers. Electrophysiologically, healthy sleepers showed enhanced right prefrontal theta power in retrieval suppression than in retrieval, indicating elevated needs of inhibitory control during memory control. In sharp contrast, this difference was absent among those with insomnia. Notably, the greater the severity of insomnia symptoms, the smaller the retrieval vs. retrieval suppression theta power differences across participants, linking inefficient top-down control of unwanted memories with low sleep qualities. ConclusionIndividuals with insomnia showed impaired memory control of aversive memories and aberrant electrophysiological activities during retrieval suppression. Future research shall investigate the causal relationship between memory control abilities and insomnia symptoms.

Rapid Eye Movement (REM) sleep makes up approximately 20% of sleep in the adult human and is altered in psychiatric and neurodegenerative conditions. REM sleep comprises two substates, during which eye movements do (phasic REM) and do not (tonic REM) occur. Tonic REM makes up 70-90% of REM sleep but its role in regulating brain function, mood and cognition remain underexplored. We investigated how seven nights of insufficient sleep (6 h time in bed), compared to sufficient sleep, alter periodic and aperiodic components of the phasic and tonic REM sleep electroencephalography (EEG), in 542 sleep recordings of 36 young adults. Associations between phasic and tonic REM sleep EEG and mood, cognitive performance, and overnight changes in cortical excitability as indexed by 1/f spectral slopes were assessed. Insufficient sleep predominantly affected tonic REM EEG components, specifically the density of theta, the amplitude, density, and frequency of alpha oscillations and the 1/f slope in the 30 to 45 Hz range. These changes associated with mood and cognitive performances, and with overnight reductions in cortical excitability. These results provide evidence for a role of tonic REM sleep in regulating mood and counteracting cognitive deterioration and excitability changes associated with insufficient sleep.

Isolated/idiopathic rapid-eye-movement (REM)-Sleep Behavior Disorder (iRBD) is characterized by dream enactment behaviors associated with loss of REM atonia. iRBD is in most cases a prodromal synucleinopathy, and emerging evidence suggests associations between RBD and other neurological and psychiatric conditions. In this study, we performed pathway-based polygenic risk score (PRS) and rare variant burden analyses to examine these potential associations. Pathway-specific PRS were constructed from genome-wide association study summary statistics of five neurodegenerative and seven psychiatric traits across 10 biologically relevant pathway categories, including a total of 279 pathways, in 1,573 iRBD cases and 16,022 controls from the International RBD Study Group and UK Biobank. Rare variant burden tests were performed in 1,264 iRBD cases and 2,581 controls. We identified multiple potential pathways indicating shared polygenic risk between RBD and both neurodegenerative and psychiatric disorders. Lewy body diseases and post-traumatic stress disorder had the most shared polygenic risk pathways in neurological and psychiatric disorders, respectively. Two pathways, the serotonin transport pathway and the chaperone-mediated autophagy pathway, showed the strongest association with iRBD, and gene-based rare variants analyses revealed five genes associated with iRBD: GBA1, PLEKHM1, LRP2, P2RX1, and HAP1. Subsequent analysis of these genes in Parkinsons disease and dementia with Lewy bodies replicated several associations. Together, these findings provide novel insights into the shared genetic architecture underlying iRBD, neurodegenerative disorders, and psychiatric traits, with implications for early identification and mechanistic understanding.

Background/ObjectivesElectromyography (EMG), video-polysomnography (vPSG), and wrist actigraphy are each used to develop diagnostic algorithms for Rapid eye movement sleep behavior disorder (RBD). However, the extent to which they capture overlapping versus distinct motor phenomena remains unknown. We evaluated the respective contributions of actigraphy, EMG and vPSG to the measurement of REM-sleep motor activity. MethodsSeventeen adults with RBD (Mount Sinai n = 9; Stanford n = 8) and eight control participants from an open Newcastle dataset underwent vPSG and concomitant wrist actigraphy. Flexor digitorum superficialis EMG activity and video-detected movements were manually scored in 3-second mini epochs. Actigraphy was quantified using an acceleration-magnitude-based activity count model. Statistical and agreement analyses were performed to assess the motor events captured by all three, any two, or by each modality independently during REM sleep. ResultsIn participants with RBD, actigraphy-derived movement load was significantly higher during REM sleep than during non-REM stages, a pattern not observed in control participants. Across 12,941 3-second mini epochs, EMG, actigraphy, and video detected 1,703, 1,613, and 811 motor events, of which 413 were detected concurrently by all three modalities. Pairwise agreement was moderate and increased from EMG-actigraphy ({kappa} = 0.27 {+/-} 0.10) to actigraphy-video ({kappa} = 0.41 {+/-} 0.12) and EMG-video ({kappa} = 0.45 {+/-} 0.15). Of EMG-detected events, 49.0% were also detected by actigraphy; of actigraphy-detected events, 37.2% were detected by EMG and 34.9% by video. Actigraphy activity counts were highest for events detected by all three modalities and lowest for actigraphy-only events. ConclusionActigraphy-measured REM-related motor activity was elevated in RBD but not in controls. EMG, actigraphy, and video captured partially overlapping motor events in RBD patient, with actigraphy showing the highest sensitivity and manually scored video the lowest.

BackgroundPreterm birth is associated with an increased risk for neurodevelopmental impairments, requiring brain monitoring using amplitude-integrated electroencephalography (aEEG). While established tools detect severe dysfunction (e.g., Hellstrom-Westas classification), methods for assessing mild to moderate impairments--such as Burdjalov scoring or expert-based Sleep-Wake Cycle identification--are subjective and require specialized training. Automated neonatal sleep-staging models usually rely on polysomnography from term infants, a resource-intensive method rarely feasible in NICUs, where simplified single-channel aEEG is standard. MethodsaEEG recordings from 40 neurologically healthy neonates (32-42 weeks PMA) were collected and annotated for quiet (QS) and non-quiet sleep (NQS) by an expert clinician. Signals were bandpass filtered, segmented into 30 s epochs, and cleaned using impedance thresholds. 69 temporal, spectral, wavelet, EMG-inspired, and aEEG-envelope features were extracted. The 5 most relevant features were selected for QS/NQS classification using several machine-learning models validated with leave-one-subject-out cross-validation. A partial least squares model was then trained on QS-derived features to predict postmenstrual age and assess correlations with brain maturation. ResultsThe k-Nearest Neighbors (KNN) classifier showed the best QS/NQS discrimination, with mean Cohens{kappa} = 0.69 {+/-} 0.14 for preterm (32-37 weeks PMA) and 0.48 {+/-} 0.21 for term infants. QS-derived features correlated strongly with postmenstrual age (PMA). The PLS model predicted PMA with an average error of 0.88 weeks (MSE = 1.33 weeks, r = 0.91), while the fully automated version using predicted QS segments yielded an error of 1.08 weeks (r = 0.86). ConclusionAutomated QS/NQS detection from single-channel aEEG is feasible in preterm neonates. Despite reduced accuracy in term infants, QS-derived features closely track brain maturation, supporting the potential of aEEG-based models for objective, early detection of neuromaturation delays in preterm infants

Introduction: Sleep-dependent memory consolidation differs by sex and maybe disrupted by Alzheimer disease (AD) risk. Whether sex moderates associations between apolipoprotein E {varepsilon}4(APOE {varepsilon}4) status, non-rapid eye movement (NREM) sleep, and memory remains unclear. Methods: Eighty cognitively unimpaired older adults completed a word-pair memory task with encoding and immediate testing occurring prior to overnight polysomnography with high-density electroencephalography (hdEEG) and delayed recall occurring after sleep. Sleep-memory associations were examined as a function of sex and APOE {varepsilon}4 status. Results: In this sample, a sex by APOE {varepsilon}4 interaction was associated with overnight memory retention, with female carriers exhibiting less overnight forgetting than female non-carriers and male {varepsilon}4 carriers. NREM sleep differed by sex and APOE {varepsilon}4 status and was associated with memory retention in {varepsilon}4 carriers. Discussion: These findings indicate sex-specific, sleep-dependent memory mechanisms associated with genetic AD risk, highlighting sleep as a potential early target for intervention, pending replication in larger samples. This study was not a clinical trial.

Background: Narcolepsy is a debilitating sleep disorder caused by hypocretin deficiency. Aside from its role to induce wakefulness, hypocretin is linked to modulated appetite and metabolism, often resulting in weight gain. Study objectives: We aimed to unravel the comprehensive epidemiological connection between narcolepsy and major cardiometabolic outcomes. Methods: We analyzed cardiovascular and metabolic disease distribution in the FinnGen study. Using longitudinal electronic health records, we assessed associations between narcolepsy, cardiac/metabolic markers, and prescriptions for relevant drugs. Results: Our findings demonstrate significant associations between narcolepsy and metabolic traits (OR [95% CI] = 2.65 [1.81, 3.89]) as well as stroke (OR = 2.36 [1.38, 4.04]). Narcolepsy patients exhibit a less favourable metabolic profile, including higher glucose levels (OR = 1.1143 [1.0599, 1.1715]) and dyslipidaemia. This is supported by increased prescriptions of insulin (OR = 2.269 [1.46, 3.53]), simvastatin (OR = 2.292 [1.59, 3.31]), and metformin (OR = 2.327 [1.66, 3.25]), reflecting high metabolic disturbances. Furthermore, positive associations with antihypertensive and antiplatelet medications were observed, consistent with elevated cardiovascular risk. Conclusion: Taken together, our findings highlight the cardiometabolic burden in narcolepsy. This study enhances understanding of the metabolic and cardiovascular consequences of narcolepsy and offers timely guidance for effective disease control.

BackgroundGrowing evidence suggests that sleep plays an important role in PTSD outcomes, potentially due to its influence on emotional memory consolidation, though these mechanisms remain unknown. This study sought to test the hypotheses that sleep neurophysiology, PTSD status, and sex moderates the degree to which the late positive potential (LPP) mediates memory accuracy for affective visual stimuli. MethodsN = 39 participants (18 female) viewed 75 negative and 75 neutral IAPS images while EEG was recorded. After viewing the images, participants took a two-hour long nap which was followed by a memory assessment. Memory accuracy was measured using d = Z(hit rate) - Z(false alarm rate), where hit rate refers to the proportion of images seen during the memory assessment that are correctly identified as being previously seen, false alarm rate refers to the proportion of images seen during the memory assessment that are incorrectly identified as being previously seen, and Z() is the inverse cumulative distribution function of the standard normal distribution function. ResultsThe early (300 - 1000 ms) and late (1000 - 1500 ms) LPP mediated enhanced discrimination accuracy for emotional compared to neural stimuli (d) (ps < 0.001). The association between the late LPP and d was moderated by sleep such that the association was stronger when participants spent proportionately more time in N3 and REM (p = 0.02). The differences in reactivity between emotional and neutral images for both the early and late LPP were attenuated in PTSD+ individuals vs. controls (ps < 0.001). Despite mediation results showing greater d for emotional compared to neutral stimuli, women showed overall worse memory accuracy for negative compared to neutral stimuli (p < 0.001) whereas men showed no difference (p = 0.64). ConclusionsN3 and REM sleep play a critical role for memory of stimuli that produce large and sustained neural responses. PTSD is marked by a diminished ability to distinguish between negative and neutral information. More research is critical to understand sex effects on emotional memory.

ObjectiveIsolated rapid-eye-movement sleep behavior disorder is a prodromal marker of synucleinopathies. However, most cases remain undiagnosed due to the insufficient predictive value of questionnaires and limited access to confirmatory video-polysomnography. We assessed a two-stage screening strategy combining a brief questionnaire on rapid-eye-movement sleep behavior disorder symptoms and other prodromes with wrist actigraphy across multiple case-control cohorts. MethodsParticipants aged 40-80 without neurodegenerative disease were recruited from five cohorts; all cases were confirmed by video-polysomnography. The questionnaire was administered to 289 participants, and 236 underwent [&ge;]14 nights of home wrist actigraphy. The wearable-based algorithm was built on four movement features (mean motor activity, activity index, short or long immobile bouts, twitch activity). Models were trained with nested cross-validation using XGBoost. ResultsThe full retrospective cohort included 396 participants (99 cases, 297 controls; mean age 64 {+/-} 11; 55% male). The dream enactment question alone achieved an area under the curve of 0.85, which improved to 0.86 using the four-item questionnaire. Actigraphy alone achieved 82% sensitivity and 84% specificity. In the subgroup completing both assessments (75 cases, 54 controls), the two-stage protocol--questionnaire followed by actigraphy--yielded 68% sensitivity and 100% specificity using the dream-enactment question alone, and 73% sensitivity and 100% specificity using the four-item questionnaire. InterpretationA two-stage protocol combining questionnaire and actigraphy demonstrated high specificity and good sensitivity for detecting isolated rapid-eye-movement sleep behavior disorder in this multicenter cohort. This low-cost, scalable strategy is compatible with widely used wearable devices and warrants validation in community-based populations.

Background: Peri-lead edema (PLE) occurs in up to 15% of Deep Brain Stimulation (DBS) cases, can cause morbidity, and its etiology remains unknown. We hypothesized that PLE represents a secondary brain injury modulated by hypoxemia, and that patients with obstructive sleep apnea (OSA) are at elevated risk. Methods: We conducted a retrospective case-control study of 121 Parkinson's disease (PD) patients undergoing DBS at a single center (2019-2024). PLE severity was quantified by CT volumetric segmentation and Hounsfield unit (HU) measures. Perioperative SpO2 and PaO2 were recorded. Polysomnography (PSG) was available in 26 patients; and the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) was administered retrospectively. Results: Symptomatic PLE occurred in 12 patients (9.9%), with onset at 3.5 (2-9) days postoperatively. PLE patients had higher body mass index (p = 0.022) and higher OSA prevalence (75% vs. 30%; p = 0.002). Perioperative SpO2 was lower in the PLE group in both the operating room and post-anesthesia care unit (PACU; p < 0.05); PaO2 was lower in the PACU (p = 0.037). In the PSG subgroup, REM Sleep Behavior Disorder (RBD) incidence was lower in PLE patients (20% vs. 60%; unadjusted p = 0.048), and PLE severity correlated significantly with sleep-related hypoxemia and respiratory indices. RBDSQ scores were positively associated with edema density (normalized HU: rho = 0.86, p = 0.024). Conclusions: OSA and perioperative hypoxemia are associated with symptomatic PLE following DBS, while RBD appears protective. Preoperative sleep evaluation and optimized perioperative airway management warrant prospective investigation as PLE prevention strategies.