Slow Wave Activity Research Articles

A Pilot Study on Video Game Training Effects on Visual Working Memory: Behavioral and Neural Insights

Background/Objectives: Recent research suggests that video games may serve as cognitive training tools to enhance visual working memory (VWM) capacity. However, the effectiveness of game-based cognitive training remains debated, and the underlying neural mechanisms, as well as the relationship between training efficacy and game design factors, are unclear. This study aimed to evaluate the impact of video game training on VWM capacity and explore its neural correlates. Methods: Two groups underwent 56 daily 20 min training sessions with two distinct video games targeting different cognitive skills: a reaction-time training game and a VWM-specific training game. Behavioral assessments included accuracy, hit response times, correct rejection response times, and Cowan’s K values. Neural correlates were measured through Negative Slow Wave (NSW) activity using EEG. Decision tree classification analyses were applied to NSW data across sessions and set sizes to identify patterns linked to VWM capacity. Results: Preliminary results are that both groups showed improvements in behavioral measures (accuracy, response times, and Cowan’s K values). NSW analyses revealed a main effect of set size in both groups, and classification results indicated that NSW patterns differed between groups, across sessions, and set sizes, supporting the relationship between NSW and VWM capacity. Conclusions: These findings contribute to understanding NSW as a neurophysiological correlate of VWM capacity, demonstrating its plasticity through video game training. Simple video games could effectively enhance behavioral and neural aspects of VWM, encouraging their potential as accessible cognitive training tools.

The Use of Magnetoencephalography in the Diagnosis and Monitoring of Mild Traumatic Brain Injuries and Post-Concussion Syndrome

Background/Objectives: The main objective of this systematic review was to explore the role of magnetoencephalography (MEG) in the diagnosis, assessment, and monitoring of mild traumatic brain injury (mTBI) and post-concussion syndrome (PCS). We aimed to evaluate the potential of some MEG biomarkers in detecting subtle brain abnormalities often missed by conventional imaging techniques. Methods: A systematic review was conducted using 25 studies that administered MEG to examine mTBI and PCS patients. The quality of the studies was assessed based on selection, comparability, and outcomes. Studies were analyzed for their methodology, evaluated parameters, and the clinical implications of using MEG for mTBI diagnosis. Results: MEG detected abnormal brain oscillations, including increased delta, theta, and gamma waves and disruptions in functional connectivity, particularly in the default mode and frontoparietal networks of patients suffering from mTBI. MEG consistently revealed abnormalities in mTBI patients even when structural imaging was normal. The use of MEG in monitoring recovery showed significant reductions in abnormal slow-wave activity corresponding to clinical improvements. Machine learning algorithms applied to MEG data demonstrated high sensitivity and specificity in distinguishing mTBI patients from healthy controls and predicting clinical outcomes. Conclusions: MEG provides a valuable diagnostic and prognostic tool for mTBI and PCS by identifying subtle neurophysiological abnormalities. The high temporal resolution and the ability to assess functional brain networks make MEG a promising complement to conventional imaging. Future research should focus on integrating MEG with other neuroimaging modalities and standardizing MEG protocols for clinical use.

Ictal EEG of benign convulsion with mild gastroenteritis with in infants and children.

There are fewer reports on the ictal electroencephalogram(EEG) of convulsions in infants and children with mild gastroenteritis (BCWG). Our study retrospectively analyzed the ictal EEG characteristics of convulsive episodes of BCWG. The seizure-phase EEGs of children diagnosed with BCWG from September 2016 to January 2022 were searched and analyzed, and a total of thirteen seizure-phase EEGs of eight cases were analyzed retrospectively. The age of onset of the disease in the eight children ranged from one year to two years and seven months. No epileptiform discharges were found during the interictal EEG. A total of thirteen epileptic seizures were monitored, of which nine were focal with secondary generalisation. Scalp EEG showed three onset of EEG seizures were in the right occipital region, two were in the right parietal and occipital regions, one was in the right parietal, occipital and posterior temporal region, one was in the right posterior temporal region, one was in the right occipital and posterior temporal region and one was in the right central and central midline region. In addition, four non-convulsive epileptic seizures, which manifested themselves as a decrease in movement and consciousness, with local δ slow-wave activity in bilateral occipital regions evolved to diffuse δ slow wave activity in epileptic seizures. Focal secondary generalised tonic clonic seizures were the main type of seizures in BCWG, and the seizure onset may been mostly in posterior cephalic cortex. It was previously unreported that some children of BCWG may combine with non-convulsive epileptic seizures with the onset of slow wave activity in the occipital region bilaterally and evolving into diffuse δ slow wave activity, which was not easily detected by parents and clinicians.

The influence of transcranial alternating current stimulation on EEG spectral power during subsequent sleep: A randomized crossover study.

To evaluate the instant impact of transcranial alternating current stimulation (tACS) on sleep brain oscillations. Thirty-six healthy subjects were randomly assigned to receive tACS and sham stimulation in a crossover design separated by a one-week washout period. After stimulation, a 2-h nap polysomnography (PSG) was performed to obtain Electroencephalogram (EEG) data and objective sleep variables, and self-reported subjective sleep parameters were collected at the end of the nap. EEG spectral analyses were conducted on the EEG data to obtain the absolute and relative power for each sleep stage during the nap. The associations between power values and objective and subjective measurements were analyzed using Spearman or Pearson correlation coefficients. The tACS group presented higher power in slow wave activity (SWA) and delta frequency bands and lower alpha, sigma and beta power values compared to the sham group during the N2 and N3 sleep stages. SWA and delta power were positively associated with sleep duration and sleep efficiency relevant parameters; while alpha, sigma and beta power were positively associated with prolonged sleep latency and wakefulness related variables. PSG, self-reported and sleep diary measured objective and subjective sleep parameters were comparable between the tACS and the sham groups. Our results support that tACS could promote sleep depth in microstructure of sleep EEG, manifesting as an increase in EEG spectral power in low frequency bands and a decrease in high frequency bands. The registration number of this study is ChiCTR2200063729.

Chronic chemogenetic slow-wave-sleep enhancement in mice.

While epidemiological associations and brief studies of sleep effects in human disease have been conducted, rigorous long-term studies of sleep manipulations and in animal models are needed to establish causation and to understand mechanisms. We have previously developed a mouse model of acute slow-wave-sleep (SWS) enhancement using chemogenetic activation of parafacial zone GABAergic neurons (PZ GABA ) in the parvicellular reticular formation of the pontine brainstem. However, it was unknown if SWS could be enhanced chronically in this model. In the present study, mice expressing the chemogenetic receptor hM3Dq in PZ GABA were administered daily with one of three chemogenetic ligands, clozapine N-oxide (CNO), deschloroclozapine (DCZ) and compound 21 (C21), and sleep-wake phenotypes were analyzed using electroencephalogram (EEG) and electromyogram (EMG). We found that SWS time is increased for three hours, and at the same magnitude for at least six months. This phenotype is associated with an increase of slow wave activity (SWA) of similar magnitude throughout the 6-month dosing period. Interestingly, at the end of the 6-month dosing period, SWA remains increased for at least a week. This study validates a mouse model of chronic SWS enhancement that will allow mechanistic investigations into how SWS promotes physiological function and prevents diseases. The approach of a rotating schedule of three chemogenetic ligands may be broadly applicable in chemogenetic studies that require chronic administration.

Spatiotemporal network dynamics and structural correlates in the human cerebral cortex in vitro.

Elucidating human cerebral cortex function is essential for understanding the physiological basis of both healthy and pathological brain states. We obtained extracellular local field potential recordings from slices of neocortical tissue from refractory epilepsy patients. Multi-electrode recordings were combined with histological information, providing a two-dimensional spatiotemporal characterization of human cortical dynamics in control conditions and following modulation of the excitation/inhibition balance. Slices expressed spontaneous rhythmic activity consistent with slow wave activity, comprising alternating active (Up) and silent (Down) states (Up-duration: 0.08 ± 0.03 s, Down-duration: 2.62 ± 2.12 s, frequency: 0.75 ± 0.39 Hz). Up states propagated from deep to superficial layers, with faster propagation speeds than in other species (vertical: 64.6 mm/s; horizontal: 65.9 mm/s). GABAA blockade progressively transformed the emergent activity into epileptiform discharges, marked by higher firing rates, faster network recruitment and propagation, and infraslow rhythmicity (0.01 Hz). This dynamical characterization broadens our understanding of the mechanistic organization of the human cortical network at the micro- and mesoscale.

Clinical and intracranial electrophysiological signatures of post-operative and post-ictal delirium.

(1) Gain insight into the mechanisms of postoperative delirium (POD). (2) Determine mechanistic overlap with post-ictal delirium (PID). Epilepsy patients undergoing intracranial electrophysiological monitoring can experience both POD and PID, and thus are suitable subjects for these investigations. POD was assessed daily after surgery. PID was assessed following seizures. Resting state data were collected following delirium assessments, during a control period, and during sleep. Slow-wave activity (SWA: 1-4Hz) and resting state functional connectivity were compared between different time points and according to delirium status. POD was present in 6 of 20 participants. Post-operatively, SWA was globally elevated in all participants but highest in POD+participants. POD+participants exhibited altered functional connectivity compared to POD-. These differences persisted even after resolution of delirium. PID was present in 7 of 15 participants and was predicted by seizures involving prefrontal cortex. PID+participants exhibited higher post-ictal SWA versus PID-; no differences in functional connectivity were observed. Post-operative and post-ictal SWA was comparable to sleep in some participants. Elevated SWA may predispose patients to both post-operative and post-ictal delirium and may indicate overlapping mechanisms. Delirium treatments focused on SWA may be most effective for ameliorating cognitive symptoms.

Control of cortical slow oscillations and epileptiform discharges with photoswitchable type 1 muscarinic ligands

Abstract Acetylcholine and the cholinergic system are crucial to brain function, including functions like consciousness and cognition. Dysregulation of this system is implicated in the pathophysiology of neurological conditions, such as Alzheimer’s disease. For this reason, cholinergic neuromodulation is relevant in both basic neuroscience and clinical neurology. In this study, we used photopharmacology to modulate neuronal activity using the novel selective type-1 muscarinic (M1) photoswitchable drugs: the agonist benzyl quinolone carboxylic acid–azo-iperoxo (BAI) and the antagonist cryptozepine-2. Our aim was to investigate the control over these cholinergic receptors by means of light, to investigate the effects of these drugs on the physiological spontaneous slow waves and on epileptic activity in the cerebral cortex. We first used transfected HEK cell cultures and demonstrated BAI's preferential activation of M1 muscarinic acetylcholine receptors (mAChRs) compared to M2 mAChRs. Next, we found that white light illumination of BAI increased the frequency of spontaneous slow wave activity in brain cortical networks of both active slices and anesthetized mice, through M1-mAChRs activation. Illumination of cryptozepine-2 with UV light effectively suppressed not only the muscarinic-induced increase slow waves frequency, but also muscarinic-induced epileptiform discharges. These findings not only shed light on the role of M1 acetylcholine receptors in the cortical network dynamics but also lay the ground for developing advanced light-based pharmacological therapies. Photopharmacology offers the potential for high precision spatiotemporal control of brain networks with high pharmacological specificity in both healthy and disease conditions.

Pharmacological enhancement of slow-wave activity at an early disease stage improves cognition and reduces amyloid pathology in a mouse model of Alzheimer's disease.

Improving sleep in murine Alzheimer's disease (AD) is associated with reduced brain amyloidosis. However, the window of opportunity for successful sleep-targeted interventions, regarding the reduction in pathological hallmarks and related cognitive performance, remains poorly characterized. Here, we enhanced slow-wave activity (SWA) during sleep via sodium oxybate (SO) oral administration for 2 weeks at early (6 months old) or moderately late (11 months old) disease stages in Tg2576 mice and evaluated resulting neuropathology and behavioral performance. We observed that the cognitive performance of 6-month-old Tg2576 mice significantly improved upon SO treatment, whereas no change was observed in 11-month-old mice. Histochemical assessment of amyloid plaques demonstrated that SO-treated 11-month-old Tg2576 mice had significantly less plaque burden than placebo-treated ones, whereas ELISA of insoluble protein fractions from brains of 6-month-old Tg2576 mice indicated lower Aβ-42/Aβ-40 ratio in SO-treated group vs. placebo-treated controls. Altogether, our results suggest that SWA-dependent reduction in brain amyloidosis leads to alleviated behavioral impairment in Tg2576 mice only if administered early in the disease course, potentially highlighting the key importance of early sleep-based interventions in clinical cohorts.

Autosomal dominant intellectual developmental disorder 60 with seizures: a case report

The patient is a 10-month and 21-day-old girl who began to show developmental delays at 3 months of age, with severe language developmental disorders, stereotyped movements, and easily provoked laughter. Physical examination revealed fair skin and a flattened occiput. At 10 months of age, a video electroencephalogram suggested atypical absence seizures, with migrating slow-wave activity observed during the interictal period. Whole exome sequencing of three family members indicated a novel mutation in the AP2M1 gene, c.508C>T (p.R170W), in the patient. A total of six cases of autosomal dominant intellectual developmental disorder 60 with seizures associated with mutations in the AP2M1 gene have been reported both domestically and internationally (including this study). The main clinical features included developmental delays (6 cases), language developmental disorders (5 cases), stereotyped movements (3 cases), a tendency to smile (1 case), and atypical absence seizures (4 cases). Interictal electroencephalograms showed widespread spike waves and spike-slow wave discharges (5 cases), and migrating slow-wave activity (1 case). The c.508C>T (p.R170W) mutation may be a hotspot for mutations in the AP2M1 gene, and its clinical features are similar to those of Angelman syndrome.

Auditory stimulation during deep sleep enhances total slow-wave activity in a young cohort: A feasibility trial.

Cognitive, metabolic and sleep benefits associated with enhancement of sleep slow waves using closed-loop auditory stimulation have been reported in adults but not in adolescents, especially in home settings. Seventeen volunteers (10F/7M; age range: 13-18 years old) participated in a 2-week, single-blind, crossover study. STIM (auditory stimulation ON) and SHAM (auditory stimulation at zero-volume) were each applied for a week (randomized order). Participants used a self-applied, single-electroencephalogram, wearable device at home. An embedded algorithm performed real-time sleep staging, detected slow-wave sleep and delivered auditory tones separated by a 1-s inter-tone interval. After each sleep session, participants completed questionnaires to report sleep quality, sleepiness (Karolinska Sleepiness Scale), and performed tasks to quantify vigilance (Psychomotor Vigilance Task) and working memory (continuous working memory performance task). Sleep architecture, count of microarousals, slow-wave amplitude, total and mean slow-wave activity (electroencephalogram power in the 0.5-4 Hz frequency band) during non-rapid eye movement sleep, sleepiness level, and cognitive performance metrics were compared between STIM and SHAM. The slow-wave amplitude during stimulation, total slow-wave activity and mean slow-wave activity were significantly higher in the STIM condition (+10.7%, +7.38% and + 7.57%). The count of microarousals, and the power in alpha and beta bands were not different between SHAM and STIM. The Pearson correlation between slow-wave activity enhancement and sleep duration (-0.83; p < 1e - 4) suggested a significant decrease in sleep duration proportional to slow-wave activity enhancement. Trending results (p < 0.1) in the STIM condition included higher number of correct continuous working memory performance task responses (+1.01 correct; p = 0.07). This research provides feasibility of auditory stimulation-based slow-wave activity in a young population.

Delta wave MRI - fMRI imaging of electrophysiological activity.

We propose a novel application of MR encephalography (MREG) to detect the frequency spectrum of endogenous slow oscillatory brain activity (delta, <4 Hz)[1]. MREG offers faster image acquisition than conventional fMRI and superior spatial localization than EEG/MEG. MREG was acquired at 0.1 s temporal resolution in a healthy adult during interleaved wakefulness and sleep to demonstrate its capability for detecting delta-band power changes associated with sleep [2] previously demonstrated by electroencephalography (EEG). For each voxel, the brain activity MREG signal was used to compute a spectrogram and whole brain image of delta-band spectral power. Delta-band power was observed to increase during sleep as compared to awake states using measures from MREG voxel-wise spectrograms and sequential whole brain spatial maps of slow wave power. This work introduced an MR technique for measuring brain slow wave activity which is sensitive to changes in the magnitude and frequency of brain activity in sleep.ABBREVIATIONS: MREG: Magnetic resonance encephalography BOLD: Blood oxygen level dependent.

A Workflow for Creating Gastric Computational Models from SPARC Scaffolds

In-silico studies are an ideal medium to model and improve our understanding of the mechanisms underlying gastric motility in health and disease. In this study, a workflow to create computational models of the stomach was developed using SPARC scaffolds. Three anatomically based finite element method (FEM) models of the rat stomach incorporating experimental measurements of muscle layer thickness and fiber orientations across the stomach were developed: (i) 2D (surface) FEM model with no thickness, (ii) 3D (volume) FEM model with a fixed thickness across the longitudinal and circular muscle layers, and (iii) 3D (volume) FEM model with varying thickness across the longitudinal and circular muscle layers. The three FEM models were subsequently used in whole-organ slow wave simulations and the impact of anatomical details on the simulation outcomes was investigated. The 3D FEM model with varying thickness was the most computationally expensive, while the 2D FEM model provided the fastest solution (a 200 s simulation took 8 min vs. 38 h to solve). The spatiotemporal profiles of the slow wave activation and propagation in the three FEM models were in good agreement. The largest temporal difference of 1 s in cellular activation was observed between the 2D FEM model and the varying thickness 3D FEM model in the most distal-stomach regions. These FEM models and developed workflow will be used in in-silico studies to improve our understanding of the structure-function relationship in the stomach and identify the optimal parameters of electrical therapies, an alternative treatment for the motility disorders in the stomach. In addition, the developed workflow can be readily used to generate computational models of other organs using SPARC scaffolds.

MCLAS adaptively rescues disease-specific sleep and wake phenotypes in neurodegeneration

Sleep alterations are hallmarks of prodromal Alzheimer's (AD) and Parkinson's disease (PD), with fundamental neuropathological processes of both diseases showing susceptibility of change upon deep sleep modulation. However, promising pharmacological deep sleep enhancement results are hindered by specificity and scalability issues, thus advocating for noninvasive slow-wave activity (SWA) boosting methods to investigate the links between deep sleep and neurodegeneration. Accordingly, we have recently introduced mouse closed-loop auditory stimulation (mCLAS), which is able to successfully boost SWA during deep sleep in neurodegeneration models. Here, we aim at further exploring mCLAS' acute effect onto disease-specific sleep and wake alterations in AD (Tg2576) and PD (M83) mice. We found that mCLAS adaptively rescues pathological sleep and wake traits depending on the disease-specific impairments observed at baseline in each model. Notably, in AD mice mCLAS significantly increases NREM long/short bout ratio, decreases vigilance state distances by decreasing transition velocities and increases the percentage of cumulative time spent in NREM sleep in the last 3h of the dark period. Contrastingly, in PD mice mCLAS significantly decreases NREM sleep consolidation, by potentiating faster and more frequent transitions between vigilance states, decreases average EMG muscle tone during REM sleep and increases alpha power in WAKE and NREM sleep. Overall, our results indicate that mCLAS selectively prompts an acute alleviation of neurodegeneration-associated sleep and wake phenotypes, by either potentiating sleep consolidation and vigilance state stability in AD or by rescuing bradysomnia and decreasing cortical hyperexcitability in PD. Further experiments assessing the electrophysiological, neuropathological and behavioural long-term effects of mCLAS in neurodegeneration may majorly impact the clinical establishment of sleep-based therapies.

Electrointestinography, ultrasonographic contractility, and borborygmi of the cecum and colon are not altered by a single episode of hand walking exercise in healthy horses.

To evaluate the effect of hand walking exercise on myoelectrical activity and contractility in normal, healthy horses. Prospective experimental design. A convenience sample of 8 horses were randomized to a control or hand walking treatment group; each horse underwent both treatments. After a 30-minute baseline electrointestinography (EIG), horses were stall rested or hand walked for 15 minutes. Electrointestinography was repeated immediately and at 2 hours. Ultrasonography and auscultation monitored cecal and left ventral colon (LVC) contractions during EIG. Electrointestinography spectral analysis obtained dominant frequency (DF), dominant power (DP), total power (TP) frequency distribution, and changes in slow-wave rhythmic activity. The median (IQR) DF in cycles per minute (cpm) was higher for the cecum (2.067 cpm; IQR, 0.633 cpm) compared to the LVC (2.0 cpm; IQR, 0.396 cpm) but was unchanged by either treatment. Cecal DP (0.0086 mV; IQR, 0.0070 mV) was higher than LVC DP (0.0068 mV; IQR, 0.0051 mV) in the hand walking group, but DP and TP were unaffected by either treatment over time. Borborygmi at all time points were unchanged in both treatment groups. Ultrasonographic contractions were similar across time in both treatment groups and correlated with borborygmi (ρ = 0.63). Dominant power did not correlate with contractions or borborygmi (P > .2081). Brief hand walking as a single strategy to increase gastrointestinal motility did not affect contractility or EIG in normal horses. Fasting and stall rest may not represent the spectrum of severity of gastrointestinal stasis observed in clinical cases. This model is directly applicable to horses fasted prior to surgical procedures.

Sleep-related epilepsies in the course of development in childhood

AbstractEpilepsy, as one of the most prevalent neurological diseases in childhood, has a strong reciprocal relationship with sleep. Sleep-associated epilepsy syndromes in childhood are mostly genetic and can be divided into (a) the group of self-limited focal epilepsies of childhood including self-limited epilepsy with autonomic seizures (SeLEAS) and self-limited epilepsy with centrotemporal spikes (SeLECTS) and (b) (non-self-limited) sleep-related hypermotor epilepsy (SHE). Sleep-accentuated (developmental and) epileptic encephalopathies (DEE/EE-SWAS, Landau–Kleffner syndrome [LKS]) are either genetic (possible transition from SeLEAS or SeLECTS) or structural, and they are characterized by continuous bilateral focal or generalized epileptic activity throughout the night with a clinical manifestation of stagnation or regression, in particular of cognition (verbal agnosia in LKS). Epilepsy syndromes with increased seizure frequency after sleep deprivation or with seizures in the transition to awakening include juvenile generalized epilepsy syndromes such as epilepsy with generalized tonic-clonic seizures alone (GTCA) or juvenile myoclonic epilepsy (JME), but also SeLECTS. Sleep is a very active process: Regeneration, reorganization, and consolidation of memory facilitate development and cognitive functioning. Epilepsy can alter sleep architecture and vice versa, which can appear as a vicious circle in epilepsies that are sleep related. Macrostructural elements of sleep such as sleep efficiency, sleep onset latency, wakefulness after sleep onset, REM and non-REM sleep fraction, as well as microstructural sleep elements such as slow-wave activity, slope of slow waves, cyclic alternating pattern (CAP), and physiological sleep figures, are important biomarkers with which to understand clinical symptoms such as cognitive stagnation and regression, to monitor treatment, but also to determine prognostic factors and will be an important tool for future studies.

Spectral Dynamics Prior to Motor Events Differ Between NREM Sleep Parasomnias and Healthy Sleepers.

The umbrella term "Disorders of Arousal" (DoA), encompassing sleepwalking, confusional arousals, and sleep terrors, refers to parasomnias manifesting during non-rapid eye movement (NREM) sleep, commonly thought to arise from an aberrant arousal process. While previous studies have detailed EEG changes linked to DoA episodes, it remains uncertain how these alterations differ from a physiological arousal process. This study directly compared brain activity between DoA episodes and arousals associated with physiological movements (motor arousal) in individuals with DoA and healthy sleepers. Fifty-three adult patients with DoA (25 males, 32.2±15.5years) and 33 control subjects (14 males, 31.4±11.4years) underwent one or more home-EEG recordings. A semiparametric regression model was employed to elucidate the complex relationship between EEG activity across channels, within and across different groups, including motor arousals in DoA (n=169), parasomnia episodes in DoA (n=361), and motor arousals in healthy sleepers (n=137). Parasomnia episodes and motor arousals in both groups were preceded by a diffuse increase in slow-wave activity (SWA) and beta power, and a widespread decrease in sigma power. However, motor arousals in DoA displayed lower beta and central sigma than in healthy sleepers. Within DoA patients, episodes were preceded by lower beta, frontal sigma, and higher SWA than motor arousals. Our findings suggest that the arousal process is altered in DOA patients, and that specific EEG patterns are required for DOA episodes to emerge. These insights will help guide future research into the underlying circuits and objective markers of DOA.

Coexistence of epilepsy or seizure and multiple sclerosis; review of the literature with a single center experience

There is evidence that the inflammatory demyelinating disorder in Multiple Sclerosis (MS) is associated with acute seizures and epilepsy. Additionally, the likelihood of developing epilepsy increases with neurodegeneration. This study aims to reveal the clinical and radiological features of MS-epilepsy/seizure coexistence. Among all patients diagnosed with MS that we followed in our center between April 2002 and July 2023, patients with a single seizure history or diagnosed with epilepsy (MS-seizure/epilepsy) were randomized 1:1 in terms of age and gender with MS patients without a diagnosis of epilepsy or seizures. Clinical (comorbidities, annualized relapse rate, disability, seizures during attacks, initial diagnosis, disease duration, disease-modifying therapies (DMTs), refractory epilepsy, anti-seizure drugs), electroencephalography (EEG) and MRI (lesion localization and new lesion(s)) data were retrospectively evaluated. The mean EDSS was 4.07±2.81. 29.4 % of patients had progressive MS (n = 10). Refractory epilepsy was 52.9 % (n = 18), and SE history was 14.7 % (n = 5). Pathology was detected in 69.7 % (n = 23) of patients in the EEG. The most common slow wave activation was detected in 51.5 % (n = 17). Refractory epilepsy was more common in cases under 45 and patients with lesions in thalamic localization. Lesions in the temporal and thalamic regions and cerebral atrophy were more common in the MS-seizure/epilepsy group. Patients with demyelinating lesions in the temporal and thalamic regions should be questioned more carefully for epilepsy, and an EEG should be performed in case of clinical suspicion. Since thalamus lesions are more common in patients with refractory epilepsy, anti-seizure treatment strategies should be applied more carefully. The presence of atrophy on MRI confirms the link between neurodegeneration processes and the development of epilepsy.

Lavender improves sleep through olfactory perception and GABAergic neurons of the central amygdala

The use of lavender as sleep aid or hypnotic agent can be traced back as early as ancient Romans and Greeks. Yet, objective experimental data on whether and how lavender enhances sleep duration or/and sleep quality remain lacking. We aimed to characterize the sleep-wake regulating effects of lavender in the mouse and to demonstrate the brain targets and neural circuits involved. A self-made precise odor delivery system combined with chronic polysomnographic recordings was employed to assess the sleep-wake effects of inhalation with lavender essential oil (LEO, extracted from lavender) and its different constituents during the light and dark phases in free-moving C57BL/6J mice. Neuroviral labeling, in situ hybridization and pharmacogenetics were combined to identify the neural circuits and targets involved. Finally, an insomniac model of DL-4-Chlorophenylalanine (PCPA)-treated mice was established to examine the sleep-inducing potential of LEO. We found that inhalation of LEO with a concentration at 25.0% during the light (inactive) phase significantly shortened the latency to non-rapid eye movement (NREM) sleep, increased the total amount of NREM sleep at the expense of wakefulness (W), and enhanced cortical EEG slow wave activities, notably delta power spectra density. We further identified linalool, d-limonene, 1,8-cineole, linalyl acetate and terpinene-4-ol as the major effective sleep-promoting monomer components. Importantly, we found that LEO no longer produced any of the above sleep-promoting effect following either nasal injection of zinc sulfate which interrupts the olfactory pathway, or pharmacogenetics silencing of central amygdala GABAergic neurons. Finally, LEO reestablished NREM sleep with short latency in PCPA-treated insomniac mice, effects comparable with those induced by a potent sedative diazepam. We have characterized the quantitative and qualitative sleep-promoting effects of LEO and its effective components via the olfactory pathway and central amygdala GABA neuronal targets. The hypnotic property of LEO is reinforced by its ability to restore sleep in insomnia. Our study thus establishes a neurobiological basis for aromatherapy of sleep disorders using lavender.

Mediating role of obstructive sleep apnea in altering slow-wave activity and elevating Alzheimer’s disease risk: Pilot study from a northern Taiwan cohort

Obstructive sleep apnea is associated with alterations in slow-wave activity during sleep, potentially increasing the risk of Alzheimer's disease. This study investigated the associations between obstructive sleep apnea manifestations such as respiratory events, hypoxia, arousal, slow-wave patterns, and neurochemical biomarker levels. Individuals with suspected obstructive sleep apnea underwent polysomnography. Sleep disorder indices, oxygen metrics, and slow-wave activity data were obtained from the polysomnography, and blood samples were taken the following morning to determine the plasma levels of total tau (T-Tau) and amyloid beta-peptide 42 (Aβ42) by using an ultrasensitive immunomagnetic reduction assay. Subsequently, the participants were categorized into groups with low and high Alzheimer's disease risk on the basis of their computed product Aβ42 ×T-Tau. Intergroup differences and the associations and mediation effects between sleep-related parameters and neurochemical biomarkers were analyzed. Forty-two participants were enrolled, with 21 assigned to each of the low- and high-risk groups. High-risk individuals had a higher apnea-hypopnea index, oxygen desaturation index (≥3%, ODI-3%), fraction of total sleep time with oxygen desaturation (SpO2-90% TST), and arousal index and greater peak-to-peak amplitude and slope in slow-wave activity, with a correspondingly shorter duration, than did low-risk individuals. Furthermore, indices such as the apnea-hypopnea index, ODI-3% and SpO2-90% TST were found to indirectly affect slow-wave activity, thereby raising the Aβ42 ×T-Tau level. Obstructive sleep apnea manifestations, such as respiratory events and hypoxia, may influence slow-wave sleep activity (functioning as intermediaries) and may be linked to elevated neurochemical biomarker levels. However, a longitudinal study is necessary to determine causal relationships among these factors. This research aims to bridge gaps in understanding how obstructive sleep apnea is associated with an elevated risk of Alzheimer's disease, providing valuable knowledge for sleep and cognitive health.