Waking EEG Research Articles

Lennox- Gastaut Syndrome (Childhood Epileptic Encephalopathy) – A Rare Case Report

Lennox-Gastaut syndrome (LGS) is a severe form of childhood epilepsy that is defined by generalized multiple type seizures, slowness of intellectual growth, and a specific EEG disturbance. Children affected may previously had infantile spasms or underlying brain disorder, but the aetiology can be idiopathic or symptomatic. The incidence of secondary epilepsy is higher in developed countries resulting in higher the incidence of disease. Lennox-Gastaut syndrome (LGS) 18 is characterized by multiple seizure types. An axial tonic seizure is the hallmark of LGS. Later on, atypical absence, atonic and myoclonic falls and recurrent status observed. Cognitive and behavioural abnormalities are common. Gastaut syndrome is usually between 2-7 years with a peak onset between 3 to 5 years. The awake EEG record shows 2-to2.5-Hz spike-and-wave and polyspike and wave discharges, which are usually diffuse and maximal bifrontal. The prognosis is unfavourable and only a minority of patients achieves seizure control. Newer antiepileptic drugs (AEDs) like felbamate lamotrigine and topiramate have been found to be useful. Anterior corpus callostomy may reduce seizure frequency in some patients. Astatic seizures preceded by a prominent tonic component are most improved by these procedures in some cases. LGS seizures are often treatment resistant and the long-term prognosis is poor.

Timing and cortical region matter: theta power differences between teenagers affected by Major Depression and healthy controls

In adults affected by Major Depressive Disorder (MDD), most findings point to higher electroencephalographic (EEG) theta power during wake compared to healthy controls (HC) as a potential biomarker aiding the diagnostic process or subgrouping for stratified treatment. Besides these group differences, theta power is modulated by time of day, sleep/wake history, and age. Thus, we aimed at assessing if the time of recording alters theta power in teenagers affected by MDD or HC. Standardized wake EEG power was assessed with high-density EEG in 15 children and adolescents with MDD and in 15 age- and sex-matched HC in the evening and morning. Using a two-way ANOVA, group, time, and their interaction were tested. In patients, the current severity of depression was rated using the Children’s Depression Rating Scale. Broadband EEG power was lower in the morning after sleep, with a significant interaction (group x time) in central regions in the 4-6 Hz range. In MDD relative to HC, theta power was decreased over occipital areas in the evening and increased over frontal areas in the morning. A higher frontal theta power was correlated with more severe depressive mood in the morning but not in the evening. This was a cross-sectional study design, including patients on antidepressant medication. In conclusion, depending on time of recording, region-specific opposite differences of theta power were found between teenagers with MDD and HC. These findings stress the importance of the time of the recording when investigating theta power’s relationship to psychopathology.

Parabrachial nucleus Vglut2 expressing neurons projection to the extended amygdala involved in the regulation of wakefulness during sevoflurane anesthesia in mice.

The parabrachial nucleus (PBN) promotes wakefulness states under general anesthesia. Recent studies have shown that glutamatergic neurons within the PBN play a crucial role in facilitating emergence from anesthesia. Our previous study indicates that vesicular glutamate transporter 2 (vglut2) expression neurons of the PBN extend into the extended amygdala (EA). However, the modulation of PBNvglut2-EA in general anesthesia remains poorly understood. This study aims to investigate the role of PBNvglut2-EA in alterations of consciousness during sevoflurane anesthesia. We first validated vglut2-expressing neuron projections from the PBN to the EA using anterograde tracing. Then, we conducted immunofluorescence staining of c-Fos to investigate the role of the EA involved in the regulation of consciousness during sevoflurane anesthesia. After, we performed calcium fiber photometry recordings to determine the changes in PBNvglut2-EA activity. Lastly, we modulated PBNvglut2-EA activity under sevoflurane anesthesia using optogenetics, and electroencephalogram (EEG) was recorded during specific optogenetic modulation. The expression of vglut2 in PBN neurons projected to the EA, and c-Fos expression in the EA was significantly reduced during sevoflurane anesthesia. Fiber photometry revealed that activity in the PBNvglut2-EA pathway was suppressed during anesthesia induction but restored upon awakening. Optogenetic activation of the PBNvglut2-EA delayed the induction of anesthesia. Meanwhile, EEG recordings showed significantly decreased δ oscillations and increased β and γ oscillations compared to the EYFP group. Furthermore, optogenetic activation of the PBNvglut2-EA resulted in an acceleration of awakening from anesthesia, accompanied by decreased δ oscillations on EEG recordings. Optogenetic inhibition of PBNvglut2-EA accelerated anesthesia induction. Surprisingly, we found a sex-specific regulation of PBNvglut2-EA in this study. The activity of PBNvglut2-EA was lower in males during the induction of anesthesia and decreased more rapidly during sevoflurane anesthesia compared to females. Photoactivation of the PBNvglut2-EA reduced the sensitivity of males to sevoflurane, showing more pronounced wakefulness behavior and EEG changes than females. PBNvglut2-EA is involved in the promotion of wakefulness under sevoflurane anesthesia. Furthermore, PBNvglut2-EA shows sex differences in the changes of consciousness induced by sevoflurane anesthesia.

Machine learning based severity classification of obstructive sleep apnea patients using awake EEG

Obstructive sleep apnea (OSA) is one of the most widespread breathing-based sleep disorders. Previous studies reported daytime sleepiness, mental fatigue, and cognitive decline in patients with OSA. The diagnosis of OSA is done with laborious overnight polysomnography (PSG) recording. This study aims to classify the severity of OSA patients according to the Apnea-Hypopnea Index (AHI) into mild and moderate to-serve groups (AHI ≥ 15) without using recorded signals during sleep, non-PSG signals and investigate the relevant features. For this purpose, 25 OSA patients participated in 3-minute eyes closed resting state EEG session on the following morning of overnight PSG recording. Time, spectral domain, and nonlinear features were extracted from the delta, theta, and alpha subbands’ of EEG signals. Several machine learning algorithms were used to classify patients’ severity. To investigate optimal feature combinations features were grouped according to their types (Time domain/spectral domain and nonlinear), their electrodes (frontal/central/parietal/occipital), and their subbands (delta/theta/alpha). Also, the Relief method was applied to select the most relevant features. A 5-fold cross validation method was used to generalize the model behaviour. Optimal feature combinations were selected according to classifiers' performances that were evaluated by accuracy, sensitivity, specificity, and area under curve (AUC) parameters when feature sets were used as input. The 15 selected features by the Relief method showed the best performances in the K-Nearest Neighbours (K = 5) classifier [accuracy: 93.33 % ± 5.27 %; sensitivity: 92.30 % ± 4.97 %; specificity: 94.14 % ± 4.24 %; AUC:0.98]. The findings establish that awake resting state EEG records might be used as a faster tool to use OSA severity level.

Permutation time irreversibility in sleep electroencephalograms: Dependence on sleep stage and the effect of equal values.

Time irreversibility (TIR) refers to the manifestation of nonequilibrium brain activity influenced by various physiological conditions; however, the influence of sleep on electroencephalogram (EEG) TIR has not been sufficiently investigated. In this paper, a comprehensive study on permutation TIR (pTIR) of EEG data under different sleep stages is conducted. Two basic ordinal patterns (i.e., the original and amplitude permutations) are distinguished to simplify sleep EEGs, and then the influences of equal values and forbidden permutation on pTIR are elucidated. To detect pTIR of brain electric signals, five groups of EEGs in the awake, stages I, II, III, and rapid eye movement (REM) stages are collected from the public Polysomnographic Database in PhysioNet. Test results suggested that the pTIR of sleep EEGs significantly decreases as the sleep stage increases (p<0.001), with the awake and REM EEGs demonstrating greater differences than others. Comparative analysis and numerical simulations support the importance of equal values. Distribution of equal states, a simple quantification of amplitude fluctuations, significantly increases with the sleep stage (p<0.001). If these equalities are ignored, incorrect probabilistic differences may arise in the forward-backward and symmetric permutations of TIR, leading to contradictory results; moreover, the ascending and descending orders for symmetric permutations also lead different outcomes in sleep EEGs. Overall, pTIR in sleep EEGs contributes to our understanding of quantitative TIR and classification of sleep EEGs.

Effect of daridorexant on sleep architecture in patients with chronic insomnia disorder: a pooled post hoc analysis of two randomized phase 3 clinical studies.

Post hoc analysis to evaluate the effect of daridorexant on sleep architecture in people with insomnia, focusing on features associated with hyperarousal. We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). We analyzed sleep-wake transition probabilities, EEG spectra, and sleep spindle properties including density, dispersion, and slow oscillation phase coupling. The wake EEG similarity index (WESI) was determined using a machine learning algorithm analyzing the spectral profile of the EEG. At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities (p < .05) and increased the probability of transitions from wake-to-N1 (p < .05), N2 (p < .05), and REM sleep (p < .05), as well as from N1-to-N2 (p < .05) compared to baseline and placebo. Daridorexant 50 mg decreased relative beta power during wake (p = .011) and N1 (p < .001) compared to baseline and placebo. During the wake, relative alpha power decreased (p < .001) and relative delta power increased (p < .001) compared to placebo. Daridorexant did not alter EEG spectra bands in N2, N3, and REM stages or in sleep spindle activity. Daridorexant decreased the WESI score during wake compared to baseline (p = .004). Effects with 50 mg were consistent between months 1 and 3 and less pronounced with 25 mg. Daridorexant reduced EEG features associated with hyperarousal as indicated by reduced wake-to-wake transition probabilities and enhanced spectral features associated with drowsiness and sleep during wake and N1. ClinicalTrials.gov NCT03545191: study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder. URL: Study Details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder | ClinicalTrials.gov ClinicalTrials.gov NCT03575104:study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping. URL: study details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping | ClinicalTrials.gov.

The arousal effect of An-Gong-Niu-Huang-Wan on alcoholic-induced coma rats: A research based on EEG

Ethnopharmacological relevanceAcute alcohol intoxication is one of the leading causes of coma. A well-regarded Chinese herbal formula, known as An-Gong-Niu-Huang-Wan (AGNHW), has garnered recognition for its efficacy in treating various brain disorders associated with impaired consciousness, including acute alcohol-induced coma. Despite its clinical effectiveness, the scientific community lacks comprehensive research on the mechanistic aspects of AGNHW’s impact on the electroencephalogram (EEG) patterns observed during alcohol-induced coma. Gaining a deeper understanding of AGNHW’s mechanism of action in relation to EEG characteristics would hold immense importance, serving as a solid foundation for further advancing its clinical therapeutic application. Aim of the studyThe study sought to investigate the impact of AGNHW on EEG activity and sleep EEG patterns in rats with alcoholic-induced coma. Materials and methodsA rat model of alcohol-induced coma was used to examine the effects of AGNHW on EEG patterns. Male Sprague-Dawley rats were intraperitoneally injected with 32% ethanol to induce a coma, followed by treatment with AGNHW. Wireless electrodes were implanted in the cortex of the rats to obtain EEG signals. Our analysis focused on evaluating alterations in the Rat Coma Scale (RCS), as well as assessing changes in the frequency and distribution of EEG patterns, sleep rhythms, and body temperature subsequent to AGNHW treatment. ResultsThe study found a significant increase in the δ-band power ratio, as well as a decrease in RCS scores and β-band power ratio after modeling. AGNHW treatment significantly reduced the δ-band power ratio and increased the β-band power ratio compared to naloxone, suggesting its superior arousal effects. The results also revealed a decrease in the time proportion of WAKE and REM EEG patterns after modeling, accompanied by a significant increase in the time proportion of NREM EEG patterns. Both naloxone and AGNHW effectively counteracted the disordered sleep EEG patterns. Additionally, AGNHW was more effective than naloxone in improving hypothermia caused by acute alcohol poisoning in rats. ConclusionOur study provides evidence for the arousal effects of AGNHW in alcohol-induced coma rats. It also suggests a potential role for AGNHW in regulating post-comatose sleep rhythm disorders.

Effect of Atypical Sleep EEG Patterns on Weaning From Prolonged Mechanical Ventilation

Approximately one-third of acute ICU patients display atypical sleep patterns that cannot be interpreted by using standard EEG criteria for sleep. Atypical sleep patterns have been associated with poor weaning outcomes in acute ICUs. Do patients being weaned from prolonged mechanical ventilation experience atypical sleep EEG patterns, and are these patterns linked with weaning outcomes? EEG power spectral analysis during wakefulness and overnight polysomnogram were performed on alert, nondelirious patients at a long-term acute care facility. Forty-four patients had been ventilated for a median duration of 38days at the time of the polysomnogram study. Eleven patients (25%) exhibited atypical sleep EEG. During wakefulness, relative EEG power spectral analysis revealed higher relative delta power in patients with atypical sleep than in patients with usual sleep (53%vs41%; P< .001) and a higher slow-to-fast power ratio during wakefulness: 4.39 vs2.17 (P< .001). Patients with atypical sleep displayed more subsyndromal delirium (36%vs6%; P= .027) and less rapid eye movement sleep (4%vs11%total sleep time; P< .02). Weaning failure was more common in the atypical sleep group than in the usual sleep group: 91%vs45%(P= .013). This study provides the first evidence that patients in a long-term acute care facility being weaned from prolonged ventilation exhibit atypical sleep EEG patterns that are associated with weaning failure. Patients with atypical sleep EEG patterns had higher rates of subsyndromal delirium and slowing of the wakeful EEG, suggesting that these two findings represent a biological signal for brain dysfunction.

Inactivation of hypocretin receptor-2 signaling in dopaminergic neurons induces hyperarousal and enhanced cognition but impaired inhibitory control

Hypocretin/Orexin (HCRT/OX) and dopamine (DA) are both key effectors of salience processing, reward and stress-related behaviors and motivational states, yet their respective roles and interactions are poorly delineated. We inactivated HCRT-to-DA connectivity by genetic disruption of Hypocretin receptor-1 (Hcrtr1), Hypocretin receptor-2 (Hcrtr2), or both receptors (Hcrtr1&2) in DA neurons and analyzed the consequences on vigilance states, brain oscillations and cognitive performance in freely behaving mice. Unexpectedly, loss of Hcrtr2, but not Hcrtr1 or Hcrtr1&2, induced a dramatic increase in theta (7–11 Hz) electroencephalographic (EEG) activity in both wakefulness and rapid-eye-movement sleep (REMS). DAHcrtr2-deficient mice spent more time in an active (or theta activity-enriched) substate of wakefulness, and exhibited prolonged REMS. Additionally, both wake and REMS displayed enhanced theta-gamma phase-amplitude coupling. The baseline waking EEG of DAHcrtr2-deficient mice exhibited diminished infra-theta, but increased theta power, two hallmarks of EEG hyperarousal, that were however uncoupled from locomotor activity. Upon exposure to novel, either rewarding or stress-inducing environments, DAHcrtr2-deficient mice featured more pronounced waking theta and fast-gamma (52–80 Hz) EEG activity surges compared to littermate controls, further suggesting increased alertness. Cognitive performance was evaluated in an operant conditioning paradigm, which revealed that DAHcrtr2-ablated mice manifest faster task acquisition and higher choice accuracy under increasingly demanding task contingencies. However, the mice concurrently displayed maladaptive patterns of reward-seeking, with behavioral indices of enhanced impulsivity and compulsivity. None of the EEG changes observed in DAHcrtr2-deficient mice were seen in DAHcrtr1-ablated mice, which tended to show opposite EEG phenotypes. Our findings establish a clear genetically-defined link between monosynaptic HCRT-to-DA neurotransmission and theta oscillations, with a differential and novel role of HCRTR2 in theta-gamma cross-frequency coupling, attentional processes, and executive functions, relevant to disorders including narcolepsy, attention-deficit/hyperactivity disorder, and Parkinson’s disease.

Optimal duration for recording EEG in children and adolescents- a prospective interventional study

PurposeThis study aimed to determine the proportion of EEG recordings yielding diagnostic findings leading to a change in diagnosis beyond a 20-minute recording window, striking a balance between diagnostic yield and clinical practicability. MethodsAt a tertiary care teaching hospital in North India, 225 subjects aged 1 month to 18 years undergoing outpatient EEG were enrolled. Patients with epileptic encephalopathies, nonepileptic phenomena, and breakthrough seizures in the last 24 hours were excluded. Two recording protocols were employed: Category A (n=163, awake recording with activation procedures for 15 minutes followed by an attempt at sleep for 60 minutes) and Category B (n=62, sleep recording for 55 minutes followed by 5 minutes of awake recording for younger children and those with impaired cognition). EEGs were prospectively reported at 20, 30, 40, 50, and 60-minute time points, with no retrospective changes allowed. ResultsAmong abnormal EEGs, the final diagnosis was changed beyond 20 minutes in 38.9% and 20.4% in categories A and B, respectively.A significant change in the final diagnosis among abnormal EEGs beyond 20 minutes was seen in- those who achieved sleep compared to those who didn't (45% versus 19%, p=0.03) in category A, and- focal compared to generalised seizures (Category A: 26.1% versus 8.3%, p=0.01; Category B: 23.8% versus 0%, p=0.02). ConclusionForty minutes of awake EEGs with/without sleep and 30 minutes of sleep EEGs achieve a final diagnosis in nearly 90%. Prolonging awake records beyond 20 minutes, incorporating sleep, is particularly beneficial in focal epilepsies.

Preoperative electroencephalographic alpha-power changes with eyes opening are associated with postoperative attention impairment and inattention-related delirium severity

BackgroundIn the eyes-closed, awake condition, EEG oscillatory power in the alpha band (7–13 Hz) dominates human spectral activity. With eyes open, however, EEG alpha power substantially decreases. Less alpha attenuation with eyes opening has been associated with inattention; thus, we analysed whether reduced preoperative alpha attenuation with eyes opening is associated with postoperative inattention, a delirium-defining feature. MethodsPreoperative awake 32-channel EEG was recorded with eyes open and eyes closed in 71 non-neurological, noncardiac surgery patients aged ≥ 60 years. Inattention and other delirium features were assessed before surgery and twice daily after surgery until discharge. Eyes-opening EEG alpha-attenuation magnitude was analysed for associations with postoperative inattention, primarily, and with delirium severity, secondarily, using multivariate age- and Mini-Mental Status Examination (MMSE)-adjusted logistic and proportional-odds regression analyses. ResultsPreoperative alpha attenuation with eyes opening was inversely associated with postoperative inattention (odds ratio [OR] 0.73, 95% confidence interval [CI]: 0.57, 0.94; P=0.038). Sensitivity analyses showed an inverse relationship between alpha-attenuation magnitude and inattention chronicity, defined as ‘never’, ‘newly’, or ‘chronically’ inattentive (OR 0.76, 95% CI: 0.62, 0.93; P=0.019). In addition, preoperative alpha-attenuation magnitude was inversely associated with postoperative delirium severity (OR 0.79, 95% CI: 0.65, 0.95; P=0.040), predominantly as a result of the inattention feature. ConclusionsPreoperative awake, resting, EEG alpha attenuation with eyes opening might represent a neural biomarker for risk of postoperative attentional impairment. Further, eyes-opening alpha attenuation could provide insight into the neural mechanisms underlying postoperative inattention risk.

Impact of an Interactive, Animation-Based Electroencephalography Curriculum on Learner Confidence and Knowledge

BackgroundThere is a national need for innovative electroencephalography (EEG) education with efficacy evaluated by rigorous statistical analysis. We created a dynamic, online resource that includes a series of animated videos at a single academic medical center. MethodsFor the animations and interactive module, we used VideoScribe and Articulate, respectively. The module comprised three chapters: (1) Origin & Technical Aspects of EEG, (2) Normal Adult EEG in Wakefulness & Sleep, and (3) Abnormal EEG, with appendices on artifacts, variants, activation procedures, seizure/epilepsy classification, and neonatal/pediatric EEG. The curriculum and knowledge assessments were reviewed independently by two fellowship-trained physicians before distribution. Linear mixed-effects models with bootstrapping were used to compare paired pre- and post-tests as well as Likert scale questionnaires. ResultsForty-nine learners participated in the pretest survey; 38 matched participants completed post-tests (78%). Learners across fields perceived benefit (100% would recommend to colleagues), indicated improved self-efficacy (P < 0.0001), and performed better on post-test knowledge assessments (54.1 vs 88.2%, P < 0.0001). In the neurology providers subgroup (n = 20), pretest scores correlated with years in training (Spearman r = 0.52, P = 0.039), neurology rotations (r = 0.70, P = 0.003), epilepsy/EEG rotations (r = 0.6, P = 0.014), and EEG teaching hours (r = 0.62, P = 0.01); content knowledge and self-efficacy improvement for neurology providers remained significant in a multivariate model adjusting for these covariates. ConclusionsThis animation-based, interactive EEG module proved effective in elevating learner confidence and knowledge across several medical specialties and training levels. Further study across institutions and subspecialties is needed to substantiate broad applicability, but our data appear promising for early EEG learners.

Comparison of sleep and wake EEG biomarkers in mild cognitive impairment and Alzheimer’s disease

AbstractBackgroundEEG slowing, a biomarker of cognitive decline in Alzheimer’s disease (AD), has been reported in wake or sleep EEG [1,2,3]. However, the relation between wake and sleep EEG and their comparative sensitivity to early stage of cognitive decline is less understood. In this study we compared sleep and wake EEG biomarkers using a common set of endpoints.MethodsParticipants included individuals with mild cognitive impairment (MCI, n = 30, ages 53‐88), Alzheimer’s disease dementia (ADem, n = 15, ages 60‐84), and controls with normal cognition (HC, n = 55, ages 50‐84). Twenty‐channel resting‐state EEG with eyes‐closed was collected during 5‐minutes of wakefulness (STAT X24). Sleep EEG recordings from AF7‐AF8 were collected in‐home and staged using Sleep ProfilerTM. Power spectral densities (PSD) and the derived Theta‐Alpha ratios were computed for wake EEG sites (counterpart bipolar montage), with the wake FP1‐FP2 compared by stage to the sleep EEG at AF7‐AF8. Significant differences in Theta‐Alpha ratios between MCI or ADem vs. HC groups were identified using independent t‐test (p&lt;0.05) with the normalized effect size measured using Hedges‐g (E.S.).ResultsCorrelation coefficients between wake Alpha, Theta power and non‐REM sleep were: r = 0.83, 0.75 for stage N1, r = 0.71, 0.66 for stage N2, and r = 0.55, 0.50 for stage N3. Based on the frontal Theta‐Alpha ratios, the ADem group showed significant EEG slowing during both wake (E.S. = 0.73) and sleep (E.S. = 1.65, 1.31, 0.61, 1.71 for N1, N2, N3, and REM) as compared to the HC, while MCI group only exhibited EEG slowing during sleep (E.S. = 0.56, 0.77, 0.51 for N1, N2 and REM). Temporal (T5‐T6) wake EEG manifested significant slowing in both ADem (E.S. = 1.21) and MCI (E.S. = 0.56) groups. Compared to the HC, ADem patients exhibited significantly less sleep time (E.S. = 0.91, p = 0.002) and less stage REM (E.S. = 1.0, p = 0.001).ConclusionsCognitive decline in the AD spectrum is associated with common signatures in both sleep and wake EEG. However, the magnitude of these effects and their spatial distribution may be different in sleep versus wakefulness. These findings support a multi modal approach to neurophysiological assessment using both sleep and wakefulness data.

Macro and microarchitectural features of sleep in Alzheimer’s dementia and mild cognitive impairment in a large clinical cohort

AbstractBackgroundRecent work has characterized polysomnographic changes in Alzheimer’s Dementia (AD) that correlate with disease severity and precede clinical diagnosis. However, relatively small sample sizes and a paucity of studies examining sleep microarchitecture have been limitations. In this study we examined sleep micro‐ and microarchitectural features in large cohorts of patients with AD and mild cognitive impairment (MCI).MethodUsing a database of over 15,000 clinical PSGs with associated clinical metadata, 125 and 173 subjects were identified with mild AD and MCI, respectively. 260 age and sex matched subjects without neurological disease were identified as healthy controls (HC). Sleep staging results were based on AASM criteria, and micro‐architectural features were assessed using an algorithm trained to predict wake (1) or sleep (0) using spectral data from 3 seconds of EEG from a unique healthy adult cohort (Wake EEG Similarity Index, WESI).ResultSleep fragmentation was apparent in both the MCI and AD cohorts (relative to healthy controls), with AD subjects demonstrating significantly more severe PSG disturbances. Healthy controls demonstrated 400 minutes of total sleep time, in contrast to 374 minutes for MCI subjects and 362 minutes for healthy controls. Healthy subjects demonstrated 33 minutes of wake after sleep onset (WASO), compared to 60 and 67 minutes for MCI and AD subjects, respectively. As has been previously reported in smaller cohorts, wakeful bouts and N1 durations were significantly prolonged for AD and (to a lesser extent) MCI subjects, while N2, N3, and REM durations were reduced (with a pronounced reduction in AD N3 percentage). Sleep microarchitectural features assessed using WESI demonstrated that AD and MCI subjects had markedly higher relative wakefulness in all sleep stages except for N3, which showed the same sleep depth as HC.ConclusionWe confirm increased sleep fragmentation and loss of deeper sleep stages, correlating to disease severity. Spectral features of all sleep stages EXCEPT N3 appear more wakeful in AD and MCI subjects ‐ suggesting microarousals or impaired sleep maintenance contribute to sleep pathology. While N3 duration was markedly reduced, depth of sleep was comparable between populations. PSG findings offer promise as early diagnostic and therapeutic targets.

How the Spreading and Intensity of Interictal Epileptic Activity Are Associated with Visuo-Spatial Skills in Children with Self-Limited Focal Epilepsy with Centro-Temporal Spikes.

This paper investigates brain-behaviour associations between interictal epileptic discharges and cognitive performance in a population of children with self-limited focal epilepsy with centro-temporal spikes (SeLECTS). Sixteen patients with SeLECTS underwent an extensive neuropsychological assessment, including verbal short-term and episodic memory, non-verbal short-term memory, attentional abilities and executive function. Two quantitative EEG indices were analysed, i.e., the Spike Wave Index (SWI) and the Spike Wave Frequency (SWF), and one qualitative EEG index, i.e., the EEG score, was used to evaluate the spreading of focal SW to other parts of the brain. We investigated associations between EEG indices and neuropsychological performance with non-parametric Spearman correlation analyses, including correction for multiple comparisons. The results showed a significant negative correlation between (i) the awake EEG score and the Block Tapping Test, a visuo-spatial short-term memory task, and (ii) the sleep SWI and the Tower of London, a visuo-spatial planning task (pcorr < 0.05). These findings suggest that, in addition to the usual quantitative EEG indices, the EEG analysis should include the qualitative EEG score evaluating the spreading of focal SW to other parts of the brain and that neuropsychological assessment should include visuo-spatial skills.

Hippocampal injections of soluble amyloid-beta oligomers alter electroencephalographic activity during wake and slow-wave sleep in rats

BackgroundSoluble amyloid-beta oligomers (Aβo) begin to accumulate in the human brain one to two decades before a clinical diagnosis of Alzheimer’s disease (AD). The literature supports that soluble Aβo are implicated in synapse and neuronal losses in the brain regions such as the hippocampus. This region importantly contributes to explicit memory, the first type of memory affected in AD. During AD preclinical and prodromal stages, people are also experiencing wake/sleep alterations such as insomnia (e.g., difficulty initiating sleep, decreased sleep duration), excessive daytime sleepiness, and sleep schedule modifications. In addition, changes in electroencephalographic (EEG) activity during wake and sleep have been reported in AD patients and animal models. However, the specific contribution of Aβo to wake/sleep alterations is poorly understood and was investigated in the present study.MethodsChronic hippocampal injections of soluble Aβo were conducted in male rats and combined with EEG recording to determine the progressive impact of Aβ pathology specifically on wake/sleep architecture and EEG activity. Bilateral injections were conducted for 6 consecutive days, and EEG acquisition was done before, during, and after Aβo injections. Immunohistochemistry was used to assess neuron numbers in the hippocampal dentate gyrus (DG).ResultsAβo injections did not affect the time spent in wakefulness, slow wave sleep (SWS), and paradoxical sleep but altered EEG activity during wake and SWS. More precisely, Aβo increased slow-wave activity (SWA; 0.5–5 Hz) and low-beta activity (16–20 Hz) during wake and decreased theta (5–9 Hz) and alpha (9–12 Hz) activities during SWS. Moreover, the theta activity/SWA ratio during wake and SWS was decreased by Aβo. These effects were significant only after 6 days of Aβo injections and were found with alterations in neuron counts in the DG.ConclusionsWe found multiple modifications of the wake and SWS EEG following Aβo delivery to the hippocampus. These findings expose a specific EEG signature of Aβ pathology and can serve the development of non-invasive and cost-effective markers for the early diagnosis of AD or other amyloid-related diseases.

A comparative study of EEG findings among subjects in seizure-remission and patients with epilepsy in a resource constrained west African psychiatric hospital.

Background: Epilepsy is one of the commonest chronic neurological disorders, most especially in developing countries of the World. Again, electroencephalography (EEG) is an important investigation in epileptology and more so in monitoring seizure remission. Thus, in a resource constrained country like Nigeria, our study aimed to determine the epileptiform activities using routine EEG recordings on subjects in seizure remission compared to those subjects with active seizures.&#x0D; Methods: In our study, and following ethical approval, standard EEG recording was carried out on convenient samples of equal number (131) of subjects with active seizure and those in seizure remission using the “Neurofax” Electroencephalography, EEG-1200 (R) machine. The EEG machine was used to carry out an awake 22-channel EEG scalp recording on each subject.&#x0D; Results: Among subjects with active seizures, the mean duration of seizure was 2.80±2.44 years, with range of 0.5 to 12.0 years. For subjects in seizure remission (SSR), the mean duration of remission was 2.41±1.03 years, with range of 1 to 5 years. Out of the 131 subjects with seizure, 37 (28.3%) had normal EEG recording; and 94 (71.7%) had abnormal EEG recordings with various forms of epileptiform activities. On the other hand, of the 131 subjects in seizure remission (SSR), nearly half, 62 (47.3%) had normal EEG recording and 69(52.7%) had abnormal (epileptiform activities) recording. The difference in these EEG findings between the two study groups was significant with F=19.29, p=0.00*; t=-2.22,&#x0D; p=0.028*; and 95% Confidence Interval, CI=-0.70 to -0.40.&#x0D; Conclusion: In addition to clinical evaluation, routine EEG recording can be used to monitor seizure remission in resource constrained countries such as Nigeria.

A genetic variation in the adenosine A2A receptor gene contributes to variability in oscillatory alpha power in wake and sleep EEG and A1 adenosine receptor availability in the human brain

The EEG alpha rhythm (∼ 8–13 Hz) is one of the most salient human brain activity rhythms, modulated by the level of attention and vigilance and related to cerebral energy metabolism. Spectral power in the alpha range in wakefulness and sleep strongly varies among individuals based on genetic predisposition. Knowledge about the underlying genes is scarce, yet small studies indicated that the variant rs5751876 of the gene encoding A2A adenosine receptors (ADORA2A) may contribute to the inter-individual variation. The neuromodulator adenosine is directly linked to energy metabolism as product of adenosine tri-phosphate breakdown and acts as a sleep promoting molecule by activating A1 and A2A adenosine receptors. We performed sleep and positron emission tomography studies in 59 healthy carriers of different rs5751876 alleles, and quantified EEG oscillatory alpha power in wakefulness and sleep, as well as A1 adenosine receptor availability with 18F-CPFPX. Oscillatory alpha power was higher in homozygous C-allele carriers (n = 27, 11 females) compared to heterozygous and homozygous carriers of the T-allele (n(C/T) = 23, n(T/T) = 5, 13 females) (F(18,37) = 2.35, p = 0.014, Wilk's Λ = 0.487). Furthermore, a modulatory effect of ADORA2A genotype on A1 adenosine receptor binding potential was found across all considered brain regions (F(18,40) = 2.62, p = 0.006, Wilk's Λ = 0.459), which remained significant for circumscribed occipital region of calcarine fissures after correction for multiple comparisons. In female participants, a correlation between individual differences in oscillatory alpha power and A1 receptor availability was observed. In conclusion, we confirmed that a genetic variant of ADORA2A affects individual alpha power, while a direct modulatory effect via A1 adenosine receptors in females is suggested.

Dusk2Dawn: an EEGLAB plugin for automatic cleaning of whole-night sleep electroencephalogram using Artifact Subspace Reconstruction.

Whole-night sleep electroencephalogram (EEG) is plagued by several types of large-amplitude artifacts. Common approaches to remove them are fraught with issues: channel interpolation, rejection of noisy intervals, and independent component analysis are time-consuming, rely on subjective user decisions, and result in signal loss. Artifact Subspace Reconstruction (ASR) is an increasingly popular approach to rapidly and automatically clean wake EEG data. Indeed, ASR adaptively removes large-amplitude artifacts regardless of their scalp topography or consistency throughout the recording. This makes ASR, at least in theory, a highly-promising tool to clean whole-night EEG. However, ASR crucially relies on calibration against a subset of relatively clean "baseline" data. This is problematic when the baseline changes substantially over time, as in whole-night EEG data. Here we tackled this issue and, for the first time, validated ASR for cleaning sleep EEG. We demonstrate that ASR applied out-of-the-box, with the parameters recommended for wake EEG, results in the dramatic removal of slow waves. We also provide an appropriate procedure to use ASR for automatic and rapid cleaning of whole-night sleep EEG data or any long EEG recording. Our procedure is freely available in Dusk2Dawn, an open-source plugin for EEGLAB.

Attenuation of homeostatic sleep response and rest-activity circadian rhythm in vitamin D deficient mice

ABSTRACT The link between vitamin D deficiency (VDD) and sleep disturbances has long been suggested. However, the direct causality between VDD, sleep disturbances, and circadian rhythm remains unclear. We aimed to characterize sleep-wake behavior and circadian rhythms in an animal model of VDD. VDD was induced by feeding vitamin D-deficient chow, and we analyzed sleep and circadian rhythm parameters. During light period, VDD mice exhibited reduced wake with more frequent wake bouts and increased NREM sleep time. However, during dark period, the wake EEG power spectrum peaked at theta band frequency, and slow-wave energy was suppressed in mice with VDD. Rest-activity analyses revealed increased circadian period, lower wheel counts, and more frequent and short activity bouts during VDD. Combining sleep and circadian data, we found significantly suppressed activities during the hours with a wake duration shorter than 30 minutes. Moreover, mice in VDD state exhibited a negative correlation between wake theta power and hourly wheel-running counts during dark period. Our data point to a direct link between VDD and disturbances in sleep and rest-activity circadian rhythm, featuring frequent wake bouts during the sleeping phase, reduced sleep pressure build-up in dark period, and reduced activity levels due to increased susceptibility to sleepiness.