A Comparison of Automatically Extracted Quantitative EEG Features for Seizure Risk Stratification in Neonatal Encephalopathy.

PURPOSE: Seizures occur in up to 40% of neonates with neonatal encephalopathy. Earlier identification of seizures leads to more successful seizure treatment, but is often delayed because of limited availability of continuous EEG monitoring. Clinical variables poorly stratify seizure risk, and EEG use to stratify seizure risk has previously been limited by need for manual review and artifact exclusion. The goal of this study is to compare the utility of automatically extracted quantitative EEG (qEEG) features for seizure risk stratification. METHODS: We conducted a retrospective analysis of neonates with moderate-to-severe neonatal encephalopathy who underwent therapeutic hypothermia at a single center. The first 24 hours of EEG underwent automated artifact removal and qEEG analysis, comparing qEEG features for seizure risk stratification. RESULTS: The study included 150 neonates and compared the 36 (23%) with seizures with those without. Absolute spectral power best stratified seizure risk with area under the curve ranging from 63% to 71%, followed by range EEG lower and upper margin, median and SD of the range EEG lower margin. No features were significantly more predictive in the hour before seizure onset. Clinical examination was not associated with seizure risk. CONCLUSIONS: Automatically extracted qEEG features were more predictive than clinical examination in stratifying neonatal seizure risk during therapeutic hypothermia. qEEG represents a potential practical bedside tool to individualize intensity and duration of EEG monitoring and decrease time to seizure recognition. Future work is needed to refine and combine qEEG features to improve risk stratification.

Macroperiodic Oscillations: A Potential Novel Biomarker of Outcome in Neonatal Encephalopathy.

PURPOSE: Neonatal encephalopathy (NE) is a common cause of neurodevelopmental morbidity. Tools to accurately predict outcomes after therapeutic hypothermia remain limited. We evaluated a novel EEG biomarker, macroperiodic oscillations (MOs), to predict neurodevelopmental outcomes. METHODS: We conducted a secondary analysis of a randomized controlled trial of neonates with moderate-to-severe NE who underwent standardized clinical examination, magnetic resonance (MR) scoring, video EEG, and neurodevelopmental assessment with Bayley III evaluation at 18 to 24 months. A non-NE cohort of neonates was also assessed for the presence of MOs. The relationship between clinical examination, MR score, MOs, and neurodevelopmental assessment was analyzed. RESULTS: The study included 37 neonates with 24 of whom survived and underwent neurodevelopmental assessment (70%). The strength of MOs correlated with severity of clinical encephalopathy. MO strength and spread significantly correlated with Bayley III cognitive percentile (P = 0.017 and 0.046). MO strength outperformed MR score in predicting a combined adverse outcome of death or disability (P = 0.019, sensitivity 100%, specificity 77% vs. P = 0.079, sensitivity 100%, specificity 59%). CONCLUSIONS: MOs are an EEG-derived, quantitative biomarker of neurodevelopmental outcome that outperformed a comprehensive validated MRI injury score and a detailed systematic discharge examination in this small cohort. Future work is needed to validate MOs in a larger cohort and elucidate the underlying pathophysiology of MOs.

Detecting slow narrowband modulation in EEG signals.

BACKGROUND: We observed an unusual modulatory phenomenon in the electroencephalogram (EEG) of pediatric patients with acquired brain injury. The modulation is orders of magnitude slower than the fast EEG background activity, necessitating new analysis procedures to systematically detect and quantify the phenomenon. NEW METHOD: We propose a method for analyzing spatial and temporal relationships associated with slow, narrowband modulation of EEG. We extract envelope signals from physiological frequency bands of EEG. Then, we construct a sparse representation of the spectral content of the envelope signal across sliding windows. For the latter, we use an augmented LASSO regression to incorporate spatial and temporal filtering into the solution. The method can be applied to windows of variable length, depending on the desired frequency resolution. RESULTS: The sparse estimates of the envelope power spectra enable the detection of narrowband modulation in the millihertz frequency range. Subsequently, we are able to assess non-stationarity in the frequency and spatial relationships across channels. The method can be paired with unsupervised anomaly detection to identify windows with significant modulation. We validated such findings by applying our method to a control set of EEGs. COMPARISON WITH EXISTING METHODS: To our knowledge, no methods have been previously proposed to quantify second order modulation at such disparate time-scales. CONCLUSIONS: We provide a general EEG analysis framework capable of detecting signal content below 0.1 Hz, which is especially germane to clinical recordings that may contain multiple hours worth of continuous data.

Resolving and characterizing the incidence of millihertz EEG modulation in critically ill children.

OBJECTIVE: We analyze a slow electrographic pattern, Macroperiodic Oscillations (MOs), in the EEG from a cohort of young critical care patients (n = 43) with continuous EEG monitoring. We construct novel quantitative methods to quantify and understand MOs. METHODS: We applied a nonparametric bilevel spectral analysis to identify MOs, a millihertz (0.004-0.01 Hz) modulation of 5-15 Hz activity in two separate ICU patient cohorts (n = 195 total). We also developed a rigorous measure to quantify MOs strength and spatial expression, which was validated against surrogate noise data. RESULTS: Strong or spatially widespread MOs appear in both high clinical suspicion and a general ICU population. In the former, patients with strong or spatially widespread MOs tended to have worse clinical outcomes. Intracranial pressure and heart rate data from one patient provide insight into a potential broader physiological mechanism for MOs. CONCLUSIONS: We quantified millihertz EEG modulation (MOs) in cohorts of critically ill pediatric patients. We demonstrated high incidence in two patient populations. In a high suspicion cohort, MOs are associated with poor outcome, suggesting future potential as a diagnostic and prognostic aid. SIGNIFICANCE: These results support the existence of EEG dynamics across disparate time-scales and may provide insight into brain injury physiology in young children.

Macroperiodic Oscillations Are Associated With Seizures Following Acquired Brain Injury in Young Children.

PURPOSE: Seizures occur in 10% to 40% of critically ill children. We describe a phenomenon seen on color density spectral array but not raw EEG associated with seizures and acquired brain injury in pediatric patients. METHODS: We reviewed EEGs of 541 children admitted to an intensive care unit between October 2015 and August 2018. We identified 38 children (7%) with a periodic pattern on color density spectral array that oscillates every 2 to 5 minutes and was not apparent on the raw EEG tracing, termed macroperiodic oscillations (MOs). Internal validity measures and interrater agreement were assessed. We compared demographic and clinical data between those with and without MOs. RESULTS: Interrater reliability yielded a strong agreement for MOs identification (kappa: 0.778 [0.542-1.000]; P < 0.0001). There was a 76% overlap in the start and stop times of MOs among reviewers. All patients with MOs had seizures as opposed to 22.5% of the general intensive care unit monitoring population ( P < 0.0001). Macroperiodic oscillations occurred before or in the midst of recurrent seizures. Patients with MOs were younger (median of 8 vs. 208 days; P < 0.001), with indications for EEG monitoring more likely to be clinical seizures (42 vs. 16%; P < 0.001) or traumatic brain injury (16 vs. 5%, P < 0.01) and had fewer premorbid neurologic conditions (10.5 vs. 33%; P < 0.01). CONCLUSIONS: Macroperiodic oscillations are a slow periodic pattern occurring over a longer time scale than periodic discharges in pediatric intensive care unit patients. This pattern is associated with seizures in young patients with acquired brain injuries.

Spectroscopy, manipulation and trapping of neutral atoms, molecules, and other particles using optical nanofibers: a review.

The use of tapered optical fibers, i.e., optical nanofibers, for spectroscopy and the detection of small numbers of particles, such as neutral atoms or molecules, has been gaining interest in recent years. In this review, we briefly introduce the optical nanofiber, its fabrication, and optical mode propagation within. We discuss recent progress on the integration of optical nanofibers into laser-cooled atom and vapor systems, paying particular attention to spectroscopy, cold atom cloud characterization, and optical trapping schemes. Next, a natural extension of this work to molecules is introduced. Finally, we consider several alternatives to optical nanofibers that display some advantages for specific applications.

Tapered optical fibers as tools for probing magneto-optical trap characteristics.

We present a novel technique for measuring the characteristics of a magneto-optical trap (MOT) for cold atoms by monitoring the spontaneous emission from trapped atoms coupled into the guided mode of a tapered optical nanofiber. We show that the nanofiber is highly sensitive to very small numbers of atoms close to its surface. The size and shape of the MOT, determined by translating the cold atom cloud across the tapered fiber, is in excellent agreement with measurements obtained using the conventional method of fluorescence imaging using a charge coupled device camera. The coupling of atomic fluorescence into the tapered fiber also allows us to monitor the loading and lifetime of the trap. The results are compared to those achieved by focusing the MOT fluorescence onto a photodiode and it was seen that the tapered fiber gives slightly longer loading and lifetime measurements due to the sensitivity of the fiber, even when very few atoms are present.

Sleep-stage scoring in the rat using a support vector machine.

Analysis and classification of sleep stages is a fundamental part of basic sleep research. Rat sleep stages are scored based on electrocorticographic (ECoG) signals recorded from electrodes implanted epidurally and electromyographic (EMG) signals from the temporalis or nuchal muscle. An automated sleep scoring system was developed using a support vector machine (SVM) to discriminate among waking, nonrapid eye movement sleep, and paradoxical sleep. Two experts scored retrospective data obtained from six Sprague-Dawley rodents to provide the training sets and subsequent comparison data used to assess the effectiveness of the SVM. Numerous time-domain and frequency-domain features were extracted for each epoch and selectively reduced using statistical analyses. The SVM kernel function was chosen to be a Gaussian radial basis function and kernel parameters were varied to examine the effectiveness of optimization methods. Tests indicated that a common set of features could be chosen resulted in an overall agreement between the automated scores and the expert consensus of greater than 96%.

Uncovering the determinants of cardiovascular disease among Indigenous people.

OBJECTIVE: This paper attempts to delineate an appropriate methodology for research into cardiovascular diseases (CVD) in the context of the Australian Indigenous population. DESIGN: Our argument proceeds in three main stages of critical analysis of the appropriate literature. First we demonstrate the extremely complex aetiology of CVD and also argue that, in any population, exposure to many of the more important risk factors at an individual or group level is generated through social and behavioural factors whose causation, persistence and reproduction are both complex and multilayered. Secondly, and having established that the aetiology and morbidity of CVD in various populations is a product of a complex and interactive hierarchy of biomedical, social and political processes, we argue that only research methodologies capable of encompassing the complete span of this hierarchy can be expected to generate results which are efficacious as a basis for intervention. Thirdly, and most importantly, we argue that in the Indigenous context a central and essential feature in the development of an appropriate methodology must be to centre Indigenous people themselves as the dominant partner in setting the research agenda and the conduct of research. RESULTS/CONCLUSIONS: We conclude that an appropriate methodology for the elucidation of the aetiology, and sequelae of CVD in Indigenous people, would go far beyond 'black box' epidemiology, would recognise the essentially social nature of chronic disease by deploying appropriate social theory within a transdisciplinary framework and would centre Indigenous people as the dominant partner in the research process.

An evaluation of the use of seizure prone rats when investigating intermediate stage sleep.

A body of literature is developing which identifies an additional stage of sleep in rats, cats and mice. Intermediate stage (IS) sleep is a measurable sleep stage that is maintained by the hyperpolarization of GABA(A) containing thalamocortical neurons. The present study attempts to clarify inconsistencies within the sleep spindle literature. Most notably, inconsistencies between those that study sleep spindles in the rat outside and within the context of IS sleep. Ten male taiep rats weighing from 400 g to 600 g, and 9-12 months of age, were used in this study. The animals were given a one-time, .9 mg/kg dose of the benzodiazepine clonazepam. The control group had more seizure activity (mean = 13.4) than the treatment group (mean = 5.2, t(1-18) = 8.859, p < .001), and had a lower number of sleep spindles (mean=10.3) than the treatment group (mean = 13.3, t(1-18) = -3.4, p < .001). In addition, spectral analysis of sleep spindles during IS and seizure activity revealed that sleep spindles are within the frequency band of 8-11Hz, while seizure activity is within the 4-7 Hz range. This data supports the hypotheses that sleep spindles are distinguishable from seizure activity.

Active sleep and its role in the prevention of apoptosis in the developing brain.

The aim of this study is to identify a possible function of Active Sleep (AS), also known as Rapid Eye Movement Sleep (REM) in humans, as a protective state during early Central Nervous System (CNS) development. Previous research suggest pharmacological agents that inhibit high levels of neuronal activity in the CNS (e.g., benzodiazepines, ethanol, and anesthetics) precipitate massive CNS programmed cell death (PCD), in developing mammals. AS is characterized by high levels of CNS activity at levels comparable to waking. AS occupies up to 75% of the circadian cycle in developing mammals (rodents from postnatal days 1-14 days (p1-p14), and humans from prenatal month seven to postnatal year one). Many studies have implicated AS as having an active role in the normal development of the visual system and have documented myriad behavioral anomalies as a result of AS deprivation. Reduced adult brain mass has also been observed after AS deprivation in developing rats during this period, however, no study to date has documented this process as it occurs (i.e., the cellular mechanisms that result in behavioral anomalies or reduced adult brain mass). The purpose of this study is to begin documentation of this process by utilizing histological techniques that identify the PCD process, if it occurs, after acute and prolonged AS deprivation in rats from ages p7 to p14 (a time of active synaptogenesis). Our methodology includes utilization of the alpha2-adrenergic receptor agonist clonidine, to deprive rat pups of AS at ages varying from p7 to p14. Pilot data from our laboratory has shown that an acute exposure to clonidine significantly reduces time spent in AS. The animals that were AS deprived also showed a statistically significant decrease in brain mass and have stained positively for PCD. If our hypotheses are correct, this research will have major implications with regard to determining the function(s) of REM sleep.