Designing a trial for neonatal seizure treatment

Neonatal seizures are widely considered a neurological emergency with a need for prompt treatment, yet they are known to present a highly elusive target for bedside clinicians. Recent studies have suggested that the design of a neonatal seizure treatment trial will profoundly influence the sample size, which may readily increase to hundreds or even thousands as the achieved effect size diminishes to clinical irrelevance. The self-limiting and rapidly resolving nature of neonatal seizures diminishes the measurable treatment effect every hour after seizure onset and any effect may potentially be confused with spontaneous resolution, precluding the value of many observational studies. The large individual variability in seizure occurrence over time and between etiologies challenges group comparisons, while the absence of clinical signs mandates quantification of seizure occurrence with continuous multi-channel EEG monitoring. A biologically sound approach that views neonatal seizures as a functional cot-side biomarker rather than an object to treat can overcome these challenges. (C) 2018 Elsevier Ltd. All rights reserved.Peer reviewe

Comparison of End-to-End Neural Network Architectures and Data Augmentation Methods for Automatic Infant Motility Assessment Using Wearable Sensors

Infant motility assessment using intelligent wearables is a promising new approach for assessment of infant neurophysiological development, and where efficient signal analysis plays a central role. This study investigates the use of different end-to-end neural network architectures for processing infant motility data from wearable sensors. We focus on the performance and computational burden of alternative sensor encoder and time series modeling modules and their combinations. In addition, we explore the benefits of data augmentation methods in ideal and nonideal recording conditions. The experiments are conducted using a dataset of multisensor movement recordings from 7-month-old infants, as captured by a recently proposed smart jumpsuit for infant motility assessment. Our results indicate that the choice of the encoder module has a major impact on classifier performance. For sensor encoders, the best performance was obtained with parallel two-dimensional convolutions for intrasensor channel fusion with shared weights for all sensors. The results also indicate that a relatively compact feature representation is obtainable for within-sensor feature extraction without a drastic loss to classifier performance. Comparison of time series models revealed that feedforward dilated convolutions with residual and skip connections outperformed all recurrent neural network (RNN)-based models in performance, training time, and training stability. The experiments also indicate that data augmentation improves model robustness in simulated packet loss or sensor dropout scenarios. In particular, signal- and sensor-dropout-based augmentation strategies provided considerable boosts to performance without negatively affecting the baseline performance. Overall, the results provide tangible suggestions on how to optimize end-to-end neural network training for multichannel movement sensor data

Early development of sleep and brain functional connectivity in term-born and preterm infants

The proper development of sleep and sleep-wake rhythms during early neonatal life is crucial to lifelong neurological well-being. Recent data suggests that infants who have poor quality sleep demonstrate a risk for impaired neurocognitive outcomes. Sleep ontogenesis is a complex process, whereby alternations between rudimentary brain states-active vs. wake and active sleep vs. quiet sleep-mature during the last trimester of pregnancy. If the infant is born preterm, much of this process occurs in the neonatal intensive care unit, where environmental conditions might interfere with sleep. Functional brain connectivity (FC), which reflects the brain's ability to process and integrate information, may become impaired, with ensuing risks of compromised neurodevelopment. However, the specific mechanisms linking sleep ontogenesis to the emergence of FC are poorly understood and have received little investigation, mainly due to the challenges of studying causal links between developmental phenomena and assessing FC in newborn infants. Recent advancements in infant neuromonitoring and neuroimaging strategies will allow for the design of interventions to improve infant sleep quality and quantity. This review discusses how sleep and FC develop in early life, the dynamic relationship between sleep, preterm birth, and FC, and the challenges associated with understanding these processes. Impact Sleep in early life is essential for proper functional brain development, which is essential for the brain to integrate and process information. This process may be impaired in infants born preterm. The connection between preterm birth, early development of brain functional connectivity, and sleep is poorly understood. This review discusses how sleep and brain functional connectivity develop in early life, how these processes might become impaired, and the challenges associated with understanding these processes. Potential solutions to these challenges are presented to provide direction for future research.Peer reviewe

The effect of reducing EEG electrode number on the visual interpretation of the human expert for neonatal seizure detection

Objectives: To measure changes in the visual interpretation of the EEG by the human expert for neonatal seizure detection when reducing the number of recording electrodes. Methods: EEGs were recorded from 45 infants admitted to the neonatal intensive care unit (NICU). Three experts annotated seizures in EEG montages derived from 19, 8 and 4 electrodes. Differences between annotations were assessed by comparing intra-montage with inter-montage agreement (K). Results: Three experts annotated 4464 seizures across all infants and montages. The inter-expert agreement was not significantly altered by the number of electrodes in the montage (p = 0.685, n = 43). Reducing the number of EEG electrodes altered the seizure annotation for all experts. Agreement between the 19-electrode montage (K-19,K-19 = 0.832) was significantly higher than the agreement between 19 and 8-electrode montages (dK = 0.114; p <0.001, n = 42) or 19 and 4-electrode montages (dK = 0.113, p <0.001, n = 43). Seizure burden and number were significantly underestimated by the 4 and 8-electrode montage (p <0.001). No significant difference in agreement was found between 8 and 4-electrode montages (dK = 0.002; p = 0.07, n = 42). Conclusions: Reducing the number of EEG electrodes from 19 electrodes resulted in slight but significant changes in seizure detection. (C) 2017 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.Peer reviewe

Analysis of infant cortical synchrony is constrained by the number of recording electrodes and the recording montage

Objective: To assess how the recording montage in the neonatal EEG influences the detection of cortical source signals and their phase interactions. Methods: Scalp EEG was simulated by forward modeling 20-200 simultaneously active sources covering the cortical surface of a realistic neonatal head model. We assessed systematically how the number of scalp electrodes (11-85), analysis montage, or the size of cortical sources affect the detection of cortical phase synchrony. Statistical metrics were developed for quantifying the resolution and reliability of the montages. Results: The findings converge to show that an increase in the number of recording electrodes leads to a systematic improvement in the detection of true cortical phase synchrony. While there is always a ceiling effect with respect to discernible cortical details, we show that the average and Laplacian montages exhibit superior specificity and sensitivity as compared to other conventional montages. Conclusions: Reliability in assessing true neonatal cortical synchrony is directly related to the choice of EEG recording and analysis configurations. Because of the high conductivity of the neonatal skull, the conventional neonatal EEG recordings are spatially far too sparse for pertinent studies, and this loss of information cannot be recovered by re-montaging during analysis. Significance: Future neonatal EEG studies will need prospective planning of recording configuration to allow analysis of spatial details required by each study question. Our findings also advice about the level of details in brain synchrony that can be studied with existing datasets or by using conventional EEG recordings. (C) 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.Peer reviewe

Use of eye tracking improves the detection of evoked responses to complex visual stimuli during EEG in infants

Objective To improve the reliability of detecting EEG responses evoked by complex visual stimuli to the level required for clinical use by integrating an eye tracker to the EEG setup and optimizing the analysis protocol. Methods Infants were presented with continuous orientation reversal (OR), global form (GF), and global motion (GM) stimuli. Eye tracking was used to control stimulus presentation and exclude epochs with disoriented gaze. The spectral responses were estimated from 13 postcentral EEG channels using a circular variant of Hotelling’s T2 test statistic. Results Among 39 healthy infants, statistically significant (pPeer reviewe

Developing Disposable EEG Cap for Infant Recordings at the Neonatal Intensive Care Unit

Long-term EEG monitoring in neonatal intensive care units (NICU) is challenged with finding solutions for setting up and maintaining a sufficient recording quality with limited technical experience. The current study evaluates different solutions for the skin–electrode interface and develops a disposable EEG cap for newborn infants. Several alternative materials for the skin–electrode interface were compared to the conventional gel and paste: conductive textiles (textured and woven), conductive Velcro, sponge, super absorbent hydrogel (SAH), and hydro fiber sheets (HF). The comparisons included the assessment of dehydration and recordings of signal quality (skin interphase impedance and powerline (50 Hz) noise) for selected materials. The test recordings were performed using snap electrodes integrated into a forearm sleeve or a forehead band along with skin–electrode interfaces to mimic an EEG cap with the aim of long-term biosignal recording on unprepared skin. In the hydration test, conductive textiles and Velcro performed poorly. While the SAH and HF remained sufficiently hydrated for over 24 h in an incubator-mimicking environment, the sponge material was dehydrated during the first 12 h. Additionally, the SAH was found to have a fragile structure and was electrically prone to artifacts after 12 h. In the electrical impedance and recording comparisons of muscle activity, the results for thick-layer HF were comparable to the conventional gel on unprepared skin. Moreover, the mechanical instability measured by 1–2 Hz and 1–20 Hz normalized relative power spectrum density was comparable with clinical EEG recordings using subdermal electrodes. The results together suggest that thick-layer HF at the skin–electrode interface is an effective candidate for a preparation-free, long-term recording, with many advantages, such as long-lasting recording quality, easy use, and compatibility with sensitive infant skin contact. Keywords: aEEG; NICU; SAH; HFPeer reviewe

Time-Varying EEG Correlations Improve Automated Neonatal Seizure Detection

The aim of this study was to develop methods for detecting the nonstationary periodic characteristics of neonatal electroencephalographic (EEG) seizures by adapting estimates of the correlation both in the time (spike correlation; SC) and time-frequency domain (time-frequency correlation; TFC). These measures were incorporated into a seizure detection algorithm (SDA) based on a support vector machine to detect periods of seizure and nonseizure. The performance of these nonstationary correlation measures was evaluated using EEG recordings from 79 term neonates annotated by three human experts. The proposed measures were highly discriminative for seizure detection (median AUC(SC): 0.933 IQR: 0.821-0.975, median AUC(TFC): 0.883 IQR: 0.707-0.931). The resultant SDA applied to multi-channel recordings had a median AUC of 0.988 (IQR: 0.931-0.998) when compared to consensus annotations, outperformed two state-of-the-art SDAs (p <0.001) and was noninferior to the human expert for 73/79 of neonates.Peer reviewe

Developing Disposable EEG Cap for Infant Recordings at the Neonatal Intensive Care Unit

Long-term EEG monitoring in neonatal intensive care units (NICU) is challenged with finding solutions for setting up and maintaining a sufficient recording quality with limited technical experience. The current study evaluates different solutions for the skin–electrode interface and develops a disposable EEG cap for newborn infants. Several alternative materials for the skin–electrode interface were compared to the conventional gel and paste: conductive textiles (textured and woven), conductive Velcro, sponge, super absorbent hydrogel (SAH), and hydro fiber sheets (HF). The comparisons included the assessment of dehydration and recordings of signal quality (skin interphase impedance and powerline (50 Hz) noise) for selected materials. The test recordings were performed using snap electrodes integrated into a forearm sleeve or a forehead band along with skin–electrode interfaces to mimic an EEG cap with the aim of long-term biosignal recording on unprepared skin. In the hydration test, conductive textiles and Velcro performed poorly. While the SAH and HF remained sufficiently hydrated for over 24 h in an incubator-mimicking environment, the sponge material was dehydrated during the first 12 h. Additionally, the SAH was found to have a fragile structure and was electrically prone to artifacts after 12 h. In the electrical impedance and recording comparisons of muscle activity, the results for thick-layer HF were comparable to the conventional gel on unprepared skin. Moreover, the mechanical instability measured by 1–2 Hz and 1–20 Hz normalized relative power spectrum density was comparable with clinical EEG recordings using subdermal electrodes. The results together suggest that thick-layer HF at the skin–electrode interface is an effective candidate for a preparation-free, long-term recording, with many advantages, such as long-lasting recording quality, easy use, and compatibility with sensitive infant skin contact. Keywords: aEEG; NICU; SAH; HFPeer reviewe