Microstate Analysis Reflects Maturation of the Preterm Brain.

Preterm neonates are at risk of long-term neurodevelopmental impairments due to disruption of natural brain development. Electroencephalography (EEG) analysis can provide insights into brain development of preterm neonates. This study aims to explore the use of microstate (MS) analysis to evaluate global brain dynamics changes during maturation in preterm neonates with normal neurodevelopmental outcome.The dataset included 135 EEGs obtained from 48 neonates at varying postmenstrual ages (26.4 to 47.7 weeks), divided into four age groups. For each recording we extracted a 5-minute epoch during quiet sleep (QS) and during non-quiet sleep (NQS), resulting in eight groups (4 age group x 2 sleep states). We compared MS maps and corresponding (map-specific) MS metrics across groups using group-level maps. Additionally, we investigated individual map metrics.Four group-level MS maps accounted for approximately 70% of the global variance and showed non-random syntax. MS topographies and transitions changed significantly when neonates reached 37 weeks. For both sleep states and all MS maps, MS duration decreased and occurrence increased with age. The same relationships were found using individual maps, showing strong correlations (Pearson coefficients up to 0.74) between individual map metrics and post-menstrual age. Moreover, the Hurst exponent of the individual MS sequence decreased with age.The observed changes in MS metrics with age might reflect the development of the preterm brain, which is characterized by formation of neural networks. Therefore, MS analysis is a promising tool for monitoring preterm neonatal brain maturation, while our study can serve as a valuable reference for investigating EEGs of neonates with abnormal neurodevelopmental outcomes.

A multi-task and multi-channel convolutional neural network for semi-supervised neonatal artefact detection.

Objective. Automated artefact detection in the neonatal electroencephalogram (EEG) is crucial for reliable automated EEG analysis, but limited availability of expert artefact annotations challenges the development of deep learning models for artefact detection. This paper proposes a semi-supervised deep learning approach for artefact detection in neonatal EEG that requires few labelled data by training a multi-task convolutional neural network (CNN).Approach. An unsupervised and a supervised objective were jointly optimised by combining an autoencoder and an artefact classifier in one multi-output model that processes multi-channel EEG inputs. The proposed semi-supervised multi-task training strategy was compared to a classical supervised strategy and other existing state-of-the-art models. The models were trained and tested separately on two different datasets, which contained partially annotated multi-channel neonatal EEG. Models were evaluated using the F1-statistic and the relevance of the method was investigated in the context of a functional brain age (FBA) prediction model.Main results. The proposed multi-task and multi-channel CNN methods outperformed state-of-the-art methods, reaching F1 scores of 86.2% and 95.7% on two separate datasets. The proposed semi-supervised multi-task training strategy was shown to be superior to a classical supervised training strategy when the amount of labels in the dataset was artificially reduced. Finally, we found that the error of a brain age prediction model correlated with the amount of automatically detected artefacts in the EEG segment.Significance. Our results show that the proposed semi-supervised multi-task training strategy can train CNNs successfully even when the amount of labels in the dataset is limited. Therefore, this method is a promising semi-supervised technique for developing deep learning models with scarcely labelled data. Moreover, a correlation between the error of FBA estimates and the amount of detected artefacts in the corresponding EEG segments indicates the relevance of artefact detection for robust automated EEG analysis.

Partial wavelet coherence as a robust method for assessment of neurovascular coupling in neonates with hypoxic ischemic encephalopathy.

In neonates with hypoxic ischemic encephalopathy, the computation of wavelet coherence between electroencephalogram (EEG) power and regional cerebral oxygen saturation (rSO2) is a promising method for the assessment of neurovascular coupling (NVC), which in turn is a promising marker for brain injury. However, instabilities in arterial oxygen saturation (SpO2) limit the robustness of previously proposed methods. Therefore, we propose the use of partial wavelet coherence, which can eliminate the influence of SpO2. Furthermore, we study the added value of the novel NVC biomarkers for identification of brain injury compared to traditional EEG and NIRS biomarkers. 18 neonates with HIE were monitored for 72 h and classified into three groups based on short-term MRI outcome. Partial wavelet coherence was used to quantify the coupling between C3-C4 EEG bandpower (2-16 Hz) and rSO2, eliminating confounding effects of SpO2. NVC was defined as the amount of significant coherence in a frequency range of 0.25-1 mHz. Partial wavelet coherence successfully removed confounding influences of SpO2 when studying the coupling between EEG and rSO2. Decreased NVC was related to worse MRI outcome. Furthermore, the combination of NVC and EEG spectral edge frequency (SEF) improved the identification of neonates with mild vs moderate and severe MRI outcome compared to using EEG SEF alone. Partial wavelet coherence is an effective method for removing confounding effects of SpO2, improving the robustness of automated assessment of NVC in long-term EEG-NIRS recordings. The obtained NVC biomarkers are more sensitive to MRI outcome than traditional rSO2 biomarkers and provide complementary information to EEG biomarkers.

Assessing Neurovascular Coupling Using Wavelet Coherence in Neonates with Asphyxia.

Brain monitoring is important in neonates with asphyxia in order to assess the severity of hypoxic ischaemic encephalopathy (HIE) and identify neonates at risk of adverse neurodevelopmental outcome. Previous studies suggest that neurovascular coupling (NVC), quantified as the interaction between electroencephalography (EEG) and near-infrared spectroscopy (NIRS)-derived regional cerebral oxygen saturation (rSO2) is a promising biomarker for HIE severity and outcome. In this study, we explore how wavelet coherence can be used to assess NVC. Wavelet coherence was computed in 18 neonates undergoing therapeutic hypothermia in the first 3 days of life, with varying HIE severities (mild, moderate, severe). We compared two pre-processing methods of the EEG prior to wavelet computation: amplitude integrated EEG (aEEG) and EEG bandpower. Furthermore, we proposed average real coherence as a biomarker for NVC. Our results indicate that NVC as assessed by wavelet coherence between EEG bandpower and rSO2 can be a valuable biomarker for HIE severity in neonates with peripartal asphyxia. More specifically, average real coherence in a very low frequency range (0.21-0.83 mHz) tends to be high (positive) in neonates with mild HIE, low (positive) in neonates with moderate HIE, and negative in neonates with severe HIE. Further investigation in a larger patient cohort is needed to validate our findings.

Functional brain maturation and sleep organisation in neonates with congenital heart disease.

OBJECTIVE: Neonates with Congenital Heart Disease (CHD) have structural delays in brain development. To evaluate whether functional brain maturation and sleep-wake physiology is also disturbed, the Functional Brain Age (FBA) and sleep organisation on EEG during the neonatal period is investigated. METHODS: We compared 15 neonates with CHD who underwent multichannel EEG with healthy term newborns of the same postmenstrual age, including subgroup analysis for d-Transposition of the Great Arteries (d-TGA) (n = 8). To estimate FBA, a prediction tool using quantitative EEG features as input, was applied. Second, the EEG was automatically classified into the 4 neonatal sleep stages. Neonates with CHD underwent neurodevelopmental testing using the Bayley Scale of Infant Development-III at 24 months. RESULTS: Preoperatively, the FBA was delayed in CHD infants and more so in d-TGA infants. The FBA was positively correlated with motor scores. Sleep organisation was significantly altered in neonates with CHD. The duration of the sleep cycle and the proportion of Active Sleep Stage 1 was decreased, again more marked in the d-TGA infants. Neonates with d-TGA spent less time in High Voltage Slow Wave Sleep and more in Tracé Alternant compared to healthy terms. Both FBA and sleep organisation normalised postoperatively. The duration of High Voltage Slow Wave Sleep remained positively correlated with motor scores in d-TGA infants. INTERPRETATION: Altered early brain function and sleep is present in neonates with CHD. These results are intruiging, as inefficient neonatal sleep has been linked with adverse long-term outcome. Identifying how these rapid alterations in brain function are mitigated through improvements in cerebral oxygenation, surgery, drugs and nutrition may have relevance for clinical practice and outcome.