Relationship Between Early Functional and Structural Brain Developments and Brain Injury in Preterm Infants.

BACKGROUND: Recent studies explored the relationship between early brain function and brain morphology, based on the hypothesis that increased brain activity can positively affect structural brain development and that excitatory neuronal activity stimulates myelination. OBJECTIVE: To investigate the relationship between maturational features from early and serial aEEGs after premature birth and MRI metrics characterizing structural brain development and injury, measured around 30weeks postmenstrual age (PMA) and at term. Moreover, we aimed to verify whether previously developed maturational EEG features are related with PMA. DESIGN/METHODS: One hundred six extremely preterm infants received bedside aEEGs during the first 72h and weekly until week 5. 3T-MRIs were performed at 30weeks PMA and at term. Specific features were extracted to assess EEG maturation: (1) the spectral content, (2) the continuity [percentage of spontaneous activity transients (SAT%) and the interburst interval (IBI)], and (3) the complexity. Automatic MRI segmentation to assess volumes and MRI score was performed. The relationship between the maturational EEG features and MRI measures was investigated. RESULTS: Both SAT% and EEG complexity were correlated with PMA. IBI was inversely associated with PMA. Complexity features had a positive correlation with the cerebellar size at 30weeks, while event-based measures were related to the cerebellar size at term. Cerebellar width, cortical grey matter, and total brain volume at term were inversely correlated with the relative power in the higher frequency bands. CONCLUSIONS: The continuity and complexity of the EEG steadily increase with increasing postnatal age. Increasing complexity and event-based features are associated with cerebellar size, a structure with enormous development during preterm life. Brain activity is important for later structural brain development.

A perinatal stress calculator for the neonatal intensive care unit: an unobtrusive approach.

OBJECTIVE: Early experience of pain and stress in the neonatal intensive care unit is known to have an effect on the neurodevelopment of the infant. However, an automated method to quantify the procedural pain or perinatal stress in premature patients does not exist. APPROACH: In the current study, EEG and ECG data were collected for more than 3 hours from 136 patients in order to quantify stress exposure. Specifically, features extracted from the EEG and heart-rate variability in both quiet and non-quiet sleep segments were used to develop a subspace linear-discriminant analysis stress classifier. MAIN RESULTS: The main novelty of the study lies in the absence of intrusive methods or pain elicitation protocols to develop the stress classifier. Three main findings can be reported. First, we developed different stress classifiers for the different age groups and stress intensities, obtaining an area under the curve in the range [0.78-0.93] for non-quiet sleep and [0.77-0.96] for quiet sleep. Second, a dysmature EEG was found in patients under stress. Third, an enhanced cortical connectivity and increased brain-heart communication was correlated with a higher stress load, while the autonomic activity did not seem to be associated to stress exposure. SIGNIFICANCE: The results shed a light on the pain and stress processing in preterm neonates, suggesting that software tools to investigate dysmature EEG might be helpful to assess stress load in premature patients. These results could be the foundation to assess the impact of stress on infants' development and to tune preventive care.

The implementation of an apnea-based perinatal stress calculator.

Early life stress in the neonatal intensive care unit (NICU) predisposes premature infants to adverse health outcomes. Although those patients experience frequent apneas and sleep-wake disturbances during their hospital stay, clinicians still rely on clinical scales to assess pain and stress burden. This study addresses the relationship between stress and apneic spells in NICU patients to implement an automatic stress detector. EEG, ECG and SpO2 were recorded from 40 patients for at least 3 hours and the stress burden was assessed using the Leuven Pain Scale. Different logistic regression models were designed to detect the presence or the absence of stress based on the signals reactivity to each apneic spell. The classification shows that stress can be detected with an area under the curve of 0.94 and a misclassification error of 19.23%. These results were obtained via SpO2 dips and EEG regularity. These findings suggest that stress deepens the physiological reaction to apneas, which could ultimately impact the neurological and behavioral development.

A brain-age model for preterm infants based on functional connectivity.

OBJECTIVE: In this study, the development of EEG functional connectivity during early development has been investigated in order to provide a predictive age model for premature infants. APPROACH: The functional connectivity has been assessed via the coherency function (its imaginary part (ImCoh) and its mean squared magnitude (MSC)), the phase locking value ([Formula: see text]) and the Hilbert-Schimdt dependence (HSD) in a dataset of 30 patients, partially described and employed in previous studies (Koolen et al 2016 Neuroscience 322 298-307; Lavanga et al 2017 Complexity 2017 1-13). Infants' post-menstrual age (PMA) ranges from 27 to 42 weeks. The topology of the EEG couplings has been investigated via graph-theory indices. MAIN RESULTS: Results show a sharp decrease in ImCoh indices in θ, (4-8) Hz and α, (8-16) Hz bands and MSC in ß, (16-32) Hz band with maturation, while a more modest positive correlation with PMA is found for HSD, [Formula: see text] and MSC in [Formula: see text], θ, α bands. The best performances for the PMA prediction were mean absolute error equal to 1.51 weeks and adjusted coefficient of determination [Formula: see text] equal to 0.8. SIGNIFICANCE: The reported findings suggest a segregation of the cortex connectivity, which favours a diffused tasks architecture on the brain scalp. In summary, the results indicate that the neonates' brain development can be described via lagged-interaction network features.

Automatic quiet sleep detection based on multifractality in preterm neonates: Effects of maturation.

This study investigates the multifractal formalism framework for quiet sleep detection in preterm babies. EEG recordings from 25 healthy preterm infants were used in order to evaluate the performance of multifractal measures for the detection of quiet sleep. Results indicate that multifractal analysis based on wavelet leaders is able to identify quiet sleep epochs, but the classifier performances seem to be highly affected by the infant's age. In particular, from the developed classifiers, the lowest area under the curve (AUC) has been obtained for EEG recordings at very young age (≤ 31 weeks post-menstrual age), and the maximum at full-term age (≥ 37 weeks post-menstrual age). The improvement in classification performances can be due to a change in the multifractality properties of neonatal EEG during the maturation of the infant, which makes the EEG sleep stages more distinguishable.