Cognitive Outcome Prediction in Infants With Neonatal Hypoxic-Ischemic Encephalopathy Based on Functional Connectivity and Complexity of the Electroencephalography Signal

Impaired neurodevelopmental outcome, in particular cognitive impairment, after neonatal hypoxic-ischemic encephalopathy is a major concern for parents, clinicians, and society. This study aims to investigate the potential benefits of using advanced quantitative electroencephalography analysis (qEEG) for early prediction of cognitive outcomes, assessed here at 2 years of age. EEG data were recorded within the first week after birth from a cohort of twenty infants with neonatal hypoxic-ischemic encephalopathy (HIE). A proposed regression framework was based on two different sets of features, namely graph-theoretical features derived from the weighted phase-lag index (WPLI) and entropies metrics represented by sample entropy (SampEn), permutation entropy (PEn), and spectral entropy (SpEn). Both sets of features were calculated within the noise-assisted multivariate empirical mode decomposition (NA-MEMD) domain. Correlation analysis showed a significant association in the delta band between the proposed features, graph attributes (radius, transitivity, global efficiency, and characteristic path length) and entropy features (Pen and SpEn) from the neonatal EEG data and the cognitive development at age two years. These features were used to train and test the tree ensemble (boosted and bagged) regression models. The highest prediction performance was reached to 14.27 root mean square error (RMSE), 12.07 mean absolute error (MAE), and 0.45 R-squared using the entropy features with a boosted tree regression model. Thus, the results demonstrate that the proposed qEEG features show the state of brain function at an early stage; hence, they could serve as predictive biomarkers of later cognitive impairment, which could facilitate identifying those who might benefit from early targeted intervention.