Multiscale entropy as a metric of brain maturation in a large cohort of typically developing children born preterm using longitudinal high-density EEG in the first two years of life.

We aimed to analyze whether complexity of brain electrical activity (EEG) measured by multiscale entropy (MSE) increases with brain maturation during the first two years of life. We also aimed to investigate whether this complexity shows regional differences across the brain, and whether changes in complexity are influenced by extrauterine life experience duration.We measured MSE of EEG signals recorded longitudinally using a high-density setup (64 or 128 electrodes) in 84 typically developing infants born preterm (<32 weeks' gestation) from term age to two years. We analyzed the complexity index and maximum value of MSE over increasing age, across brain regions, and in function of extrauterine life duration, and used correlation matrices as a metric of functional connectivity of the cerebral cortex.We found an increase of strong inter-channel correlation of MSE (R > 0.8) with increasing age. Regional analysis showed significantly increased MSE between 3 and 24 months of corrected age in the posterior and middle regions with respect to the anterior region. We found a weak relationship (adjusted R= 0.135) between MSE and extrauterine life duration.These findings suggest that brain functional connectivity increases with maturation during the first two years of life. EEG complexity shows regional differences with earlier maturation of the visual cortex and brain regions involved in joint attention than of regions involved in cognitive analysis, abstract thought, and social behavior regulation. Finally, our MSE analysis suggested only a weak influence of early extrauterine life experiences (prior to term age) on EEG complexity.