Maturation of Sleep EEG Complexity in Preterm Newborns: Insights from Lempel-Ziv and Joint Lempel-Ziv Analyses

The development of the sleep-wake cycle reflects the progressive structural and functional maturation of the brain. However, the organization of neural dynamics during prematurity remains incompletely understood. In this study, we analyzed the EEG from 54 polysomnographic recordings obtained from 39 preterm infants, grouped according to postmenstrual age (PMA) into three categories: 30-31, 32-33 and 34-35 weeks. Lempel-Ziv Complexity (LZC) and Joint Lempel-Ziv Complexity (JLZC) of the electroencephalogram (EEG) were analyzed during active sleep (AS), quiet sleep (QS), and indeterminate sleep (IS). LZC computed from the raw, unfiltered recordings were significantly higher during QS than during AS and increased with PMA during AS. To further refine the analysis, LZC was also evaluated separately in the low-frequency (1-15.5 Hz) and high-frequency (16-30 Hz) EEG bands. In the low-frequency band, LZC was consistently higher during QS than during AS, an effect that was most pronounced in more immature groups. Furthermore, LZC increased with maturation particularly during AS. Sleep-state comparisons of LZC in the high-frequency EEG band also revealed higher values during QS than during AS across all PMA groups. Moreover, in contrast to the low-frequency band, LZC progressively decreased with advancing PMA both in AS and QS, suggesting that the neural mechanisms underlying low- and high-frequency EEG activity follow distinct maturational trajectories. Interestingly, larger LZC in the temporal cortex and interhemispheric differences were detected in the 32-33 PMA group. On the other hand, JLZC analysis revealed greater joint spatiotemporal dynamics across EEG channels during QS than during AS, with consistently higher JLZC values in temporal regions and lower in occipital regions. Together, these findings show that these complexity metrics distinguishes sleep states and captures maturational changes in EEG activity in preterm infants. These results provide novel insights into early brain development and suggest potential quantitative biomarkers of neonatal brain maturation.