Characterization of aperiodic and theta activity in preterm infants using EEG: Insights into cerebral maturation and inter-individual variability

Preterm birth may disrupt maturation of brain networks and functional activity, including theta oscillations that play a key role in early network development. Traditional EEG spectral analyses show marked development of theta power in early infancy, but these approaches mix oscillatory and non-oscillatory activity, limiting insights into the underlying mechanisms. Using spectral parameterization, we assessed the development of aperiodic activity and periodic theta power in very preterm (born before 32 weeks gestational age, GA) and full-term infants, and examined inter-individual variability among preterms. High-density EEG was acquired during active/REM sleep at term-equivalent age (TEA) and 2 months corrected age (2mCA) in preterm (n = 41) and full-term (n = 13) infants. Spectral parameterization allowed extracting metrics of aperiodic activity (offset, exponent) and periodic theta power, globally and across spatial clusters of electrodes. From TEA to 2mCA, offset, exponent, and theta power increased with no differences between preterms and full-terms. At TEA, aperiodic activity metrics were stronger in anterior compared with posterior areas, but this regional landscape shifted by 2mCA due to pronounced changes in posterior areas from TEA to 2mCA. Within preterms, inter-individual variability in EEG metrics at TEA was partly explained by clinical risk factors (male sex, lower GA, being small for GA, and invasive ventilation) and variations in brain microstructure, as assessed with diffusion MRI: higher theta power correlated with more advanced cortical maturation. These findings indicate that EEG spectral parameterization combined with spatial analysis provides a sensitive framework for characterizing early brain maturation and vulnerabilities associated with prematurity.