Neonatal brain activity and the effect of preterm birth on long-term brain function during childhood and adolescence
Authors:   , van 't Westende Charlotte 
Published: October 2023

In the first part, we investigated brain activity during the neonatal period. Chapter 2 described a systematic review in which an overview was given of the currently available evidence on associations between neonatal quantitative EEG measures (measured before 46 weeks of postmenstrual age) and long-term neurodevelopmental outcomes (at two years of age or older). Conclusions were derived from 24 studies and findings indicated that several quantitative amplitude-integrated and conventional EEG measures, including amplitude, background pattern and power spectrum-related measures, were associated with long-term outcomes in several domains, including the cognitive and motor domains.
In Chapter 3, we investigated the development of functional connectivity during the very early stages of brain development. We found negative associations between postmenstrual age and the functional brain connectivity measure Phase Lag Index (PLI) in all frequency bands (delta, theta, lower alpha, upper alpha, beta, gamma, broadband). The strongest negative association was found in the delta frequency band and strongest connectivity decreases were present between pairs of electrodes with at least one electrode covering the central sulcus.
The findings of Chapter 3 were replicated in Chapter 4. Comparable to the strong negative relation between postmenstrual age and PLI in the delta frequency band in Chapter 3, we found strong negative longitudinal associations between the PLI and postmenstrual age for the delta frequency band and broadband analyses on the group level. The findings showed that there was a strong correlation between quiescence and PLI calculations and suggest that quiescence periods in the neonatal EEG may play an important role in the observed trend of functional connectivity measures during the preterm period.
The second part of this thesis focused on the effect of extremely and very preterm birth on long-term brain activity during childhood and adolescence. In Chapter 5, a group of 55 extremely and very preterm born children was investigated. Quantitative EEG measures were compared between extremely and very preterm born children and showed that relative power and functional connectivity in the upper alpha frequency band were significantly higher in the very preterm born group. In addition, very preterm born children showed more integrated networks than extremely preterm born children in the upper alpha frequency band. There was a significant positive correlation between motor outcome and relative upper alpha power, but no associations were found between cognitive outcomes and quantitative EEG measures.
In Chapter 6, we investigated associations between motor outcome and structural MRI based brain volumes (white matter, deep gray matter, cerebellum, and ventricles), white matter integrity as assessed using diffusion tensor imaging (fractional anisotropy and mean, axial and radial diffusivity), and EEG derived brain activity (relative upper alpha power and upper alpha functional connectivity). In addition to the associations between motor outcome and relative upper alpha power and upper alpha functional connectivity that were found in Chapter 5, ventricular volume, radial diffusivity and mean diffusivity were also significantly correlated to motor outcome.
Chapter 7 was designed to explore differences in functional connectivity, as measured by the PLI and amplitude envelope correlation-corrected version (AEC-c), and network organization in all frequency bands between 47 very preterm born adolescents and 54 age-matched term born controls at 13 years of age. Very preterm born adolescents had higher PLI connectivity and less differentiated network organization in the beta frequency band based on PLI and AEC-c analyses. Lower AEC-c connectivity was associated with higher academic performance and attention skills and less differentiated AEC-c networks were found in those with higher arithmetic skills, reading comprehension and IQ scores over the whole study population (i.e. very preterm born adolescents and controls).