Electroencephalographic functional connectivity analysis in preterm infants

Preterm birth coincides with a critical period of brain development and can disturb the early organization of both the structural network and the large-scale functional connections within it, which are imperative for normal neurocognitive development. Despite the well-mapped structural connectome, the development of the functional networks, and the effects of prematurity on them, are poorly understood. Further, recent endeavours to improve neurocritical care of preterm infants via environmental enrichment (EE) strategies exerted in the neonatal intensive care unit (NICU) lack assessment of the direct effects on their therapeutic target, functional brain networks. Scalp electroencephalography (EEG) provides a method for recording cortical activity with high temporal resolution. Functional cortico-cortical networks may be identified by estimating interareal synchronization between the phase or amplitude attributes of cortical signals from distinct brain regions with measures of functional connectivity (FC). There is extensive research on FC in adults, but studies on neonates are scarce and require specific methods adapted for the physiological and technical requirements of this population. This Thesis uses FC analysis methods optimized on neonates to study the developing functional networks on preterm populations during the neonatal period. In Study I, prematurity-related changes in FC were investigated at term age, and correlations between functional networks and later neurodevelopmental outcomes were explored. Spectrally and regionally distinct network differences were found between the cohorts, and the correlation of networks to later clinical outcomes was found to be amplified in the preterm cohort. In Study II, the effects of Family Nurture Intervention (FNI), a bedside EE intervention aiming to facilitate the parent-infant emotional contact, on functional networks were assessed at term age. The results showed a clinically relevant change in the FC levels of infants receiving FNI, which even rendered the intervention cohort comparable to a cohort of healthy term-born controls. In Study III, the development of distinct neuronal coupling modes was investigated during the neonatal period from the last trimester to the first weeks after term age. The findings indicated differential development of different coupling modes, providing developmental growth charts which are consistent with established neonatal neurophysiological mechanisms. The results together give new insight on the functional networks of preterm infants, on their longitudinal development, and on the effect of the endogenous parent-infant contact on network development. This Thesis supports FC measures as a clinically relevant tool with potential for use in both basic scientific research and clinical intervention studies in neonates.