Imprints of extreme prematurity on functional brain networks in school-aged children and adolescents

Cognitive functions emerge from dynamic functional interplay of cortical and subcortical areas that form networks. Preterm birth poses a risk for the formation and functionality of brain networks which may lead to severe brain dysfunctions. Infants born extremely preterm have the highest risk of developing neurocognitive impairments. However, it is still poorly understood how functional brain networks are organized and linked with the cognitive impairments in extremely prematurely born children and adolescents. We applied network-based statistics to study functional network connectivity during two brain-states, resting-state (Rest) and visuospatial working memory n-back tasks (Task), in a unique cohort of extremely preterm-born school-aged children and adolescents (n = 24, mean age 10.3 y, range 7.4-16.4 y) with normal general cognitive abilities and in their term-born peers (n = 22, mean age 9.5 y, range 7.4-13.7 y). We found significant group differences in functional connectivity strength in networks that support complex cognitive performance. The preterm group, compared with controls, modulated functional connectivity between Rest and Task differently within the dorsal attention (DAN, p = 0.016), default mode (DMN, p = 0.026) and visual (VN, p = 0.022) networks, and between DMN - DAN (p = 0.024), DMN - ventral attention network (VAN) (p = 0.035), and DMN - frontoparietal network (FPN) (p = 0.015). The groups also showed opposite age-related changes in connectivity strength within the DAN (Task, p = 0.005; Rest, p = 0.012), DMN (Task, p = 0.015) and FPN (Task, p = 0.002), and between the DAN - VAN (p = 0.047) and DAN - FPN (p = 0.009) during Rest, and FPN - VAN (p =0.028), DAN - FPN (p = 0.006), DMN - DAN (p = 0.042), DMN - VAN (p = 0.023), and DMN - FPN (p = 0.007) during Task. In controls, stronger within-network connectivity associated with better n-back task performance, whereas in the preterm group, stronger between-network connectivity associated with poorer performance. These results suggest that adjustment of functional connectivity to the cognitive demands supports successful performance in school-aged children and adolescents and that extremely preterm birth compromises the dynamics and developmental trajectories of brain networks.