Neural basis of language trajectories in extremely preterm children

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PROJECT SUMMARY/ABSTRACT Prematurity is a public health crisis impacting 10% of children. Children born extremely preterm (EPT) have a significant risk for language difficulties which can adversely impact quality of life. Current tools do not account for trajectories, focus on risk factors which are often not modifiable, and fail to prioritize outcomes that matter to families. There is a critical need for advanced neuroimaging studies of extremely preterm children at preschool age, a dynamic period of language development, to investigate the trajectories of language development and to evaluate the neural basis of difficulties in language in preterm children as compared to term comparisons. The proposed study will address this need by leveraging an existing cohort of 35 children born at <27 weeks gestation who are part of the Neonatal Research Network (NRN) Follow-up study and have received language assessments at 2 years corrected age in Cincinnati to be seen again at 3-3.5 years corrected. We will recruit 35 term comparison children to undergo the same language assessments and magnetoencephalography (MEG) and structural MRI at the same time point. Additionally, we will coordinate data collection with the Children’s Hospital of Philadelphia, an NRN site and frequent collaborator, to increase the power and validity of our research findings. Our previous studies of language and neuroimaging in preterm children have shown a specific pattern of increased brain activity in preterm children with normal language development as compared to term children. We therefore hypothesize that the trajectory of language skills in preterm children will relate to functional connectivity measured by MEG as children perform language tasks, representing a positive adaptation in the setting of prematurity-induced dysmaturation. The objective of the proposed study is to assess the trajectory of and neural mechanisms underlying language delay in EPT (including auditory encoding, processing of naturalistic speech during stories listening, and covert verb generation). The first aim is to assess the trajectory of language skills from 2 to 3 years of age in extremely preterm children (at least 35 from Cincinnati, at least 85 across sites). The second aim is to assess language skills at 3 years of age, including expressive language or talking, in EPT and age-matched TC (at least 35 from Cincinnati, at least 85 across sites). The third aim is to assess the brain activity and connectivity supporting language in EPT and describing any differences between EPT and TC during language tasks (stories listening, verb generation auditory encoding) using MEG. We will relate this to language trajectories for the group of EPT children. More comprehensive assessments of language skills and neuroimaging during this dynamic critical period will help elucidate the mechanisms underlying normal and delayed language development and will be highly hypothesis-generating for future longitudinal work promoting neuroprotective strategies for preterm children.