Clinical Center for NICHD/Neonatal Research Network

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ABSTRACT Children born extremely preterm (EP) (<27 weeks gestational age (GA)) are atincreased risk of having a languagedisorder or late language emergence 1-5. The proposed study seeks to identify the neural circuit mechanisms and socio-demographic factors that contribute to variable language outcome in extremely preterm (EP) children at 3 years corrected age (CA). This supplemental funding application is submitted as one of a pair of applications from the University of Pennsylvania/Children's Hospital of Philadelphia (Penn/CHOP) and Cincinnati Children's Hospital Medical Center (CCHMC). The PIs at Penn/CHOP and CCHMC, Drs. DeMauro and Merhar, are PIs of the NICHD Neonatal Research Network (NRN) Clinical Centers at their respective institutions, which serve as the parent studies for the current proposal. The NRN follows all infants born EP and other high-risk infants from birth to 22-26 months CA, collecting developmental outcomes and therapies received, and perinatal, medical, and socio-demographic data. For the proposed project, they engaged highly motivated and qualified junior faculty with expertise in neural imaging and language development from both sites (Dr. Chen from CHOP; Dr. Barnes-Davis from CCHMC). The proposed study employs a suite of magnetoencephalography (MEG) neural measures and language assessments to evaluate if task-based neural measures are differentially associated with variable receptive and expressive language outcome in EP children at 3 years CA in comparison to term-born controls (TC) children. Using tasks developed by Dr. Chen and Dr. Barnes-Davis, neural measures of interest are: (1) auditory encoding processes = M50 latency 6-15, (2) functional connectivity during receptive (story listening) and expressive (verb generation) language processes = weighted phase lag index (wPLI) 16, 17, and (3) resting-state (RS) peak alpha frequency (PAF), a brain rhythm associated with connectivity between neural networks 18-20. Leveraging both the existing CHOP NRN cohort with neonatal and completed developmental data at age 2 years and a CHOP longitudinal TC cohort who have completed longitudinal neuroimaging and developmental data from birth to age 2, MEG and language measures will be obtained in 60 EP and 60 TC children at 3-3.5 years CA. The same MEG task data and language outcome measures will be obtained in the EP and TC cohorts at CCHMC, for a total enrollment of 100 EP and 100 TC participants across two sites, enhancing the power and generalizability of the proposed study. Sharing of methods and data across the two centers permits rapid and efficient data collection of a socioeconomically diverse EP sample. It is anticipated that the elucidation of neural risk factors will provide increased specificity to the nature of variable language outcome in young children born EP. Study findings are also expected to lead to timely and more tailored clinical interventions that shape the maturation of language neural networks and specifically meet the goal of the TALK NOSI, “to engage in activities that will help to elucidate the unique trajectories and needs of late talking children.”