Neural markers of late language emergence in preschool children born very and extremely preterm

ABSTRACT Children born extremely preterm (EP; <27 weeks gestational age (GA)) and very preterm (VP; 28 – 32 weeks GA)) are at high risk of having language-related deficits [1-5] compared to term-born control (TC) children. Little is known regarding the neural mechanisms that contribute to the substantial variation in the rate of language development in EP/VP children, with no explanation why some EP/VP preschoolers with delayed language ‘catch up,’ while others receive a diagnosis of language disorder at school age. The PI’s team has extensive experience obtaining brain function (magnetoencephalography (MEG)) and brain structure (magnetic resonance imaging (MRI)) data in infants and young children, with studies from the PI and others showing that variability in language development is due to between-subject variability in the maturation of neural-circuit activity, such as variability across children in their ability to rapidly encode auditory information (i.e., measured via the auditory M50 response latency [39]). Employing a longitudinal design and using multimodal neuroimaging (MEG and MRI), this R01 will identify neural mechanisms contributing to the heterogeneity of language trajectory in EP/VP children at 3, 4, and 5 years corrected age (CA), improving upon already identified clinical and socio-demographic risk factors. This R01 leverages the PI’s current TALK supplement study (3UG1HD068244-13S1), in which MEG, MRI, and language measures are obtained from EP (N = 60) and TC (N = 60) children at age 3 years (Time 1). For this proposed R01, follow-up brain imaging and language measures for these EP and TC children will be obtained at age 4 (Time 2) and 5 years (Time 3), and a new cohort of VP children (N=60) will be recruited and assessed at all 3 time points (3, 4, 5 years corrected age (CA)) to evaluate the specificity of findings across a broader spectrum of prematurity. Source localization is used to examine neural-circuit activity associated with auditory encoding and with receptive and expressive language processes in brain space. Study aims examine group differences in these auditory cortex and language neural measures as well as determine the degree to which the neural measures (single-time-point and rate-of-change) improve prediction of language trajectory and language outcome at 5 years CA, above and beyond clinical/socio-demographic risk factors. The proposed R01 has high impact and captures the maturation of language associated neural activity (local and network activity) that is associated with language ability (current and future). It is anticipated that the elucidation of neural risk factors will provide increased specificity with respect to the nature of variable language outcome in preterm preschoolers. Study findings will advance our mechanistic understanding of neural circuit contributing to language delay and late talking in preterm young children, the R01 study goals in line with the TALK Initiative goal “to create longitudinal datasets and identify optimal measures for differentiating developmental trajectories in late talking children across time.”