Biomarkers of Developmental Language Disorder and Their Relationship to Language Impairment

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Project Summary/Abstract The goal of the proposed fellowship is to explore the relationship between brain function and language impairment in children with Developmental Language Disorder (DLD) by investigating two measures of brain function, cerebral blood flow (CBF) and functional connectivity. DLD is a pervasive developmental disorder with childhood onset that can persist into adulthood and affect psychosocial relationships and socioeconomic outcomes, yet little is understood about the brain correlates of DLD. It is believed that some combination of genetic and environmental factors influences brain development in this population, but the relatively few neuroimaging studies have revealed inconsistencies regarding the ways in which these factors contribute to language impairment. We argue that functional brain differences may underlie these discrepancies. Therefore, the research proposed here addresses the critical need to better characterize the underlying neurobiological mechanisms that contribute to language impairment in children with DLD. In alignment with the NIDCD’s mission, this project seeks to identify biomarkers of DLD that can inform development of targeted interventions aimed at improving the functional outcomes for people with DLD. This will be achieved by comparing resting state CBF patterns in children with DLD (ages 9-11) to typically developing (TD) age-matched peers (Aim 1). Currently there are only a handful of studies that have investigated CBF in DLD, but these studies had poorly matched participants and used invasive and spatially limited methods. To our knowledge, this project will be the first to utilize arterial spin labeling, a non-invasive method for capturing whole brain CBF patterns. In addition, we will compare intrinsic functional connectivity (iFC) patterns within the language network in these two groups using functional connectivity MRI (Aim 2). To date, there are no studies that have investigated iFC in DLD, yet this method has revealed relationships between altered functional architecture and behavior in other neurodiverse populations, making it reasonable to suspect that children with DLD may also demonstrate a similar relationship. Finally, we will compare the relationship between the two measures from aims 1 and 2 to scores on linguistic and non-linguistic assessments to determine if they are related to language behavior (Aim 3). We will also investigate whether there is a correlation between CBF and functional connectivity patterns, as research has revealed that some neurodiverse populations demonstrate deviations in these patterns when compared to neurotypical populations. The proposed research will provide a novel approach to understanding the connection between underlying brain function and language behavior in DLD. The applicant’s experienced training team and available resources through two highly productive research institutions and mentoring labs, make them well- suited for completing the proposed research and contributing important findings to a critical and understudied area of research.