Developmental delay (DD) describes the heterogeneous symptoms associated with delay in one or more key aspects of development, including physical, cognitive, communication, social/emotional, and adaptive development. DD is associated with specific diagnoses, such as autism spectrum disorder (ASD), and with global delay or intellectual disability. In some cases the etiology of the delay is known, whereas in other cases, etiology is unknown. The heterogeneity of DD poses problems for identifying underlying mechanisms that may inform intervention and could set them on an optimal trajectory for success and recovery. Although there is significant focus on ASD specifically, many children are first served through early intervention under the broad diagnostic umbrella of DD. Unfortunately, little is known about brain mechanisms or clinical phenotypes associated with shared etiologies in DD, due mainly to the technical challenges of characterizing children at a young age, both behaviorally and with neuroimaging. However, technological advances in both acquisition and denoising of functional connectivity (FC) data may now provide an opportunity to explore these processes in situ. The overarching aim of the proposed study is to explore shared neurobiological etiology in DD and ASD by examining clinical and neurobehavioral indicators, including resting-state fMRI and child clinical outcomes. This proposed research will build on the strengths of our lab by studying two cohorts of children with disabilities, including DD and ASD, that we recruited in early childhood and are following longitudinally. These 255 children in our study cohorts are now in middle childhood. Middle childhood is a time of significant brain changes, including the initiation of large structural changes, such as myelination and synaptic pruning [17, 2], putatively critical in the pathophysiology of ASD [18?20]. Preliminary data from 34 5- and 6-year old children with DD strongly demonstrate the feasibility of our approach and our ability to successfully scan young children with DD and ASD. In the proposed research we will recruit 120 children from our existing cohorts (N = 80 DD; N = 40 ASD) and characterize their clinical and neuropsychological functioning and examine FC through resting-state fMRI. We will apply a recent denoising pipeline [25] from the Human Connectome Project (HCP) to minimize motion-related artifacts in resting-state scans with an admittedly challenging cohort in order to test our hypotheses of shared and unique neurobiological etiology of DD and ASD. Although there is little consensus about the best approach for minimizing micromovements in FC data, this exploratory project will quantify and test the effect of motion. Further, this project is specifically designed to provide extensive open data sharing of all the data that are acquired, so that other novel pipelines could replicate or extend this work readily. If successful, this work could provide novel intervention targets for treatment of DD and provide a roadmap for characterizing children during this critical time period.

Public Health Relevance

Little is known about brain mechanisms associated with developmental delay (DD) and autism spectrum disorder (ASD), due to symptom heterogeneity and difficulties with brain imaging children with disabilities. Understanding brain mechanisms may lead to more effective interventions with this population, a public health priority. This proposal seeks to identify common and unique brain patterns in children (ages 6?10 years) with DD and ASD by tackling technical challenges of collecting MRI data in this population and through data sharing.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Child Psychopathology and Developmental Disabilities Study Section (CPDD)
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Gilotty, Lisa
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University of Oregon
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