Creating Normative Functional Brain Atlases during Infancy There is an increasing interest in exploring the mechanisms underlying early brain functional development using the resting state fMRI (rsfMRI) technique. Such explorations are promising for the detection of early functional connectivity biomarkers that are essential for the development of early diagnosis and intervention schemes for different pediatric neurological disorders such as cerebral palsy and epilepsy. However, given the dramatic functional evolution between infancy and adulthood, there are noteworthy difficulties for early developmental studies which include both the definition of infant-appropriate regions of interest (ROIs) and the accurate interpretation of the resulting functional connectivity patterns. Therefore, the establishment of infant-specific functional brain atlases represents an urgent mission for more rapid progress in the field. Our team has extensive experience in using rsfMRI to delineate normal brain functional connectivity development patterns during infancy and has accumulated a large sample of normal singleton infants (N=174) with longitudinal rsfMRI scans during the first two years of life. The availabilityof such a large-scale dataset provides us a unique opportunity to establish normative functional brain atlases during infancy. In fact, we have demonstrated the feasibility of such an endeavor and delineated the sub-regional functional segregation profile of the insula and thalamus during the first two years of life. Building on these previous experiences and leveraging the large-scale pre-existing data, the proposed study aims to establish a set of normative functional atlases for the first two years of life. Additionally, we will utilize existing behavioral data (i.e., Mullen Sores) measured at 1 and 2 years of age to evaluate the behavioral relevance and significance of the established functional atlases (Aim 1). Secondly, another equally important and unique dataset consisting of 120 dizygotic (DZ) and 88 monozygotic (MZ) twin infants scanned at the same age interval is also available and will be used to: i) independently validate the atlases established based on singleton infants; and ii) examine the associated genetic and environmental contributions to the functional atlases (Aim 2). Upon successful completion of the proposed project, we expect that a software package containing the established infant-specific normative functional brain atlases together with their behavioral correlation, genetic association, and environmental influences, will be made freely available to the early brain development research community to foster more rapid progress in the field (Aim 3). The approach is innovative because it will be the first to apply established functional connectivity clustering techniques to infant data and create normative functional brain atlases during infancy. The proposed research is significant because it is expected to provide the research community with an unprecedented set of references to expedite future explorations of the functional mechanisms underlying both normal and abnormal early brain development.

Public Health Relevance

The establishment of infant-specific functional brain atlases represents an urgent mission for more rapid progress in the study of early brain development. Based on a large sample of normal developing infants including both singletons and twins with longitudinal rsfMRI scans during the first two years of life, this project aims to build a set of normative functional-connectivity-based brain atlases to expedite future explorations of the functional mechanisms underlying both normal and abnormal early brain development

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (NOIT)
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Babcock, Debra J
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Cedars-Sinai Medical Center
Los Angeles
United States
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Gilmore, John H; Knickmeyer, Rebecca C; Gao, Wei (2018) Imaging structural and functional brain development in early childhood. Nat Rev Neurosci 19:123-137
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