Longitudinal assessment of human brain connectome changes across the birth transition in both term and preterm pregnancies

PROJECT SUMMARY/ABSTRACT My research goal is to meaningfully advance our understanding of human brain development during the early stages of human life by pairing advanced neuroimaging approaches with rich, multi-level biobehavioral assessment strategies. To date, I have obtained extensive training in fMRI data processing, brain network analysis, and a basic understanding of deep learning. My career development plan builds on this knowledge base by enhancing my technical skillset and providing crucial, intensive training in developmental neuroscience, infant behavioral assessment, and advanced longitudinal statistical methodologies. The completion of the proposed research and training is essential preparation for my future as leader of a cross- disciplinary team seeking to innovate and advance early human clinical and developmental neuroscience research. Research Project: Understanding the sequence and timing of brain functional circuit development at the beginning of human life is critically important from both normative and clinical perspectives. Yet, we presently lack rigorous examination of the longitudinal emergence of human brain functional circuitry over the birth transition. Using multiple cutting-edge methodologies, the goal of this K99/R00 is to map developmental trajectories and construct a brain maturational index for each individual (the “brain age”) for this period (Aim 1). In the K99 portion of this award, we will leverage the largest available fetal functional MRI dataset known to us, with more than 450 longitudinal fetal and neonatal fMRI scans collected in healthy volunteers. We will also address an important public health issue, prematurity, by comparing the developmental trajectory and the “brain age” between cases born preterm and those delivered at term (Aim 2). The R00 project will relate brain development across birth to infant behavioral outcomes and explore the putative role of maternal immune activation (MIA) (Aim 3). The significance of this work lays in its potential for unveiling fundamental aspects of brain development at the beginning of human life, and in development of a new longitudinal basis for drawing comparisons between typical and atypical development. Armed with knowledge about disruptions in early developing circuitry, we can begin to develop therapies with potential to directly target affected systems. The innovation of the work lays in utilization of the one-of-the-kind longitudinal perinatal imaging dataset, in implementation of the state-of-the-art fMRI data processing methodology, in being the first to map both typical and atypical brain development over the birth transition, and in being the first to develop a brain imaging- derived maturational index beginning before birth.