Early Developmental Determinants and Pathways in Down syndrome - This Pathway to Independence Award (K99/R00) will facilitate my transition to an independent scientist who conducts innovative research on mechanisms and pathways of developmental and cognitive risk outcomes in Down syndrome (DS). Down syndrome is the most common childhood genetic disorder and characterized by substantial phenotypic impairments across several areas of development, including motor, attention, communication, and cognition. There has been virtually no investigation, however, into the developmental pathways of early phenotypic impairments in motor or attention, or their role as determinants for impaired cognitive or communication outcomes in DS. Motor and attention are key developmental domains effortlessly coordinated to support communication and cognitive learning in typical development. Delayed achievement of key motor milestones in DS – postural control in particular – has serious implications for the development of infant attention, as well as for outcomes related to communicative and cognitive functioning through compromised learning opportunities. Therefore, I propose to investigate the dynamic influence between postural control and attention in infants with DS and determine their mutual or distinct role in impaired communication and cognitive outcomes at 24-months in DS. I will characterize the behavioral and physiological features of postural control and attention by quantifying the kinematics of postural variability and defining heart-rate phases of attention. I will examine the dynamics of how these features influence one another during discrete learning opportunities, and also across development to inform their role as determinants on communication and cognitive risk outcomes in DS. Examining the biobehavioral concordance between these constructs is an innovative, precise, and multi-method approach that can yield better insight into the developmental complexity in DS. This will be accomplished across three complementary studies that will provide advanced training and employ cutting-edge methodology. Training initiatives will be accomplished across two studies implemented during the mentored K99 phase, and then systematically applied to a longitudinal study during the independent R00 phase. The specific aims across these studies are: 1) Identify differences in physiological and behavioral facets of attention at 12-months and their role in communication and cognitive skill outcomes at 24-months as a function of postural control in infants with DS (K99 phase); 2) Determine the concordance across biobehavioral facets of attention and the reciprocal association between biobehavioral attention and postural control at 9, 12, and 18-months in infants with DS (K99/R00 phase); and 3) Characterize the biobehavioral pathways and developmental dynamics of attention and postural control across 9, 12, and 18-months and test whether these domains have a shared or unique influence on communication or cognitive skill outcomes at 24-months in DS (R00 phase). This novel and multi-method biobehavioral approach will shed light on the pathogenesis of impaired motor and attention in DS. Further, findings will contribute to advanced phenotyping approaches of infant development in DS and serve as an initial step in the development of targeted interventions. My team of incredibly strong mentors and one collaborator is uniquely poised to assist and promote my training and research goals, and to ensure my successful transition to an independent scientist.
