Project Summary Babies are a highly vulnerable population for which the ability to diagnose atypical vs. typical visual cortex development and intervene early could not be of greater importance. However, how infant visual cortex develops microstructurally and functionally is largely unknown outside primary visual cortex (V1). The goal of this research is to fill glaring gaps in knowledge by: (i) Using innovative quantitative (qMRI), diffusion (dMRI), and functional (fMRI) magnetic resonance imaging, to longitudinally measure and examine the relationship between microstructural and functional development of the human visual system during the first two years of life (Aim 1). (ii) Using advanced histological and quantitative methods in pediatric samples of visual cortex, determine the biological underpinnings of microstructural development (Aim 2). Specifically, Aim 1a will use qMRI and dMRI to longitudinally measure the microstructural development of infant visual cortex from 0-24 months. We will: (i) test if development varies across visual areas, and (ii) examine if microstructural development is associated with tissue pruning or proliferation. Aim 1b will use dMRI and qMRI to longitudinally measure the microstructural development of the white matter tracts of the infant visual system from 0-24 months and examine the relation between white and gray matter development. Aim 1c will use fMRI to: (i) examine the development of cortical responses to visual contrast, which rely on processing in V1, and responses to visual categories, which rely on processing in high-level visual regions in ventral temporal cortex (VTC), and (ii) determine if and how functional development is related to microstructural development in the same infants. Aim 2 will augment and validate in vivo metrics using ex vivo histology in tissue samples of 0-24 months-olds. Aim 2a will use quantitative histology to (i) measure the development of cortical myelination in V1 and VTC, and (ii) relate histological data to in vivo metrics to determine which neuroimaging metrics are coupled with myelination. Aim 2b will: (i) quantify the densities of multiple cell types (all cells, neurons, astrocytes, and oligodendrocytes) in V1 and VTC, and (ii) test if development varies across cortical expanses and if it is tied to myelination. Aim 2c will use transcriptomic analyses to determine gene expression pathways and elucidate molecular signaling pathways associated with microstructural development in V1 and VTC. The proposed research is highly innovative and groundbreaking as it will provide the first combined in vivo and ex vivo measurements of the microstructural and functional development of human visual cortex in infancy. This research is important as it will not only fill significant gaps in knowledge but also will develop novel, cutting-edge, and open-source methodologies for quantitative measurements of cortical microstructure that are linked to biological mechanisms. Thus, the proposed...