Integrate neuroimaging, molecular quantitation, and cytoarchitecture to elucidate the development of myelination in human visual cortex. - PROJECT SUMMARY/ABSTRACT Visual areas show heightened plasticity in the first year of life, making this time period a key window for identifying and intervening in the case of developmental atypicalities. Myelination is a likely mediator of experience- dependent plasticity in visual cortex, as it occurs rapidly in the first two years of life and can influence neuronal communication, learning, and memory. Yet, little is known about the contribution of myelination to the development of human visual circuits. To address these gaps in knowledge, the goal of this research is twofold: 1) Using innovative quantitative magnetic resonance imaging (qMRI), longitudinally measure the microstructural development of the human visual system during the first year of life, and (ii) Using advanced histological methods in pediatric and adult samples of visual cortex, determine the development of myelination in visual cortex and validate in vivo metrics of microstructural development. In three visual areas with distinct functional development (primary V1 in calcarine sulcus, place-selective cortex in collateral sulcus, and face-selective cortex in fusiform gyrus), I will (i) test the hypothesis that human visual areas with prolonged functional development (i.e. face-selective area) exhibit prolonged myelination and (ii) validate whether the development of myelin can be measured with specific qMRI metrics. First, I will use histology to map the development of myelin across visual cortex (Aim 1). Next, I will use qMRI to determine the in vivo longitudinal development of visual cortex microstructure (Aim 2). Finally, I will validate whether myelination can explain in vivo measures of cortical development using a combination of in vivo and ex vivo qMRI, quantitative mass spectrometry, and histology (Aim 3). Achieving these aims will resolve the contribution of myelin to the development of human visual cortex and validate which MR metrics can be used as potential diagnostic tools in atypical neurodevelopment. My sponsor, Dr. Kalanit Grill-Spector, is an expert in pediatric in vivo neuroimaging, and our collaborator, Dr. Mercedes Paredes, is an expert in pediatric ex vivo histology. Their combined expertise and strong mentorship will guarantee my training goals are met: developing a strong neurodevelopmental research question, completing the proposed research, and obtaining training crucial to furthering my future career goals. An F31 NRSA fellowship would enable me to cultivate my neurodevelopmental and human neuroimaging skillsets, progressing me towards my goal of becoming an academic principal investigator studying activity-dependent myelination in health and disease to develop interventions in cases of atypical myelination.
