Longitudinal investigation of neuroplasticity during pregnancy using multiple imaging modalities - Modified Project Summary/Abstract Section The peripartum period is a time of dramatic neurobiological change, but these changes are not well understood across time. The peripartum period is also marked with high rates of depression. As such, the proposed research project aims to characterize brain changes prospectively across pregnancy to better understand the implications of neurobiological changes on mental health. Our multidisciplinary team has the necessary expertise (developmental neuroscience, peripartum mental health, imaging science, bioethics, and maternal– fetal medicine) to safely conduct an advanced neuroimaging study with this understudied population. Our team members have worked together to administer repeated magnetic resonance imaging (MRI) scans with multiple scan modalities to examine within- and between-person alterations in brain structure and function during this period of neurobiological change. Data from our preliminary studies scanning pregnant women longitudinally provide the foundation for this innovative project. In 100 pregnant women we will use advanced multimodal MRI (structural, diffusion, and functional MRI) to study brain changes across 9 months of pregnancy using an accelerated longitudinal design with planned missingness so that each participant contributes only 4 scans across their pregnancy. First, we aim to characterize changes in brain structure and function across pregnancy, including the magnitude and pattern of change in various brain volume metrics, white matter microstructure, and functional connectivity (Aim 1). Preliminary data suggests a .41% decrease in total brain volume per week during pregnancy, as well as decreases in cortical volume, gray matter, and cortical thickness. Second, we aim to investigate hormonal changes (cortisol, estradiol, progesterone, and testosterone) underlying alterations in brain structure and function (Aim 2). Our preliminary data suggest that increases in progesterone level partially explain reductions in gray matter volume, while surges in progesterone and estradiol levels may be linked to increased white matter microstructure. Third, we aim to examine the potential functional consequences of brain changes (Aim 3). To explore the potential functional consequences of changes in brain structure and function, we will collect EEG data in response to reward and threat, assess self-reported negative affect, and evaluate cognitive function using the NIH toolbox. Participants will also report on peripartum depressive symptoms at each assessment wave and again at 8 weeks postpartum. The project's innovative planned missingness design will provide unprecedented insights into the neurobiological changes that occur across the full course of pregnancy without overburdening participants. By filling the knowledge gap regarding brain changes during pregnancy, the findings will set the foundation for translational work given the impact peripartum depression has on individuals and their families.