Visual Cortex as a Window to Microstructural and Functional Development of the Human Brain

项目摘要 婴儿是一个非常脆弱的群体，诊断非典型视觉皮层与典型视觉皮层的能力 发展和及早干预是最重要。然而，婴儿的视觉皮层是如何发育的， 在初级视觉皮层（V1）之外，微结构和功能在很大程度上是未知的。本研究的目的 通过以下方式填补知识的巨大空白：（i）使用创新的定量（qMRI），扩散（dMRI）和功能 （fMRI）磁共振成像，纵向测量和检查之间的关系， 人类视觉系统在生命最初两年的微观结构和功能发育（目标1）。 (ii)使用先进的组织学和定量方法，在儿童视皮层样本中， 微结构发展的生物学基础（目标2）。具体而言，目标1a将使用qMRI和dMRI 纵向测量0-24月龄婴幼儿视皮层的微结构发育。我们将： 测试发展是否在视觉区域之间变化，以及（ii）检查微结构发展是否与 组织修剪或增殖。目的1b将使用dMRI和qMRI纵向测量显微结构 0-24个月婴儿视觉系统的白色物质束的发育，并检查 在白色和灰质发育之间。目的1c将使用功能磁共振成像：（i）检查皮质发育 对视觉对比度的反应，依赖于V1中的处理，以及对视觉类别的反应，依赖于 在腹侧颞叶皮层（VTC）的高级视觉区域的处理，以及（ii）确定是否以及如何功能 发育与同一婴儿的微结构发育有关。Aim 2将在 在0-24月龄的组织样品中使用离体组织学的体内度量。目标2a将使用定量组织学 （i）测量V1和VTC中皮质髓鞘形成的发展，以及（ii）将组织学数据与体内 这些指标用于确定哪些神经成像指标与髓鞘形成相关联。目标2b将：㈠量化 V1和VTC中多种细胞类型（所有细胞、神经元、星形胶质细胞和少突胶质细胞）的密度，以及（ii）测试 如果发育在不同的皮层扩张中变化，如果它与髓鞘形成有关。Aim 2c将使用转录组学 分析以确定基因表达途径并阐明与以下相关的分子信号传导途径 V1和VTC的显微结构发展。拟议的研究具有高度创新性和开创性， 它将提供第一个结合在体内和体外测量的微观结构和功能， 人类视觉皮层在婴儿期的发育。这项研究很重要，因为它不仅将填补重大空白， 知识，而且还将开发新的，尖端的，开源的定量方法， 皮质微结构的测量与生物机制有关。因此，建议的研究 具有广泛的社会和临床影响，因为它将导致非侵入性生物标志物的发展，以诊断 婴儿的非典型视觉皮层发育，导致早期发明和更好的终身结果。

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 research has broad societal and clinical impact as it will lead to development of non-invasive biomarkers to diagnosis atypical visual cortex development in infants, leading to early inventions and better life-long outcomes.