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

项目摘要 婴儿是一个高度脆弱的人群，对他们来说，诊断非典型与典型视觉皮质的能力 发展和及早干预是最重要的。然而，婴儿视觉皮质是如何发育的 除了初级视觉皮质(V1)外，在显微结构和功能上基本上是未知的。这项研究的目的是 是通过：(I)使用创新的定量(QMRI)、扩散(DMRI)和功能 (FMRI)磁共振成像，纵向测量并检查两者之间的关系 生命头两年期间人类视觉系统的显微结构和功能发育(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确定 微结构发育的生物学基础(目标2)。具体来说，Aim 1a将使用qMRI和dMRI 对0~24月龄婴儿视皮层的微结构发育进行纵向测量。我们会：(I) 测试不同视觉区域的发育是否不同，以及(Ii)检查微结构发育是否与 组织修剪或增殖。目标1b将使用dmri和qmri来纵向测量显微结构 0~24月龄婴儿视觉系统白质束发育及其关系探讨 白质和灰质发育之间的关系。Aim 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中的加工，而对视觉类别的反应依赖于 在腹侧颞叶皮质(VTC)的高级视觉区域进行处理，以及(Ii)确定是否起作用以及如何起作用 发育与同一婴儿的微结构发育有关。AIM 2将增强和验证 在0-24个月龄婴儿的组织样本中使用体外组织学进行活体测量。Aim 2a将使用定量组织学 目的：(I)测量V1和VTC皮质髓鞘形成的发展，以及(Ii)将组织学数据与体内的情况联系起来 用于确定哪些神经成像指标与髓鞘形成有关的指标。目标2b将：(1)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 如果发育随皮质的不同而不同，如果它与髓鞘形成有关。Aim 2c将使用转录切割技术 分析以确定基因表达途径并阐明与之相关的分子信号途径 V1和VTC的显微结构发育。拟议的研究具有很高的创新性和开创性，因为 它将首次提供体内和体外相结合的显微结构和功能测量 婴儿期人类视皮层的发育。这项研究很重要，因为它不仅将填补重大空白 在知识方面，还将开发新颖、尖端和开源的量化方法 与生物机制有关的皮质微结构的测量。因此，拟议的研究 具有广泛的社会和临床影响，因为它将导致诊断的非侵入性生物标志物的发展 婴儿的非典型视皮层发育，导致早期发明和更好的终生结果。

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.