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

视觉皮层是人脑微观结构和功能发育的窗口

基本信息

批准号：
10612974
负责人：
Kalanit Grill-Spector
金额：
$ 59.9万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10612974
关键词：
Age Astrocytes Biological Biological Markers Brain Categories Cells Childhood Clinical Collaborations Contrast Sensitivity Coupled Custom Data Development Diagnosis Diffusion Diffusion Magnetic Resonance Imaging Functional Magnetic Resonance Imaging Gene Expression Generations Genes Goals Histologic Histology Human Human Development Imaging Device Individual Infant Infant Development Iron Knowledge Life Link Measurement Measures Methodology Methods Mission Molecular Multimodal Imaging Myelin Neurons Oligodendroglia Outcome Pathway interactions Personal Satisfaction Proliferating Relaxation Research Sampling Signal Pathway Societies Structure Systems Development Temporal Lobe Testing Tissue Sample Tissue-Specific Gene Expression Tissues Vision Visual Visual Cortex Visual System Vulnerable Populations area striata cell type clinically significant computerized tools extrastriate visual cortex gray matter imaging modality improved in vivo infancy innovation invention multimodal neuroimaging myelination neuroimaging neuromechanism novel open source response tool transcriptomics vision development white matter

项目摘要

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.

项目概要婴儿是一个高度脆弱的人群，能够诊断非典型与典型视觉皮层发展和早期干预非常重要。然而，婴儿视觉皮层是如何发育的在初级视觉皮层（V1）之外，其微观结构和功能在很大程度上是未知的。本研究的目标的目标是通过以下方式填补明显的知识空白：(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生命头两年期间人类视觉系统的微观结构和功能发育（目标 1）。 (ii) 在儿科视觉皮层样本中使用先进的组织学和定量方法，确定微观结构发育的生物学基础（目标 2）。具体来说，目标 1a 将使用 qMRI 和 dMRI 纵向测量 0-24 个月婴儿视觉皮层的微观结构发育。我们将：（一）测试不同视觉区域的发育是否存在差异，以及 (ii) 检查微观结构发育是否与组织修剪或增殖。目标 1b 将使用 dMRI 和 qMRI 纵向测量微观结构 0-24 个月婴儿视觉系统白质束的发育并检查其关系白质和灰质发育之间。目标 1c 将使用功能磁共振成像来：(i) 检查皮质的发育对视觉对比度的响应依赖于 V1 中的处理，对视觉类别的响应依赖于 V1 中的处理腹侧颞叶皮层 (VTC) 高级视觉区域的处理，以及 (ii) 确定是否以及如何发挥功能发育与同一婴儿的微观结构发育有关。目标 2 将在使用 0-24 个月大的组织样本的离体组织学进行体内指标。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育情况，以及 (ii) 将组织学数据与体内联系起来确定哪些神经影像学指标与髓鞘形成相结合。目标 2b 将：(i) 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) 测试不同皮质区域的发育是否存在差异，以及是否与髓鞘形成有关。 Aim 2c 将使用转录组学分析以确定基因表达途径并阐明与相关的分子信号传导途径 V1 和 VTC 中的微观结构发展。拟议的研究具有高度创新性和开创性它将首次提供微观结构和功能的体内和离体组合测量人类视觉皮层在婴儿期的发育。这项研究很重要，因为它不仅可以填补重大空白知识方面，还将开发新颖的、前沿的、开源的定量方法与生物机制相关的皮质微观结构的测量。因此，拟议的研究具有广泛的社会和临床影响，因为它将导致非侵入性诊断生物标志物的开发婴儿视觉皮层发育不典型，导致早期发明和更好的终生结果。