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

• 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
• 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

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.

项目摘要 婴儿是一个高度脆弱的人群，诊断非典型与典型视觉皮层的能力 开发和介绍不可能更重要。但是，婴儿视觉皮层如何发展 微观结构和功能上在很大程度上是未知的主要视觉皮层（V1）。这项研究的目标 （i）使用创新的定量（QMRI），扩散（DMRI）和功能性来填补知识中的明显空白 （fMRI）磁共振成像，纵向测量并检查 人类视觉系统在生命的头两年中的微观结构和功能发展（AIM 1）。 （ii）在视觉皮层的小儿样本中使用先进的组织学和定量方法，确定 微观结构发展的生物基础（AIM 2）。具体而言，AIM 1A将使用QMRI和DMRI 纵向测量婴儿视觉皮层的微观结构发育从0-24个月开始。我们将：（i） 测试开发是否在视觉区域各不相同，（ii）检查微结构发展是否与 组织修剪或增殖。 AIM 1B将使用DMRI和QMRI纵向测量微观结构 从0-24个月开始开发婴儿视觉系统的白质区域并检查关系 在白色和灰质的发展之间。 AIM 1C将使用fMRI进行：（i）检查皮质的发展 对视觉对比的响应，依赖于V1中的处理以及依赖视觉类别的响应 在腹侧颞皮层（VTC）中的高级视觉区域进行处理，（ii）确定功能是否以及如何功能 发展与同一婴儿的微观结构发展有关。 AIM 2将增加并验证 在0-24个月大的组织样品中使用离体组织学的体内指标。 AIM 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相关联 确定哪些神经影像学指标与髓鞘形成的指标。 AIM 2B将：（i）量化 V1和VTC中多种细胞类型的密度（所有细胞，神经元，星形胶质细胞和少突胶质细胞），以及（ii）测试 如果在皮质膨胀以及与髓鞘相关的情况下的发展变化。 AIM 2C将使用转录组 分析以确定基因表达途径并阐明与 V1和VTC中的微观结构发展。拟议的研究是高度创新性和开创性的 它将提供第一个合并的体内和离体测量值 在婴儿期的人类视觉皮层的发展。这项研究很重要，因为它不仅会填补大量空白 在知识上，还将开发出新颖，尖端和开源方法的定量方法 与生物学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，因为它将导致非侵入性生物标志物的发展来诊断 婴儿的非典型视觉皮层发展，导致早期发明和更好的终身结果。