Neuroimaging and histological investigations of human visual cortex development

项目摘要 广泛的研究已经阐明了成人视觉皮层的功能和结构。但 由于两个主要原因，人类视觉皮层的发育机制在很大程度上是未知的。一是 缺乏关于人脑初级视皮层（区域）以外发育的宏观和微观解剖学数据 V1）。其次，以前对大脑发育的微观结构研究主要是在动物模型中进行的， 这些模型不足以阐明人类视觉皮层的发育，视觉皮层的结构 在其他哺乳动物中不存在，并且比其他物种表现出更持久的发展。 为了解决这一明显的知识差距，我们提出了一个开创性的研究项目， 在斯坦福大学的Grill-Spector实验室之间产生了一个令人兴奋的新合作， 儿科体内神经成像和加州大学旧金山分校的Paredes实验室，他是人类儿科组织学专家， 死后脑组织的体视学在这里，我们建议衡量人类的结构发展， 使用神经影像学和免疫组织化学（IHC）方法研究婴儿期视觉皮层。前 将使用非侵入性神经成像来确定视觉皮层纵向的宏观结构发育， 出生后第一年的3个时间点。后者将在死后婴儿大脑中使用IHC和体视学， 阐明细胞群体及其微观结构如何发展。我们建议专注于主要视觉 皮质（V1），以及面部和位置选择区域，因为它们（i）可以在个体大脑中识别， 宏观解剖标志单独，（ii）位于不同的细胞结构区域，和（iii）显示差异 发育：V1首先成熟，面部选择性区域最后成熟。在目标1中，我们将测量体内结构 婴儿视觉皮层的发育。使用定量磁共振成像（qMRI）的创新 和扩散磁共振成像（dMRI），我们将首次在体内测量结构发展 3个时间点的初级视皮层（V1）和高级视皮层（面部和位置选择区域） 在生命的第一年（2，7和12个月）。在目标2中，我们将定量测量细胞和 人类视觉皮层的微结构发展。利用免疫组化，我们将检查细胞的发育， 类型（神经元，星形胶质细胞，少突胶质细胞）和细胞结构（树枝状，突触和髓鞘） 婴儿大脑样本，包括距状沟（V1所在的地方），FG（面部选择性区域 驻留）和CoS（其中位置选择区域驻留）。我们将测试是否相同的微观结构机制 发生在V1和高级视觉皮层，并从IHC数据产生模型，以与神经成像数据相关， 目标1.这项拟议中的研究将提供关键数据，填补视觉皮层知识的重大空白。 发展，并将铺平了一个新的，先进的方法，定量，地面实况测量 婴儿大脑皮层的微观结构我们的研究结果对发展非- 典型和非典型脑发育的侵入性生物标志物。

PROJECT SUMMARY Extensive research has elucidated the function and structure of adult human visual cortex. However, the developmental mechanisms of human visual cortex are largely unknown for two main reasons. First, there is a paucity of macro-and micro-anatomical data on human brain development outside primary visual cortex (area V1). Second, prior microstructural research on brain development has been done mostly in animal models, but these models are inadequate for elucidating the development of human visual cortex, which has structures that do not exist in other mammals and shows a more protracted development than other species. To address this glaring gap in knowledge, we propose a groundbreaking research project that will generate an exciting, new collaboration between the Grill-Spector lab at Stanford University, who is expert in pediatric in vivo neuroimaging and the Paredes lab at UCSF, who is expert in human pediatric histology and stereology in postmortem brain tissue. Here, we propose to measure the structural development of human visual cortex during infancy using neuroimaging and immunohistochemistry (IHC) methods. The former will use noninvasive neuroimaging to determine macrostructural development of visual cortex longitudinally over 3 timepoints during the first year of life. The latter will use IHC and stereology in postmortem infant brains to elucidate how cellular populations and their microstructures develop. We propose to focus on primary visual cortex (V1), as well as face- and place-selective regions as they (i) can be identified within individual brains from macroanatomical landmarks alone, (ii) are located in different cytoarchitectonic regions, and (iii) show differential development: V1 matures first and face-selective regions last. In Aim 1, we will measure in vivo structural development of visual cortex in infants. Using innovations in quantitative magnetic resonance imaging (qMRI) and diffusion magnetic resonance imaging (dMRI) we will measure for the first time in vivo structural development of primary visual cortex (V1) and high-level visual cortex (face- and place-selective regions) during 3 timepoints in the first year of life (2, 7, and 12 months). In Aim 2, we will quantitatively measure cellular and microstructural development of human visual cortex. Using IHC, we will examine the development of cell types (neurons, astrocytes, oligodendrocytes) and cellular structures (arborization, synapses, and myelin) of infant brain samples that include the calcarine sulcus (where V1 resides), FG (where face-selective regions reside), and CoS (where place-selective regions reside). We will test if the same microstructural mechanisms occur in V1 and high-level visual cortex and produce models from IHC data to relate to neuroimaging data in Aim 1. The proposed research will provide key data that will fill significant gaps in knowledge on visual cortex development, and will pave a new, cutting-edge methodology for quantitative, ground-truth measurements of cortical microstructure in infants. The outcome of our research has important implications for developing non- invasive biomarkers of typical and atypical brain development.