Neuroimaging and histological investigations of human visual cortex development

项目总结 大量的研究已经阐明了成人视皮层的功能和结构。然而， 由于两个主要原因，人类视觉皮质的发育机制在很大程度上是未知的。首先，有一个 缺乏关于人脑初级视皮层(区)外发育的宏观和微观解剖数据 V1)。其次，之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，但 这些模型不足以解释人类视觉皮质的发育，视觉皮质的结构 在其他哺乳动物中不存在，并显示出比其他物种更持久的发育。 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，该项目将 在斯坦福大学Grill-Spector实验室之间产生令人兴奋的新合作，该实验室是 加州大学旧金山分校的儿科活体神经成像和帕雷德斯实验室，他是人类儿科组织学和 死后脑组织的体视学研究。在这里，我们建议衡量人类的结构发展 用神经成像和免疫组织化学(IHC)方法研究婴儿期的视皮层。前者 将使用非侵入性神经成像来确定视皮层纵向的宏观结构发育 在生命的第一年中有3个时间点。后者将在婴儿死后大脑中使用IHC和体视学来 阐明细胞群体及其微观结构是如何发展的。我们建议将重点放在主要视觉上 皮层(V1)，以及面孔和位置选择区域，因为它们(I)可以在个体大脑中从 单独的宏观解剖标志，(Ii)位于不同的细胞构筑区域，以及(Iii)显示不同的 发展：V1首先成熟，脸部选择区域最后。在目标1中，我们将在体内测量结构 婴幼儿视皮层的发育。利用定量磁共振成像(QMRI)中的创新 和扩散磁共振成像(DMRI)，我们将首次测量活体结构的发展 初级视皮层(V1)和高级视皮层(面孔和位置选择区域)在3个时间点的变化 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 人眼视皮层的微结构发育。利用免疫组化技术，我们将研究细胞的发育。 神经细胞的类型(神经元、星形胶质细胞、少突胶质细胞)和细胞结构(树突、突触和髓鞘) 婴儿大脑样本，包括距骨沟(V1所在的区域)、FG(面部选择区域 驻留)和Cos(位置选择区域驻留的位置)。我们将测试相同的微观结构机制是否 发生在V1和高级视觉皮质，并从IHC数据生成模型，以与 目标1.拟议的研究将提供关键数据，填补视觉皮质知识的重大空白 发展，并将铺平一种新的、尖端的方法，定量地、基本真实地衡量 婴儿大脑皮质的微结构。我们的研究结果对开发非 典型和非典型脑发育的侵袭性生物标志物。

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.