Applications of high resolution fMRI in ultra-high field (7T) in revealing developmental disorders underlying amblyopia

总结 弱视是由于儿童早期双眼视觉的破坏而导致的视觉障碍。这 障碍影响视觉皮层内的精细尺度结构的功能，例如视觉皮层中的眼优势柱。 纹状视皮层（V1）和神经柱，包括视觉内的大细胞和小细胞流 区域V2、V3、V3 A、V4和MT。这种发育障碍导致各种知觉障碍， 2D空间失真，3D感知敏锐度下降和异常的整体运动感知。 弱视是最常见的视觉障碍之一，影响世界上大约3%的人。 人口（仅美国就有1000万人）。尽管弱视的患病率很高， 影响视知觉，我们的知识，其影响的视觉皮层处理很大程度上是有限的， 基于动物中的侵入性技术（例如单细胞记录）的发现。这主要是由于技术 常规神经成像技术的局限性（例如，低空间分辨率），通常用于人类 研究，与那些受弱视影响的皮质结构的大小相比。 然而，随着高分辨率神经成像技术的最新进展，基于使用超高场 扫描仪，现在可以定位和研究精细尺度皮层结构的功能特性， 受弱视影响的人，非侵入性地。利用这些先进的技术，我们已经提供了 人类V1中眼优势列的少数直接体内证据之一（Nasr和Tootell，2016）， 深度-（Nasr等人，2016; Nasr和Tootell，2016）和颜色敏感（Nasr等人，2016; Tootell和Nasr， 2017; Nasr和Tootell，2018）人类纹外视觉区的神经柱。这些发现，加上我们的 本建议所附的初步结果表明，利用这些现代 神经成像技术，神经损伤的基础弱视可以揭示和仔细检查直接在 人类与动物研究的空间尺度相当。 在这个项目的过程中，我们将使用尖端的高分辨率神经成像技术 Martinos生物医学成像中心提供给我们，以揭示弱视对视觉系统的影响。 这个项目的结果不仅从根本上改变了我们可以理解神经系统的尺度， 人类弱视的潜在机制，而且1）引入了新的生物标志物， 用于弱视分类和2）提供新的工具来评估弱视治疗的有效性 在没有任何生理学证据的情况下，这些问题仍在争论中。

Summary Amblyopia is a visual impairment due to the disruption of binocular vision during early childhood. This disorder affects the function of fine-scale structures within visual cortex, such as ocular dominance columns in the striate visual cortex (V1) and neural columns that comprise magno- and parvo-cellular streams within visual area V2, V3, V3A, V4 and MT. This developmental disorder leads to a variety of perceptual impairments from 2D spatial distortion, to decreased acuity in 3D perception and abnormal global motion perception. Amblyopia is one of the most common visual disorders, affecting approximately 3% of the world’s population (i.e. 10 million people in the US alone). Despite the high prevalence of amblyopia and its severe impact on visual perception, our knowledge of its impact on visual cortical processing is largely limited to findings based on invasive techniques (e.g. single cell recordings) in animals. This is mainly due to technical limitations (e.g. low spatial resolution) of conventional neuroimaging techniques, commonly used in human studies, compared to the size of those cortical structures affected by amblyopia. However, with recent advances in high-resolution neuroimaging techniques, based on using ultra-high field scanners, it is now possible to localize and study functional properties of the fine-scale cortical structures, affected by amblyopia, in humans non-invasively. Using these advanced techniques, we have already provided one of the few direct in vivo evidence for ocular dominance columns in human V1 (Nasr and Tootell, 2016) and depth- (Nasr et al., 2016; Nasr and Tootell, 2016) and color-sensitive (Nasr et al., 2016; Tootell and Nasr, 2017; Nasr and Tootell, 2018) neural columns within human extrastriate visual areas. These findings, plus our preliminary results enclosed with this proposal suggest that, by taking advantage of these modern neuroimaging techniques, neural impairments underlying amblyopia can be revealed and scrutinized directly in humans with a spatial scale comparable to animal studies. During the course of this project, we will use the cutting-edge high resolution neuroimaging technology available to us in the Martinos Center for Biomedical Imaging to reveal impacts of amblyopia on visual system. The results of this project not only fundamentally change the scale at which we can understand the neural mechanisms underlying amblyopia in human, but also 1) introduces new biomarkers that can be potentially used for amblyopia classification and 2) provides new tools to assess effectiveness of amblyopia treatments which are still debated in the absence of any physiological evidence.