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

摘要 弱视是一种由于儿童早期双眼视觉障碍而导致的视力损害。这 障碍影响视皮质内细微结构的功能，如眼优势柱 纹状视皮层(V1)和神经柱，构成视觉内的大细胞流和小细胞流 V2、V3、V3A、V4和MT区。这种发育障碍会导致各种知觉障碍， 2D空间失真，导致3D知觉敏锐度下降和全局运动知觉异常。 弱视是最常见的视觉障碍之一，影响着世界上约3%的 人口(即仅美国就有1000万人)。尽管弱视的高流行率和严重的 对于视觉感知的影响，我们对其对视觉皮质处理的影响的了解在很大程度上限于 基于动物的侵入性技术(例如，单细胞记录)的发现。这主要是由于技术上的原因 人类常用的传统神经成像技术的局限性(如低空间分辨率) 研究，与那些受弱视影响的皮质结构的大小进行比较。 然而，随着最近高分辨率神经成像技术的进步，基于使用超高场 扫描仪，现在可以定位和研究精细皮质结构的功能特性， 受弱视影响，在人类中无侵入性。使用这些先进的技术，我们已经提供了 人类V1眼优势柱的为数不多的直接活体证据之一(Nasr和Tootell，2016)和 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)人类纹外视觉区域内的神经柱。这些发现，加上我们的 这项提案所附的初步结果表明，通过利用这些现代技术 神经成像技术，弱视潜在的神经损害可以直接在 人类的空间尺度可与动物研究相媲美。 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 在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理解神经的尺度 弱视的潜在机制，但也1)引入了新的生物标志物，可能是潜在的 用于弱视分类和2)提供了评估弱视治疗效果的新工具 在没有任何生理证据的情况下，这一点仍然存在争议。

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.