Orthographic and phonological selectivity in dyslexia: an fMRI study

描述（由申请人提供）：阅读在我们的文化社会中是至关重要的；不幸的是，5-12%的人患有遗传性的发展性阅读障碍，这是一种与其他认知能力和教育机会相关的意外的阅读困难。现代成像技术表明，典型的读者依赖于两条左侧通路：一条介导语音处理的背侧回路和一条腹侧视觉通路，包括专门用于快速识别单个单词的“视觉词形区”（VWFA）。这些途径在阅读障碍中是如何受到影响的，一直是一个深入研究的话题。目前大多数理论认为语音处理的缺陷是主要问题，成像研究揭示了在比较阅读困难和非阅读困难的读者时，左顶叶皮层的生理和解剖差异。与此同时，有许多报道称腹侧视觉通路的活动减少，腹侧视觉通路代表了阅读系统中另一个重要的部分，导致语义获取。该应用程序的长期目标是采用一种新的技术方法，从而更好地表征这些腹侧和背侧流的神经基础以及阅读障碍的差异。迄今为止，功能性磁共振成像（fMRI）技术一直受到这样一个事实的限制，即选择性神经元的密度以及它们调谐的宽度对测量的平均活动有贡献。然而，FMRI快速适应（FMRI - RA）更直接地探测神经元选择性，并允许更好地表征神经元水平的处理及其与行为的联系。如果我们要理解在当前的阅读障碍研究中关于大脑不同区域的低活性和高活性的发现，这是至关重要的，因为对这些结果的解释有些有限。具体来说，该项目将通过比较有和没有阅读困难的成年人，来检查阅读困难患者相对于典型读者在语音和正字法表征方面的选择性差异。该研究将首先验证一个假设，即具有正常真实单词阅读能力（尽管假单词阅读能力较差）的成人阅读障碍患者在其VWFA（保留左VWFA或右VWFA补偿）中对真实单词表现出正常的选择性，而那些真实单词阅读能力较差的阅读障碍患者则没有；真正的单词阅读能力与VWFA的选择性相关（目的1）。其次，本研究将验证以下假设：由于语音编码的缺陷，阅读障碍成人在左顶叶皮层的语音加工选择性低于典型阅读者，而假词阅读能力与顶叶选择性相关（Aim 2）。这些研究将使我们第一次有可能测量失读症患者大脑活动的特异性，而不仅仅是激活水平。如果我们要了解导致阅读障碍的机制，这些信息是至关重要的，重要的是，指导应该采用哪些干预措施，因为目前的治疗可能会影响不同的大脑系统。推进这一领域可以减少受损读者的数量，并限制阅读障碍对教育和职业的有害影响。

DESCRIPTION (provided by applicant): Reading is paramount in our literate society; unfortunately it does not come easily to 5-12% of the population who suffer the heritable condition of developmental dyslexia, a reading difficulty unexpected in relation to other cognitive abilities and the provision of educational opportunities. Modern imaging technology has demonstrated that typical readers rely on two left-lateralized pathways: A dorsal circuit mediating phonological processing and a ventral, visual pathway, including the "visual word form area", VWFA, specialized for the fast recognition of single words. How these pathways are affected in dyslexia, has been a topic of intense research. Most current theories posit a weakness in phonological processing as the primary problem and imaging studies have revealed physiological and anatomical differences in left parietal cortex when comparing dyslexic and non- dyslexic readers. At the same time, there are many reports of decreased activity in the ventral visual pathway, which represents another important part of the reading system leading to semantic access. The application's long-term objective is to employ a novel technical approach that will lead to better characterization of the neural bases of both these ventral and dorsal streams and differences in dyslexia. To date, functional magnetic resonance imaging (fMRI) technology has been limited by the fact that the density of selective neurons as well as the broadness of their tuning contributes to the average activity measured. FMRI rapid adaptation (fMRI- RA), however, probes neuronal selectivity more directly and allows a better characterization of neuron-level processing and its link to behavior. This is critical if we are to understand findings about hypo- and hyper- activity reported in various regions of the brain in current studies of dyslexia, as the interpretation of these results has been somewhat limited. Specifically, the project will examine selectivity differences in phonological and orthographic representations in dyslexic relative to typical readers by comparing adults with and without dyslexia. The study will first test the hypothesis that adults with dyslexia who have normal real word reading skills (albeit poor pseudoword reading) show normal selectivity for real words in their VWFA (preserved left VWFA or right VWFA compensation), while those dyslexics with poor real word reading skills do not; and that real word reading ability correlates with selectivity in the VWFA (Aim 1). Secondly, the study will test the hypothesis that adults with dyslexia, due to their weaknesses in phonological coding, show less selectivity for phonological processing in left parietal cortex than typical readers, and that pseudoword reading ability correlates with parietal selectivity (Aim 2). These studies will make it possible, for the first time, to gauge specificity of brain activity in dyslexia rather than simply activation levels. This information is critical if we are to understand the mechanisms that lead to disorders of reading and importantly, guide which interventions should be applied, as current treatments are likely to impact different brain systems. Advancing this field could reduce the number of impaired readers and limit the detrimental educational and vocational consequences of dyslexia. PUBLIC HEALTH RELEVANCE: Developmental dyslexia is a common (5-12% of the population) reading disability, unexpected in relation to other cognitive abilities and the provision of educational opportunities. A new imaging method will be used to better understand the specificity of the brain circuits involved in reading by comparing dyslexic and non- dyslexic college students. The results will advance our understanding of the mechanisms that lead to disorders of reading and potentially guide future interventions, eventually reducing the number of impaired readers and limiting the detrimental educational and vocational consequences of dyslexia.