Orthographic and phonological selectivity in dyslexia: an fMRI study

描述（由申请人提供）：阅读在我们的识字社会中是至关重要的;不幸的是，它并不容易达到5-12%的人口谁遭受遗传条件的发展性阅读障碍，一个阅读困难意想不到的关系到其他认知能力和教育机会的提供。现代成像技术表明，典型的读者依赖于两个左侧化的途径：背侧电路介导的语音处理和腹侧，视觉通路，包括“视觉词形区”，VWFA，专门用于快速识别单个单词。这些通路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。目前的大多数理论认为，语音加工的弱点是主要问题，成像研究揭示了在比较有阅读障碍者和无阅读障碍者时，左顶叶皮层的生理和解剖差异。与此同时，也有许多关于腹侧视觉通路活动减少的报道，腹侧视觉通路是导致语义通达的阅读系统的另一个重要部分。该应用程序的长期目标是采用一种新的技术方法，这将导致更好地表征这些腹侧和背侧流的神经基础和诵读困难的差异。迄今为止，功能性磁共振成像（fMRI）技术一直受到以下事实的限制，即选择性神经元的密度以及它们调谐的广泛性有助于测量的平均活动。功能磁共振快速适应（fMRI- RA），然而，探测神经元的选择性更直接，并允许更好地表征神经元水平的处理及其与行为的联系。这是至关重要的，如果我们要了解在目前的阅读障碍研究中报告的大脑不同区域的低活动和高活动的发现，因为对这些结果的解释有些有限。具体来说，该项目将检查选择性差异，在语音和正字法表示在诵读困难相对于典型的读者比较成人与无诵读困难。该研究将首先检验以下假设：具有正常真实的单词阅读技能（尽管伪词阅读能力较差）的诵读困难成人在其VWFA中对真实的单词表现出正常的选择性（保留左侧VWFA或右侧VWFA补偿），而具有较差真实的单词阅读技能的诵读困难者则没有;以及真实的单词阅读能力与VWFA中的选择性相关（目标1）。其次，本研究将验证以下假设：由于语音编码的弱点，阅读障碍的成年人在左顶叶皮层的语音加工中表现出比普通读者更少的选择性，并且假词阅读能力与顶叶选择性相关（目标2）。这些研究将使人们有可能，第一次，以衡量特定的大脑活动在诵读困难，而不是简单的激活水平。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，指导应该应用哪些干预措施，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，并限制阅读障碍的有害教育和职业后果。 公共卫生相关性：发展性阅读障碍是一种常见的（占人口的5-12%）阅读障碍，与其他认知能力和教育机会的提供相比是意想不到的。将使用一种新的成像方法，通过比较有阅读障碍和无阅读障碍的大学生，更好地了解参与阅读的大脑回路的特异性。这些结果将促进我们对导致阅读障碍的机制的理解，并可能指导未来的干预措施，最终减少受损读者的数量，并限制阅读障碍的有害教育和职业后果。

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.