Neural Mechanisms Underlying Compensation in Dyslexia

基于解码的阅读障碍(RD；或阅读障碍)是一种非常普遍的神经发育障碍， 通常会持续到成年。成年期识字率低对社会经济和社会发展产生负面影响 教育结果，这反过来又影响到后代的结果。尽管意义重大 结果，对成年RD患者的研究严重滞后。人们也越来越有兴趣了解 RD中的补偿机制，被认为发育到成年期。研发中的薪酬允许 对于效率较低但功能强大的阅读能力，并被认为得到了替代语言的支持， 认知和感觉加工策略及其潜在的神经通路。这与 更典型的“阅读网络”存在于左侧后脑系统。神经认知机制的研究进展 然而，人们对薪酬的理解还远远不够。这在一定程度上是因为 补偿一直是模棱两可的，而且因为功能磁共振方法最常用于 薪酬研究本质上是相互关联的。例如，目前尚不清楚 被提议的补偿过程与补偿RD中的阅读行为或是否 它们都是附属物。不同的替代神经通路被招募和贡献的程度 对个体补偿能力的差异也是未知的。这项建议解决了这些科学问题 通过在我们过去关于成人RD的神经认知机制和补偿方面的工作而产生的差距 实验性神经调节技术，经颅磁刺激(TMS)，结合多模式 神经成像，包括伽马氨基丁酸(GABA)和谷氨酸的磁共振波谱(MRS)，以及 功能核磁共振。在这项建议中，(1)我们将确定代偿RD成人的神经认知特征 与持续阅读困难的成人和没有阅读障碍的典型读者相比 历史。我们还确定了神经认知机制和潜在的个体差异在当前 阅读能力(与过去的RD诊断无关)和过去的RD诊断(无论当前阅读能力如何)。 (2)在实验假设检验范式中使用经颅磁刺激(TMS)，我们将 发现关键神经短时功能重组的潜在过程及其对阅读的影响 节点被认为是阅读、研发和补偿的关键。通过TMS诱导的神经调节，我们 系统地测试关于被认为与补偿有关的因果过程的假设。(3)在 以解决有关代偿过程潜在的神经化学机制的假说 和途径，我们将发现区域特定水平的GABA是如何对大脑皮层的调节至关重要的 兴奋性，预测对TMS诱导的(元)可塑性的反应。这样的工作不仅将推动研发理论的发展 和补偿，但最终可能会改进战略，推动干预模式并取得成功 无论是患有RD的儿童还是成人，在RD方面的补偿。

Decoding-based reading disorder (RD; or dyslexia) is a highly prevalent neurodevelopmental disorder that often persists into adulthood. Poor literacy in adulthood has negative impact on socioeconomic and educational outcomes, which in turn affect the outcomes of subsequent generations. Despite significant consequences, research on RD adults is severely lagging. There is also increasing interest in understanding compensatory mechanisms in RD, which are thought to develop into adulthood. Compensation in RD allows for less efficient but functional reading abilities, and is thought to be supported by alternative linguistic, cognitive and sensory processing strategies and their underlying neural pathways. This is in contrast to the more typical `reading network' found in the left posterior brain system. Neurocognitive mechanisms of compensation are however, far from understood. This in part because the operational definitions of compensation have been ambiguous, and because functional MRI approaches most often used in compensation research are inherently correlational in nature. For example, it is currently unknown whether the proposed compensatory processes are causally related to reading behaviors in compensated RD or whether they are epiphenomena. The degree to which various alternative neural pathways are recruited and contribute to individual differences in compensatory abilities is also unknown. This proposal addresses these scientific gaps by building on our past work on the neurocognitive mechanisms of adult RD and compensation using an experimental neuromodulation technique, transcranial magnetic stimulation (TMS), coupled with multimodal neuroimaging including MR Spectroscopy (MRS) of gamma-aminobutyric acid (GABA) and glutamate, and functional MRI. In this proposal, (1) We will identify neurocognitive profiles of compensated RD adults compared to persistent RD adults with continued reading difficulties as well as typical readers with no RD history. We also identify neurocognitive mechanisms and networks underlying individual differences in current reading ability (regardless of past RD diagnosis) and past RD diagnosis (regardless of current reading ability). (2) Using transcranial magnetic stimulation (TMS) within an experimental, hypothesis testing paradigm, we will discover the processes underlying short-term functional reorganization and its impact on reading in key neural nodes thought to be critical for reading, RD and compensation. Through TMS-induced neuromodulation, we systematically test hypotheses regarding causal processes thought to be involved in compensation. (3) In order to address hypotheses regarding the neurochemical mechanisms underlying compensatory processes and pathways, we will discover how regionally specific levels of GABA, important for modulation of cortical excitability, predict responses to TMS-induced (meta)plasticity. Such work will not only advance theories of RD and compensation, but ultimately may improve strategies to promote intervention models and successful compensation in RD, in both children and adults with RD.