Neural Mechanisms Underlying Compensation in Dyslexia

阅读障碍补偿的神经机制

• 批准号: 10215578
• 负责人: FUMIKO HOEFT
• 金额: $ 65.37万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10215578
• 关键词: Address; Adult; Affect; Attenuated; Behavior; Behavioral; Brain; Child; Clinical; Cognitive; Coupled; Cross-Sectional Studies; Development; Developmental reading disorder; Diagnosis; Dyslexia; Financial compensation; Foundations; Functional Magnetic Resonance Imaging; Generations; Glutamates; Impairment; Individual; Individual Differences; Intervention; Knowledge; Language; Lead; Left; Linguistics; Link; Literature; Location; Magnetic Resonance Spectroscopy; Measures; Modality; Modeling; Nature; Neural Pathways; Neurobiology; Neurocognitive; Neurodevelopmental Disorder; Neuronal Plasticity; Outcome; Parietal; Parietal Lobe; Pathway interactions; Performance; Population; Precentral gyrus; Prevalence; Process; Protocols documentation; Reader; Reading; Reading Disabilities; Reading Disorder; Recording of previous events; Research; Sensory; Site; Synapses; System; Techniques; Testing; Time; Transcranial magnetic stimulation; Work; base; design; early childhood; gamma-Aminobutyric Acid; improved; interest; literacy; multimodality; neurobiological mechanism; neurochemistry; neuroimaging; neuromechanism; neuroregulation; novel; novel strategies; predicting response; reading ability; reading difficulties; recruit; relating to nervous system; repetitive transcranial magnetic stimulation; response; socioeconomics; theories; therapy resistant

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.

基于解码的阅读障碍（RD;或诵读困难）是一种高度流行的神经发育障碍， 通常会持续到成年。成人识字率低对社会经济和 教育成果，这反过来又影响到后代的成果。尽管取得了重大 结果，对RD成人的研究严重滞后。人们也越来越有兴趣了解 RD的补偿机制，被认为会发展到成年期。研发补偿允许 对于效率较低但功能性的阅读能力，并且被认为是由替代语言支持的， 认知和感觉处理策略及其潜在的神经通路。这与 在左后脑系统中发现更典型的“阅读网络”。神经认知机制 然而，赔偿问题还远未得到理解。这部分是因为， 补偿一直是模糊的，因为功能性MRI方法最常用于 薪酬研究在本质上具有内在的相关性。例如，目前尚不清楚 提出的补偿过程与补偿RD中的阅读行为有因果关系， 它们是附带现象。各种替代神经通路被招募和贡献的程度 补偿能力的个体差异也是未知的。该提案涉及这些科学 通过建立我们过去对成人RD和补偿的神经认知机制的工作， 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γ-氨基丁酸（GABA）和谷氨酸的MR波谱（MRS），以及 功能性磁共振成像在这项建议中，（1）我们将确定补偿RD成人的神经认知概况 与持续阅读困难的持续RD成人以及无RD的典型阅片者相比 历史我们还确定了神经认知机制和网络的个体差异， 阅读能力（不考虑既往RD诊断）和既往RD诊断（不考虑当前阅读能力）。 (2)使用经颅磁刺激（TMS）在实验，假设检验范式，我们将 发现短期功能重组的潜在过程及其对阅读的影响， 被认为对阅读、RD和补偿至关重要的节点。通过TMS诱导的神经调节，我们 系统地测试假设的因果过程被认为是参与补偿。(3)在 为了解决有关代偿过程的神经化学机制的假设， 和途径，我们将发现如何区域特定水平的GABA，重要的是调制皮层 兴奋性，预测对TMS诱导的（Meta）可塑性的反应。这些工作不仅对RD理论的发展具有重要意义 和补偿，但最终可能改善策略，促进干预模式和成功 RD的补偿，在儿童和成人RD。