Neural Mechanisms Underlying Compensation in Dyslexia

阅读障碍补偿的神经机制

基本信息

批准号：
10442430
负责人：
FUMIKO HOEFT
金额：
$ 65.4万
依托单位：
UNIVERSITY OF CONNECTICUT STORRS
依托单位国家：
美国
项目类别：
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/10442430
关键词：
Address Adult Affect Attenuated Behavior Behavioral Brain Child Clinical Cognitive Compensation Coupled Cross-Sectional Studies Development Developmental reading disorder Diagnosis Dissociation Dyslexia Education Functional Magnetic Resonance Imaging Generations Glutamates Impairment Individual Individual Differences Intervention Knowledge Language Left Linguistics Link Literature Location Magnetic Resonance Spectroscopy Measures Modality Modeling Nature Neural Pathways Neurobiology Neurocognitive Neurodevelopmental Disorder Neuronal Plasticity Outcome 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 comparison control design early childhood gamma-Aminobutyric Acid improved interest literacy multimodal neuroimaging neural neurobiological mechanism neurochemistry neuroimaging neuromechanism neuroregulation novel novel strategies predicting response reading ability reading difficulties recruit repetitive transcranial magnetic stimulation response socioeconomics theories therapy resistant

项目摘要

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;或阅读障碍）是一种高度普遍的神经发育障碍经常持续到成年。成年中的识字差对社会经济和教育成果又影响了后代的结果。尽管很重要后果，对RD成年人的研究严重滞后。对理解也越来越兴趣 RD中的补偿机制，被认为成年。 RD的赔偿允许具有效率较低但功能性的阅读能力，被认为是由替代语言支持的，认知和感官处理策略及其潜在的神经途径。这与在左后脑系统中发现的更典型的“阅读网络”。神经认知机制然而，赔偿远非理解。这部分是因为补偿是模棱两可的，并且由于功能性MRI方法最常用于薪酬研究本质上是固有的相关性。例如，目前尚不清楚建议的补偿过程与补偿Rd中的阅读行为有因果关系他们是Epiphenomena。招募各种替代神经途径的程度并贡献在补偿能力方面的个体差异也是未知的。该提案解决了这些科学通过建立我们过去关于成人RD神经认知机制的工作，并使用实验性神经调节技术，经颅磁刺激（TMS），与多模式结合神经影像学包括γ-氨基丁酸（GABA）和谷氨酸的MR光谱法（MRS），以及功能性MRI。在此提案中，（1）我们将确定补偿RD成年人的神经认知概况与持续的RD成年人相比，持续阅读困难以及没有RD的典型读者历史。我们还确定了当前个体差异的基础神经认知机制和网络阅读能力（无论过去的RD诊断如何）和过去的RD诊断（无论目前的阅读能力如何）。（2）在实验性假设测试范式中使用经颅磁刺激（TMS），我们将发现短期功能重组的基础过程及其对关键神经阅读的影响节点被认为对阅读，路和补偿至关重要。通过TMS诱导的神经调节，我们系统地检验有关因果过程所涉及的因果过程的假设。（3）英寸为了解决有关补偿过程基础神经化学机制的假设和途径，我们将发现区域特定水平的GABA水平，对皮质调节很重要兴奋性，预测对TMS诱导的（元）可塑性的响应。这样的工作不仅会推进RD的理论和补偿，但最终可能会改善促进干预模型和成功的策略 RD的RD赔偿。