Neurochemistry as a moderator of brain networks for reading

有效的语音处理为学习阅读提供了基础，这一过程依赖于 视觉符号与其相应语音的成功联系。虽然因果关系 语音加工，印刷-语音整合和流畅阅读之间的关系，以及它们的基本原理 尽管这些机制仍在讨论之中，但这些进程都需要精确的定时机制。的基础 这些定时机制是两种神经递质，谷氨酸（Glu）和γ-氨基丁酸（GABA）， 在皮层兴奋性和产生相应的慢和快神经振荡中起主要作用 音节率和音素率。我们最近发表了第一个神经化学 使用磁共振波谱（MRS）将Glu升高与阅读缺陷联系起来的证据， 紧急读者额外的初步研究表明Glu与阅读相关的功能性MRI之间存在联系。 激活、连接性和试验间变异性、神经振荡和阅读能力，以及 区域特异性（左侧而非右侧）上级颞叶GABA，神经振荡，颞叶听觉加工 和阅读。根据这些发现，我们提出并测试了一个基于人类和动物研究的模型， 将升高的Glu（和Glu/GABA失衡）与过度兴奋和神经噪声联系起来，这是一个关键因素， 阅读障碍（RD）的近端贡献者，通过其对神经振荡，区域激活和 功能性连接。我们进一步假设，分布区域内神经噪音的复合效应 在远程区域联系上，使精确定时和预测编码机制的综合过程， 例如多模态整合，尤其是阅读，特别容易受到激发/抑制影响 不平衡在150名具有广泛阅读能力的儿童（8-9岁）中，我们将检查关系 神经化学，神经振荡，功能激活和功能连接之间的关系（目标1），以及如何 这些关系的变化预测了感觉处理（包括视觉-听觉）的个体差异。 [AV]整合）和印刷语音整合（目标2）。这项研究不仅有助于最终 目标是构建阅读和RD的因果模型，但也提供了有关生物学的关键信息。 可能适合补救的途径。

Efficient phonological processing provides a basis for learning to read, a process that relies on successful linking of visual symbols to their corresponding speech sounds. Although the causal relationship between phonological processing, print-speech integration and fluent reading, as well as their underlying basic mechanisms are still under debate, these processes all require precise timing mechanisms. Fundamental to these timing mechanisms are two neurotransmitters, glutamate (Glu) and γ-aminobutyric acid (GABA), which play major roles in cortical excitability and the generation of slow and fast neural oscillations that correspond respectively to the rates of syllabic and phonemic rates. We have recently published the first neurochemical evidence linking elevated Glu with reading deficits using Magnetic Resonance Spectroscopy (MRS) in emergent readers. Additional preliminary studies suggest links between Glu, reading-related functional MRI activation, connectivity and trial-to-trial variability, neural oscillation and reading ability, as well as links between regionally-specific (left but not right) superior temporal GABA, neural oscillation, temporal auditory processing and reading. From these findings we propose and test a model, grounded by human and animal studies, that links elevated Glu (and Glu/GABA imbalance) to hyperexcitablity and neural noise, which manifests as one key proximal contributor of reading disability (RD) by its impact on neural oscillation, regional activation, and functional connectivity. We further posit that the compounding effects of neural noise within distributed regions on long-range regional links make integrative processes that precise timing and predictive coding mechanisms, such as multimodal integration and especially reading, particularly susceptible to excitation/inhibition imbalance. In 150 children (ages 8-9) with a wide range of reading abilities, we will examine relationships between neurochemistry, neural oscillation, functional activation, and functional connectivity (Aim 1), and how variation in these relationships predicts individual differences in sensory processing (including auditory-visual [AV] integration), and print-speech integration (Aim 2). The proposed study not only contributes to the ultimate goal of constructing a causal model of reading and RD, but also provides critical information about biological pathways potentially amenable to remediation.