Neurochemistry as a moderator of brain networks for reading

神经化学作为阅读大脑网络的调节者

• 批准号: 9176803
• 负责人: FUMIKO HOEFT
• 金额: $ 64.04万
• 依托单位: HASKINS LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9176803
• 关键词: Age; Animal Model; Animals; Area; Auditory; Behavior; Behavioral; Biological; Brain; Child; Childhood; Code; Cognitive; Coupling; Data; Development; Electroencephalography; Etiology; Exclusion; Exercise; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Generations; Genetic; Genetic Research; Glutamates; Goals; Heterogeneity; Human; Individual Differences; Inferior; Intervention; Investigation; Knowledge; Language; Learning; Learning Disorders; Left; Link; Magnetic Resonance Spectroscopy; Measurement; Measures; Medial; Mediating; Modeling; Multimodal Imaging; Neurobiology; Neurons; Neurotransmitters; Noise; Pathway interactions; Phase; Phenotype; Play; Printing; Process; Publishing; Reader; Reading; Reading Disabilities; Research; Risk; Role; Sampling; Sensory; Sensory Process; Severities; Signal Transduction; Speech; Speech Sound; System; Testing; Time; Training; Variant; Visual; Visual Cortex; base; brain behavior; causal model; design; gamma-Aminobutyric Acid; in vivo; life-long learning; literacy; migration; neurochemistry; phonology; reading ability; reading difficulties; relating to nervous system; remediation; response; stem

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.

高效的语音处理为学习阅读提供了基础，这一过程依赖于 成功地将视觉符号链接到其相应的语音。尽管因果关系 语音加工、纸语整合和流利阅读之间的关系及其基础 机制仍在争论中，这些过程都需要精确的计时机制。基础到 这些计时机制是两种神经递质，谷氨酸(Glu)和γ-氨基丁酸(GABA)，它们 在皮质兴奋性和相应的慢、快神经振荡的产生中起主要作用 分别为音节率和音节率。我们最近发表了第一种神经化学物质 用磁共振波谱(MRS)研究谷氨酸升高与阅读障碍的关系 新兴读者。其他初步研究表明，谷氨酸和阅读相关的功能磁共振之间存在联系 激活、连通性和试验之间的变异性、神经振荡和阅读能力，以及 区域特异性(左侧但不是右侧)上颞叶GABA、神经振荡、颞叶听觉处理 还有读书。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，该模型 将升高的Glu(和Glu/GABA失衡)与过度兴奋和神经噪音联系在一起，这表现为一键 阅读障碍(RD)的近端贡献者，通过其对神经振荡、区域激活和 功能连接。我们进一步假设，分布区域内的神经噪声的复合效应 在远程区域链路上使综合过程精确地定时和预测编码机制， 例如多模式整合，尤其是阅读，特别容易受到激励/抑制 不平衡。在150名具有广泛阅读能力的儿童(8-9岁)中，我们将考察人际关系 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加工(包括听觉-视觉)的个体差异 [视听]一体化)和印刷--语音一体化(目标2)。拟议的研究不仅有助于最终 目标是构建阅读和研发的因果模型，但也提供了关于生物学的关键信息 有可能采取补救措施的途径。