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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

基本信息

批准号：
9975908
负责人：
FUMIKO HOEFT
金额：
$ 61.84万
依托单位：
HASKINS LABORATORIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9975908
关键词：
Age Animal Genetics 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 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 Pharmacology Phase Phenotype Play Process Publishing Reader Reading Reading Disabilities Research Risk Role Sampling Sensory Severities Signal Transduction Speech Speech Sound System Testing Time Training Variant Visual Visual Cortex auditory processing base brain behavior causal model design gamma-Aminobutyric Acid in vivo life-long learning literacy migration multimodality neurochemistry phonology reading ability reading difficulties relating to nervous system remediation response stem

项目摘要

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.

有效的语音处理为学习阅读提供了基础，而学习阅读的过程依赖于视觉符号与其相应的语音的成功链接。虽然因果关系语音处理、字语整合和流利阅读之间的关系及其背后的基础机制仍在争论中，这些过程都需要精确的计时机制。基本的这些计时机制是两种神经递质：谷氨酸 (Glu) 和 γ-氨基丁酸 (GABA)，它们在皮质兴奋性以及相应的慢速和快速神经振荡的产生中起重要作用分别为音节率和音素率。我们最近发表了第一个神经化学物质使用磁共振波谱 (MRS) 证明 Glu 升高与阅读缺陷有关的证据新兴读者。其他初步研究表明 Glu 与阅读相关的功能 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，以及之间的联系区域特异性（左但非右）颞上 GABA、神经振荡、颞听觉处理和阅读。根据这些发现，我们提出并测试了一个以人类和动物研究为基础的模型，将升高的 Glu（和 Glu/GABA 失衡）与过度兴奋和神经噪音联系起来，这表现为一个关键阅读障碍 (RD) 的近端影响因素是其对神经振荡、区域激活和功能连接。我们进一步假设分布式区域内神经噪声的复合效应在远程区域链接上进行精确计时和预测编码机制的集成过程，例如多模式整合，尤其是阅读，特别容易受到激发/抑制的影响不平衡。我们将在 150 名具有广泛阅读能力的儿童（8-9 岁）中检查人际关系神经化学、神经振荡、功能激活和功能连接（目标 1）之间的关系，以及如何这些关系的变化预示着感觉处理（包括听觉-视觉）的个体差异 [AV] 集成）和打印语音集成（目标 2）。拟议的研究不仅有助于最终构建阅读和 RD 因果模型的目标，但也提供了有关生物学的关键信息可能适合修复的途径。