# Neurochemistry as a moderator of brain networks for reading

> **NIH NIH R01** · HASKINS LABORATORIES, INC. · 2020 · $618,428

## Abstract

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.

## Key facts

- **NIH application ID:** 9975908
- **Project number:** 5R01HD086168-05
- **Recipient organization:** HASKINS LABORATORIES, INC.
- **Principal Investigator:** FUMIKO HOEFT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $618,428
- **Award type:** 5
- **Project period:** 2016-08-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975908

## Citation

> US National Institutes of Health, RePORTER application 9975908, Neurochemistry as a moderator of brain networks for reading (5R01HD086168-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9975908. Licensed CC0.

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