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 ?-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.

Public Health Relevance

The proposed research will provide links between neural oscillations, BOLD signal, neurochemistry, perceptual and cognitive measure, and reading ability, critical for the development of a comprehensive and mechanistic model of the neurobiological underpinnings of reading disability (RD), a life-long learning disorder that afflicts 5-10% of the Nation's children. Moreover, the proposed research will provide important foundational knowledge about biologic pathways, which may suggest pharmacological agents that can supplement and enhance effects from more conventional reading interventions.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD086168-03
Application #
9527842
Study Section
Language and Communication Study Section (LCOM)
Program Officer
Miller, Brett
Project Start
2016-08-01
Project End
2021-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Haskins Laboratories, Inc.
Department
Type
DUNS #
060010147
City
New Haven
State
CT
Country
United States
Zip Code
Del Tufo, Stephanie N; Frost, Stephen J; Hoeft, Fumiko et al. (2018) Neurochemistry Predicts Convergence of Written and Spoken Language: A Proton Magnetic Resonance Spectroscopy Study of Cross-Modal Language Integration. Front Psychol 9:1507
Caverzasi, Eduardo; Mandelli, Maria Luisa; Hoeft, Fumiko et al. (2018) Abnormal age-related cortical folding and neurite morphology in children with developmental dyslexia. Neuroimage Clin 18:814-821
Malins, Jeffrey G; Pugh, Kenneth R; Buis, Bonnie et al. (2018) Individual Differences in Reading Skill Are Related to Trial-by-Trial Neural Activation Variability in the Reading Network. J Neurosci 38:2981-2989
Xia, Zhichao; Zhang, Linjun; Hoeft, Fumiko et al. (2018) Neural Correlates of Oral Word Reading, Silent Reading Comprehension, and Cognitive Subcomponents. Int J Behav Dev 42:342-356
Patael, Smadar Z; Farris, Emily A; Black, Jessica M et al. (2018) Brain basis of cognitive resilience: Prefrontal cortex predicts better reading comprehension in relation to decoding. PLoS One 13:e0198791
Landi, Nicole; Malins, Jeffrey G; Frost, Stephen J et al. (2018) Neural representations for newly learned words are modulated by overnight consolidation, reading skill, and age. Neuropsychologia 111:133-144
Hendren, Robert L; Haft, Stephanie L; Black, Jessica M et al. (2018) Recognizing Psychiatric Comorbidity With Reading Disorders. Front Psychiatry 9:101
Chyl, Katarzyna; Kossowski, Bartosz; D?bska, Agnieszka et al. (2018) Prereader to beginning reader: changes induced by reading acquisition in print and speech brain networks. J Child Psychol Psychiatry 59:76-87
Xia, Zhichao; Hancock, Roeland; Hoeft, Fumiko (2017) Neurobiological bases of reading disorder Part I: Etiological investigations. Lang Linguist Compass 11:
Haft, Stephanie L; Hoeft, Fumiko (2017) Poverty's Impact on Children's Executive Functions: Global Considerations. New Dir Child Adolesc Dev 2017:69-79

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