MRS ANALYSIS: READING DISABILITY/ESTROGEN EFFECTS

Yale University, New Haven CT

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Abstract

Description: (Adapted from applicant's description) The long-term objective of this project is to use magnetic resonance spectroscopy (MRS) to better define the nature of the deficit in reading disability (dyslexia), and to understand how estrogen acts on the neurochemistry of a brain region involved in reading. With MRS and its ability to assess the neurochemical function of key inhibitory and excitatory neuronal systems, it is now possible to study the brain function in RD readers and the effects of estrogen at a cellular and biochemical level. In Specific Aim 1, MRS will be used to measure levels of N-acetyl-aspartate (NAA) and gamma-aminobutyric acid (GABA) in the posterior reading area (parietal-temporal) of nonimpaired (NI) and reading disabled (RD) readers. If there is a decrease in total neuronal density or energetic status, a reduction in NAA levels is anticipated. If there is a specific alteration of energetic status involving inhibitory neuronal function, a decrease in GABA level is expected. In Specific Aim 2, MRS will be used to measure the rate of glucose oxidation in glutamate containing neurons in the left parietal-temporal region of the brains of RD and NI adult subjects during a reading task. The investigators expect to find decreased neuronal glucose oxidation during a phonology task in RD subjects compared to NI subjects, indicating an inappropriately low level of excitatory neuronal activity. An imbalance between excitation and inhibition may be a fundamental defect responsible for the impairment seen in RD subjects. In Specific Aim 3, MRS will be used to measure GABA levels in the parietal-temporal region of NI postmenopausal women on and off estrogen. If GABA levels are altered by estrogen, it suggests that the inhibitory neural system may be a link to understanding how estrogen effects reading performance. By applying advanced MRS techniques to the study of brain function, this project is a logical and innovative approach to elucidate the cellular mechanisms underlying a cognitive process (reading) and its impairment (reading disability).