# Robust 1H MRSI of GABA, Glutamate, Glutamine, and Glutathione

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $420,179

## Abstract

Project Abstract
 Understanding neurotransmitter activity is fundamental to elucidating normal and diseased neuronal
function, with glutamate (Glu) and γ-aminobutyric acid (GABA) being the brain's primary excitatory and
inhibitory neurotransmitters. Such understanding is particularly critical in autism spectrum disorder (ASD), a set
of neurodevelopment disorders characterized by persistent deficits in social communication and restricted,
repetitive, and stereotyped patterns of behavior. Although varying in presentation and severity, ASD occurs in
all ethnic and socioeconomic groups, has a lifelong duration, and affects an estimated 1 out of 68 children in
the United States. Unfortunately, the etiologies of these disorders are not fully understood, and this technical
development proposal to develop novel non-invasive imaging tools for studying ASD brain neurochemical
biomarkers is in response to NIH PA 10-158 “Research on Autism Spectrum Disorders”. The innovations to be
evaluated under this project will help not only investigating ASD, but also other neuropsychiatric and
neurodevelopmental disorders where advanced imaging techniques are needed.
 Despite the heterogeneity of ASD, patients may share final common biochemical pathways and potentially
be responsive to similar treatments, and ASD is now hypothesized to result from an imbalance between
excitatory and inhibitory neurotransmitters. Known as the “E/I balance” theory, findings from both animal
models and humans suggest ASD is characterized by hyper-excitability in critical brain regions due to
increased Glu and/or decreased GABA. While in vivo evidence of such neurochemical imbalances is beginning
to emerge through the use of J-edited 1H magnetic resonance spectroscopy (MEGA-PRESS being the current
method of choice) robust in vivo measurements are time-consuming and problematic. Glu measurement is
straightforward, but separation from closely related glutamine (Gln) is difficult. Furthermore, co-edited
macromolecules (MMs) overlap the targeted GABA signal and account for 40-60% of the detected signal,
leading investigators to refer to the resulting data as GABA+MMs or simply GABA+. MRS-detected MMs are
also reported to exhibit regional variations, variability across normal subjects, and dependence on both age
and pathology. Even for single-voxel studies, prior proposed MM-suppression techniques are not widely used,
being either time-consuming or highly sensitive to B0 magnetic field variations.
 This proposal seeks to overcome these limitations via the systematic design, implementation, and testing
of robust MM-suppressed J-edited single-voxel (Aims 1 and 2) and multi-voxel (Aim 3) sequences to measure
these targeted neurochemicals, yielding time-efficient measurements from multiple brain regions. These new
tools will be used to assess neurochemical imbalances in adolescent patients diagnosed with ASD (Aim 4).

## Key facts

- **NIH application ID:** 9910230
- **Project number:** 5R01MH110683-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Daniel M Spielman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $420,179
- **Award type:** 5
- **Project period:** 2017-06-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9910230

## Citation

> US National Institutes of Health, RePORTER application 9910230, Robust 1H MRSI of GABA, Glutamate, Glutamine, and Glutathione (5R01MH110683-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9910230. Licensed CC0.

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