Journal Article

GABA and glutamate levels correlate with MTR and clinical disability: Insights from multiple sclerosis

Nantes, Julia C., Zhong, Jidan, Koski, Lisa, Holmes, Scott A., Narayanan, Sridar, Hoge, Richard D., Brown, Robert A., Proulx, Sébastien

2017

Overview

Converging areas of research have implicated glutamate and γ-aminobutyric acid (GABA) as key players in neuronal signalling and other central functions. Further research is needed, however, to identify microstructural and behavioral links to regional variability in levels of these neurometabolites, particularly in the presence of demyelinating disease. Thus, we sought to investigate the extent to which regional glutamate and GABA levels are related to a neuroimaging marker of microstructural damage and to motor and cognitive performance. Twenty-one healthy volunteers and 47 people with multiple sclerosis (all right-handed) participated in this study. Motor and cognitive abilities were assessed with standard tests used in the study of multiple sclerosis. Proton magnetic resonance spectroscopy data were acquired from sensorimotor and parietal regions of the brains’ left cerebral hemisphere using a MEGA-PRESS sequence. Our analysis protocol for the spectroscopy data was designed to account for confounding factors that could contaminate the measurement of neurometabolite levels due to disease, such as the macromolecule signal, partial volume effects, and relaxation effects. Glutamate levels in both regions of interest were lower in people with multiple sclerosis. In the sensorimotor (though not the parietal) region, GABA concentration was higher in the multiple sclerosis group compared to controls. Lower magnetization transfer ratio within grey and white matter regions from which spectroscopy data were acquired was linked to neurometabolite levels. When adjusting for age, normalized brain volume, MTR, total N-acetylaspartate level, and glutamate level, significant relationships were found between lower sensorimotor GABA level and worse performance on several tests, including one of upper limb motor function. This work highlights important methodological considerations relevant to analysis of spectroscopy data, particularly in the afflicted human brain. These findings support that regional neurotransmitter levels are linked to local microstructural integrity and specific behavioral abilities that can be affected in diseases such as multiple sclerosis. •Method optimized for obtaining accurate estimates of GABA levels with 1H-MRS in MS.•Neurometabolite levels are linked to regional MTR, a marker of microstructural damage.•Elevated sensorimotor GABA levels are linked to motor performance of MS participants.

• Publisher: Elsevier Inc,Elsevier Limited,Elsevier
• Subject: Adult / Brain / Cognitive ability / Data processing / Demyelination / Disabled Persons / Female / GABA / gamma-Aminobutyric Acid - metabolism / Glutamate / Glutamic Acid - metabolism / Gray Matter - diagnostic imaging / Gray Matter - metabolism / Handedness / Hemispheric laterality / Humans / Magnetic resonance spectroscopy / Magnetization transfer ratio / Male / Medical imaging / Middle Aged / Motor task performance / Multiple sclerosis / Multiple Sclerosis - diagnostic imaging / Multiple Sclerosis - metabolism / Multiple Sclerosis - physiopathology / Myelin / Neuroimaging / Neurotransmitters / NMR / Nuclear magnetic resonance / Patients / Proton magnetic resonance spectroscopy / Proton Magnetic Resonance Spectroscopy - methods / Sensorimotor system / Severity of Illness Index / Spectroscopy / Spectrum analysis / Substantia alba / White Matter - diagnostic imaging / White Matter - metabolism / γ-Aminobutyric acid