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Research ArticlePEDIATRICS
Open Access

GABA and Glutamate in Children with Primary Complex Motor Stereotypies: An 1H-MRS Study at 7T

A.D. Harris, H.S. Singer, A. Horska, T. Kline, M. Ryan, R.A.E. Edden and E.M. Mahone
American Journal of Neuroradiology November 2015, DOI: https://doi.org/10.3174/ajnr.A4547
A.D. Harris
From the Russell H. Morgan Department of Radiology and Radiological Science (A.D.H., A.H., R.A.E.E.), Department of Neurology (H.S.S., T.K.), Department of Pediatrics (H.S.S.), and Department of Psychiatry and Behavioral Sciences (E.M.M.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Neuropsychology (M.R., E.M.M.) and F.M. Kirby Center for Functional Brain Imaging (A.D.H., A.H., R.A.E.E.), Kennedy Krieger Institute, Baltimore, Maryland.
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H.S. Singer
From the Russell H. Morgan Department of Radiology and Radiological Science (A.D.H., A.H., R.A.E.E.), Department of Neurology (H.S.S., T.K.), Department of Pediatrics (H.S.S.), and Department of Psychiatry and Behavioral Sciences (E.M.M.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Neuropsychology (M.R., E.M.M.) and F.M. Kirby Center for Functional Brain Imaging (A.D.H., A.H., R.A.E.E.), Kennedy Krieger Institute, Baltimore, Maryland.
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A. Horska
From the Russell H. Morgan Department of Radiology and Radiological Science (A.D.H., A.H., R.A.E.E.), Department of Neurology (H.S.S., T.K.), Department of Pediatrics (H.S.S.), and Department of Psychiatry and Behavioral Sciences (E.M.M.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Neuropsychology (M.R., E.M.M.) and F.M. Kirby Center for Functional Brain Imaging (A.D.H., A.H., R.A.E.E.), Kennedy Krieger Institute, Baltimore, Maryland.
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T. Kline
From the Russell H. Morgan Department of Radiology and Radiological Science (A.D.H., A.H., R.A.E.E.), Department of Neurology (H.S.S., T.K.), Department of Pediatrics (H.S.S.), and Department of Psychiatry and Behavioral Sciences (E.M.M.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Neuropsychology (M.R., E.M.M.) and F.M. Kirby Center for Functional Brain Imaging (A.D.H., A.H., R.A.E.E.), Kennedy Krieger Institute, Baltimore, Maryland.
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M. Ryan
From the Russell H. Morgan Department of Radiology and Radiological Science (A.D.H., A.H., R.A.E.E.), Department of Neurology (H.S.S., T.K.), Department of Pediatrics (H.S.S.), and Department of Psychiatry and Behavioral Sciences (E.M.M.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Neuropsychology (M.R., E.M.M.) and F.M. Kirby Center for Functional Brain Imaging (A.D.H., A.H., R.A.E.E.), Kennedy Krieger Institute, Baltimore, Maryland.
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R.A.E. Edden
From the Russell H. Morgan Department of Radiology and Radiological Science (A.D.H., A.H., R.A.E.E.), Department of Neurology (H.S.S., T.K.), Department of Pediatrics (H.S.S.), and Department of Psychiatry and Behavioral Sciences (E.M.M.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Neuropsychology (M.R., E.M.M.) and F.M. Kirby Center for Functional Brain Imaging (A.D.H., A.H., R.A.E.E.), Kennedy Krieger Institute, Baltimore, Maryland.
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E.M. Mahone
From the Russell H. Morgan Department of Radiology and Radiological Science (A.D.H., A.H., R.A.E.E.), Department of Neurology (H.S.S., T.K.), Department of Pediatrics (H.S.S.), and Department of Psychiatry and Behavioral Sciences (E.M.M.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Neuropsychology (M.R., E.M.M.) and F.M. Kirby Center for Functional Brain Imaging (A.D.H., A.H., R.A.E.E.), Kennedy Krieger Institute, Baltimore, Maryland.
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Abstract

BACKGROUND AND PURPOSE: Complex motor stereotypies are rhythmic, repetitive, fixed, purposeful but purposeless movements that stop with distraction. They can occur in otherwise normal healthy children (primary stereotypies) as well in those with autism spectrum disorders (secondary stereotypies). The underlying neurobiologic basis for these movements is unknown but is thought to involve cortical-striatal-thalamo-cortical pathways. To further clarify potential neurochemical alterations, gamma-aminobutyric acid (GABA), glutamate, glutamine, N-acetylaspartate, and choline levels were measured in 4 frontostriatal regions by using 1H MRS at 7T.

MATERIALS AND METHODS: A total of 18 children with primary complex motor stereotypies and 24 typically developing controls, ages 5–10 years, completed MR spectroscopy at 7T. Single voxel STEAM acquisitions from the anterior cingulate cortex, premotor cortex, dorsolateral prefrontal cortex, and striatum were obtained, and metabolites were quantified with respect to Cr by using LCModel.

RESULTS: The 7T scan was well tolerated by all the participants. Compared with the controls, children with complex motor stereotypies had lower levels of GABA in the anterior cingulate cortex (GABA/Cr, P = .049; GABA/Glu, P = .051) and striatum (GABA/Cr, P = .028; GABA/Glu, P = .0037) but not the dorsolateral prefrontal cortex or the premotor cortex. Glutamate, glutamine, NAA, and Cho levels did not differ between groups in any of the aforementioned regions. Within the complex motor stereotypies group, reduced GABA to Cr in the anterior cingulate cortex was significantly associated with greater severity of motor stereotypies (r = −0.59, P = .021).

CONCLUSIONS: These results indicate possible GABAergic dysfunction within corticostriatal pathways in children with primary complex motor stereotypies.

Abbreviations

ACC
anterior cingulate cortex
CMS
complex motor stereotypies
DLPFC
dorsolateral prefrontal cortex
GABA
gamma-aminobutyric acid
Gln
glutamine
Glu
glutamate
PMC
premotor cortex
  • © 2016 American Society of Neuroradiology

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GABA and Glutamate in Children with Primary Complex Motor Stereotypies: An 1H-MRS Study at 7T
A.D. Harris, H.S. Singer, A. Horska, T. Kline, M. Ryan, R.A.E. Edden, E.M. Mahone
American Journal of Neuroradiology Nov 2015, DOI: 10.3174/ajnr.A4547

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GABA and Glutamate in Children with Primary Complex Motor Stereotypies: An 1H-MRS Study at 7T
A.D. Harris, H.S. Singer, A. Horska, T. Kline, M. Ryan, R.A.E. Edden, E.M. Mahone
American Journal of Neuroradiology Nov 2015, DOI: 10.3174/ajnr.A4547
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