title: GABA and Glutamate in Children with Primary Complex Motor Stereotypies: An 1H-MRS Study at 7T.
abstract: OBJECTIVE
  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 (1)H MRS at 7T.
  
  
  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.
authors.affiliation: From the Russell H. Morgan Department of Radiology and Radiological Science (A.D.H., A.H., R.A.E.E.) F.M. Kirby Center for Functional Brain Imaging (A.D.H., A.H., R.A.E.E.), Kennedy Krieger Institute, Baltimore, Maryland. ashley.harris2@ucalgary.ca.
authors.forename: A D
authors.identifier: http://orcid.org/0000-0003-4731-7075
authors.initials: AD
authors.lastname: Harris
authors.affiliation: Department of Neurology (H.S.S., T.K.) Department of Pediatrics (H.S.S.).
authors.forename: H S
authors.identifier: http://orcid.org/0000-0002-8906-7679
authors.initials: HS
authors.lastname: Singer
authors.affiliation: From the Russell H. Morgan Department of Radiology and Radiological Science (A.D.H., A.H., R.A.E.E.) F.M. Kirby Center for Functional Brain Imaging (A.D.H., A.H., R.A.E.E.), Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: A
authors.identifier: http://orcid.org/0000-0002-1044-409X
authors.initials: A
authors.lastname: Horska
authors.affiliation: Department of Neurology (H.S.S., T.K.).
authors.forename: T
authors.identifier: http://orcid.org/0000-0002-0286-2187
authors.initials: T
authors.lastname: Kline
authors.affiliation: Department of Neuropsychology (M.R., E.M.M.).
authors.forename: M
authors.identifier: http://orcid.org/0000-0002-9887-5264
authors.initials: M
authors.lastname: Ryan
authors.affiliation: From the Russell H. Morgan Department of Radiology and Radiological Science (A.D.H., A.H., R.A.E.E.) F.M. Kirby Center for Functional Brain Imaging (A.D.H., A.H., R.A.E.E.), Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: R A E
authors.identifier: http://orcid.org/0000-0002-0671-7374
authors.initials: RA
authors.lastname: Edden
authors.affiliation: Department of Psychiatry and Behavioral Sciences (E.M.M.), The Johns Hopkins University School of Medicine, Baltimore, Maryland Department of Neuropsychology (M.R., E.M.M.).
authors.forename: E M
authors.identifier: http://orcid.org/0000-0002-5022-1499
authors.initials: EM
authors.lastname: Mahone
mesh_terms: D001921:Brain / Q000378:metabolism*; D002648:Child; D005260:Female; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D066244:Proton Magnetic Resonance Spectroscopy; D019956:Stereotypic Movement Disorder / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid