GABA and Glutamate in Children with Primary Complex Motor Stereotypies: An 1H-MRS Study at 7T
A D Harris1, H S Singer2, A Horska3
1From 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.
Insights
Children with primary complex motor stereotypies show lower gamma-aminobutyric acid (GABA) levels in specific brain regions. This suggests potential GABAergic dysfunction in the corticostriatal pathways, impacting movement control.
Area of Science:
- Neuroscience
- Child Neurology
- Neuroimaging
Background:
- Complex motor stereotypies involve repetitive movements in children, potentially linked to autism spectrum disorders.
- The neurobiological basis is unclear but involves frontostriatal pathways.
- Investigating neurochemical alterations is crucial for understanding these conditions.
Purpose of the Study:
- To measure levels of key neurotransmitters, including gamma-aminobutyric acid (GABA), in frontostriatal regions of children with primary complex motor stereotypies.
- To explore potential neurochemical differences compared to typically developing children using advanced magnetic resonance spectroscopy.
Main Methods:
- 18 children with primary complex motor stereotypies and 24 controls (ages 5-10) underwent 7 Tesla (7T) magnetic resonance spectroscopy.
- Metabolite levels (GABA, glutamate, glutamine, NAA, choline) were quantified in the anterior cingulate cortex, premotor cortex, dorsolateral prefrontal cortex, and striatum.
- Data were analyzed using LCModel with creatine (Cr) as a reference.
Main Results:
- Children with complex motor stereotypies exhibited significantly lower GABA levels in the anterior cingulate cortex and striatum compared to controls.
- No significant differences were found in glutamate, glutamine, N-acetylaspartate, or choline levels between groups.
- Reduced GABA in the anterior cingulate cortex correlated with increased motor stereotypy severity in affected children.
Conclusions:
- The findings suggest a potential GABAergic dysfunction within the corticostriatal pathways in children with primary complex motor stereotypies.
- This highlights the role of inhibitory neurotransmission in the pathophysiology of these movement disorders.
- Further research into GABAergic system modulation may offer therapeutic targets.
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 (1)H 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.
