Measurement of Glutamate and GABA in Motor Pathways: A 1H-MRS at 7 Telsa Study

Grant Type
Grant Year
Institution Location
Institution Organization Name
Johns Hopkins University School of Medicine, Baltimore, MD
Investigators Name
Singer, Harvey S., MD

Alterations in synaptic neurotransmission within cortico-striatal-thalamo-cortical (CSTC) circuits have been strongly implicated in the pathophysiology of tics. Recent human and rodent studies, suggest the presence of distinct cortical-striatal pathways for flexible goal-directed (ventromedial prefrontal cortex—VMPFC, to caudate) and habitual (pre-motor to putamen) behaviors with important contributory roles for the dorsolateral prefrontal cortex (DLPFC) and hippocampus. Glutamate, a major excitatory transmitter, has been previously hypothesized to have a major role in TS and a recent positron emission tomography study has suggested a widespread abnormality of the inhibitory GABAergic system. Glutamate and GABA are both essential neurotransmitters within CSTC circuits. These neurotransmitters can now be readily quantified using high field strength (7 Tesla) 1H-MR spectroscopy, a methodology without significant risks. The goals of this study are to: 1) quantify in children with Tourette syndrome (TS) and typically developing control children the patterns of glutamate and GABA within brain regions associated with habitual and goal-directed behaviors, and, 2) to examine (in the TS group) the interrelationships between glutamate and GABA in various brain regions with several clinical variables including tic severity, age of symptom onset, and severity of ADHD. Five specific brain regions, including the premotor cortex, VMPFC, DLPFC, striatum and hippocampus, will be evaluated. Data will be collected using single voxel 1H-MR spectroscopy obtained at 7.0 Tesla, in 40 unmedicated children with TS, ages 6-12 years and compared to 40 age- sex-matched typically developing children. Children with the formal diagnosis of Obsessive Compulsive Disorder and/or other anxiety disorder (based on a Diagnostic Interview for Children and Adolescents, DICA-IV, screen) will be excluded from this study. Other diagnostic and neuropsychological screening assessments include IQ, Yale Global Tic Severity Scale, Children’s Yale-Brown Obsessive Compulsive Scale, Connor’s Rating Scale, and the Multidimensional Anxiety Scale for Children. All participants will receive mock scan training prior to the actual 1H MRS scan. The measurement of both glutamate and GABA will provide important information on functional interactions between excitatory and inhibitory cortical and striatal neurons in TS. The identification of a specific chemical abnormality within the brain of a child with TS has obvious neurobiological and therapeutic implications. Harvey S. Singer, M.D., Alena Horska, Ph.D. & Mark Mahone, Ph.D. Johns Hopkins University School of Medicine, Baltimore, MD Award: $149,912 Tourette Association of America Inc. – Research Grant Award 2013-2014