Transcranial Magnetic Stimulation for Children With Tourette's Syndrome

Study Overview
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Brief Summary
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Tics are the core symptom of Tourette syndrome. These are repetitive, sudden, semi-voluntary movements or sounds. In some children, these tics can be especially bad and require treatment, however, options are limited. It is only with time and practice that youth with Tourette syndrome are better able to suppress their tics. For these reasons, new interventions are needed. The investigators will target a brain region involved in tics called the supplementary motor area. Using low frequency repetitive transcranial magnetic stimulation, the investigators will inhibit the activity, in a similar way to the tic suppression that develops with age. The investigators propose the following objectives: (Aim 1) The investigators hypothesize that Tourette syndrome symptom severity (as measured by the Yale Global Tic severity Scale) will decrease with low frequency repetitive transcranial magnetic stimulation targeting the supplementary motor area. (Aim 2) The investigators further hypothesize that improvement in Tourette syndrome symptoms will be moderated by low frequency repetitive transcranial magnetic stimulation induced changes in GABA and glutamate in the supplementary motor area, and changes in the functional connectivity between the supplementary motor area and primary motor cortex. Eleven children (7-12 years of age) with Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation (five times a week for three weeks). After the three weeks, they will look for changes in tic severity and brain chemistry and function. By developing a novel avenue for treating Tourette syndrome, they can directly impact the care of children by reducing the severity of tics and improving quality of life.

Detailed Description
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Background Tourette syndrome is very common. It affects over 80,000 Canadian youth. Tics are the core symptom of Tourette syndrome. These are repetitive, sudden, semi-voluntary movements or sounds. In some children, these tics can be especially bad and require treatment, however, options are limited. Medications for Tourette syndrome carry significant risk of side effects. Behavioral treatments, like habit reversal therapy, show promise and are safe, but are difficult to apply to younger children. It is only with time and practice that youth with Tourette syndrome are better able to suppress their tics. Finally, neither medication nor behavior therapies directly target the root cause of the tics. For these reasons, new interventions are needed. Specific Objectives The investigators will target a key brain region involved in tics. It is called the supplementary motor area. Using low frequency repetitive transcranial magnetic stimulation, they will inhibit the activity of that brain region, in a similar way to the tic suppression that develops with age. The investigators propose the following specific objectives: (Aim 1) The investigators will characterize the effect of low frequency repetitive transcranial magnetic stimulation of the supplementary motor area on Tourette syndrome symptoms. They hypothesize that Tourette syndrome symptom severity (as measured by the Yale Global Tic severity Scale) will decrease with low frequency repetitive transcranial magnetic stimulation targeting the supplementary motor area. (Aim 2) The investigators will identify the changes in brain metabolites (glutamate and GABA) and functional connectivity caused by low frequency repetitive transcranial magnetic stimulation that normalize brain activity. They hypothesize that improvement in Tourette syndrome symptoms will be moderated by low frequency repetitive transcranial magnetic stimulation induced changes in GABA and glutamate in the supplementary motor area. This will be assessed with proton magnetic resonance spectroscopy, potentiation of GABAergic neurotransmission assessed with short-interval cortical inhibition, and changes in the functional connectivity between the supplementary motor area and primary motor cortex. Methods Eleven children (7-12 years of age) with Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation (5 times a week for three weeks). The investigators will assess the key variables with interviews and brain imaging of the children before and after the three-week intervention. After the three weeks, they will look for changes in tic severity and brain chemistry and function. Expected Results The investigators have pioneered transcranial magnetic stimulation applications in child and adolescent populations. By developing a novel avenue for treating Tourette syndrome, they can directly impact the care of children by reducing the severity of tics and improving quality of life.

Official Title
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TICS: Transcranial Magnetic Stimulation for Children With Tourette's Syndrome

Conditions
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Tourette Syndrome

Intervention / Treatment
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* Device: Low frequency repetitive transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males Right-handed Exclusion Criteria: Female Left-handed Comorbid Attention Deficit Hyperactivity Disorder

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low frequency rTMS<br>Eleven children (7-12 years of age) with Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation (5 times a week for three weeks). | Device: Low frequency repetitive transcranial magnetic stimulation<br>* Baseline high-resolution anatomical magnetic resonance images will allow individualized neuronavigation (Brainsight 2, Rogue Research, Montreal QC) to co-register the transcranial magnetic stimulation Airfilm coil (Magistim, UK) precisely to the supplementary motor area as defined by functional magnetic resonance imaging. Interventional low frequency repetitive transcranial magnetic stimulation parameters will be: intensity 100% resting motor threshold, frequency 1 Hz, duration = 20 minutes (1200 stimulations). Treatments will occur on each weekday at the same time of day for three weeks (15 total). These are standard parameters for low frequency repetitive transcranial magnetic stimulation and are well tolerated in children.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Yale Global Tic Severity Scale | Measure of tic severity using the Yale Global Tic Severity Scale (YGTSS). This is the standard measure for studies of Tourette's syndrome. The Global Severity Score has a range of 0- 100. A higher score on all scales suggests greater severity of tics. | Four weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glutamate Concentration | Glutamate concentration in the supplementary motor area | Four weeks | 
| Functional Connectivity | Functional connectivity between the supplementary motor area and primary motor cortex as measured with resting state functional magnetic resonance imaging (rs-fMRI). T-value is the fMRI statistic that shows the level of connectivity. The higher the T-value, the greater the level of connectivity. | Four weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tourette Syndrome, Children, Tics