rTMS to Reduce Tics

Specific Aim1: Using a paradigm of Transcranial Magnetic Stimulation called Continuous Theta Burst Stimulation (cTBS) to reduce tics in Tourette Syndrome subjects

Hypothesis1: cTBS, compared to sham stimulation, will reduce tic severity by at least 25% as measured by the Yale Global Tic Severity Scale

Specific Aim2: Using cTBS to further understand neural correlates of tic generation

Hypothesis2: Functional MRI BOLD signal activation pattern will change after cTBS and this change will correlate with clinical improvement in tic severity

Tourette syndrome (TS) is characterized by multiple motor and phonic tics. Current understanding of tic generation is thought involve the cortico-basal-thalamic-cortical circuit. At this time, only two medications are FDA-approved for tic treatment, while many more are used in an off-label fashion with only partial success. Despite multiple approaches for tic suppression, patients with severe tics are often left with inadequate relief. Repetitive Transcranial Magnetic Stimulation (RTMS) is a new technology which allows for noninvasive stimulation of the brain. In few pilot studies, RTMS reduced tic severity when targeting the Supplementary Motor Area (SMA). In this study, we propose to use a specific paradigm of RTMS called Continuous Theta Burst Stimulation (cTBS) over SMA to treat pediatric and adult patients with tics. We will utilize functional MRI (fMRI) to identify each subject's SMA for individualized stimulation. We hypothesize that this stimulation technique can reduce tic severity when compared to sham stimulation. This proposal is novel because 1) cTBS is offered as a new RTMS paradigm to reduce tics and 2) combination of RTMS and fMRI allows us to investigate the effects of cortical stimulation on the neural correlates of tic generation.

• Device: Repetitive Transcranial Magnetic Stimulation (RTMS)
  Repetitive Transcranial Magnetic Stimulation (RTMS) is a relatively new technology that allows for targeted noninvasive stimulation of the brain. RTMS is currently FDA-cleared for the treatment of refractory depression. It is also used experimentally to treat seizures, spasticity, dystonia and other neuropsychiatric conditions
  Other Name: rTMS, TBS, TMS
• Device: Transcranial Magnetic Stimulation
  Each session will last at most 180 minutes and the motor responses to TMS are recorded with surface EMG electrodes taped to the skin. The signal is amplified, and filtered (100/1000 Hz) (Coulbourn Instruments, Allentown, PA) before being digitized at 2 kHz and stored for off-line analysis using Signal® software and a Micro1401 interface (Cambridge Electronic Design, Cambridge, UK).

Inclusion Criteria:1. Children or adults with Tourette Syndrome, tic disorder, chronic motor or vocal tics disorder ages 10 to 60 years.

2. Current tics with Yale Global Tic Severity Scale (YGTSS) score > 10. 3. If subject is on tic-suppressing medication(s) at the time of recruitment, no medication or dose changes allowed within the past seven days.

4. If subject receives botulinum toxin injection for tic management, the injection must be at least twelve weeks prior to the day of the study.

5. After the TBS sessions, no tic-suppression medications can be changed for at least one week.

6. All patients ages 10 to 60 years old with Tourette Syndrome, tic disorder, chronic motor or vocal tics disorder will be offered to participate in the study. If the patient decides to participate in the study, our study coordinator will obtain informed consent from the adult participant, or at least one parent of the pediatric participant. The consent form is written in English; the form is also written in a manner understandable by the person signing the form. The adult participant, the parent(s) of participant or the pediatric participant does not have to make a decision at the time of clinic visit, thus, minimizing coercion to participate.

-

Exclusion Criteria:1. Implanted brain stimulator, vagal nerve stimulator, VP shunt, aneurysm clip, cardiac pacemaker, or implanted medication port.

2. Prior ischemic or hemorrhagic stroke or traumatic brain injury. 3. History of seizure or epilepsy 4. If female, pregnant or sexually active and not using birth control. Abstinence will be permitted at the discretion of the TS clinicians, consistent with other IRB approved studies involving this population.

-