Protocol Number: 08-N-0215

Title:

Understanding the Anatomy and Physiology of the Sensory Experience and its Role in Generating Tics in Tourette Syndrome

Number:

08-N-0215

Summary:

Objectives:

We will investigate whether the sensory experience that precedes motor tics in Tourette syndrome is generated in the peripheral nervous system and whether it is necessary to generate motor tics.

Study Population:

We will study 35 individuals with a diagnosis of Tourette syndrome who can describe a sensory experience preceding their tics, and 10 who deny a sensory prodrome.

Design: A Three-Part Study

Part I: peripheral anesthesia

We will determine if the sensory symptom is initiated within the peripheral nervous system and what effect its inhibition has on tic production. Subcutaneous and intramuscular anesthesia will be administered on different days to the site of the sensory experience. Injection of a different limb (in the same subject on different days) will serve as a control. Sensory and motor phenomena will be recorded before and after anesthesia.

Part II: MEG recording

We will identify the cortical site that processes the sensory experience using magnetoencephalography (MEG). Subjects will indicate the onset of a sensory experience and surface EMG will indicate tic onset. For each subject, activity corresponding to 100 sensory experiences will be averaged. Subjects with Tourette syndrome but no sensory experience preceding their tics will provide a control. The anatomical correlate of localized signals will be visualized using MRI.

Part III: rTMS inhibition

We will test whether the sensory experience is necessary for generating a motor tic. We will inhibit the sensory experience using repetitive transcranial magnetic stimulation (rTMS) over the cortical region identified by MEG. Low intensity rTMS will be applied as a control. Sensory experiences and motor tics will be recorded before and after rTMS.

Staged Study:

This will be a staged, exploratory study. In phase 1, we will study 5 adult subjects each for part I and part II. Data analysis of this phase will guide decision making in phase 2 in at least 2 specific ways: 1) whether there is a conserved site identified by MEG to be targeted by rTMS for all subjects, and 2) whether the procedures are well-tolerated and safe enough to allow for the inclusion of adolescent children, ages 14 and older. Phase 2 will involve completion of each of the three parts, with 20 subjects each.

Outcome Measures:

For parts I and III, the outcome measures will be 1) inhibition of the sensory experience, and 2) the relationship between inhibition of sensory and motor phenomena. For part II, the outcome measure will be localizing an electromagnetic signal corresponding to the sensory experience.

Sponsoring Institute:

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Subjects must be 18-65 years of age of any race, gender, or handedness. They must be able to sit for at least 2 hours and remain at the testing site for up to 8 hours. They must be able to follow instructions and participate in reporting sensory experiences. The upper extremity tic to be studied must occur at least once a minute, but no more frequently than once every 5 seconds. Individuals with comorbid attention deficit disorder (ADD or ADHD) or with obsessive-compulsive disorder (OCD) will not be excluded.

EXCLUSION CRITERIA:

1. Inability to stop taking all central-acting medications, including those used to treat tics, for at least one week prior to the study

2. Current use of coumadin, heparin, or lovenox

3. Any additional movement disorder, including tremor, myoclonus, or dystonia

4. A diagnosis of major depression or bipolar disorder

5. Frequent or severe headaches

6. Any history of or current experience of hallucinations

7. Any history of a seizure or epilepsy or a family history of epilespy

8. Any prior brain injury, brain tumor or other lesion, stroke, or surgery

9. A diagnosis of increased intracranial pressure

10. Any history of cardiac or respiratory problems following local anesthesia with the lidocaine or novocaine type of drug (part I only).

11. A history of significant heart disease

12. Any history of hearing problems (part III only)

13. Any of the following: pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or shrapnel fragments (part II and III only)

14. Any history of work as a welder or metal worker (part II and III only)

15. Current pregnancy

Special Instructions:

Currently Not Provided

Keywords:

Repetitive TMS (rTMS)

Magnetoencephalogram

Transcranial Magnetic Stimulation (TMS)

Tourette Syndrome

Tic Disorder

Recruitment Keyword(s):

None

Condition(s):

Tic Disorder

Tourette Syndrome

Investigational Drug(s):

None

Investigational Device(s):

Figure 8 Coil and MagStim 200

Intervention(s):

None

Supporting Site:

National Institute of Neurological Disorders and Stroke

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Aoki KR. Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A. Neurotoxicology. 2005 Oct;26(5):785-93. Epub 2005 Jul 5. Review.

Alary F, Sim›es C, JousmŠki V, Forss N, Hari R. Cortical activation associated with passive movements of the human index finger: an MEG study.Neuroimage. 2002 Mar; 15(3):691-6.

Banaschewski T, Woerner W, Rothenberger A. Premonitory sensory phenomena and suppressibility of tics in Tourette syndrome: developmental aspects in children and adolescents. Dev Med Child Neurol. 2003 Oct; 45(10):700-3.

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