Role of the Sensory Experience in Generating Motor Tics in Tourette Syndrome
Condition: Tic Disorder; Tourette Syndrome
MeSH terms: Tourette Syndrome; Tics; Tic Disorders; Syndrome
Study type: Observational

Summary: 
      This study will investigate the sensation that many people with Tourette syndrome (TS)
      experience before they have a motor tic. It will also test whether blocking the sensation
      causes the tic to stop.

      People between 18 and 65 years of age with TS who have at least once tic involving an arm may
      be eligible for this 3-part study. Those enrolled may participate in all parts or in part 1
      or part 2. Those who choose to participate in part 3 must first complete part 2. All must
      stop taking medication for TS and any other medication that may affect the brain for at least
      1 week before the study.

      Part 1

      After numbing the skin or muscles of the arm or leg where a pre-tic sensation is experienced,
      the response of the nerves will be tested by asking subjects to rate the strength of the
      sensation after a pinprick and by stimulating the nerves with small electrical shocks. Then,
      over the course of approximately one hour, subjects will report pre-tic sensations while
      their motor tics are counted. The onset of each tic will be identified with EMG, a test using
      electrodes on the skin to indicate the activity of the muscles.

      Part 2

      Subjects brain waves are recorded using magnetoencephalography (MEG) while they are
      experiencing tics andpre-tic sensory experiences. MEG is a test that records magnetic field
      changes produced by brain activity. Subjects sit in a chair under a dome containing magnetic
      field detectors. They watch a clock and report the time a sensory experience starts. Tics are
      recorded with EMG. Later, a standard MRI of the brain (scan using a magnetic field and radio
      waves) is done to see which parts of the brain produced the activity recorded with MEG.

      Part 3

      Repetitive transcranial magnetic stimulation (rTMS) is used to try to stop the pre-tic
      sensations. For TMS, the subject sits in a chair. A wire coil is held on the subject s scalp,
      and a brief electrical current is passed through the coil, creating a magnetic pulse that
      stimulates a region of the brain. The goal of this stimulation is to reduce the sensory
      experience that precedes a tic in one region of the body. During stimulation, the subject
      hears a click and may feel a pulling sensation on the skin under the coil. There may be a
      twitch in the muscles of the face, arm or leg. This study uses a pattern of repeated pulses
      delivered in short bursts. Following each train of pulses, the effect of the stimulation on
      sensation will be tested by asking the subject to rate the strength of a pinprick and of a
      vibration. In addition, the nerves are stimulated with small shocks to evaluate the effect of
      the TMS on nerve activity. To determine the effect of TMS on the pre-tic sensation, subjects
      are asked to watch a clock and report when they are having a sensory experience. The effect
      on motor tics will be evaluated by using EMG to indicate the tics.
    

Detailed description: 
      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 may result from altered
      sensory gating, and whether it is necessary to generate motor tics.

      Study Population:

      We will study 100 subjects. Thirty-five individuals with a diagnosis of Tourette syndrome who
      can describe a sensory experience preceding their tics, and 10 who deny a sensory prodrome
      for a total of 45 subjects. We will also study 55 Healthy volunteers ages 18-65..

      Design: A Two-Part Study

      Part I: MEG recording

      We will determine the extent to which CNS responses to tactile and auditory stimuli
      habituate. Subjects will be presented with trains of stimuli, repeated 80 times. At the end
      of each of these blocks, a questionnaire will ascertain the subject s perception of these
      stimuli. CNS responses to the stimuli will be recorded using MEG and analyzed first for
      localization, and then for amplitude and frequency characteristics. Healthy volunteers will
      be included as a control group.

      Part II: 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 prior and ongoing imaging studies in our group. 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 20 adult subjects for
      part II. Data analysis of this phase will determine 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 both parts, with 20 subjects each.

      Outcome Measures:<TAB>

      For part II, the outcome measures will be 1) inhibition of the sensory experience, and 2) the
      relationship between inhibition of sensory and motor phenomena. For part I, the outcome
      measure will be degree of habituation in TS subjects as compared to that in healthy
      volunteers.
    

Time perspective: Prospective
Keywords: Repetitive TMS (rTMS); Magnetoencephalogram; Transcranial Magnetic Stimulation (TMS); Tourette Syndrome; Tic Disorder; Tourete Syndrome