Neurophysiology of Task-Specificity of Focal Hand Dystonia
Condition: Focal Dystonia
MeSH terms: Dystonia; Dystonic Disorders
Study type: Observational

Summary: 
      This study will examine how the brain coordinates movement in patients with focal hand
      dystonia. Patients with dystonia have muscle spasms that cause uncontrolled twisting and
      repetitive movement or abnormal postures. In focal dystonia, just one part of the body, such
      as the hand, neck or face, is involved. This study will use transcranial magnetic stimulation
      (TMS, see below) to study how the brain plans movement.

      Healthy volunteers and patients with focal hand dystonia 18 years of age and older may be
      eligible for this study. Healthy subjects may participate in one, two or three of the
      experiments described below. Patients with dystonia may participate in experiments one and
      three.

      Before each experiment, each subject is asked about his/her medical and neurologic history,
      complete questionnaires and will undergo a brief physical examination.

      Experiment 1

        -  Surface EMG: Small electrodes are taped to the skin over the arm to measure the
           electrical activity of muscles.

        -  TMS: A wire coil is held on the subject's scalp. A brief electrical current is passed
           through the coil, creating a magnetic pulse that stimulates the brain. During the
           stimulation, the subject may be asked to tense certain muscles slightly or perform other
           simple actions. The stimulation may cause a twitch in muscles of the face, arm, or leg,
           and the subject may hear a click and feel a pulling sensation on the skin under the
           coil.

      Experiment 2 (Two visits.)

        -  Visit 1: Magnetic resonance imaging (MRI): This test uses a magnetic field and radio
           waves to obtain images of body tissues and organs. The patient lies on a table that is
           moved into the scanner (a metal cylinder), wearing earplugs to muffle loud knocking and
           thumping sounds that occur during the scanning process. The procedure lasts about 90
           minutes, during which time the patient will be asked to lie still for up to 30 minutes
           at a time.

        -  Visit 2: Surface EMG and TMS

      Experiment 3

      -Surface EMG and TMS - During the TMS, subjects are asked to respond to shapes on a computer
      screen by pushing a button or pressing a foot petal.
    

Detailed description: 
      Objective

      Currently, there is no cure for focal hand dystonia (FHD). FHD research has focused
      predominantly on the motor execution abnormality in the primary motor cortex, while the
      task-specific nature of FHD has received less attention. Task-specificity suggests that the
      underlying task-to-motor output relationship is intact for many activities and dysfunctional
      for an important minority of tasks. The premotor cortex plays a key role in this relationship
      in health and, likely, plays an equally important role in disordered movement. The goal for
      this research proposal is to understand the underlying physiology and contribution of the
      premotor cortex in FHD.

      Study population

      We intend to study adult patients with FHD and healthy volunteers on an outpatient basis. In
      a task-specific dystonia of the hand known as writer's cramp, handwriting is abnormal due to
      posturing and muscle spasm, whereas other tasks done with the affected hand are normal. The
      disordered relationship between task-to-motor output in FHD is potentially modifiable if the
      correct target and therapeutic modality are identified.

      Design

      In a series of three experiments, we propose to use transcranial magnetic stimulation (TMS)
      to examine the circuitry of the premotor to motor cortex connections in FHD, to interrupt
      motor planning in FHD, and to define premotor cortex somatotopy. In Experiment 1, TMS will be
      used to test the hypothesis that there is deficient inhibition from premotor to motor cortex
      in patients with FHD at rest, during voluntary movement and while maintaining a task-specific
      position. In Experiment 2, TMS will be used to identify whether there is a somatotopic
      organization relevant to the inhibitory premotor-motor cortex interaction in healthy
      volunteers. In Experiment 3, to address the role of motor planning dysfunction in the
      task-specific nature of FHD, we will use TMS to evaluate the premotor-motor cortex inhibition
      during a reaction time task.

      Outcome measures

      The primary outcome measure of Experiment 1 will be change in MEP peak-to-peak amplitude
      between patients and healthy volunteers at rest and in two motor conditions. In Experiment 2,
      the primary outcome measure will be the location of the TMS coil for optimizing inhibition
      from leg premotor cortex to motor cortex compared to the coil location from arm premotor
      cortex to motor cortex. Finally, in Experiment 3, the primary outcome measure will be the
      change in reaction time from baseline to the test condition with transient TMS-induced
      interruption in premotor cortex function.
    

Keywords: Focal Hand Dystonia; Motor Planning; Transcranial Magnetic Stimulation (TMS); MRI (Magnetic Resonance Imaging); FHD; Writer's Cramp; Healthy Volunteer; HV