Propensity to Develop Plasticity in the Parieto-Motor Networks in Dystonia From the Perspective of Abnormal High-Order Motor Processing
Condition: Writer's Cramp; Healthy Volunteers; Cervical Dystonia
MeSH terms: Dystonia; Dystonic Disorders; Torticollis
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Background:

      - People with dystonia have muscle contractions they can t control. These cause slow,
      repeated motions or abnormal postures. People with dystonia have abnormalities in certain
      parts of the brain. Researchers want to study the activity of two different brain areas in
      people with writer s cramp and cervical dystonia.

      Objective:

      - To compare brain activity in people with dystonia to that in healthy people.

      Eligibility:

        -  Right-handed people ages of 18-65 with cervical dystonia or writer s cramp.

        -  Healthy volunteers the same ages.

      Design:

        -  Participants will be screened with a physical exam. They will answer questions about
           being right- or left-handed.

        -  At study visit 1, participants will:<TAB>

        -  Have a neurological exam.

        -  Answer questions about how their disease impacts their daily activities.

        -  Have a structural magnetic resonance imaging (MRI) scan. Participants will lie on a
           table that can slide <TAB>in and out of a metal cylinder. This is surrounded by a strong
           magnetic field.

        -  Do 2 simple computer tasks.

        -  At study visit 2:

        -  Participants will have transcranial magnetic stimulations (TMS) at 2 places on the head.
           Two wire coils will be held on the scalp. A brief electrical current creates a magnetic
           pulse that affects brain activity. Muscles of the face, arm, or leg might twitch.
           Participants may have to tense certain muscles or do simple tasks during TMS. They may
           be asked to rate any discomfort caused by TMS.

        -  Muscle activity in the right hand will be recorded by electrodes stuck to the skin of
           that hand.
    

Detailed description: 
      Objective:

      The purpose of this protocol is to improve understanding of the pathophysiology of dystonia
      by performing an electrophysiological study using plasticity induction protocols based on
      dual-site transcranial magnetic stimulation (TMS). We hypothesize that dystonic patients have
      enhanced responsiveness to plasticity induction in the parieto-motor network. The clinical
      significance of such an enhanced plasticity will be evaluated by correlating the plasticity
      measurements with subjects' performance on two tasks engaging high-order motor processing and
      involving the parietal cortex.

      Study population

      This study will explore the parieto-motor network (PAR study). There will be two independent
      arms in each study: one will compare patients with writer s cramp (WC) and age-matched
      healthy volunteers (HV); and the other one will compare patients with cervical dystonia (CD)
      with age-matched HVs. The power analysis of thePAR study indicates that we need to enroll 17
      patients and 17 healthy volunteers in each arm, with an additional 3 added to account for
      drop-outs. Therefore, we request a maximum of 20 subjects per patient group and 40 subjects
      for the control groups.

      Design

      Subjects will come for one screening visit and two outpatient study visits. During the first
      study visit patients will be scored clinically for dystonia. They will also undergo a
      structural magnetic resonance imaging (MRI) to locate the parietal target during the
      stimulation session. At least 24 hours later, during study visit two, subjects will receive
      TMS. TMS-induced electromyographic (EMG) activity of hand muscles will be recorded as motor
      evoked potentials (MEPs). Using single TMS shocks, we will measure at baseline, the
      input-output (I-O) curve for the right first dorsal interosseous (FDI) muscle MEPs. Then, the
      subjects will receive a plasticity induction protocol aiming to induce plasticity in the
      pathway linking the posterior parietal (PP) cortex and the primary motor cortex (M1). To that
      end, transcranial stimulation will be applied repeatedly (100 pairs) to the left angular
      gyrus in the PP cortex and to the left M1. At the end of the intervention, the I-O curve will
      be measured again over the next 50 minutes.

      Outcome measures

      The amplitude of the MEPs in the I-O curves gives information about corticospinal
      excitability as a function of TMS stimulation. The primary outcome measure will be the
      relative change of the MEP size with respect to time (before and 15-20 min after the
      plasticity intervention). The difference in MEP size will be compared between the HV and the
      patient groups using a T test.
    

Intervention name(s): TMS
Intervention type(s): Device
Intervention description(s): single TMS pulses at intensities in random order from 0 to 100% (increasing at 5% intervals) of stimulator output at a frequency of 0.1 Hz. Three pulses will be delivered at each intensity. MEPs will be recorded and their amplitudes will be plotted against the corresponding stimulation intensity. This curve will provide three significant parameters: (a) S50 intensity (intensity for which we get a MEP 50 % of its maximal size); (b) estimated resting motor threshold (RMT): the abscissa where the tangent to the slope crosses the x axis; and (c) the maximum MEP ( plateau value).
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Parietal Lobe; Plasticity; Dystonia; Transcranial Magnetic Stimulation (TMS)