Improving Hand Movement Training Through Electrical Stimulation of the Brain
Condition: Metaplasticity
Study type: Observational

Summary: 
      This study will determine if applying electrical stimulation of the brain can influence
      training to perform finger movements. The study may provide information that can be used to
      design rehabilitation therapies for people who have lost the ability to move a part of their
      body, such as an arm, leg, or hand following a stroke.

      Healthy volunteers 18-50 years of age may be eligible for this study. Candidates are screened
      with a medical history, physical examination, MRI (if one has not been done within the last
      year), questionnaire to evaluate memory and attention and a pregnancy test for women who can
      become pregnant.

      Participants have the following tests and procedures in seven sessions over about 8 weeks:

        -  Questionnaires to test attention, fatigue and mood before, during and after each session

        -  Surface electromyography: Electrodes are filed with a conductive gel and taped to the
           skin over one small hand muscle to measure the electrical activity of muscles.

        -  Transcranial magnetic stimulation: A wire coil is held on the scalp. A brief electrical
           current passes through the coil to stimulate 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.

        -  Transcranial direct stimulation (tDCS) before and during motor training: Small, wet
           sponge electrodes are applied to the head - one above the eye and the other on the back
           of the head. A small electrical current is passed between them. The subject may feel an
           itching or tingling sensation under the electrodes or see light flashes.

        -  Motor learning under tDCS: tDCS is repeated while the subject performs the training
           task. The training task consists of performing voluntary brisk thumb movements in a
           direction opposite to TMS-induced movement directions, during 30 minutes. Training
           blocks are in 10-minute segments and tDCS is applied during the first 20 minutes.

        -  Behavioral measurements: Evaluation of learned movement tasks.
    

Detailed description: 
      OBJECTIVES:

      Training leads to performance improvements and motor learning. Cortical plasticity associated
      with training (use-dependent plasticity, UDP) contributes to performance improvements after
      brain lesions such as stroke. Recently, several interventional strategies have been proposed
      to enhance UDP, including pharmacological approaches and brain stimulation. The magnitude of
      improvements identified with these techniques is limited. It would be very useful to enhance
      UDP beyond the limited effects of previously proposed interventions.

      One strategy recently proposed to enhance the effect of brain stimulation techniques on the
      cerebral cortex is metaplasticity. This strategy focuses on the purposeful manipulation of
      cortical activity before applying brain stimulation. For example, previous work demonstrated
      that the magnitude of increase in cortical excitability elicited by stimulation of the
      primary motor cortex (M1) is more prominent if stimulation is applied on a hypoactive M1. An
      initial down-regulation of M1 activity (i) amplifies the effect of a subsequent intervention
      that increases M1 activity, and (ii) reduces inter-individual variability.

      It is unknown if this metaplasticity strategy can enhance the beneficial effects of anodal
      tDCS (tDCS anodal) on training effects as it does with cortical excitability, an issue of
      scientific and clinical interest, and the overall hypothesis of this protocol.

      Here, we will test the hypothesis that metaplasticity (tDCS cathodal) followed by tDCS anodal
      plus motor training will result in more prominent UDP than control interventions.

      STUDY POPULATION

      6 healthy adult volunteers for parameters estimation plus 25 healthy adult volunteers (total
      = 31 healthy adult volunteers)

      DESIGN

      In this protocol, down-regulation of M1 activity will be accomplished by applying tDCS
      cathodal, a tool extensively described in the literature to induce this effect. Therefore, we
      will test the effects of this metaplasticity intervention on the beneficial action of tDCS
      anodal to M1 in combination with motor training (MT). After a familiarization session,
      subjects will participate in 6 randomized sessions in a cross-over design:

        1. Preconditioning tDCS cathodal followed by Intervention tDCS anodal plus MT Purpose
           Target metaplasticity condition

        2. Preconditioning Sham followed by Intervention Sham plus MT Purpose Effects of motor
           training alone

        3. Preconditioning Sham followed by Intervention tDCS anodal plus MT Purpose Mild
           improvement in training effects

        4. Preconditioning tDCS cathodal followed by Intervention Sham plus MT Purpose Effects of
           tDCS cathodal alone on MT

        5. Preconditioning tDCS anodal followed by Intervention Sham plus MT Purpose Effects of
           polarity on tDCS effects

        6. Preconditioning tDCS anodal followed by Intervention tDCS anodal plus MT Purpose Control
           for the metaplasticity condition

      MT will consist of brisk repetitive thumb movements in a direction opposite to the baseline
      direction of thumb movements evoked by focal transcranial magnetic stimulation (TMS), in a
      well-characterized UDP protocol.

      The primary outcome measure reflecting the encoding of a motor memory will be the increased
      proportion of TMS-evoked movements falling within the target training zone (TTZ) as a
      function of MT and metaplasticity interventions.
    

Keywords: Transcranial Direct Current Stimulation (tDCS); Transcranial Magnetic Stimulation (TMS); Motor Learning; Brain Plasticity; Healthy Volunteer; HV