Long-Term Improvement in Motor Learning by Transcranial Direct Current Stimulation
Condition: Healthy Volunteers
Study type: Observational

Summary: 
      This study will examine whether continuous use of transcranial direct current stimulation
      (tDCS) in combination with motor training can lead to long-term improvement in movement
      performance beyond what can be achieved with motor training alone.

      Healthy normal volunteers 18-80 years of age who are clearly right- or left-handed may be
      eligible for this study. Each candidate is screened with a medical history, clinical and
      neurological examination, questionnaires to evaluate memory, attention, and handedness and a
      brain MRI, if one has not been done by NINDS within 12 months of entering the study. Pregnant
      women may not participate.

      The study involves 10 sessions (in addition to the screening visit) over 3 months. Sessions
      1-5 are completed over 5 consecutive days. Sessions 6-10 are divided over the remaining time.
      Participants are randomly assigned to one of three groups: 1) tDCS during motor training; 2)
      tDCS after training; or 3) training with sham tDCS. During these sessions, participants
      perform a pinch force task (squeezing a small device between the thumb and forefinger) and
      visuomotor tasks (using a device to move the cursor on a computer screen to various targets
      and holding the cursor in place for 1 second).

      During the motor training and performance sessions, participants have the following
      procedures.

        -  TMS measurements: A wire coil is held on the scalp, and 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.

        -  tDCS: 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. Some sessions are done with sham tDCS.

        -  Surface electromyography: Electrodes are filled with a conductive gel and taped to the
           skin over one small hand muscle to measure the electrical activity of muscles.

        -  Behavioral measurements: Evaluation of learned movement tasks

        -  Questionnaires to evaluate the subject's attention, fatigue and mood before and after
           testing
    

Detailed description: 
      OBJECTIVES:

      Motor practice and use over one session leads to use-dependent plasticity. When practice is
      repeated over multiple sessions, motor performance continues improving until a plateau in
      performance, the so-called ceiling effect is reached. This issue is particularly important in
      neurorehabilitative treatments in which patients usually reach a ceiling effect without
      further improvement. Thus, it would be desirable to modify ceiling effects in motor
      rehabilitation. The purpose of this protocol is to determine if repeated applications of
      TDCS, a form of non-invasive cortical stimulation known to transiently improve performance,
      in association with training, could elicit additional improvements in motor performance
      beyond the ceiling effect identified during performance of a visuomotor training task.

      We will test the hypothesis that anodal TDCS applied over M1 in temporal relation with motor
      training will lead to more prominent long-term learning of a visuomotor task relative to sham
      stimulation (which would document the ceiling effect) in healthy individuals and chronic
      stroke patients and traumatic brain injury (TB1) patients..

      STUDY POPULATION:

      We plan to study 177 healthy volunteers (part 1) and 60 chronic stroke patients (part 2) and
      50 TB1 patients with 50 additional healthy volunteers (part 3). Therefore, an overall
      enrollment of 337 participants is planned.

      DESIGN:

      The study will follow a parallel design. Healthy volunteers (part 1) and stroke patients
      (part 2)will be randomly allocated to one of three groups. Each group will receive anodal
      TDCS or sham in a fixed time frame related to motor training (during or immediately after
      motor training). TB1 patients and healthy volunteers (part 3) will be randomly allocated to
      one of two groups. Each group will receive either sham or anodal tDCS during training.

      Healthy volunteers and stroke patients will participate in 10 sessions. First, they will
      train a visuomotor task (VMT) on 5 consecutive days while receiving sham stimulation (group
      3) or TDCS during (group 1), or immediately after (group 2) the training. Performance of the
      VMT will be re-evaluated at 30, 60 and 90 days after the first training session.

      Traumatic brain injury (TB1) patients and a group of healthy volunteers (part 3) will
      participate in 6 sessions. First, they will train a visumomotor task (VMT) on 3 consecutive
      days while receiving anodal tDCS or sham stimulation during the training. Performance of the
      VMT will be re-evaluated at 30, 60, and 90 days after the first training session.

      OUTCOME MEASURES:

      Primary outcome measure will be the percentage change (from baseline to day 8 in healthy
      volunteers and stroke patients, and from baseline to day 3 in traumatic brain injury) in the
      total time necessary to complete 15 correct trials of the visuomotor task.

      Secondary outcome will be accuracy (no. of errors) and timing (speed) variability of force
      adaptation in the visuomotor task (Celnik, own data), and pinch force at all other time
      points, including day 5 as a measure of learning over the training period and 3 months as a
      measure for long-term retention. In the patient group the Jebsen Taylor Test will be used to
      assess gross motor function. To better understand the mechanisms underlying the proposed
      behavioral gains, we will use single- and paired pulse transcranial magnetic stimulation
      (TMS) to identify corticomotor excitability changes. Furthermore the volunteers will answer
      several questionnaires to evaluate fatigue and mood (PANAS) and perform short
      neuropsychological control task to control for changes in attention and memory function.
    

Keywords: Transcranial Direct Current Stimulation (TDCS); Motor Learning; Transcranial Magnetic Stimulation (TMS); Cortical Re-Organization; Neuroplasticity; Neurorehabilitation; TBI; Stroke; Healthy Volunteer; HV