Transcranial Direct Current Stimulation to Improve Hand Movement in Stroke Patients
Condition: Stroke
MeSH terms: Stroke
Study type: Observational

Summary: 
      This study will examine whether hand movement in stroke patients can be improved by applying
      electrical stimulation to the side of the brain affected by the stroke. It will compare the
      effects of similar brain stimulations in stroke patients and healthy volunteers.

      Healthy, right-handed normal volunteers and stroke patients between 18 and 80 years of age
      may be eligible for this study. Patients' stroke must have occurred at least 3 months before
      entering the study and affect one side of the brain only. Candidates are screened with a
      medical history, brain MRI, and evaluation of memory and attention span. Pregnant women are
      excluded from the study.

      The study involves seven 2-day sessions over the course of about 8 weeks, with each session
      separated by at least 1 week. During each session participants practice a pattern of hand
      movements and their accuracy in performing the movements is evaluated before and after brain
      electrical stimulation. The movements include a complex finger sequence, a simple finger
      sequence, a peg test (placing wooden pegs in holes on a board), a hand function test (turning
      over cards, picking up small objects with one hand and placing them in a can, picking up
      small objects with a spoon and placing them in a can, stacking checkers, moving light cans,
      and moving heavy cans), and a box and block test (picking up and moving blocks from one box
      to another).

      The first day of each 2-day session lasts about 5 hours and includes the following:

        -  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.

        -  Motor learning under tDCS: tDCS is repeated while the subject performs different finger
           movements. A new pattern of finger movements is taught 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.

        -  Behavioral measurements: Evaluation of learned movement tasks

        -  Questionnaires to evaluate the subject's attention, fatigue and mood before and after
           testing

      The second day of each session lasts about 2 hours and includes the TMS measurements and
      behavior measurements.
    

Detailed description: 
      Objectives: Recent advances in neuroscience may be helpful in designing more accurate
      neurorehabilitative strategies to decrease post-stroke disability. First, recovery is more
      extensive when the interhemispheric balance of activity favors the ipsilesional primary motor
      (M1Ipsilesional) and premotor (PMIpsilesional) cortices. Second, non-invasive transcranial
      direct current stimulation (tDCS) over M1Ipsilesional may help to transiently improve motor
      performance in stroke patients. Third, in healthy volunteers, training combined with cortical
      stimulation of M1 (which plays a critical role in motor learning) leads to up-regulation of
      corticomotor excitability, improved motor learning, and use-dependent plasticity. Since
      stroke patients have to re-learn how to control their paretic hand, enhancing their learning
      capacity by adequate tuning of M1Ipsilesional with tDCS could promote plastic reorganization
      that supports functional improvement. Finally, another factor to be considered is that
      functional changes elicited by cortical stimulation depend on the previous activity state
      (metaplasticity). Therefore, we hypothesize that implementing metaplastic changes will
      enhance motor learning gains induced by tDCS in chronic stroke patients to a larger extent
      than a control intervention in both stroke patients and healthy volunteers.

      Study Population: 20 healthy subjects for safety issues and parameter optimization; 31
      patients with a single cortical or sub-cortical stroke; and 31 matched healthy controls.

      Design: To test our hypothesis, we will precondition M1Ipsilesional with cathodal tDCS (which
      transiently down-regulates activity in this site) and then apply anodal tDCS to
      M1Ipsilesional during a motor sequence learning with the paretic hand. After a
      familiarization session, real and sham tDCS will be applied in 6 randomized sessions in a
      crossover design. Learning will be evaluated one day after each tDCS/sham session.

      The primary outcome measure will be the number of learned sequences correctly played on a
      keyboard in a 30-second period. TMS will be used 1) to interfere with the activity of
      different cortical motor areas as a marker of their respective contribution to paretic hand
      control before and after the metaplasticity intervention and 2) to measure corticomotor
      excitability changes associated with the interventions. This will provide descriptive
      information on the neural substrates underlying behavioral gains, important for
      hypothesis-generation and power analysis in future investigations.
    

Keywords: Motor Recovery; Transcranial Direct Current Stimulation (tDCS); Homeostatic Plasticity; Ipsilesional Primary Motor Cortex; Paretic Fingers Motor Sequence; Motor Cortex; Motor Function; Motor Learning; Premotor Cortex; Primary Motor Cortex; Stroke; Healthy Volunteer; HV