Enhancing Motor Task Training by Action Observation Watching Others Perform the Task
Condition: Motor Memory
Study type: Observational

Summary: 
      This study will determine how the brain learns a new motor task when the subject practices
      the task and watches others perform it (action observation) at the same time.

      Healthy normal volunteers between 18 and 55 years of age may be eligible for this study.
      Candidates are screened with a medical history, general and neurological exam, and a brain
      MRI if one has not been done within 12 months of entering the study. Participants undergo one
      or both of the following experiments:

        1. Effect of Transcranial Magnetic Stimulation on Motor Training and Action Observation

           Subjects participate in at least 12 4-hour test sessions, separated by at least 1 day.
           Each session includes the following:

             -  Functional MRI (fMRI): MRI scanning uses a magnetic field and radio waves to
                produce images of the brain. For fMRI, the subject performs tasks during the scan
                to allow researchers to see brain changes that occur during performance of the
                activity.

             -  Transcranial magnetic stimulation (TMS): For this test, a wire coil is held on the
                scalp. A brief electrical current passes through the coil to stimulate the brain.
                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.
                During the stimulation, the subject is asked to: 1) perform the training task (make
                brisk thumb movements); 2) watch a video showing the hand of another person
                performing the same task; and 3) perform the task and watch the video at the same
                time, synchronizing his or her movements with those observed in the video.

             -  Surface electromyography: Electrodes are filled with a conductive gel and taped to
                the skin over a hand muscle to measure the electrical activity of the muscle.

             -  Behavioral measurements: Evaluation of learned movement tasks.

             -  Questionnaires to test attention, fatigue and mood before, during and after each
                test session.

        2. Effect of Pharmacological Agents on Motor Training and Action Observation

      Subjects participate in no more than 12 5-hour test sessions, separated by at least 2 days.
      In the course of the 12 sessions, subjects receive each of three medications -
      dextromethorphan, scopolamine and rivastigmine - three times and a placebo (pill with no
      active ingredient) three times. During each session, subjects have TMS measurements,
      behavioral measurements and electromyography as described in experiment 1.
    

Detailed description: 
      Motor training (MT) elicits formation of motor memories in the human primary motor cortex.
      Observing another individual perform motor training (Action Observation, AO) also results in
      formation of motor memories in M1. AO enhances motor training effects (MT+AO) on the
      formation of motor memories. Possible underlying mechanisms include long-term potentiation
      (LTP), a process influenced by N-methyl-D-aspartate (NMDA) receptor activation,
      gamma-aminobutyric acid (GABA), norepinephrine (NE), dopamine and acetylcholine (Ach), taking
      place at the confluence of inputs from PMv over the primary motor cortex (M1).

      The purpose of this protocol is to gain insight into the mechanisms underlying motor memory
      formation by MT+AO. We plan to perform two different types of experiments: In experiment 1,
      we will modulate activity in PMv using TMS to investigate the role of this cortical area on
      motor memory formation induced by MT+AO. In experiment 2, we will test the effects of single
      doses of (a) the NMDA receptor antagonist dextromethorphan, (b) the muscarinic receptor
      antagonist scopolamine, both known to disrupt LTP, and (c) the cholinesterase inhibitor
      rivastigmine, which enhances LTP.

      The primary outcome measure of motor memory formation will be the percentage of TMS-evoked
      movements that fall within the training target zone (TTZ) before and after MT+AO. The
      secondary outcome measure will be the percentage of TMS-evoked movements that fall within TTZ
      before and after MT alone and AO alone.

      Expected results are (1) upregulation of activity in PMv using 0.1 Hz TMS will enhance motor
      memory formation induced by MT+AO more than sham TMS and downregulation of PMv using 0.9 Hz
      TMS and (2) dextromethorphan and scopolamine will decrease but rivastigmine will increase
      motor memory formation induced by MT+AO with placebo. This study may provide useful
      information on the mechanisms underlying the beneficial effects of action observation on
      neuroplasticity.
    

Keywords: Action Observation; Motor Memory; Transcranial Magnetic Stimulation (TMS); Use-Dependent Plasticity; Healthy Volunteer; HV