Detecting a Reward Signal in the Motor Cortex
Condition: Healthy
Study type: Observational

Summary: 
      This study will use transcranial magnetic stimulation (TMS) to determine whether the activity
      in the brain when someone wins something affects the part of the brain that controls
      movement. Studies have shown that the brain releases signals to mark rewards for certain
      behavior, like the activity the brain generates when an animal receives food or drink after
      performing a certain action. This study will look for a way to detect this kind of signal in
      humans.

      Healthy volunteers between 18 and 60 years of age are eligible for this study. Participants
      undergo TMS during two experiments slot machine stimulation and key sequence (see below). For
      TMS, a wire coil is held on the subject s scalp. A brief electrical current is passed through
      the coil, creating a magnetic pulse that stimulates the brain. The stimulation may cause
      twitching in muscles of the face, arm or leg, and there may be a pulling sensation on the
      skin under the coil. The effect of TMS on the muscles is detected with small metal disk
      electrodes taped onto the skin of the arms or legs.

      The stimulation strength needed to activate the hand muscles is determined at the beginning
      of each experiment. To do this, the subject sits with his or her arms and hand relaxed.
      Magnetic pulses of varying strengths are applied in order to find the right strength. Also, a
      series of 45 pairs of magnetic pulses is administered so close to each other that they
      produce only one movement. Measurements of the movements generated serve as a baseline for
      comparison with movements generated during the experiments.

      Slot Machine Simulation

      Subjects play a computer game similar to a slot machine. They press a button to start the
      game and watch as three barrels of the machine spin into place. Subjects can win $0.25, $1or
      $5 if all three barrels match when they stop spinning. If all three barrels do not match,
      subjects do not win any money, except in rare instances, when they are awarded money even
      when all three barrels do not match. In one trial in this experiment, subjects receive
      transcranial magnetic stimulation after they see the second barrel stop spinning. In another
      trial, they receive the stimulation after the third barrel stops spinning.

      Key Sequence

      Subjects see a letter on a computer screen and press a combination of the three keyboard keys
      G, H, and J. If they press the keys in the right order and under the time limit, they win $1.
      At some point, the letter displayed changes, and the subjects must guess a new combination to
      earn money. Each of the letters corresponds to its own combination of key presses. A few
      moments after the subjects see whether they pressed the keys in the right order, they receive
      TMS.
    

Detailed description: 
      Objectvie:

      The role of mesencephalic dopamine neurons in reward processing has been established in
      primates using electrophysiological techniques and in humans using functional neuroimaging.
      Their role is thought to be dual: i) they show sustained activity with the expectation of a
      future reward and ii) a phasic response after reward. Animal data indicate that these
      neurons, located in the midbrain areas A8-10, behave as a single functional unit when
      activated. They have rich projections to both the prefrontal and motor cortices where they
      synapse on interneurons and cortical pyramidal cells, producing primarily inhibition. Though
      their function is not fully understood, these projections clearly play an important role in
      motivation and learning. Since there are no electrophysiological techniques available to
      detect dopaminergic or inhibitory activity in the human prefrontal cortex, our objective is
      to develop a paradigm to detect a reward related signal in the primary motor cortex, where
      transcranial magnetic stimulation can be used to measure brief events.

      Study Population:

      The population that we will study will be healthy volunteers between the ages of 18-60,
      without any significant medical history, contraindication to TMS or history of addictive
      behavior.

      Design:

      Our hypothesis is that the dopamine reward-related signal will alter level of evocable
      inhibition in primary motor cortex. Using behavioral paradigms that deliver intermittent
      reward, we aim to demonstrate a difference in the amount of cortical inhibition, i) when
      reward is expected compared to when reward is not expected ii) after rewarded compared to
      unrewarded trials iii) when reward follows a variable effortful response, and iv) when there
      is uncertainty as to whether a reward will be administered. If we are unable to produce a
      signal in the motor cortex with these simple paradigms, we will look for a reward-related
      change in inhibition when the rewarded behavior is the associative learning of a motor
      sequence. We will control for effects of variations in attention related to the experimental
      task, but not specific for reward, with a similar behavioral paradigm that manipulates
      attention and expectation.

      Outcome Measures:

      The outcome measures will be changes in the conditioned/unconditioned MEP for each reward
      condition.
    

Keywords: Transcranial Magnetic Stimulation (TMS); Dopamine; Gambling; Healthy Volunteer; HV