Detecting a Reward Signal in the Motor Cortex

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.