Objective: The role of mesencephalic dopamine neurons in reward processing has been established in primates using electrophysiological techniques and in humans using functional neuroimaging. 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. We recently developed a paradigm to detect reward-related signals in the primary motor cortex, using transcranial magnetic stimulation (TMS), and demonstrated increased inhibition in primary motor cortex under conditions of increased reward expectancy. These results suggest that motor learning, which depends critically on the motor cortex, may be influenced by reward, which may take the form of simple performance feedback in humans. This kind of feedback also allows subjects to predict the outcome of actions.

Thus, our present objective is to investigate the influence of reward/feedback/prediction on the activity of primary motor cortex during motor learning and in particular during instances of increased reward expectancy.

Further, we will examine the role of a brain derived neurotrophic factor (BDNF) single nucleotide polymorphism on motor learning.

Study Population: The population that we will study will be healthy volunteers between the ages of 18-50, without any significant medical history or contraindication to functional magnetic resonance imaging (fMRI).

Design: All experiments will employ within- or between-subjects fMRI and magnetic resonance spectroscopy (MRS) to measure changes in activations of different cortical areas in response to motor learning and reward.

Outcome Measures: The outcome measures will be (a) graded changes in blood oxygen level-dependent (BOLD) in response to motor learning and reward and (b) variations in GABA concentration in response to motor learning and reward, and c) variations in response time in the behavioral performance of a learning task.