Neural Mechanisms of Motivated Movement

项目总结

Project Summary Movements are influenced by motivation. Consider a basketball player shooting a free-throw. Depending on the stakes of the outcome of the shot, performance can vary greatly. Top athletes rise to the challenge, and perform better during a game than they do during practice. But when the stakes are inordinately high, like when the game is on the line, even skilled players can “choke under pressure”, and under-perform right when it matters the most. What are the neural mechanisms whereby motivation affects motor performance? Here we propose a targeted set of experiments to dissect the neural mechanisms of motivated movement. Our work is guided by a conceptual model that is premised on decades of research into the function of the dopamine system. Put simply, we posit that dopamine modulates the activity of populations of neurons in the primary motor cortex. The level of dopamine is determined by the size of the expected reward. Neurons in motor cortex are activated by dopamine, as well as by volitional motor commands. We hypothesize that dopamine interacts with the ongoing neural control of behavior: Moderate amounts of dopamine improve the fidelity of movement-related signals in the motor cortex, but unusually high levels of dopamine actually interfere with neural activity patterns in motor cortex, perhaps by making them too variable or poorly-formed to trigger a successful movement. If we can show that this picture (or something like it) is true, then we can, for the first time, establish a direct link between motivation and motor control, mediated by whole-brain circuits involved in the performance of a skilled movement. Our approach relies on our recently established animal model: Rhesus monkeys exhibit the same behavioral performance profile that humans do. That is, they show improved performance as motivation increases, but then when the stakes get unusually high, they also choke under pressure. To our knowledge, this effect has never been demonstrated in a nonhuman animal, which makes monkeys the ideal model system in which we can begin to understand the neurophysiological mechanisms whereby motivation and movement mix in the human brain. Here, using this unique model, we first study how reward modulates the motor cortical control of movement, and test several hypotheses regarding how reward might mediate neural noise and behavioral variability. Second, we test how these reward-related modulations influence the planning, initiation, and execution of reach. Third, we record from midbrain dopaminergic reward processing circuits, to establish moment-by-moment links between dopamine activity and ongoing motor performance, and probe causal effects of cortical dopamine. Our studies stand to unveil the neural mechanisms of reward-based changes in motor control, with several clinical implications: (1) In Parkinson’s disease, the death of dopaminergic neurons results both in a loss of movement vigor and also a degradation in the quality of movement. This study will be among the first that will show a direct link between dopamine activity and both motivation and motor performance. (2) In stroke, rehabilitation can be a tedious and frustrating experience. Our work can show how the right motivational structure can improve motor performance and perhaps learning. (3) Our work also has relevance for brain-computer interfaces (BCI), through the design of systems that can extract stable motor-control signals despite shifts in motivation.