Previous lesion and imaging studies have identified a number of brain areas involved in retrieval and production of movement sequences. However, the neural mechanisms responsible for selecting optimal movement sequences are not well understood. According to reinforcement algorithms, the outcome of a movement is evaluated with a value function, which is defined as the expected sum of temporally discounted future rewards resulting from that movement. It is also assumed that at each time step, the animal selects the movement with the maximal value function. This framework has successfully accounted for various forms of reward-related activities in multiple brain areas. Nevertheless, the possibility that reinforcement learning algorithms can account for the neural processes of sequence selection has not been previously explored. The experiments proposed in this application will first test whether the value functions of individual movements are represented in the spike rates of neurons in the frontal cortex. These experiments will be carried out in monkeys performing specific behavioral tasks, and single-unit and local field potential activities will be recorded from the lateral and medial frontal cortex using a multi-electrode recording system. Following experiments will then test the hypothesis that neurons encoding value functions of individual movements contribute to sequence selection by favoring a particular movement with a large action value, and determine whether changes in their activity during learning follow the predictions of reinforcement learning algorithms. The causal relationship between the action-value related activities and sequence selection will be also tested using the method of reversible inactivation. It is also hypothesized that the neural representation of value functions is independent of specific effectors, and this hypothesis will be tested by comparing the neural activity associated with the same eye and hand movement sequences. Finally, the hypothesis that synchronous spikes and/or phase-locked oscillation in neural activity plays a special role in transmitting signals related to movement sequences will be tested. The results from these experiments will provide a novel insight into the brain mechanisms underlying the organization of sequential behavior
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