Project Summary Behavioral control is a fundamental component of executive control and requires the ability to suppress actions, thoughts, and desires. Deficits in behavioral control are thought to be at the core of many public health concerns in the United States. Nevertheless, currently little is known about the mechanisms underlying behavioral control and what leads to failures of control. Response inhibition and self-control, two key aspects of behavioral control, are often hypothesized to be the result of a uniform neuronal mechanism for impulse control, but they have typically been studied independently, and it is possible that the brain contains separate neuronal mechanisms for motor and motivational control. Neuroimaging and lesion studies in humans have implicated a network of prefrontal regions in self-control, as well inhibitory motor control, including frontal eye field (FEF), supplementary eye field (SEF), pre-supplementary motor area (preSMA), dorsolateral prefrontal cortex (DLPFC), and ventrolateral prefrontal cortex (VLPFC). However, it is not clear if the neuronal circuits of motor control and self-control are identical or separate. In our proposed experiments, we will investigate prefrontal mechanisms for self-control and response inhibition in these areas. Comparing the mechanisms for both types of control requires tasks that allow identification of signals involved in response inhibition and self-control. We will train monkeys both in a novel self-control task developed by us (requiring motivational control) and in the classic stop signal task (requiring motor control). This will allow us to identify circuit level mechanisms of self-control and response inhibition. Our Aim 1 is to determine if the neural mechanisms of response inhibition and self-control in prefrontal cortex are shared or distinct. We will record the neural activity of multiple neurons in FEF, SEF, preSMA, DLPFC and VLPFC. By testing identical sets of prefrontal neurons in both tasks, we will identify neuronal activity underlying each control mechanism and determine if identical or separate circuits are responsible for both forms of executive control. Our Aim 2 is to determine if different areas in prefrontal cortex causally contribute to response inhibition and self- control. Preliminary data show that inactivation of SEF by cooling will bias behavioral outcomes toward failures of self-control. This indicates a causal role of SEF in self-control. We will systematically test the causal role of FEF, SEF, preSMA, DLPFC and VLPFC in response inhibition and self-control, by inactivating each of these areas and observe behavior in the delayed gratification and stop signal tasks. Inactivating one area, while simultaneous recording in other areas will determine if neuronal representations of response inhibition or self-control are causally dependent on activity in other parts of the network of prefrontal regions.