Abstract. Physiological and psychological factors, such as homeostatic needs or emotional state, underlie the decisions we make. A growing body of evidences suggests that these factors shift the baseline firing rate of neurons across the brain, thereby changing the initial conditions that inform our decisions. The goal of the proposed research is to understand how internal states, a term that encompass these factors, are represented in the brain and how they may alter decision making. In the remainder of my graduate training under Prof. Katalin Gothard (the F99 portion of this application), I will evaluate the role of interoceptive afferent signals signals originating in the body and communicated to the brain via the vagus nerve and spinal cord, in driving baseline firing rate in the anterior cingulate cortex (ACC) during an approach-avoidance conflict task. To do this, I will selectively manipulate the balance between sympathetic and parasympathetic tone in the viscera using glycopyrrolate, a pharmacological agent that does not cross the blood-brain barrier but blocks parasympathetic muscarinic receptors in the body. I will record neurons from the ACC of rhesus macaques while they perform an approach-avoidance conflict task before and after glycopyrrolate administration. Preliminary results indicate that this manipulation increases avoidance behavior. I hypothesize that the sympathetic-dominated visceral state induced by glycopyrrolate will significantly alter the baseline firing rate of ACC neurons, and that the new baseline firing rate will be predictive of increased avoidant decisions. Through this project, I will receive training in the behavioral training of animals, neurophysiological techniques, and computational approaches to data analyses. My co-sponsor, Dr. Aaron Batista at the University of Pittsburgh, will help me use the “computation through dynamics” framework for the analysis of my data. For my postdoctoral training (the K00 portion of this application), I propose to evaluate the role of the ACC in driving prosocial decision making and generating other- oriented value representations in the dorsolateral prefrontal cortex (dlPFC). I will record neurons from the dlPFC and optogenetically inhibit projection neurons in the ACC while marmoset monkeys perform a social decision- making task. I hypothesize that inhibiting the ACC, which has been shown to respond more when conspecifics are rewarded than when the monkey itself receives a reward, will reduce prosocial behavior and shift the baseline firing rate of dlPFC neurons toward firing rates that are predictive of antisocial decisions. This project will evaluate the neural circuits that underlie prosocial behavior in marmosets and provide me with critical training in the use of causal genetic manipulations in non-human primates. Overall, the training I will attain by performing these experiments will prepare me for a career as an independent researcher where I will continue to study how internal and external signals affect social and cognitive decision-making.

Project Narrative: Various physiological and psychological variables influence our decision making, but little is known about how the brain represents factors like heart rate or emotional state, or the neural mechanisms by which these factors bias the decision-making process. Here I propose to evaluate these mechanisms by recording from the non- human primate prefrontal cortex while they perform social and non-social decision-making tasks and either visceral or brain physiology is manipulated. The research described herein will provide a strong backbone upon which I will receive training in experimental and computational neurophysiology, as well as in the use of causal genetic manipulations in non-human primates.