Fear learning and regulatory processes have been the focus of intense scientific inquiry in recent years, as converging evidence shows these processes play a crucial role in the emergence and treatment of stress and anxiety disorders. Much research has focused on fear extinction learning, in which an individual learns to update their representation of a conditioned fear stimulus after multiple presentations of that stimulus unpaired with an aversive outcome. Exposure-based cognitive behavioral therapy is based on this form of learning. While this form of therapy is highly effective, return of fear is common after treatment. To further optimize exposure-based therapies, it’s important to better understand factors that mediate fear extinction learning performance. One such factor is anxiety/stress. Research shows stress elicited prior to extinction can enhance or attenuate extinction performance. But the paradigms used in these studies elicit acute physiological stress, not the kind of anxious anticipation that characterizes threat-related disorders. States of anxious anticipation could play a unique modulatory role on fear extinction learning performance. Furthermore, there is evidence for sex-specific differences in stress sensitivity, suggesting a potential interactive effect of anxiety and sex on fear extinction learning. Finally, evidence suggests individual differences in intolerance of uncertainty play a role in modulating fear regulatory processes. Here, we will use a Pavlovian fear learning paradigm to test the impact of anticipatory anxiety on fear extinction learning and extinction retrieval. We will also measure neurobiological correlates of anxious anticipation and test the extent to which any differences in extinction learning are associated with different levels, balance and timing of noradrenergic and glucocorticoid expression. To address the substantial sex-specific disparity in prevalence of fear-related disorders, we will test the interactive effects of anxiety and biological sex on fear extinction learning. Finally, we will examine potential interactive effects of individual variability in Intolerance of Uncertainty, independent of trait anxiety, and states of anxious anticipation on fear extinction learning. This study is in line with the mission and goals of the NIH in several ways. For one, by studying anxious states, biological sex and trait differences as mediators of fear extinction learning, this research will contribute to a growing knowledge base that’s being used to develop more personalized treatment approaches for fear-related disorders. This is in accordance with the broad goals of advancing brain science to better understand mental illness and to improve therapeutic interventions, both of which are central to NIH’s strategic plan for research. The Negative Valence Systems and Arousal and Regulatory Systems parts of the RDoC Matrix served as a guiding force in the development of this proposal.