Contextual modulation of fear and extinction using immersive virtual reality - PROJECT SUMMARY/ABSTRACT Anxiety-related psychopathology is a serious detriment to mental health in the United States, with 19.1% of adults in the U.S. experiencing it annually. While current treatments yield symptom recovery in about 50% of patients, relapses remain a significant challenge. While context plays a crucial role in modulating perceived threat in animals, studying its effects in humans is limited by a lack of ecologically valid methods. The Aims of this application leverage immersive virtual reality (VR) to investigate how emotional and environmental contexts shape threat acquisition and extinction, with the aim of informing strategies to enhance treatment efficacy and reduce relapse. To this end, I draw on two experimental literatures, emotion induction and multi-context extinction, to model and examine the interplay between emotion, context, and fear learning. Aim 1 of this proposal will investigate the effects of mood induction on threat learning and extinction to test whether state-dependent factors contribute to responses to threat traditionally attributed to trait-level psychopathology. Findings on how mood or emotional states influence threat expectancy are mixed, potentially due to limited ecological validity, subjective interpretation, or variability in sensory engagement, problems that can be addressed by using immersive VR. Using VR experiences, participants will undergo emotion induction (positive, negative, or neutral) prior to Pavlovian threat conditioning or extinction. Fear induction may serve as a model for anxiety-related disorders, better simulating emotional states experienced by affected individuals and providing a more ecologically valid translational model for research in healthy subjects. This aim will also address fundamental theoretical questions about whether “fear conditioning” is directly modulated by an individual’s emotional state of fear. In Aim 2, I will examine neural correlates of multi-context extinction in ecologically valid VR environments. While threat learning is easily generalized across contexts, extinction is context specific. Thus, threat that is suppressed in the extinction context often reappears in a different context. This phenomenon, known as contextual renewal, often leads to the resurgence of fear in new settings, presenting a major challenge for psychotherapy. In animals, multi-context extinction is shown to reduce context specificity and strengthen extinction generalization. This aim builds and improves upon limited human research by employing immersive 3D environments inside an MRI environment and utilizing functional connectivity and advanced multivariate pattern analysis of fMRI data. The Aims laid out in this proposal will significantly enhance our understanding of the neurobehavioral mechanisms underlying emotion and contextual influences on threat learning and extinction. Through this training grant, I will gain expertise in virtual reality task design, fMRI multivariate pattern analysis, and the neuroscience of emotions, fear, and learning. Completion of these Aims will expand knowledge of the neuroscience of emotional learning and threat generalization and contribute to future treatments of anxiety- related psychopathology.
