Avoidance is a core feature of posttraumatic stress disorder (PTSD) that is associated with an exacerbation of PTSD symptoms, an increase in suicide attempts, and worse treatment outcomes. However, the underlying neurobehavioral mechanisms through which avoidance behavior impairs recovery from PTSD are poorly understood. The persistent and pervasive relationship between avoidance and impaired recovery emphasizes the need to adapt treatment strategies, such as Prolonged Exposure therapy, with the potential to circumvent long-lasting psychopathology. Extensive preclinical work demonstrates that activation of the striatum, amygdala, and prelimbic cortex (PL) is necessary for avoidance behavior, and that inactivating projections between these regions impairs avoidance expression. Avoidance behavior in healthy humans also depends on functional connectivity of the amygdala with both the striatum and dorsal anterior cingulate cortex (dACC; human analog of PL). Research on avoidance and its impact on fear extinction in trauma-exposed adults is lacking. The goal of this training project is to test the hypothesis that greater avoidance behavior in trauma-exposed adults will be associated with worse extinction recall, and that these effects are mediated by increased functional connectivity of the amygdala with the striatum and dACC. We focus on real-time avoidance as our primary measure of avoidance behavior. We will test this hypothesis in 50 individuals reporting exposure to a Criterion A trauma, defined by the Clinician-Administered PTSD Scale-5. Participants will undergo a validated virtual reality (VR)- based Pavlovian fear learning/extinction paradigm during functional magnetic resonance imaging (fMRI) and psychophysiological recordings. During the task, participants will be allowed to approach (move towards) and avoid (move away from) conditioned stimuli that are associated with an aversive stimulus in their VR environment, allowing us to determine real-time avoidance behavior. This fellowship study provides an important scientific advancement in understanding mechanisms of avoidance psychopathology in trauma-exposed adults. With key training from the mentoring team in methodological and mechanistic approaches (fear learning, fMRI, skin conductance, multivariate statistics, assessment of psychopathology) at an urban research university holding the Carnegie Foundation?s highest classification for research, this project is ideally suited for the F31 mechanism. This training project will provide PI Zabik with the critical skills and research training to subsequently expand on this work as a postdoctoral research fellow, identifying other risky behaviors and their impact on treatment responsiveness and long-term remittance in persons with PTSD. It will also prepare PI Zabik for a career committed to identifying targets for therapeutic intervention.
Despite the link between persistent avoidance behavior and impaired recovery from a traumatic event, the neurobehavioral mechanisms that underlie this association are poorly understood. This study will test how avoidance impacts extinction of fear and its underlying brain mechanisms in an adult population. This project is an important step towards understanding mechanisms of impaired trauma recovery, which will lay a critical foundation for identifying interventions with the potential to alleviate prolonged trauma-related symptoms in adults.
