Project Summary Individuals with depression and anxiety have difficulty inhibiting their response to emotional information, resulting in problematic attentional bias and altered brain connectivity. Individuals who have experienced life stress demonstrate similar deficits, perhaps representing one mechanism by which early life stress and chronic life stress contribute to the development of internalizing psychopathology such as depression and anxiety. Although understanding dysfunction in emotion inhibition appears critical to characterizing how experience across the lifespan contributes to deficits in emotion regulation and subsequent psychopathology, little is known about the associated neural mechanisms. Successful inhibition of response to emotional distraction in favor of responding to task-relevant information relies on complex and dynamic regulatory processes as well as a variety of cognitive functions, such as attention and memory. In healthy individuals, the effects of emotional context on the success of emotion inhibition differ as a function of the valence (positive or negative) and arousal (low or high) of the context. In light of this, the proposed project examines the time course of neural activity associated with emotion inhibition, emphasizing functional connectivity between brain regions, and utilizes a novel protocol that pairs a color-word Stroop foreground task with an emotional image context. This combination is designed to identify the impact of task-irrelevant emotional context (image emotion) on the automatic, implicit inhibition of response to task-irrelevant information (word content) in favor of task- relevant information (word color). Utilizing event-related brain potentials (ERPs) and EEG oscillatory analyses, the project will determine the time course of neural activity associated with emotion inhibition along with dynamic interactions between brain regions. The effects of early life stress (ELS) and current life stress (CLS) on these processes will then be considered, focusing on associated alterations in the structure and function of the brain areas associated with stress response and emotion processing, such as temporo-parietal, insula, dACC, and prefrontal cortex. Disruptions in these regions are associated with biased attention, cognitive inflexibility, and emotion dysregulation. This project will attempt to identify neural changes associated with depression and anxiety during emotion inhibition as well as the role of ELS and CLS in those relationships. This project has implications for interventions that may prevent or ameliorate internalizing disorders by characterizing neural mechanisms in adult emotion regulation and their vulnerability to stress. Due to the diverse academic and technological resources available, UCLA is an ideal environment in which to pursue this project. Over the course of NRSA funding, the applicant will be exposed to extensive training in relevant methods (ERP, EEG, MRI) and guided towards an in-depth understanding of the relevant concepts (depression, anxiety, affective neuroscience, life stress). The proposed mentors are well equipped to guide training at all levels of the project, including data collection, analysis, and manuscript preparation.

Project Narrative Individuals with depression and anxiety have difficulty inhibiting their response to emotional information, resulting in increased attentional bias to negative information. Examining brain connectivity may reveal neural alterations associated with dysfunctional emotion regulation, which would have important implications for understanding brain development and the prevention and treatment of mental illness. These biases are likely impacted by an individual's exposure to life stress; therefore, identifying how stressors impact risk for depression and anxiety via associated alterations in inhibitory processes may lead to a deeper understanding of the mechanisms by which stress affects emotional function and dysfunction in adults.