The Impact of Anxiety on Neurobehavioral Correlates of Conditioned Fear Generalization

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 DESCRIPTION (provided by applicant): A poor ability to discriminate between objects that pose a legitimate danger and those that are safe underlies a variety of anxiety disorders. Although a tendency to overgeneralize fear to uncertain or ambiguous stimuli that have minimal resemblance to threat cues has emerged as a reliable pathologic correlate, no studies to date have provided a direct test of how anxiety directly causes such an outcome. The research proposed here represents the first test of how anxiety, induced using a translational procedure that mimics previous animal models, influences fear overgeneralization at neural and behavioral levels. As highlighted by the RDoC Negative Valence Systems Workshop, distinct brain systems underlie fear (i.e., a phasic response to specific cues) and anxiety (i.e., a state of sustained apprehension about unpredictable harm). The overall goal of our research is to reveal the interaction of these two neural systems (i.e., to determine how anxiety enhances fear- based responding to ambiguous stimuli). To reduce the confounding effects of chronic morbidity that have impeded clear conclusions in previous work, we will use a community-based sample that is free of psychiatric illness. We will also use a powerful within-subjects experimental design in which each individual acts as his or her own control. First, we will determine how anxious arousal influences the generalization of cue-specific fears using an innovative brain-based measure (steady state electroencephalography) that indexes fluctuations in attention processing. We will complement this new cortical measure of attention with measures of defensive reflex responding (startle) that are commonly used in animal models of fear and anxiety. In the second aim, we will tap into a specific index of functional brain connectivity to determine how higher brain regions communicate with lower order sensory areas to facilitate the representation of specific stimuli that vary in similarity to a conditioned danger cue. In particulr, we will test the hypothesis that neural connectivity of higher-order and sensory areas plays a pivotal functional role in the threat-related attention abnormalities commonly reported in anxiety. Our findings will shed new light onto the mechanisms that go awry in clinical anxiety disorders, the most common category of psychiatric illnesses.