Feed Forward Visual System Function in High Trait Anxiety

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Project Abstract High trait anxiety (HTA) is associated with increased risk for mood and anxiety disorders. Individuals with HTA show elevated fear responses to threatening situations, and react with fear to situations that are not threatening. Individuals with HTA generalize threat, such that neutral or familiar visual stimuli are processed as though they are threatening or potentially threatening. The persistence of such processing differences across a broad range of visual stimuli suggests dysfunction in a basic visual mechanism. Indeed, there is evidence from the anxiety disorders literature for increased blood oxygen level dependent (BOLD) signal in visual cortex among those with higher anxiety. Despite evidence for elevated visual activity, the dominant model for the pathophysiology of anxiety posits aberrant top-down or effortful processing, mediated by prefrontal projections to the amygdala. However, this model cannot account for findings of elevated visual cortex activity that occur in response to a range of stimuli and at an early latency. This early latency indicates a preattentive mechanism that precedes prefrontal involvement. A feed forward model emphasizing the role of implicit processing in visual cortices better explains the literature than the traditional top-down model. This project employs functional magnetic resonance imaging (fMRI) methods in a sample of young adults ranging continuously trait anxiety. Aim 1 characterizes visual system function in HTA across a range of stimuli, while Aim 2 determines the relative contributions of both the proposed bottom-up model and the traditional, top-down model to trait anxiety, symptom severity, and quality of life both concurrently and at follow up. This project tests a novel neural target (visual cortex) associated with a trans-diagnostic risk factor (HTA), to inform new approaches to intervention. The training aims for this award dovetail with the research aims, and emphasize mentored and didactic training crucial to the success of this project. The principle investigator (PI) has assembled a team of experts to provide mentorship and advanced training in 1) the functional neuroanatomy of implicit visual perception in health and in mood and anxiety disorders, 2) advanced methods training, including dynamic causal modeling and statistical analysis, and 3) the conduct of clinical anxiety disorders research. The PI has outlined a detailed training plan to accomplish these aims, to include workshops, formal collaborations with expert consultants, and coursework. His co-mentors, Dr. Mary Phillips and Dr. Jay Fournier, have established track records in psychiatric neuroimaging research. Research and training activities will take place at the University of Pittsburgh. The University of Pittsburgh is committed to the career development of junior faculty and the Department of Psychiatry and has a longstanding record of excellence in psychiatric neuroimaging and affective neuroscience research. The training aims will build on the PI's preparation as a psychiatric neuroscientist with expertise in fMRI, allowing him to establish himself as an independent investigator. The PI's long term goal is to conduct neuroscientific research to inform novel visual system-based interventions to prevent psychiatric disorders.