Neural Substrates of Decision-making in Anxiety

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DESCRIPTION (provided by applicant): Anxiety affects how people process stimuli and select actions. High Trait Anxious (HTA) subjects are more sensitive than Normatively Trait Anxious (NTA) subjects to detect threat-related material. The consequences of this perceptual bias for the selection of action have been little studied and the neural basis underlying the selection of action in anxious subjects is poorly understood. Behavioral studies of patients with panic disorder and studies with HTA subjects support the hypothesis that increased anxiety is associated with increased error sensitivity, i.e., an undesired or incorrect outcome is more likely to change ongoing response strategies. In addition, HTA subjects show increased risk aversion in a simple decision-making task. Neuroimaging studies have implicated rostral and dorsal anterior cingulate (ACC), which receive input from limbic and non-limbic structures including the amygdala, as critical neural substrates for conflict detection and cognitive or affective evaluative processing. Preliminary studies show that HTA subjects relative to NTA subjects show increased activation of rostral and dorsal ACC during decision-making. This proposal aims to elucidate the behavioral characteristics and neural substrates in HTA subjects during decision-making. Experiments will be conducted with age-, gender-, education-, ethnicity-, comorbidity- matched college students that are > 85 percentile on the Spielberger Trait Anxiety Inventory (HTA) and a normative group that are within the 40th- 60th percentile on this inventory (NTA) to examine a behavioral and a neural substrate hypothesis as well as the relationship between these hypotheses: (1) In comparison to NTA subjects: HTA subjects show increased sensitivity to errors in a decision-making task; HTA subjects show decreased risk-taking in a simple decision-making task. (2) In comparison to NTA subjects: HTA subjects show increased activation in dorsal ACC during a simple decision-making task; HTA subjects show increased rostral ACC activation during anticipation of a potential adverse outcome during the risk-taking decision-making task. Results from these experiments will provide important data toward a neurocognitive and neural substrate model of anxiety and anxiety disorders. In addition, identifying dysfunctional neurocognitive processes and underlying neural substrates will enable us to better specify anxiety-based intermediate phenotypes.