Objectives: The goal of this proposal is to study temperament and risk-taking as vulnerability factors for anxiety. Studies have documented that behaviorally inhibited (BI) children are at risk for anxiety disorders. This vulnerability may be associated with neural circuits underlying behavioral tendencies, such as components of the prefrontal cortex (PFC), striatum, and amygdala. Regarding risk-taking behavior, certain high risktaking adolescents also carry enhanced vulnerability to anxiety. We use fMRI, EEG, and MEG to examine activity in PFC, cingulate, amygdala, and striatum, and functional connectivity with resting state methodology in two cohorts, one probing temperament and the other one risk-taking.

Study Population: A total of 1410 individuals/ infants (0-40 yo) will be studied. Subjects must be between the ages of 2 months to 14 months, or between the ages of 7 years and 60 years old at the time of enrollment, as the measures we are utilizing are designed for subjects who are in those age ranges. This sample comprises 2 sets of study groups. First, the BI group includes individuals with (1) high motor arousal/high negative affect in early infancy to novelty and sustained BI (BI), (2) high motor arousal/high positive affect to novelty and sustained temperamental exuberance (exuberant), (3) average levels of both reactivity/affect from infancy to childhood (controls), or (4) high or low levels of parent-reported BI based on scores on the Behavioral Inhibition Questionnaire. Second, the risk-taking group includes 4 subgroups representing the interaction of two levels of anxiety (low, high) and two levels of risk-taking (low, high). Finally, a group of healthy individuals will be recruited as controls. Participants will be studied through the age of 60 because both the risk for and expressions of psychopathology continue to change throughout early adulthood.

Design: Assessments will include psychiatric, behavioral, and neuropsychological batteries. The protocol uses fMRI and MEG/EEG paradigms targeting different emotional, social, cognitive, motivational, and learning processes during activation studies, as well as the intrinsic function of the brain measured during a resting state.

Outcome Measures and Predictions: The main outcome measures are fMRI BOLD signal changes, physiological, neuropsychological and behavioral variables. The proposed fMRI studies will test 2 sets of hypotheses. The first refers to the BI cohort. BI subjects will exhibit (1) enhanced amygdala activation to mild threats (e.g., angry facial), (2) PFC perturbations in associative learning, (3) abnormal fronto-amygdala connectivity, (4) heightened striatal and inferior PFC activation to reward stimuli, (5) unique neural patterns of attention bias and social challenges, (6) differential changes with age as a function of BI status (7) infants of differing temperaments will exhibit structural and functional differences in brain regions associated with salience and ventral attention networks. The second set of hypotheses pertains to the risk-taking cohort. (1) anxious adolescents will activate striatal regions in response to reward more strongly than non-anxious adolescents; (2) risk-takers will also activate striatal regions in response to reward more strongly than non-risk takers; (3) we expect an interaction between risk-taking and anxiety-related factors, such as a potentiation of striatal