Anxiety is one of the most common disorders affecting children and adolescents worldwide. The average age of onset for clinical anxiety is in adolescence, a key period of brain and behavioral development that marks the transition from childhood to adult independence. Despite these overlapping developmental timelines, phenotypic anxiety is often characterized by persistent avoidant behavior which conflicts with normative hallmarks of adolescence such as risk taking and exploration. While research suggests that shared neural mechanisms contribute to both the rise of anxiety and risk taking in adolescence, the field has primarily studied these two topics in isolation, precluding the opportunity to understand how brain development contributes to both phenotypes during this period and identify factors that promote healthy development across decision-making and mental health domains. The studies presented in this dissertation aim to fill this gap in the literature by examining the concurrent development of anxiety symptoms and risky decision-making behaviors in a diverse sample of children and adolescents living in the greater Los Angeles Area over two timepoints separated by 1-3 years. At each timepoint, participants completed a clinical interview and an fMRI scan while performing tasks aimed at measuring risky decision-making and cognitive control. Results from Study 1 suggest that anxious adolescents engage in a similar degree of risky behavior as their peers but report negative perceptions of their own decision-making and struggle with making decisions in the face of approach-avoidance conflict. Anxious adolescents also demonstrated altered associations between fronto-striatal circuitry and risky behavior such that reduced prefrontal regulation and heightened striatal connectivity was associated with risk avoidance in high anxiety, while these same neural markers were associated with risk taking in low anxiety. Study 2 investigated how approach motivations and anxiety interact to influence adolescent risky decision-making and neural functioning, revealing that the association between anxiety and risk taking is dependent on adolescent approach motivations: anxious adolescents with low approach motivations were risk averse and inhibited, while anxious adolescents with high approach motivations were risk taking and impulsive. Approach motivations and anxiety showed opposing associations with communication between the striatum, amygdala, and prefrontal cortex during risky decision-making and in the resting adolescent brain, highlighting the competing influences of both anxiety and approach motivations on brain and behavioral correlates of risk taking in adolescence. Whole-brain striatal connectivity patterns during risk taking and risk avoidance showed a high degree of overlap in adolescents with low anxiety but showed divergence in adolescents with high anxiety, again suggesting that the sensitized adolescent striatum plays an important role in anxiety and avoidance. In Study 3, longitudinal analyses revealed average group increases in risk taking and decreases in self-reported anxiety symptoms as participants progressed through adolescence, although clinician-rated anxiety scores increased over time. Adolescents who increased in anxiety reported decreases in positive perceptions and increases in negative perceptions of their decision-making over time. Neural response during risk avoidance was linked to the development of both anxiety and risk taking such that increases in anxiety were reflected in increases in striatal connectivity during risk avoidance, while changes in risk taking were reflected in changes in amygdala connectivity during risk avoidance. Increases in anxiety were associated with increased neural generalization across risk avoidance and response inhibition and decreased conflict processing during risk avoidance, while increases in risky behavior were associated with increased neural generalization across risk avoidance and risk taking and heightened conflict processing during risk avoidance. Finally, amygdala and striatal response during risk avoidance interacted to predict the emergence of clinician-rated anxiety over time. Taken together, results from this dissertation help to delineate the shared behavioral and neural mechanisms that contribute to anxiety and risky decision-making in adolescents and highlight the potential of leveraging these shared mechanisms to promote positive approaches to decision-making amongst developing youth.

Internalizing symptoms and disorders – such as anxiety and depression – increase in adolescence (Meyer and Lee, 2019) and can interact with youth brain and behavioral development. As youth develop, changing biological and environmental factors necessitate developing novel skills, such as emotion regulation and reward-based learning strategies, while balancing new drives toward risk-taking. Given how complex and in-flux this period of life is, investigating the role of internalizing symptoms in a variety of adolescent behaviors is crucial for better understanding how to support youth through this dynamic developmental stage. The studies in this dissertation examine how internalizing symptoms relate to brain development – specifically, functional connectivity and activity associated with emotion regulation and reward learning – as well as risk-taking in the real world. Chapter 1 provides a general introduction to the research outlined in the following chapters. Chapter 2 describes research relating internalizing symptomatology in subclinical youth to amygdala-whole brain functional connectivity. Findings demonstrate that the relationship between internalizing symptoms and amygdala connectivity is stronger in girls than boys, and that youth generally demonstrate greater connectivity between the amygdala and regions associated with emotional processing as a function of greater internalizing symptoms. In Chapter 3, findings from the first study to investigate brain and behavioral differences in emotion regulation between youth with and without anxiety are presented. Youth with anxiety regulated their emotions to the same extent as non-anxious peers; however, regulation may have been especially effortful for youth with anxiety as they demonstrated stronger prefrontal cortex activation and connectivity with the amygdala during regulation. Research presented in Chapter 4 characterizes the relationship between anxiety severity and reward learning in a subclinical sample. While all youth were capable of learning stimulus-reward associations, youth with higher anxiety allocated value toward non-rewarding stimuli to a greater extent and showed a stronger relationship between brain activity and behavior; furthermore, within this group, those with the highest intolerance of uncertainty showed the least reward network activation when receiving rewards. Finally, Chapter 5 examines racial disparities in the juvenile justice system, as well as tracks the longitudinal change in internalizing symptoms alongside criminal offending. Black youth, and to a slightly lesser extent Latino youth, faced the greatest disparities through system processing. All youth demonstrated greater improvements in internalizing symptoms alongside decreased offending, showing the tight relationship between mental health and criminal offending. Taken together, results from this dissertation demonstrate the varied effects of internalizing symptoms on adolescent brain and behavioral development. As such, these studies present a multi-disciplinary look at the role of mental health in the lives of adolescents.

Adolescence and early adulthood are marked by increased exposure to novel situations, frequently accompanied by failure and uncertainty about future success. Decision-making in these contexts is often motivated intrinsically, without explicit promise for future reward. However, little is known about the neural systems that support perseverance in the face of challenge when extrinsic reward is not offered. In this dissertation, a multi-method program of research was employed to investigate the neurobiological contributors to perseverance in a sample of 13- to 30-year-olds (N=99, 61 females). Findings indicate perseverance is associated with differential neural response to the motivational value of information and regulation of neural systems tracking affective signals associated with negative feedback. Of particular import were motivational and value systems located in the striatum and medial prefrontal cortex, salience regions including the insula, and connectivity between the executive control system and fronto-insular regions. This research also identified age-related differences in perseverance decisions and neural functioning during a novel task assessing situational factors associated with motivation. Younger participants were less likely to persevere and demonstrated increased superior frontal gyrus activation to negative feedback, potentially reflecting less clear representation of the motivational value of negative feedback. A developmental shift toward increased valuation of positive feedback compared with monetary reward was also observed, consistent with extant understanding of reward sensitivity during adolescence. Finally, this research demonstrates individual differences in deliberative thinking and inflammation are associated both with perseverance behavior and neural response. Older participants reported more deliberative thinking, which was associated with perseverance and reduced activation in the salience network in response to negative feedback. Among adolescents, perseverance was associated with higher concentrations of the pro-inflammatory cytokine interleukin-6, which was in turn associated with reduced insula activation. These individual difference findings highlight the importance of neural and biological response to feedback as a contributor to perseverance. Intrinsically motivated perseverance is associated with numerous positive benefits and this dissertation makes a substantial contribution to explicating how situational factors contribute to engaging with challenge despite failure.