Project Abstract Conduct problems, which include aggression and rule-breaking behavior, in children and adolescence are significant risk factors for future criminal behavior. One possible mechanism involves atypical development of brain structure and/or function implicated in reward and punishment processing in at-risk individuals. Reduced reward sensitivity may drive maladaptive reward seeking behavior via attempts to “normalize” reward-related neural reactivity, and may result in compromised learning of appropriate behaviors. On the other hand, weakened punishment sensitivity may increase the risk of antisocial behavior because the individual failing to form associations between cues and negative consequence does not have anxiety and anticipatory fear whenever contemplating the engagement in an antisocial act. However, most of the prior research is cross-sectional. The objective of this study is to understand the origin and development of conduct problems from a longitudinal perspective, by repeatedly assessing the risk factors (impaired reward/ punishment processing) from childhood to adolescence, identifying the vulnerable neural substrates underpinning these processes, and determining the modulating effects of environmental factors (i.e., parent- child relationship). Capitalizing on an existing cohort whose neurobehavioral measures were objectively assessed at 8-9 years and again at 9-10 years (SC2HD076044, PI: Gao), the current project proposes to re-assess the participants annually starting at 14-15 years for three years. We will assess biological and social risk factors using a battery identical (with age-appropriate modifications) to the one used in prior studies, as well as age- appropriate psychosocial risk factor and behavioral outcome assessments. Moreover, I will build upon my current SC3 funding (SC3GM118233, PI: Gao) and utilize a longitudinal multi-modal Magnetic Resonance Imaging (MRI) approach to study the changes in function of the circuitry implicated in reward/punishment processing (using fMRI) and the white-matter connections (using Diffusion Tensor Imaging) across a 1.5-year period from the same cohort. My central hypotheses are that atypical development of reward/punishment processing from childhood to adolescence will be associated with more conduct problems, and that positive parent-child relationship will buffer the effect of neural vulnerability on the development of behavioral problems. Completion of this project will advance the mission of the NIH BRAIN Initiative to “understand the circuits and patterns of neural activity that give rise to mental experience and behavior”. Understanding the neural and autonomic mechanisms that contribute to the reward/punishment processing related to conduct problems has the potential to uncover underlying psychopathological processes involved in the development of these problems, and will improve etiological models that provide the foundation for intervention and treatment.

Project Narrative The proposed research investigates how reward and punishment processing system development is determined by neural substrates and quality of relationship within the family as they relate to conduct problems in adolescence using a longitudinal multi-modal neuroimaging approach. It is relevant to public health because determination of the biomarkers and the neural pathways through which environmental factors influence conduct problems will increase our understanding of the etiology and psychopathological processes involved in the development of behavioral problems in youths and antisocial personality disorder in adults. This knowledge has potential implications for the development of more effective diagnosis, prevention, and treatment of disruptive behavior disorders.