as they affect not only individuals but also society as a whole. High impulsivity is associated with a myriad of poor outcomes including psychopathology, substance use disorders, low educational and occupational attainment, poor physical health, and high accident rates [11-17]. Impulsivity presents on a spectrum and persons with attention-deficit/ hyperactivity disorder (ADHD) lie at the extreme of the continuum. In this revised competing R01 renewal we propose a four-time-point longitudinal study design, adding the acquisition of two time points to the previous two acquisitions of the initial cohort using task-based functional and diffusion tensor (DTI) neuroimaging data, with a new emphasis on how emotional functioning relates to impulsivity. To address the dimensional nature of impulsivity we will also add a group of individuals with subclinical ratings of impulsivity, to explore how the full range and persistence of impulsivity over time affects outcomes. We will now extend the age range from the initial data collection at 12 to 25 years to 15 to 30 years in the previously recruited neurotypicals (NT) and participants with ADHD. We will focus on impulsivity-related outcomes that are more likely to emerge in the 15 to 30-year age span such as irritability, emotional lability, psychiatric and substance use disorders, self-harm and suicide attempts, and academic and occupational dysfunction. We hypothesize that the strength of the structural connectivity between (1) the dorsolateral prefrontal cortex (DLPFC) and dorsal striatum pathway will predict individual differences in impulsivity, with greater negative coupling between the DLPFC and dorsal striatum associated with greater impulse control. We posit that this connection will strengthen with maturity. We also hypothesize that increased connectivity strength between (2) the ventral striatum and the amygdala will predict more impulsive behavior. We aim to characterize in a multi-modal (fMRI, DTI, behavior) longitudinal imaging investigation: (a) how these changes emerge from early adolescence through young adulthood and (b) how these developmental changes are reflected in persons ranging from typical through elevated and significant impulsivity. Furthermore, we will assess how brain connectivity and behavior differ between persons with ADHD who continue to express impulsive decisions (persisters) versus those who are no longer making impulsive decisions (remitters) during the transition into young adulthood. We will also assess how functioning in these neural systems (e.g., DLPFC & striatum) may be moderated by and associated with irritability and degree of emotional regulation. Extending an aim from the original grant, we will test the relation between brain functioning and real-world functioning, including occupational achievement, presence of psychopathology, self-harm, and substance use disorders. We will also assess what factors lead to more resilience. At the conclusion of our study we will identify age-specific targets for decreasing impulsivity and preventing self-harm during a period of heightened vulnerability and opportunity.
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