The broad aim of the proposed program of work is to investigate neurobiological and cognitive mechanisms underlying impulse control (externalizing) problems. The proposed work builds on the applicant's involvement in the development of a hierarchical model of externalizing. The core idea of this model is that a general vulnerability factor, labeled externalizing, underlies and unites psychopathological syndromes involving antisocial behavior and substance dependence, as well as personality traits reflecting impulsivity and aggression. These problems are conceptualized in terms of deficits involving anterior brain regions, although researchers are only really beginning to understand how these regions work. The most established correlate of externalizing problems is reduced amplitude of the P300 event-related potential (ERP) brain component. However, neural mechanisms underlying P300 are distributed and not well understood. Thus, studies of P300 amplitude reductions have not produced good models about the neural mechanisms involved. Researchers have recently begun investigating amplitude reductions in the error-related negativity (ERN) ERP brain component related to externalizing-related disorders. The ERN is understood to involve a relatively strong activation of the anterior cingulate cortex (ACC), providing a clearer target for study. Current models of the ERN suggest that it is best understood as an ACC activation which is influenced by other brain regions depending on the circumstances, particularly the PFC. The goal of the proposed work is to investigate the roles of the PFC and ACC during the ERN under different task circumstances, and then to investigate how these relationships are modulated in individuals with externalizing problems. The primary training components involve developing skills in direct approaches to the measurement of specific brain regions to address the question of the relationship between the PFC and ACC in externalizing psychopathology. Recent years have seen incredible growth in methods for localizing neural sources, and currently available techniques offer strong possibilities for inferring ACC and PFC sources using ERP, magnetic resonance imaging (MRI), and combined (multimodal) ERP and MRI approaches. The proposed training activities would provide training in all three approaches, with mentorship by a leading expert in this field. The candidate also brings strong expertise in joint time-frequency (TF) analysis, an emerging computational method for electrophysiological signals. An important secondary goal is to integrate TF approaches with these neural source localization methods, to create cutting-edge methods neural source methods. The long term goal is for the candidate to become an independent investigator focused on externalizing psychopathology, employing cutting-edge methods for inferring neural sources as described. ? ? ? ? ?
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