A brain imaging study on conditioning deficits in antisocial youths

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 DESCRIPTION (provided by applicant): Disruptive behavior disorders (DBDs), which include conduct disorder and oppositional defiant disorder, are among the most common and important clinical disorders in children. Neurobiological markers could in theory bring objective information to the diagnostic process. Failure to form associations between cues and negative consequences may result in lack of anxiety and anticipatory fear whenever the individual contemplates the engagement in an antisocial act, thus leading to more antisocial behavior. Similarly, inability to differentiate cues that predict rewards and non-predictive cues may result in compromised stimulus- reinforcement learning of appropriate behaviors. It is unknown why some children develop DBDs and why they do not learn to substitute inappropriate behaviors with appropriate behaviors, as typically-developing children do. The long term goal of this study is to identify neural mechanisms that contribute to the emotional learning deficits associated with DBDs. The central hypotheses are atypical activation in brain circuitries, including amygdala, striatum, and ventromedial prefrontal cortex (vmPFC), will be associated with disruptive behaviors in youths in the context of appetitive and aversive conditioning. Hypotheses will be tested by pursuing three specific aims: 1) to determine the neural substrates underlying appetitive and aversive conditioning to secondary reinforcers in youths; 2) to determine the functional abnormality in the brains of youths at risk for DBDs, and 3) to determine the unique neurobiological covariates of callous-unemotional (CU) personality traits, the downward extension of psychopathy, and disruptive behaviors in high-risk youths. This study plans to acquire brain imaging data from a community sample of 68 (34 high- and 34 low- risk) 11- to 12-year-olds when they are undergoing a classical conditioning paradigm with monetary gain and monetary loss as reinforcers. Preliminary results have indicated that our conditioning paradigm is valid in eliciting electrodermal conditioning responses, and have linked disruptive behaviors with electrodermal conditioning deficits to monetary reinforcers. The research proposal is innovative because: (1) for the first time it uses fMRI to determine the neural substrates underlying appetitive and aversive conditioning deficits in children at risk for DBDs, (2) it investigates the neural bases of conditioning using socially meaningful reinforcers (monetary loss or gain), and (3) it determines the unique neurobiological covariates of disruptive behaviors and CU personality traits in high-risk youths. NIH support of this proposal will provide the applicant with the experience necessary to transition into an independent investigator. Determination of the neural mechanisms that contribute to the conditioning deficits related to DBDs has the potential to uncover underlying psychopathological processes involved in the development of DBDs. This knowledge has potential implications for clinical diagnosis and behavioral modification treatment programs, and may help to target treatment efforts on those children in most need.