In previous work, we primarily used neuropsychological investigations to determine the functional impairments associated with CD+CU. We identified that adolescents with this disorder showed marked difficulties with: (1) the recognition of fearful expressions, a neuropsychological marker of amygdala dysfunction;(2) a basic form of emotional learning, stimulus-reinforcement association, which is critical for socialization (and also is amygdala dependent);(3) decision making reliant on the appropriate representation of outcome reinforcement information, a neuropsychological marker of dysfunction within ventromdial prefrontal cortex. In our most recent work, we have used event related functional Magnetic Resonance Imaging to directly assess whether the amygdala and ventromedial prefrontal cortex is functioning atypically in adolescents with CD+CU. In particular, in one study we specifically addressed the neural responses of adolescents with CD+CU to fearful and angry expressions. An appropriate response to expressions, particularly fearful expressions, is important for moral socialization. This study revealed that adolescents with CD+CU showed reduced amygdala responses to fearful expressions and reduced connectivity between the amygdala and ventromedial prefrontal cortex when processing fearful expressions when compared with both typically developing adolescents and adolescents with Attention Deficit Hyperactivity Disorder (ADHD). Interesting, there were no group differences in the response to angry expressions. The processing of this expression is not typically reliant on the amygdala. In short, this study suggested: First, specificity in the nature of the impairment seen in adolescents with CD+CU the dysfunctional responding was specific for fearful expressions and not seen to neutral or angry expressions. Second, selectivity of the impairment in adolescents with CD+CU comparable impairment was not seen in adolescents with ADHD. In another recent fMRI study with adolescents with CD+CU, we examined the functioning of ventromedial frontal cortex and other frontal systems during reversal learning. Reversal learning indexes the individuals ability to change a response when it is no longer being rewarded. This ability is important because it reduces the probability that the individual with experience frustration and rage on the basis of continuing to do actions that no longer achieve their goals. In our previous neuropsychological work, we had observed that adolescents with CD+CU had marked difficulties with reversal learning. In our recent fMRI study, we identified the neural basis of this difficulty. Specifically, while typically developing adolescents and adolescents with ADHD, as well as healthy adults, show a reduced response within ventromedial frontal cortex when an action results in an unexpected punishment (a cue that behavior should change), adolescents with CD+CU do not. This prediction error signal is particularly important for learning and making sure that the individual does not return to now bad response. In our current work, we have concentrated on determining the computational details of the orbital frontal cortex impairment in this population. Specifically, it now appears that youth with CD+CU face particular difficulties in using orbital frontal cortex (and caudate) to generate prediction errors. Prediction errors occur when an individual receives unexpected reward/ punishment or when they fail to receive the reward/ punishment they were expecting. Prediction errors are important because they are critical cues to engage in rapid learning. Difficulties in emotional learning are at the heart of the difficulties with socialization in this population.

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Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2009
Total Cost
$1,236,950
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
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Meffert, Harma; Thornton, Laura C; Tyler, Patrick M et al. (2018) Moderation of prior exposure to trauma on the inverse relationship between callous-unemotional traits and amygdala responses to fearful expressions: an exploratory study. Psychol Med 48:2541-2549
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Hwang, Soonjo; Meffert, Harma; VanTieghem, Michelle R et al. (2017) Neurodevelopmental Changes in Social Reinforcement Processing: A Functional Magnetic Resonance Imaging Study. Clin Psychopharmacol Neurosci 15:369-381
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Blair, R J R (2017) Emotion-based learning systems and the development of morality. Cognition 167:38-45
White, Stuart F; Geraci, Marilla; Lewis, Elizabeth et al. (2017) Prediction Error Representation in Individuals With Generalized Anxiety Disorder During Passive Avoidance. Am J Psychiatry 174:110-117

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