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中文摘要
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在以前的工作中,我们主要使用神经心理学调查,以确定与CD+CU相关的功能障碍。 我们发现,患有这种疾病的青少年在以下方面表现出明显的困难:(1)识别恐惧表情,这是杏仁核功能障碍的神经心理学标志;(2)情绪学习的基本形式,刺激-强化联想,这对社会化至关重要(也是杏仁核依赖性的);(3)决策依赖于结果强化信息的适当表征,这是腹内侧前额叶皮层功能障碍的神经心理学标志。 在我们最近的工作中,我们使用事件相关功能磁共振成像直接评估杏仁核和腹内侧前额叶皮质是否在CD+CU青少年中发挥功能。 特别是,在一项研究中,我们专门研究了CD+CU青少年对恐惧和愤怒表情的神经反应。 对表达,特别是恐惧表达的适当反应,对道德社会化很重要。 这项研究表明,与正常发育的青少年和注意缺陷多动障碍(ADHD)青少年相比,CD+CU青少年对恐惧表情的杏仁核反应减少,杏仁核和腹内侧前额叶皮层之间的连接减少。 有趣的是,在对愤怒表情的反应上没有群体差异。 这种表达的处理通常不依赖于杏仁核。 简而言之,这项研究表明:首先,在CD+CU青少年中观察到的损伤性质的特异性,功能障碍反应特异于恐惧表情,而不是中性或愤怒表情。 第二,选择性的损害,在青少年与CD+CU可比的损害是没有看到在青少年多动症。 在另一项最近的功能磁共振成像研究与青少年CD+CU,我们检查了腹内侧额叶皮层和其他额叶系统在逆转学习的功能。 重复学习是指个体在不再受到奖励时改变反应的能力。 这种能力很重要,因为它减少了个人在继续做不再实现目标的行动的基础上经历挫折和愤怒的可能性。 在我们以前的神经心理学工作中,我们观察到CD+CU青少年在逆转学习方面有明显的困难。 在我们最近的功能磁共振成像研究中,我们确定了这种困难的神经基础。 具体来说,虽然通常发展中的青少年和患有ADHD的青少年,以及健康的成年人,当一个行为导致意外的惩罚(行为应该改变的线索)时,腹内侧额叶皮层的反应会减少,但患有CD+CU的青少年不会。 这个预测误差信号对于学习和确保个体不会回到现在的不良反应特别重要。 在我们目前的工作中,我们集中精力确定在这个人口的眶额叶皮层损伤的计算细节。 具体来说,现在看来,患有CD+CU的年轻人在使用眶额叶皮层(和尾状核)产生预测错误方面面临特殊困难。 当一个人收到意外的奖励/惩罚或当他们没有收到他们期待的奖励/惩罚时,预测错误就会发生。 预测错误很重要,因为它们是参与快速学习的关键线索。 情感学习困难是这一人群社会化困难的核心。
英文摘要
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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