Emotional dysfunction and childhood behavioral disturbance

这个项目已经建立了一系列关于行为障碍(CD)基础的核心神经生物学发现，特别是具有冷酷无情特征(减少内疚和同理心)的CD。一年来，我们取得的主要成就有： 首先，在这一方案的早期工作中，我们证明了CD+CU与对他人恐惧的处理受损有关，这种损害与杏仁核对这种表达的反应减少有关。今年，我们对比了这一缺陷的两个突出解释：(A)杏仁核对这种表达(情绪位置)的反应从根本上降低；(B)过度反应的自上而下的注意系统将注意力引导到刺激的非情绪特征，从而减少情绪反应(注意位置)。我们的工作显示了对情感立场的支持。患有CD+CU的青少年表现出与自上而下注意控制有关的系统的适当(即不增强)招募，杏仁核对恐惧的反应只有在低注意负荷条件下才能观察到组内差异。此外，在第二项研究中，我们证明了CD+CU的注意力效应似乎是由他们的情绪缺陷驱动的。因此，注意力定向的减少(以及调节这种定向的神经系统的招募)对于恐惧的表达是有选择性的。 其次，在这一方案的早期工作中，我们证明了Cd+CU与基于奖惩的决策受损有关，这种损害与眼眶额叶皮质和尾状核内的功能障碍有关。然而，我们之前的工作并不涉及神经反应数据的计算建模，因此，尽管我们知道这些区域功能失调，但我们不知道它们是如何功能失调的。特别是，有两个核心流程对成功的决策至关重要。第一个是预测误差信号；也就是说，发出结果比个人预期的更好或更差的信号。这一点至关重要，因为结果越令人惊讶，个体就越需要改变他们对导致这一结果的行为的奖惩预期。第二个是期望值；即表示在执行行动后可能获得的奖励或惩罚。这一点至关重要，因为个人越不善于预测未来的奖惩，他们做出的决定就越糟糕。在过去一年的工作中，我们证明了这两个过程在患有CD+CU的年轻人中都受到了损害。这些年轻人在尾状核内的预测错误信号方面表现出严重的损害，在眼眶额叶皮质和脑岛内的预期值的表征方面也有显著的损害。在进一步的工作中，我们发现在社会交换任务的背景下，这些区域的非典型反应与个体水平的CU特征有关。 关键的是，这项工作使我们能够确定客观的生物标记物，这些标记物可以用于正在进行的工作，以评估该人群的治疗效果。

This project has established a series of core neuro-biological findings regarding the basis of Conduct Disorder (CD), particularly CD with Callous-Unemotional traits (reduced guilt and empathy). Over the past year, our main achievements have been the following: First, in earlier work on this protocol, we demonstrated that CD+CU is associated with impaired processing of the fear of others and this impairment is associated with a reduced response by the amygdala to this expression. This year we contrasted two prominent explanations for this deficit: (a) a fundamental reduction in responsiveness of the amygdala to this expression (the emotion position); (b) an over-responsive top down attentional system directing attention to non-emotional features of the stimulus and thus reducing the emotional response (the attention position). Our work revealed support for the emotion position. Youth with CD+CU showed appropriate (i.e., not enhanced) recruitment of systems implicated in top down attentional control and group differences in amygdala responses to fear were only observed under low attentional load conditions. Moreover, in a second study, we demonstrated that attention effects seen in CD+CU appeared to driven by their emotional deficits. Thus reductions in attention orienting (and the recruitment of neural systems mediating this orientation) were selective for fearful expressions. Second, in earlier work on this protocol, we demonstrated that CD+CU is associated with impaired reward/punishment based decision making and this impairment related to dysfunction within orbital frontal cortex and caudate. However, our previous work did not involve computational modeling of the neural response data and thus although we knew these regions were dysfunctional we did not know how they were dysfunctional. In particular, there are two core processes critical for successful decision making. The first of these is prediction error signaling; i.e., signaling than an outcome is better or worse than the individual expected it to be. This is critical because the more surprising the outcome, the more the individual needs to alter their reward/punishment expectation of the action that gave this outcome. The second is expected value; i.e., representing the likely reward or punishment that will be received following performance of the action. This is critical because the poorer the individual is at predicting future rewards/ punishments, the poorer the decisions they will make. In work conducted over the past year, we demonstrated that both of these processes are impaired in youth with CD+CU. These youth show profound impairment in prediction error signaling within caudate and significant impairment in the representation of expected value within orbital frontal cortex and the insula. In further work, we showed atypical responding in these regions in the context of a social exchange task relate specifically to the individuals level of CU traits. Critically, this work has allowed us to identify objective bio-markers that can be used in on-going work to assess treatment efficacy in this population.