Emotional dysfunction and childhood behavioral disturbance

情绪功能障碍和儿童行为障碍

• 批准号: 8556955
• 负责人: james r blair
• 金额: $ 121.95万
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8556955
• 关键词: Achievement; Adolescent; Affective; Aggressive behavior; Amygdaloid structure; Attention; Behavior; Behavioral; Biological; Childhood; Computer Simulation; Conduct Disorder; Control Groups; Data; Decision Making; Disease; Emotional; Emotions; Empathy; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Guilt; Impairment; Individual; Insula of Reil; Intervention Studies; Mediating; Neurobiology; Outcome; Performance; Population; Positioning Attribute; Process; Protocols documentation; Punishment; Rewards; Rights; Risk; Series; Signal Transduction; Stimulus; Suggestion; System; Treatment Efficacy; Work; Youth; base; callous unemotional trait; cognitive neuroscience; directed attention; economic cost; expectation; frontal lobe; neural recruitment; outcome forecast; relating to nervous system; response; showing emotion; social

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.

该项目已经建立了一系列核心神经生物学发现，关于行为障碍（CD）的基础，特别是CD与无情的特征（减少内疚和同情）。 过去一年，我们取得的主要成就如下： 首先，在本协议的早期工作中，我们证明了CD+CU与他人恐惧的受损处理有关，这种损伤与杏仁核对这种表达的反应减少有关。 今年，我们对比了两种对这种缺陷的突出解释：（1）杏仁核对这种表达（情绪位置）的反应性从根本上降低;（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上，从而降低了情绪反应（注意位置）。我们的工作显示了对情绪立场的支持。 患有CD+CU的青年表现出适当的（即，没有增强）的招聘系统牵连在自上而下的注意力控制和组的差异，杏仁核反应的恐惧，只有在低注意力负荷条件下观察。 此外，在第二项研究中，我们证明了在CD+CU中看到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募集）对恐惧的表达是有选择性的。 第二，在本协议的早期工作中，我们证明了CD+CU与基于奖励/惩罚的决策受损有关，这种损伤与眶额皮质和尾状核内的功能障碍有关。 然而，我们之前的工作并没有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，有两个核心过程对成功的决策至关重要。 第一个是预测误差信号;即，信号比结果更好或更坏比个人预期的。 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产生这一结果的行为的奖励/惩罚预期。 第二个是期望值;即，代表执行该动作后可能收到的奖励或惩罚。 这一点很关键，因为个体越不善于预测未来的奖励/惩罚，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CD+CU的青年中受到损害。 这些年轻人在尾状核内的预测错误信号中表现出严重的损伤，在眶额皮层和小脑内的预期值的代表性中表现出显著的损伤。 在进一步的工作中，我们在社会交换任务的背景下，这些区域的非典型反应，具体涉及到个人水平的CU特征。 重要的是，这项工作使我们能够确定客观的生物标志物，可用于正在进行的工作，以评估在这一人群中的治疗效果。