Using CBT to examine circuitry of frustrative non-reward in aggressive children

描述(由申请者提供)：果非奖赏是指对戒除或阻止奖赏的反应，最显著的是反应性攻击。反应性攻击的神经机制包括杏仁核对挫折的反应增强，以及前额叶区域的活动不足，从而削弱了情绪调节。这是一项关于认知-行为疗法(CBT)在高攻击性儿童中的随机对照试验的建议，旨在解释沮丧的非奖励结构的大脑-行为关系。由于CBT教授情绪调节技能，这项研究的第一个目标是检查CBT对攻击性的积极反应是否与杏仁核(与情绪唤醒相关的大脑区域)的活动减少，以及与情绪认知控制相关的大脑区域(包括背侧前扣带回皮质和腹内侧额前皮质)的活动增加有关。证明情绪调节回路的关键节点的改变与反应性攻击的减少有关，这将为支持挫折性非奖赏结构的有效性提供证据。第二个目标是探讨具有冷漠-无情绪特质的攻击性儿童社会情绪知觉受损和奖赏敏感性受损的生物标志物对CBT反应的调节作用。80名在多个传统诊断类别中具有高攻击性的儿童，年龄在8岁到16岁之间，将被随机分配接受12次CBT或12次支持性心理治疗。临床结果将通过在基线、中点和终点评估时收集的攻击性行为的父母评级以及由独立评估者(盲评者)分配的临床总体印象量表的改善分数来衡量。在基线和终点的fMRI扫描和脑电记录过程中，儿童还将执行挫折诱导Go-NoGo任务和情绪面孔感知任务。挫折诱导Go-NoGo任务包括观看一系列物体，并根据预先确定的实验条件按下按钮。在任务的一部分，挫折是由于失去了可以换取奖励的点数而引起的。在早期的fMRI研究中，这项任务被证明参与了情绪调节的神经回路。这一大胆信号的主要对比将是 区别：(1)Go-NoGo任务的中性与挫折障碍，(2)中性与情绪面孔，(3)Go-NoGo任务的正确与不正确的Go测试。诱发相关电位感兴趣的主要变量是：(1)NOGO试验的N_2分量，(2) P3成分用于纠正和反馈与错误围棋试验相关的消极情绪，以及(3)N170和N250事件相关电位与面孔感知任务有关。与NIMH战略研究重点一致，如果功能神经成像和电生理变量可以识别 对于攻击性的认知-行为疗法，这可以提供一种基于神经科学的分类方案，将改善有攻击性行为的儿童的治疗结果。

DESCRIPTION (provided by applicant): Frustrative non-reward is defined by reactions elicited in response to withdrawal or prevention of reward, most notably reactive aggression. The neural mechanisms of reactive aggression involve heightened amygdala arousal in response to frustration coupled with hypoactivity of prefrontal regions that subserve emotion regulation. This is a proposal for a randomized controlled trial of cognitive-behavioral therapy (CBT) in children with high levels of aggression aimed at explicating the brain-behavior relationship of the frustrative non-reward construct. Because CBT teaches emotion regulation skills, the first objective of the study is to examine whether positive response to CBT for aggression will be associated with decreased activity in the amygdala, the brain area associated with emotional arousal, and increased activity in the brain areas associated with cognitive control of emotion, including the dorsal anterior cingulate cortex and ventromedial prefrontal cortex. Demonstrating that a change in the key nodes of the emotion regulation circuitry is associated with a reduction of reactive aggression will provide evidence to support the validity of the frustrative non-reward construct. The second objective is to explore the moderating effects of the biomarkers of impaired socioemotional perception and reward sensitivity in aggressive children with callous-unemotional traits on response to CBT. Eighty children with high levels of aggression across multiple traditional diagnostic categories, ages 8 to 16, will be randomly assigned to receive 12 sessions of CBT or 12 sessions of Supportive Psychotherapy. Clinical outcomes will be measured by the parent-ratings of aggressive behavior collected at baseline, midpoint and endpoint evaluations and the Improvement Score of the Clinical Global Impression Scale assigned by an independent evaluator (blinded rater). Children will also perform a frustration-induction Go-NoGo task and a task of emotional face perception during fMRI scanning and EEG recording at baseline and endpoint. The frustration-induction Go-NoGo task involves viewing a stream of objects and pressing the button in response to pre-determined experimental conditions. During a portion of the task, frustration is induced by loss of points that can be exchanged for a reward. This task has been shown to engage the neural circuitry of emotion regulation in an earlier fMRI study. The main contrasts of interest for the BOLD signal will be the difference between: (1) neutral versus frustration blocks of the Go-NoGo task, (2) neutral versus emotional faces, and (3) correct versus incorrect Go trials of the Go-NoGo. The main variables of interest for the evoked-related potentials will be: (1) the N2 component to the NoGo trials, (2) P3 component to correct and Feedback-Related Negativity to the incorrect Go trials, and (3) N170 and N250 ERPs to the face perception task. Consistent with the NIMH Strategic Research Priorities, if functional neuroimaging and electrophysiological variables can identify children who respond to cognitive-behavioral therapy for aggression, this can provide a neuroscience- based classification scheme that will improve treatment outcomes for children with aggressive behavior.