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

描述（由申请人提供）：挫折性非奖励的定义是在撤回或阻止奖励时引起的反应，最明显的是反应性攻击。反应性攻击的神经机制涉及杏仁核对挫折的高度唤醒，以及有助于情绪调节的前额叶区域的活动减退。这是一项针对高攻击性儿童的认知行为治疗（CBT）的随机对照试验，旨在阐明挫折性非奖励结构的大脑行为关系。由于CBT教授情绪调节技能，因此该研究的第一个目标是检查对CBT的攻击性积极反应是否与杏仁核（与情绪唤起相关的大脑区域）活动的减少以及与情绪认知相关的大脑区域活动的增加有关。控制情绪，包括背侧前扣带回皮质和腹内侧前额叶皮质。 证明情绪调节回路的关键节点的变化与反应性攻击的减少相关，将提供证据支持挫折性非奖励结构的有效性。第二个目标是探讨社会情绪知觉和奖励敏感性受损的生物标志物在冷酷-无情绪特质的攻击性儿童对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至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。临床结局将通过基线、中点和终点评价时收集的攻击行为的父母评分以及独立评价者（设盲评价者）分配的临床总体印象量表的改善评分进行测量。儿童还将在fMRI扫描和基线和终点EEG记录期间执行挫折诱导Go-NoGo任务和情绪面部感知任务。挫折诱导Go-NoGo任务包括观看一系列物体并按下按钮以响应预先确定的实验条件。在任务的一部分，挫折感是由可以换取奖励的积分损失引起的。在早期的功能磁共振成像研究中，这项任务已经被证明可以参与情绪调节的神经回路。BOLD信号的主要对比将是 之间的差异：（1）Go-NoGo任务的中性与挫折块，（2）中性与情绪面孔，（3）Go-NoGo任务的正确与不正确围棋试验。诱发相关电位感兴趣的主要变量将是：（1）NoGo试验的N2分量，（2） P3成分用于纠正错误的Go试验和反馈相关负性;（3）N170和N250用于面孔知觉任务。与NIMH战略研究优先事项一致，如果功能神经成像和电生理变量可以识别儿童， 这可以提供一个基于神经科学的分类方案，将改善具有攻击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.