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

描述（由申请人提供）：挫折性无奖励被定义为对退缩或阻止奖励的反应，最明显的是反应性攻击。反应性攻击的神经机制包括对挫折反应的杏仁核觉醒增强，以及负责情绪调节的前额叶区域活动减弱。本研究建议在高水平攻击儿童中进行认知行为治疗（CBT）的随机对照试验，旨在阐明挫折性非奖励构念的脑-行为关系。因为CBT教授情绪调节技巧，所以该研究的第一个目标是检查对攻击行为的CBT的积极反应是否与杏仁核（与情绪唤醒相关的大脑区域）的活动减少和与情绪认知控制相关的大脑区域（包括背前扣带皮层和腹内侧前额叶皮层）的活动增加有关。证明情绪调节回路关键节点的变化与反应性攻击的减少有关，将为支持沮丧非奖励结构的有效性提供证据。第二个目的是探讨具有冷酷无情特征的攻击性儿童的社会情绪知觉和奖励敏感性受损的生物标志物对CBT反应的调节作用。80名年龄在8到16岁之间，具有多种传统诊断类别的高攻击性的儿童将被随机分配接受12次CBT治疗或12次支持性心理治疗。临床结果将通过父母在基线、中点和终点评估时收集的攻击行为评分和由独立评估者（盲法评估者）分配的临床总体印象量表的改善分数来衡量。在fMRI扫描和基线和终点EEG记录期间，儿童还将执行挫折诱导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，并根据预先确定的实验条件按下按钮。在部分任务中，玩家会因为失去积分而受挫，而这些积分可以用来换取奖励。在早期的fMRI研究中，这项任务已被证明涉及情绪调节的神经回路。BOLD信号的主要对比将是

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.