Neural Mechanisms of Cognitive-Behavioral Therapy for Aggression in Children and Adolescents: Design of a Randomized Controlled Trial Within the National Institute for Mental Health Research Domain Criteria Construct of Frustrative Non-Reward

Abstract

Objective: We present the rationale and design of a randomized controlled trial of cognitive-behavioral therapy (CBT) for aggression in children and adolescents, which is conducted in response to the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) approach initiative. Specifically, the study is focused on the brain-behavior associations within the RDoC construct of frustrative non-reward. On the behavioral level, this construct is defined by reactions elicited in response to withdrawal or prevention of reward, most notably reactive aggression. This study is designed to test the functional magnetic resonance (fMRI) and electrophysiological (EEG) correlates of aggression and its reduction after CBT.

Methods: Eighty children and adolescents with high levels of aggression across multiple traditional diagnostic categories, ages 8-16, will be randomly assigned to receive 12 sessions of CBT or 12 sessions of supportive psychotherapy. Clinical outcomes will be measured by the ratings of aggressive behavior collected at baseline, midpoint, and endpoint evaluations, and by the Improvement Score of the Clinical Global Impressions Scale assigned by an independent evaluator (blinded rater). Subjects 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.

Results: Consistent with the NIMH strategic research priorities, if functional neuroimaging and EEG variables can identify subjects who respond to CBT for aggression, this can provide a neuroscience-based classification scheme that will improve treatment outcomes for children and adolescents with aggressive behavior.

Conclusions: 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.

Figures

FIG. 1.

Flow chart of study design.

FIG. 2.

Frustration-induction Go-NoGo task. Upper panel shows latency windows for stimulus presentation and correct responses by three task blocks. Lower panel shows a sample of the task stimuli. A color version of this figure is available in the online article at www.liebertpub.com/cap.

FIG. 3.

Example of stimuli in the emotional face perception task. A color version of this figure is available in the online article at www.liebertpub.com/cap.

FIG. 4.

(A) Voxels found to show significant treatment-related change in differential activation during recovery versus winning conditions in a single exemplar participant. (B) Extracted beta values for the recovery minus winning contrast reflecting change in emotion regulation activation following treatment in the dorsal anterior cingulate (dACC) and ventral medial prefrontal cortex (vmPFC). A color version of this figure is available in the online article at www.liebertpub.com/cap.