The goal of the Neuroscience and Novel Therapeutics Unit (NNT) is to develop and test psychological treatments for anxiety and irritability, two of the most common and impairing pediatric mental health problems. Despite their prevalence and public health impact, advances in treatment have stalled. To capitalize on this opportunity, NNT deploys an experimental medicine approach. First, we identify and probe mechanistically relevant behaviors and corresponding brain-based dysfunction. Second, we develop interventions modifying putative behavioral and neural targets integrating in vivo, mobile metrics. Our work implicates two psychological processes in both anxiety and irritability: (1) aberrant threat processing, and (2) impaired inhibitory control. Exposure therapy, a behavioral technique, engages both threat (e.g., salience network) and inhibition (e.g., executive control networks). Exposure therapy is a first line treatment for anxiety disorders. However, the neural mechanisms mediating improvement remain unknown. Critically, the clinical application beyond fear-based disorders has only recently been considered. Both clinically impairing irritability and anxiety are stimulus-evoked, high arousal, negative valence states, with differential downstream behavioral manifestations.

In this presentation, I will present two studies. First, in a large, unmedicated sample of youth with anxiety disorders and healthy controls, we identified specific brain-based regions associated with clinical improvement in anxiety (e.g., fronto-parietal regions), as well as subcortical circuitry (e.g., amygdala) showing sustained dysfunction following exposure therapy. Second, because like fear, anger is an acute stimulus driven emotional state, we conceptualized, tested, and demonstrated efficacy for a novel application of exposure therapy for youth with impairing irritability and anger. I will also share some early work where we are augmenting our work on brain-based behavioral therapeutics by developing, assessing, and validating digital mobile health applications.