UC San Diego

Rationale. Irritability during early childhood is a prominent predictor of long-term psychopathology and functional impairment. Despite its clinical significance, the underlying mechanisms of irritability are not fully understood. Inhibitory control, a key component of executive functioning, is the process of suppressing goal-irrelevant prepotent responses, and it is heavily involved in the self-regulation of emotions and behaviors. During early childhood, inhibitory control develops rapidly, playing an important role in children’s socio-emotional and academic functioning as they transition into formal schooling. However, limited work has examined the inhibitory control-related neural correlates of irritability during this critical developmental stage.Designs. This study utilized the data drawn from the Brains in Growth-Emotions (BIG-Emotions) Study, a longitudinal study investigating change in irritability across early childhood. Children aged 5 to 6 (N = 184, Mage = 6.18, SD = 0.50) completed a child-friendly Go/No-Go task during MRI data acquisition. Irritability was assessed using the parent-report Multidimensional Assessment Profiles Temper Loss scale (MAPS-TL). Irritability-related neural correlates of successful inhibition, failed inhibition, and failed attention control were examined using whole-brain activation analyses and functional connectivity of six seed regions (left/right anterior cingulate cortex, amygdala, ventral striatum) with the rest of the brain.Results. Elevated irritability during early childhood was associated with greater activation in precuneus and visual processing regions during failed inhibition (i.e., incorrect No-Go). During failed attention control (i.e., incorrect Go), elevated irritability was associated with increased activation, as well as aberrant anterior cingulate, amygdala, ventral striatum functional connectivity, in several executive functioning, emotion regulation, visual processing, and default mode regions. No significant results emerged for activation or connectivity for the irritability × successful inhibition interaction.Relevance. The findings of this study provided support for the significance of inhibitory control processes in regulating irritability and contributed to the current understanding of neural mechanisms underlying irritability during early childhood, which can inform the development of targeted prevention and intervention for irritability and related psychopathology.