(PS3-55) Distinct Functional Connectivity Signatures of Phasic and Tonic Irritability in Children

Abstract Text: Irritability, characterized by an increased proneness to frustration and anger, is one of the most common reasons children and adolescents are referred for treatment evaluation. Irritability is a transdiagnostic risk factor associated with the emergence of internalizing and externalizing psychopathologies, including anxiety and depression. Prior work suggests that irritability is a multifaceted construct comprising both tonic (persistent negative mood) and phasic (acute temper outburst) components, which may have distinct neural associations. Neuroimaging studies have implicated large-scale brain networks, particularly those involved in emotion regulation and cognitive control, in the pathophysiology of irritability. However, despite the increasing recognition of the differences between phasic and tonic irritability, the neural mechanisms differentiating these subcomponents remain poorly understood in youth. The purpose of the current study was to investigate the unique relationships between phasic and tonic irritability and large-scale network connectivity in a large sample of children. Participants included 9- to 10-year-old children (N = 9,802) from the Adolescent Brain Cognitive Development (ABCD) Study. Resting state fMRI data (20 minutes of passive viewing) was acquired with multiband echo-planar imaging and processed using standard procedures. Functional connectivity was quantified using Fisher-transformed correlations within and between large-scale networks and subcortical regions, with rigorous quality control to minimize motion-related artifacts. Sum scores for phasic and tonic irritability were derived at baseline using previously established items from the Child Behavior Checklist and analyzed in relation to 306 connectivity network variables from the Gordon parcellation (12 within-network, 66 between-network, and 228 network-subcortical regions). Only one member from each family was included, and study site was included as a covariate in all analyses. The relationship between phasic irritability and functional connectivity was assessed while controlling for tonic irritability, and vice versa, to isolate unique associations. Multiple comparisons were accounted for using false discovery rate (FDR) correction. After correcting for multiple comparisons and controlling for tonic irritability, phasic irritability showed significant associations with within-network connectivity of the dorsal attention network, and between-network connectivity involving the default-mode network, dorsal attention network, retrosplenial temporal network, sensorimotor hand network, and the fronto-parietal network. No significant associations were found for tonic irritability after parsing out the variance shared with phasic irritability. These findings highlight the specific associations of phasic irritability with large-scale brain networks, particularly those involving cognitive and emotional processing. These results contribute to a better understanding of the neural mechanisms underlying irritability’s tonic and phasic components and may inform future research on targeted interventions for individuals experiencing phasic irritability in particular.