3 - (SYM 95) Brain Connectivity and Anger Attribution Bias in Irritable Youth

Background: Pediatric irritability is a transdiagnostic symptom characterized by a proneness to anger, particularly in the context of frustration. Neuroimaging studies individually demonstrate altered brain reactivity and connectivity related to irritability, but taken together, they fail to converge to support a single pathophysiological model (Lee et al., 2022; Nielsen et al., 2021). A limitation of prior work may be the focus on irritability broadly, rather than comprised of multiple affective domains. Investigating specific affective domains, such as anger, may help account for the considerable heterogeneity seen in symptom presentations, long-term outcomes, and diagnoses in irritable children.

Methods: The present study examined the resting state functional connectivity (rsFC) of the amygdala in relation to anger attribution bias in a sample of young children (5-9 years old; N=60; 55% White, 26.7% Hispanic) with clinically significant irritability, characterized by impairing emotional outbursts. Anger attribution biases were assessed using the Assessment of Children’s Emotional Skills (ACES), which yields three measures of anger attribution bias based on their interpretation of social situations, social behaviors, and facial expressions. Children completed the ACES among other measures, as well as a resting state functional magnetic resonance imaging scan. ACES scores were entered into a general linear model to examine associations with rsFC of the bilateral amygdalae.

Results: Overall, irritable children demonstrated significant biases in attributing anger to others across all three ACES domains. Anger attribution biases exhibited distinct patterns of amygdala functional connectivity. Greater biases towards attributing anger in social situations were associated with reduced rsFC of the bilateral amygdalae with the fusiform/lingual gyri and lateral occipital cortex. Further, greater bias towards attributing anger to others based on their behaviors was associated with heightened rsFC of the right amygdala with the left middle frontal gyrus and greater bias towards attributing anger to facial expressions positively predicted right amygdala-precuneus rsFC.

Conclusion: Findings implicate functional connections among regions of default mode and frontoparietal networks associated with anger attribution biases in clinically irritable children. Longitudinal studies are needed to determine the putative role of anger attribution bias in the etiology and long-term outcomes of pediatric irritability.