Individuals with Intermittent Explosive Disorder Exhibit Idiosyncratic Neural Responses during Social-emotional Processing

Abstract Intermittent explosive disorder (IED) is associated with impulsive aggression in ambiguous social contexts. Prior neuroimaging studies have treated IED as a homogenous group, but identical social situations may elicit divergent responses across IED individuals. Here, we test the hypothesis that IED is characterized by idiosyncratic neural responses to social cues during naturalistic social-emotional processing. IED individuals and healthy controls completed a validated paradigm where they were presented with video vignettes of interpersonal interactions while undergoing fMRI. We computed the intersubject correlation (ISC) in neural time courses between pairs of participants to quantify neural similarity, and assessed whether similarity differed between Healthy-Healthy and IED-IED dyads using Bayesian multilevel models, controlling for self-reported emotional responses and intention attributions for each vignette. Healthy-Healthy dyads showed significantly higher ISC than IED-IED dyads, indicating that neural responses to the videos were similar among healthy participants, but idiosyncratic in IED individuals. These effects were observed in regions in the default mode and salience networks, including the precuneus, medial prefrontal cortex, superior temporal sulcus, insula, and dorsal anterior cingulate cortex. Individuals with IED exhibited idiosyncratic neural responses during naturalistic social-emotional processing, even after accounting for differences in emotional reaction and intention attribution. This neural idiosyncrasy may reflect atypical integration of social cues, giving rise to maladaptive interpretations and impulsive aggression. Assessing neural synchrony during ecologically valid paradigms offers a promising tool for identifying neural markers of interpersonal dysfunction and informing targeted interventions.