Neuroticism is associated with increased amygdala connectivity to hippocampal and prefrontal regions during emotional...

Neuroticism, a stable personality trait marked by heightened negative affect and emotional volatility, is a well-established transdiagnostic risk factor for internalizing psychopathology. While early research emphasized amygdala hyperreactivity as a core neural correlate, emerging evidence suggests that neuroticism may be more accurately characterized by dysfunctional connectivity between the amygdala and broader regulatory networks involved in emotion processing and cognitive control. In this cross-sectional fMRI study, 115 healthy adults completed a classification task involving negative emotional facial expressions. Neuroticism was assessed using a latent factor score derived from five validated self-report instruments. Brain activity and psychophysiological interaction analyses were conducted using both region-of-interest and whole-brain approaches. Associations between neural measures and neuroticism were tested using robust regression, controlling for age and sex. No evidence was found for an association between neuroticism and regional brain activity. However, higher neuroticism was associated with increased task-dependent functional connectivity between the amygdala and both the hippocampus and dorsolateral prefrontal cortex. Whole-brain analyses further revealed associations between neuroticism and amygdala coupling with regions implicated in emotion regulation and salience processing, including the anterior insula and dorsal cingulate cortex. These findings support the conceptualization of neuroticism as a network-level phenomenon, characterized by dysregulated interactions within fronto-limbic and salience circuits, rather than by localized changes in brain activity. Specifically, increased amygdala-hippocampal and amygdala-prefrontal connectivity may underlie the persistence and regulation difficulties of negative emotions that characterize the neurotic phenotype.