Neuroticism/negative emotionality is associated with increased reactivity to uncertain threat in the bed nucleus of the stria terminalis, not the amygdala.

Neuroticism or negative emotionality (N/NE)-the propensity to experience and express more intense, frequent, or persistent negative affect-is a fundamental dimension of mammalian temperament. Elevated levels of N/NE are associated with a wide range of practically important outcomes, from marital stability and socioeconomic attainment to mental illness and premature death. Despite this, our understanding of the brain bases of N/NE remains far from complete. Converging lines of mechanistic and neuroimaging evidence suggest that N/NE reflects heightened reactivity to genuinely threatening stimuli in the extended amygdala, a circuit encompassing the dorsal amygdala in the region of the central nucleus (Ce) and the lateral division of the neighboring bed nucleus of the stria terminalis (BST), and that this association may be more evident when threat is uncertain. Here, we used a combination of approaches-including a multi-trait, multi-occasion composite of N/NE and neuroimaging assays of threat anticipation and perception-to demonstrate that individuals with a more negative disposition show heightened BST activation during uncertain-threat anticipation. A series of cross-validated, robust regression analyses revealed that N/NE is uniquely predicted by BST reactivity to uncertain-threat anticipation. In contrast, N/NE was unrelated to Ce activation during the anticipation of threat or to extended amygdala activation during the presentation of 'threatening' faces. Follow-up analyses revealed inconsistent evidence of between-task convergence in the BST and Ce, suggesting that threat-anticipation and emotional-face paradigms are not interchangeable probes of extended amygdala function. Collectively, these observations lay the foundation for the kinds of prospective-longitudinal and mechanistic studies that will be necessary to determine causation and, ultimately, to develop improved interventions for extreme N/NE.