On the role of neural error monitoring in clinical research: An integrative model of altered error-related brain activity and psychopathology

Human learning and as a result, the improvement of cognitive and behavioral performance, relies heavily on the ability of the brain to monitor errors. Event-related potentials such as the error-related negativity (ERN) enable us to observe and measure these brain processes. Meta-analytical evidence indicates that a trait-like attenuated ERN may serve as a biomarker for externalizing and thought disorders, whereas an elevated ERN is associated with increased risk for internalizing disorders. In this review, we synthesize previous research and propose an integrative model of error-related brain activity and psychopathology, highlighting the role of an altered ERN as a risk marker and its trajectories toward clinical symptoms. Early shaping factors during childhood and adolescence (i.e., genetics, gender/sex, cognition, temperament, and the psychosocial environment) contribute to a trait-like hypo- or hyperactive error monitoring system that reflects vulnerability to mental health impairments. The translation from vulnerability to psychopathology is further catalyzed by individual factors (i.e., gender/sex/hormones and temperament/personality traits) as well as environmental influences (i.e., susceptibility to adverse life events and interpersonal stress). Underlying latent symptom dimensions along the lines of threat sensitivity and risk tolerance, may explain why only certain clinical phenotypes are associated with altered ERN amplitudes. Overall, our integrative model provides a framework for future research to further investigate each of these associations, the directions of effects, or even entire pathways. Moreover, a neurobiological understanding of psychopathology may inform the development of tailored and personalized interventions.