Because anxiety disorders appear to follow developmental trajectories that begin early in development, it may be useful to examine the neurodevelopmental correlates of specific cognitive processes that have been linked to anxiety. For instance, the error-related negativity (ERN) is a negative deflection in the event-related potential that is maximal approximately 50 ms following the commission of errors at fronto-central electrode sites, and has consistently been found to be more negative among anxious adults. Much less, however, is known about anxiety and the ERN in children—especially when this relationship develops. We recorded event-related potentials (ERPs) while 55 children aged 8 to 13 performed an arrow version of the flankers task. Parents and children both reported on children’s anxiety. Results suggest that the relationship between the ERN and anxiety changes as a function of age. Among older children, a larger (i.e., more negative) ERN was significantly related to increased anxiety based on parent report. Although the relationship was less robust, the relationship between ERN and anxiety was opposite among younger children. These results are discussed in terms of existing work on anxiety and the ERN, and the need for longitudinal and developmental studies on the relationship between ERN and anxiety.
The Error-related Negativity (ERN) currently appears as a physiological measure in relation to three RDoC constructs: Cognitive Control, Sustained Threat, and Reward Learning. We propose a conceptual model in which variance in the ERN reflects individual differences in the degree to which errors are evaluated as threatening. We also discuss evidence for the placement of the ERN in the ‘Sustained Threat’ construct, as well as evidence that the ERN may more specifically reflect sensitivity to endogenous threat. Following this, we present data from a sample of 515 adolescent females demonstrating larger ERN in relation to self-reported checking behaviors, but only in older adolescents, suggesting that sensitivity to internal threat and the ERN-checking relationship may follow a developmental course as adolescents develop behavioral control. In contrast, depressive symptoms were linked to smaller ERN, and this association was invariant with respect to age. Collectively, these data suggest that the magnitude of the ERN is sensitive both to specific anxiety-related processes and depression, in opposing directions that may reflect variation in internal threat sensitivity. We discuss directions for future research, as well as ways in which findings for the ERN complement and challenge aspects of the current RDoC matrix.
There is growing interest in psychophysiological and neural correlates of psychopathology, personality, and other individual differences. Many studies correlate a criterion individual difference variable (e.g., anxiety) with a psychophysiological measurement derived by subtracting scores taken from two within-subject conditions. These subtraction-based difference scores are intended to increase specificity by isolating variability of interest. Using data on the error-related negativity (ERN) and correct response negativity (CRN) in relation to generalized anxiety disorder (GAD), we highlight several conceptual and practical issues with subtraction-based difference scores and propose alternative approaches based on regression. We show that ERN and CRN are highly correlated, and that the DERN (i.e., ERN 2 CRN) is correlated in opposite directions both with ERN and CRN. Bivariate analyses indicate that GAD is related to DERN and ERN, but not CRN. We first show that, by using residualized scores, GAD relates both to a larger ERN and smaller CRN. Moreover, by probing the interaction of ERN and CRN, we show that the relationship between GAD and ERN varies by CRN. These latter findings are not evident when using traditional subtraction-based difference scores. We then completed follow-up analyses that suggested that an increased P300 in anxious individuals gave rise to the apparent anxiety/CRN relationship observed. These findings have important conceptual implications for facilitating the interpretability of results from individual difference studies of psychophysiology.
Feedback negativity (FN) is an event-related potential elicited by monetary reward and loss; it is thought to relate to reward-related neural activity and has been linked to depression in children and adults. In the current study, we examined the stability of FN, and its relationship with depression in adolescents, over 2 years in 45 8- to 13-year-old children. From Time 1 to Time 2, FN in response to monetary loss and in response to monetary gain showed moderate to strong reliability (rs = .64 and .67, respectively); these relationships remained significant even when accounting for related variables. FN also demonstrated high within-session reliability. Moreover, the relationship between a blunted FN and greater depression observed at Time 1 was reproduced at Time 2, and the magnitude of FN at Time 1 predicted depressive symptomatology at Time 2. These findings are consistent with the hypothesis that FN and its relationship with depression remain consistent over the course of development, and that FN may prospectively predict later depressive symptomatology. The current results suggest that FN may be suitable as a biomarker of depressive symptoms during adolescence.
Event-related potentials (ERPs) are direct measures of brain activity that can be leveraged for clinically meaningful research. They can relate robustly both to continuous measures of individual difference and to categorical diagnoses in ways that clarify similarities and distinctions between apparently related disorders and traits. ERPs can be linked to genetic risk, can act as moderators of developmental trajectories and responses to stress, and can be leveraged to identify those at greater risk for psychopathology, especially when used in combination with other neural and self-report measures. ERPs can inform models of the development of, and risk for, psychopathology. Finally, ERPs can be used as targets for existing and novel interventions and prevention efforts. We provide concrete examples for each of these possibilities by focusing on programmatic research on the error-related negativity and anxiety, and thus show that ERPs are poised to make greater contributions toward the identification, prediction, treatment, and prevention of mental disorders.
Considering that anxiety disorders frequently begin before adulthood and often result in chronic impairment, it is important to characterize the developmental pathways leading to the onset of clinical anxiety. Identifying neural biomarkers that can predict the onset of anxiety in childhood may increase our understanding of the etiopathogenesis of anxiety, as well as inform intervention and prevention strategies. An event-related potential (ERP), the error-related negativity (ERN) has been proposed as a biomarker of risk for anxiety and has previously been associated with concurrent anxiety in both adults and children. However, no previous study has examined whether the ERN can predict the onset of anxiety disorders. In the current study, ERPs were recorded while 236 healthy children, approximately 6 years of age, performed a Go/No-Go task to measure the ERN. Three years later, children and parents came back to the lab and completed diagnostic interviews regarding anxiety disorder status. Results indicated that enhanced error-related brain activity at age 6 predicted the onset of new anxiety disorders by age 9, even when controlling for baseline anxiety symptoms and maternal history of anxiety. Considering the potential utility of identifying early biomarkers of risk, this is a novel and important extension of previous work.
Overall, 22 studies were included in the current review. A number of patterns emerged, including: 1.) The ERN is enhanced in clinically anxious children at all ages (6-18 years old), regardless of the task used to measure the ERN. 2.) Studies focusing on anxiety symptoms and temperamental fear suggest that the relationship between the ERN and normative anxiety may change across development. 3.) The ERN can predict the onset of anxiety disorders across different developmental periods. 4.) The ERN relates to other markers of risk for anxiety (e.g., aversive startle potentiation) in children and adolescents.
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