Targeting self-reported and neural error sensitivity: Short- and long-term effects of a one-week online intervention

An Experimental Therapeutics Approach to the Development of a Novel Computerized Treatment Targeting Error-Related Brain Activity in Young Children

ERROR-RELATED BRAIN ACTIVITY AS AN ENDOPHENOTYPE OF OBSESSIVE-COMPULSIVE DISORDER

The pathophysiology of obsessive-compulsive disorder (OCD) involves increased activity in cortico-striatal circuits connecting the anterior cingulate cortex (ACC) with other brain regions. The error-related negativity (ERN) is a negative deflection in the event-related potential following an erroneous response and is thought to reflect ACC activity. This study was done to assess the ERN as a biomarker for OCD by comparing ERN amplitudes in pediatric OCD patients, unaffected siblings of pediatric OCD patients, and healthy controls. The ERN and correct response negativity (CRN) were measured during an Eriksen flanker task to assess performance monitoring in 40 youth with a lifetime diagnosis of OCD, 19 unaffected siblings of OCD patients, and 40 unrelated healthy comparison subjects ranging in age from 10 to 17 years. ERN and CRN amplitudes were compared between groups using linear regression by the generalized estimating equation method to account for correlated data. Compared to healthy controls, ERN amplitude was significantly increased in both pediatric OCD patients and unaffected siblings. There were no significant group differences in CRN amplitude. ERN amplitude in patients was unrelated to OCD symptom severity, current diagnostic status, or treatment effects. Increased error-related brain potentials were observed not only in pediatric OCD patients but also in unaffected siblings. The results provide evidence that enhanced error-related brain activity may serve as a biomarker for OCD in youth that is independent of the presence of clinical symptoms. The ERN may be a useful quantitative phenotype in genetic studies of OCD.

The error-related negativity (ERN) is a negative deflection in the event-related potential following a mistake that is often increased in patients with obsessive-compulsive disorder (OCD). The relationship of the ERN to comorbid major depressive disorder (MDD) has not been examined in adolescents with OCD. This study compared ERN amplitudes in OCD patients with MDD (OCD+MDD), OCD patients without MDD (OCD-MDD), MDD patients, and healthy controls (HC). The ERN, correct response negativity, and accuracy were measured during a flanker task to assess performance monitoring in 53 adolescents with a lifetime diagnosis of OCD, 36 adolescents with a lifetime diagnosis of MDD, and 89 age-matched HC of 13-18 years. Fourteen OCD patients had a history of MDD. ERN amplitude was significantly increased in OCD patients compared to HC and significantly correlated in OCD patients with age at OCD symptom onset, particularly in the OCD - MDD patients. The ERN was significantly enlarged in OCD+MDD patients compared to HC, but not in MDD patients compared to HC. There was a trend for an increased ERN amplitude in OCD - MDD patients compared to HC. OCD patients were significantly less accurate than either MDD patients or HC. An enlarged ERN is a neural correlate of adolescent OCD that is associated with age at OCD symptom onset. Adolescents with OCD may have impaired cognitive control on a flanker task. Follow-up studies with larger samples may determine whether an enlarged ERN in adolescents with OCD is associated with a higher risk for MDD.

Overactive performance monitoring, as measured by the error-related negativity in the event-related brain potential, represents one of the most robust psychophysiological alterations in obsessive-compulsive disorder (OCD). It has been proposed as an endophenotype for OCD because it is heritable and more prevalent in families of OCD patients. Consistent with this notion, it is also independent of symptom profile and symptom severity in cross-sectional studies. Longitudinally, it has been shown to be state independent in pediatric patients with OCD. The purpose of the present study was to investigate the state dependency of error monitoring by examining adult OCD patients before and after symptom reduction through cognitive-behavioral therapy (CBT). Error-related and correct-related negativity as electrophysiological indicators of performance monitoring were recorded from 45 OCD patients and 39 healthy comparison subjects while performing a flanker task. Patients were assessed before starting and after completing a standard 30-session CBT, including exposure and response prevention, and healthy comparison subjects were tested after a comparable time interval. Pretreatment, patients with OCD were characterized by enhanced error-related and correct-related negativity compared with healthy comparison subjects. This difference persisted after treatment when symptoms were substantially reduced. There was no significant correlation between symptom improvement and changes in performance monitoring and no difference in performance monitoring between treatment responders and nonresponders. This is the first longitudinal study in adult OCD patients showing stability of enhanced error monitoring following successful symptom reduction through CBT. It supports the hypothesis that overactive performance monitoring is an endophenotype that indicates vulnerability for OCD.

Objective: The error-related negativity (ERN) is a negative deflection in the event-related potential after an incorrect response, which is often increased in patients with obsessivecompulsive disorder (OCD). However, the relation of the ERN to comorbid tic disorders has not been examined in patients with OCD. This study compared ERN amplitudes in patients with tic-related OCD, patients with non‐tic-related OCD, and healthy controls. Method: The ERN, correct response negativity, and error number were measured during an Eriksen flanker task to assess performance monitoring in 44 youth with a lifetime diagnosis of OCD and 44 matched healthy controls ranging in age from 10 to 19 years. Nine youth with OCD had a lifetime history of tics. Results: ERN amplitude was significantly increased in patients with OCD compared with healthy controls. ERN amplitude was significantly larger in patients with non‐tic-related OCD than in patients with tic-related OCD or controls. ERN amplitude had a significant negative correlation with age in healthy controls but not in patients with OCD. Instead, in patients with non‐tic-related OCD, ERN amplitude had a significant positive correlation with age at onset of OCD symptoms. ERN amplitude in patients was unrelated to OCD symptom severity, current diagnostic status, or treatment effects. Conclusions: The results provide further evidence of increased error-related brain activity in pediatric OCD. The difference in the ERN between patients with tic-related and those with non‐tic-related OCD provides preliminary evidence of a neurobiological difference between these two OCD subtypes. The results indicate the ERN is a trait-like measurement that may serve as a biomarker for non‐tic-related OCD. J. Am. Acad. Child Adolesc. Psychiatry, 2012;51(9):902‐910. Key Words: anxiety disorder, tic disorder, brain potential, performance monitoring, biomarker

Error-Related Negativity and Tic History in Pediatric Obsessive-Compulsive Disorder

Research on the neural response to errors has an important role in the Research Domain Criteria (RDoC) project, since it is likely to link psychopathology to the dysfunction of neural systems underlying basic behavioral functions, with the error-related negativity (ERN) appearing as a unit of measurement in three RDoC domains. A recent report builds on previous research by examining the ERN as a measure of the sustained threat construct and providing evidence that the ERN may reflect sensitivity more specifically to endogenous threat. Data from 515 adolescent females indicate that the ERN was enlarged primarily in older adolescents with self-reported checking behaviors, although it was blunted in adolescents with depressive symptoms regardless of age. Potential future studies for replicating and extending the research on the ERN and obsessive-compulsive (OC) behaviors are discussed, including studies that more fully characterize OC symptom dimensions, studies that integrate other measures of error-related brain activity and use computational modeling, studies that combine longitudinal, family, and molecular genetic measures, and interventional studies that specifically modulate error-related brain activity in individuals with OC behaviors.

Performance Monitoring: A Transdiagnostic Biomarker of Adaptive Behavior in Mental Disorders

The ERN as a neural index of changes in performance monitoring following attention training in pediatric obsessive-compulsive disorder

Withdrawn/Depressed Behaviors and Error-Related Brain Activity in Youth With Obsessive-Compulsive Disorder

Overactive performance monitoring, indexed by greater error-related brain activity, has been frequently observed in individuals with obsessive-compulsive disorder (OCD). Similar alterations have been found in individuals with major depressive and generalized anxiety disorders. The main objective was to extend these findings by investigating performance monitoring in individuals with social anxiety disorder (SAD) and to evaluate the specificity of performance-monitoring changes in OCD. Event-related potentials were used to examine error-related brain activity during a flanker task in 24 individuals with OCD, 24 individuals with SAD, and 24 healthy controls with no history of neurological or psychiatric disorders. Error-related negativity (ERN) and correct-related negativity served as electrophysiological indicators for performance monitoring. Enhanced ERN was expected for both clinical groups, but differential associations with clinical symptoms were explored. ERN amplitudes were larger in individuals with OCD and SAD than in healthy controls. Correlational analyses did not reveal significant associations between ERN and clinical symptomatology in OCD, but a significant correlation with depressive symptoms was found in the SAD group. These findings further strengthen the idea that overactive performance monitoring is independent of clinical symptoms in OCD. Furthermore, it may also represent a transdiagnostic vulnerability indicator, although the relationship with clinical symptoms observed in the SAD group needs additional evaluation.

Application of attentional bias modification training to modulate hyperactive error-monitoring in OCD

Obsessive-compulsive disorder (OCD) is a complex and heterogeneous disorder that is associated with high personal and societal costs. Feelings of doubt, worry, and repetitive behavior, key symptoms of OCD, have been linked to hyperactive error signals in the brain. The error-related negativity (ERN) represents a validated marker of error processing in the ERP. Increased ERN amplitudes in OCD have been reported very robustly over the last 20years. This article integrates results from 38 studies analyzing the ERN in OCD, using a quantitative meta-analysis. Meta-regressions were used to examine potential moderators such as task type, symptom severity, age, and sample size. The meta-analysis reveals a robust increase of ERN in OCD patients compared to healthy participants in response-conflict tasks (SMD -0.55) that is not modulated by symptom severity and age. No increase in ERN in OCD was observed in tasks that do not induce response conflict (SMD -0.10). In addition to the meta-analysis, the current article reviews evidence supporting that increased ERN amplitudes in OCD fulfill central criteria for an endophenotype. Further, the specificity of increased ERN amplitudes for OCD and its suitability as a potential transdiagnostic endophenotype is discussed. Finally, the clinical utility and clinical applications are examined. Overall, the evidence that increased ERN amplitudes represent a promising endophenotype indicating vulnerability for OCD is compelling. Furthermore, alterations in ERN are not limited to OCD and may constitute a transdiagnostic endophenotype. Altered neural error signals might serve as a diagnostic or predictive marker and represent a promising target for interventions.

Introduction Rumination is a risk factor for the development of depression among adolescents. However, not all at-risk youth develop depression, suggesting the presence of factors that moderate risk patterns. Error-related negativity (ERN), an event-related potential indexing cognitive error processing, has been associated with both rumination and internalizing symptoms. However, it remains unknown whether ERN interacts with rumination to predict youth internalizing symptoms and if the interaction effects are specific to depression and anxiety symptoms. The current study examined the interplay of ERN and rumination in the 12-month prospective prediction of anxiety and depressive symptoms in a sample of youth. Method Participants included 60 youth (ages 9–16, 88% female) enrolled in a study on the intergenerational transmission of depression. At baseline, youth completed a self-report measure of rumination and a Flanker error monitoring task during electroencephalography to measure ERN. Youth completed self-report measures of depressive and anxiety symptoms at baseline and 12-month follow-up. Results Results revealed a two-way interaction between baseline child ERN and rumination in the prediction of 12-month depressive symptoms. Follow-up analysis indicated that greater baseline rumination predicted increases in depressive symptoms at 12-months for youth exhibiting a more enhanced ERN, but not for youth demonstrating a blunted ERN. This effect remained after covarying for child age, race, sex, and maternal depression history. Results revealed no significant interactive effect between child ERN and rumination in predicting 12-month anxiety symptoms. Discussion These findings highlight the unique interplay of rumination and neural error processing in the prospective prediction of youth depressive symptoms. If replicated, these results would suggest that rumination-targeted prevention programs may be particularly effective for reducing depressive symptoms among youth exhibiting an enhanced ERN.