Anja Riesel

Overactive Error-Related Brain Activity as a Candidate Endophenotype for Obsessive-Compulsive Disorder: Evidence From Unaffected First-Degree Relatives

OBJECTIVEnHyperactivity in frontal-striatal circuits is assumed to be involved in the pathophysiology of obsessive-compulsive disorder (OCD). In line with that, electrocortical correlates of overactive performance monitoring have been found to be associated with OCD independent from symptom state. The purpose of the present study was to elucidate whether overactive performance monitoring may represent a candidate endophenotype for OCD. In this case, unaffected first-degree relatives of OCD patients should also show this trait.nnnMETHODnAmplitudes of the error-related negativity and the correct-related negativity in the event-related brain potential during a flanker task were used to assess performance monitoring in three carefully matched groups: 30 patients with OCD, 30 unaffected first-degree relatives of OCD patients, and 30 healthy comparison subjects.nnnRESULTSnRelative to the healthy comparison subjects, both unaffected first-degree relatives and OCD patients showed increased error-related brain potentials. No significant correlation was obtained between amplitudes and symptom severity measures, neither in patients nor in first-degree relatives.nnnCONCLUSIONSnIncreased error-related brain potentials were observed not only in OCD patients but also in unaffected first-degree relatives. Overactive error monitoring may reflect a trait marker for OCD that is independent of the presence of clinical symptoms. Thus, enhanced error-related brain activity represents a candidate neurocognitive endophenotype for OCD.

The ERN is the ERN is the ERN? Convergent validity of error-related brain activity across different tasks

Error-processing is increasingly examined using the error-related negativity (ERN) and error positivity (Pe) - event-related potentials (ERPs) that demonstrate trait-like properties and excellent reliability. The current study focuses on construct validity by applying a multitrait-multimethod approach, treating error-related ERPs (i.e., ERN, Pe and the difference between error minus correct, referred to as ΔERN and ΔPe, respectively) as traits measured across multiple tasks (i.e., Flanker, Stroop, and Go/NoGo). Results suggest convergent validity of these ERPs ranging between .62 and .64 for ΔERN. Values were somewhat smaller for ERN (range .33-.43), Pe (range .37-.49) and ΔPe (range .30-.37). Further, the correlations for ERN and Pe are higher within components across tasks than between different components suggesting discriminant validity. In conclusion, the present study revealed evidence for convergent and discriminant validity of error-related ERPs, further supporting the use of these components as psychophysiological trait markers.

Punishment has a lasting impact on error‐related brain activity

The current study examined whether punishment has direct and lasting effects on error-related brain activity, and whether this effect is larger with increasing trait anxiety. Participants were told that errors on a flanker task would be punished in some blocks but not others. Punishment was applied following 50% of errors in punished blocks during the first half of the experiment (i.e., acquisition), but never in the second half (i.e., extinction). The ERN was enhanced in the punished blocks in both experimental phases--this enhancement remained stable throughout the extinction phase. More anxious individuals were characterized by larger punishment-related modulations in the ERN. The study reveals evidence for lasting, punishment-based modulations of the ERN that increase with anxiety. These data suggest avenues for research to examine more specific learning-related mechanisms that link anxiety to overactive error monitoring.

Error-related brain activity in the age of RDoC: A review of the literature.

The ability to detect and respond to errors is critical to successful adaptation to a changing environment. The error-related negativity (ERN), an event-related potential (ERP) component, is a well-validated neural response to errors and reflects the error monitoring activity of the anterior cingulate cortex (ACC). Additionally, the ERN is implicated in several processes key to adaptive functioning. Abnormalities in error-related brain activity have been linked to multiple forms of psychopathology and individual differences. As such, the component is likely to be useful in NIMHs Research Domain Criteria (RDoC) initiative to establish biologically-meaningful dimensions of psychological dysfunction, and currently appears as a unit of measurement in three RDoC domains: Positive Valence Systems, Negative Valence Systems, and Cognitive Systems. In this review paper, we introduce the ERN and discuss evidence related to its psychometric properties, as well as important task differences. Following this, we discuss evidence linking the ERN to clinically diverse forms of psychopathology, as well as the implications of one unit of measurement appearing in multiple RDoC dimensions. And finally, we discuss important future directions, as well as research pathways by which the ERN might be leveraged to track the ways in which dysfunctions in multiple neural systems interact to influence psychological well-being.

Overactive performance monitoring in obsessive–compulsive disorder is independent of symptom expression

Overactive performance monitoring has been consistently reported in obsessive–compulsive disorder (OCD). OCD is a clinically heterogeneous disorder and is characterized by several symptom dimensions that may have partially distinct neural correlates. We examined whether performance-monitoring alterations are related to symptom severity and symptom dimensions. Electrocortical correlates of performance monitoring were assessed in 72 OCD patients and 72 matched healthy comparison participants during a flanker task. Amplitudes of the error- and correct-related negativity as well as delta and theta power were used to quantify performance-monitoring activity, and a composite measure was derived using factor analysis. Symptom dimension scores were obtained from the Yale-Brown Obsessive Compulsive Scale symptom checklist. OCD patients showed increased electrocortical responses associated with correct and erroneous responses compared to healthy comparison participants. In patients, no correlations were obtained between performance monitoring and global symptom severity as well as lifetime symptom dimension scores. Only a statistical trend was found that higher symmetry/hoarding scores were associated with reduced performance-monitoring activity. For present symptom dimensions scores, an association with rituals/superstitious symptoms was obtained such that higher scores were associated with greater performance-monitoring activity. However, for both dimensions, subjects with low scores or high scores on each dimension were characterized by overactive performance monitoring compared to healthy controls. Overactive brain processes during performance monitoring are a neural correlate of OCD that is independent of global symptom severity and can be observed for all symptom dimensions. This supports the notion of overactive performance monitoring being a candidate endophenotype for OCD.

Overactive Performance Monitoring as an Endophenotype for Obsessive-Compulsive Disorder: Evidence From a Treatment Study

OBJECTIVEnOveractive 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).nnnMETHODnError-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.nnnRESULTSnPretreatment, 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.nnnCONCLUSIONSnThis 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.

Show me the Money: The impact of actual rewards and losses on the feedback negativity

The feedback negativity (FN) is an event-related potential component which is typically conceptualized as a negativity in response to losses that is absent in response to gains. However, there is also evidence that variation in the FN reflects the neural response to gains. The present study sought to explore these possibilities by manipulating the context in which loss and gain feedback was presented in a straightforward gambling task. In half the blocks, participants could win or lose money (Value condition), and in half the blocks, participants could not win or lose any money (No Value condition). The degree to which losses and gains were differentiated from one another (i.e., the ΔFN) was greater in the Value condition than in the No Value condition. Furthermore, though the responses to loss feedback and gain feedback were each enhanced in the Value condition relative to the No-Value condition, the effect of the monetary manipulation was substantially larger for the positivity to gains than the negativity to losses. This is consistent with the notion that the FN might reflect two independent processes, but that variation in the FN depends more upon the response to rewards than losses.

Performance monitoring in obsessive-compulsive disorder and social anxiety 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.

Modulation of hyperactive error signals in obsessive-compulsive disorder by dual-task demands.

Brain correlates of performance-monitoring have been shown to be hyperactive in patients with obsessive-compulsive disorder (OCD), indexed by enhanced amplitudes of the error-related negativity (ERN) in the event-related potential (ERP). This hyperactivity was found to be temporally stable, independent of symptom remission, and could not be further increased by punishing committed errors. The current study examined whether the ERN in OCD is generally insensitive to modulatory influences or can be decreased by manipulation of task demands. Twenty-two OCD patients and 22 control participants performed a flanker task alone or with a concurrent n-back task to manipulate attentional resource allocation. Response-related ERP data were examined. OCD patients showed enhanced ERN-amplitudes in the standard flanker (ηp2 = .13). In both groups a significant decrease in ERN was found under dual-task conditions (ηp2 = .72) that was larger in the OCD group (ηp2 = .14), resulting in a nonsignificant ERN group difference in dual-task conditions. The current study replicated enhanced performance-monitoring in OCD as indexed by higher ERN-amplitudes. Importantly, it further showed a larger ERN-reduction with dual-task demands in patients compared to healthy participants. These results suggest that overactive performance-monitoring was normalized in patients with OCD by experimental conditions. Changing the attentional focus appears to be an effective strategy in modifying hyperactive error-signals in OCD and might be a target for innovative interventions.

Performance monitoring in obsessive–compulsive disorder: A temporo-spatial principal component analysis

Hyperactive performance monitoring is a robust finding in obsessive–compulsive disorder (OCD). Patients show increased amplitudes of the error-related negativity (ERN) and correct-related negativity (CRN). Recently, two temporo-spatial factors were shown to contribute to both ERPs in healthy individuals. In the present study, it was investigated whether the factor structure underlying ERN and CRN is similar in OCD and which factors differ between groups. A principal component analysis (PCA) was employed to investigate the temporo-spatial factor structure of ERN and CRN. Twenty-six OCD patients and 26 healthy controls conducted a flanker task. EEG data were analyzed as conventional ERP components and as factor scores derived from temporo-spatial PCA. ERP results showed expected increases in ERN and CRN amplitudes in OCD patients. For both groups, the PCA confirmed the assumed factor structure of a central and a fronto-parietal factor contributing to ERN and CRN. Factor scores of both factors were differently affected by response correctness in OCD. Alterations in factor scores indicate increased activity in both an outcome-independent monitoring process and an error-sensitive process, contributing to overactive performance monitoring in OCD.