Error-related electrocortical responses are enhanced in children with obsessive-compulsive behaviors

The error-related negativity (ERN or Ne) and positivity (Pe) are event-related potential components elicited during simple discrimination tasks after an error response. The ERN and Pe have a fronto-central scalp distribution and may be an indirect measure of anterior cingulate (AC) activity as it relates to performance monitoring. Brain imaging studies suggest that obsessive-compulsive disorder (OCD) is associated with exaggerated activity of the AC while electrophysiological studies have found an association between OCD and pronounced ERNs in adults. The present study explored the relation between obsessive-compulsive behaviors, the ERN, and the Pe in a sample of nonclinical 10-year-old children. It was found that more parent-reported obsessive-compulsive behaviors were associated with larger ERN and Pe components in the children. Results suggest unique contributions of the ERN and Pe in predicting obsessive-compulsive behaviors.     

The erring brain: Error‐related negativity as an endophenotype for OCD—A review and meta‐analysis

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 20 years. 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.     

Anxiety and error-related brain activity

Error-related negativity (ERN/Ne) is a component of the event-related brain potential (ERP) associated with monitoring action and detecting errors. It is a sharp negative deflection that generally occurs from 50 to 150 ms following response execution and has been associated with anterior cingulate cortex (ACC) activity. An enhanced ERN has been observed in patients with obsessive-compulsive disorder (OCD)--reflecting abnormal ACC activity hypothesized as part of the pathophysiology of OCD. We recently reported that the ERN is also enhanced in a group of college students with OC characteristics. The present study extended these findings by measuring the ERN in college undergraduates who scored high on either the Penn State Worry Questionnaire (PSWQ) or a combined version of the Snake (SNAQ) and Spider (SPQ) Questionnaires. Results indicate that, like OC subjects, subjects who score high on a measure of general anxiety and worry have enhanced error-related brain activity relative to both phobic and non-anxious control subjects. The enhanced ERN was found to generalize beyond OCD within the anxiety spectrum disorders but also shows some specificity within these disorders.     

Performance monitoring among non-patients with obsessive-compulsive symptoms: ERP evidence of aberrant feedback monitoring

Electrophysiological studies have shown that obsessive-compulsive disorder (OCD) is associated with hyperactive performance monitoring, as indexed by the error-related negativity (ERN). The aim of the present study was to determine whether feedback monitoring is enhanced in addition to error monitoring among young adults with obsessive-compulsive symptomatology during performance of a learning task. The ERN was equivalent in amplitude for low and high OC groups. The feedback-related negativity (FRN) was more negative following presentation of incorrect feedback relative to correct feedback for the low OC group. For the high OC group, the FRN was equivalent in amplitude for correct and incorrect feedback. Young adults with high levels of obsessive-compulsive symptoms demonstrate aberrant feedback monitoring characterised by a lack of differentiation to the valence of feedback. This pattern of results may be indicative of a cognitive bias in outcome prediction associated with obsessive-compulsive symptomatology.     

Performance monitoring and error significance in patients with obsessive-compulsive disorder

Performance monitoring has been consistently found to be overactive in obsessive-compulsive disorder (OCD). The present study examines whether performance monitoring in OCD is adjusted with error significance. Therefore, errors in a flanker task were followed by neutral (standard condition) or punishment feedbacks (punishment condition). In the standard condition patients had significantly larger error-related negativity (ERN) and correct-related negativity (CRN) ampliudes than controls. But, in the punishment condition groups did not differ in ERN and CRN amplitudes. While healthy controls showed an amplitude enhancement between standard and punishment condition, OCD patients showed no variation. In contrast, group differences were not found for the error positivity (Pe): both groups had larger Pe amplitudes in the punishment condition. Results confirm earlier findings of overactive error monitoring in OCD. The absence of a variation with error significance might indicate that OCD patients are unable to down-regulate their monitoring activity according to external requirements.     

Association between symptom severity and internal capsule volume in obsessive-compulsive disorder

Neurobiological models support an involvement of white matter tracts in the pathophysiology of obsessive-compulsive disorder (OCD), but there has been little systematic evaluation of white matter volumes in OCD using magnetic resonance imaging (MRI). We investigated potential differences in the volume of the cingulum bundle (CB) and anterior limb of internal capsule (ALIC) in OCD patients (n = 19) relative to asymptomatic control subjects (n = 15). White matter volumes were assessed using a 1.5T MRI scanner. Between-group comparisons were carried out after spatial normalization and image segmentation using optimized voxel-based morphometry. Correlations between regional white matter volumes in OCD subjects and symptom severity ratings were also investigated. We found significant global white matter reductions in OCD patients compared to control subjects. The voxel-based search for regional abnormalities (with covariance for total white matter volumes) showed no specific white matter volume deficits in brain portions predicted a priori to be affected in OCD (CB and ALIC). However, large clusters of significant positive correlation with OCD severity scores were found bilaterally on the ALIC. These findings provide evidence of OCD-related ALIC abnormalities and suggest a connectivity dysfunction within frontal-striatal-thalamic-cortical circuits. Further studies are warranted to better define the role of such white matter alterations in the pathophysiology of OCD, and may provide clues for a more effectively targeting of neurosurgical treatments for OCD.     

Factor analysis of obsessive-compulsive disorder YBOCS-SC symptoms and association with 5-HTTLPR SERT polymorphism.

Symptoms defining obsessive-compulsive disorder (OCD) are diverse. Factor analyses of OCD symptoms have been used to evaluate obsessive-compulsive phenotypes that are thought to be more homogenous than the macro phenotype. There is evidence that three factors (symmetry/ordering, obsessions/checking, and hoarding) are familial and preliminary evidence that repetitive rituals are associated with a functional polymorphism in the promotor region of the serotonin transporter gene (5-HTTLPR). The goal of this study was to examine relationships between OCD symptom dimensions and 5-HTTLPR. We genotyped 153 subjects who met DSM-IV criteria for OCD. We used the Yale-Brown obsessive-compulsive scale symptom checklist (YBOCS-SC) to assess OCD symptoms. Using principle components analysis, we derived four factors from the 13 symptom categories of the YBOCS-SC in this patient sample, which replicated previous factor analyses of this scale. The frequencies of the S allele and the SS genotype were associated with the second factor including obsessions regarding symmetry and compulsions involving repeating, counting, and ordering/arranging. This study may contribute to understanding of molecular genetic features underlying the appearance of symptom clusters in OCD.     

Heritability and clinical features of multigenerational families with obsessive-compulsive disorder and hoarding.

To date, only one complete genome screen for obsessive-compulsive disorder (OCD) has been published. That study identified a region of suggestive linkage (maximum lod score of 2.25) with a relatively small sample size (N = 56; 27 with OCD). Additional complete genome screens are needed to confirm this finding and identify other regions of linkage. We present the clinical characteristics and power to detect linkage of 11 multigenerational families with OCD and hoarding (N = 92; 44 with OCD), as well as heritability estimates for several quantitative traits. Families with at least two individuals with OCD were identified through probands with childhood-onset OCD. Expected lod scores were calculated for simulated genetic marker data under an additive and two dominant models assuming a dense SNP marker map. All affected individuals had an early age of onset (18 or younger). Hoarding was present in 46% of subjects. Obsessive-compulsive symptoms and hoarding were highly heritable. The maximum mean expected lod score was 3.31 for OCD and 1.39 for hoarding. We found reasonable power to detect regions of interest (lod = 2) for OCD in these families, but will need to expand our family collection to have adequate power to detect regions of interest for hoarding.     

The anterior cingulate as a conflict monitor: fMRI and ERP studies

We propose that the anterior cingulate cortex (ACC) contributes to cognition by detecting the presence of conflict during information processing, and to alert systems involved in top-down control to resolve this conflict. Here, we review several functional magnetic resonance imaging (fMRI) and event-related potential (ERP) studies that have used simple response interference tasks, and propose that ACC activity is activated prior to the response during correct conflict trials and reflected in the frontocentral N2, and immediately following error trials and reflected in the error-related negativity (ERN). Furthermore, we suggest that certain disturbances in cognition and behavior in common mental disorders such as schizophrenia and obsessive-compulsive disorder (OCD) can be understood as resulting from alteration in performance monitoring functions associated with this region of the brain.     

Reliability of the ERN across multiple tasks as a function of increasing errors

Event‐related potential (ERP) studies of error‐processing have characterized the error‐related negativity (ERN) as a negative deflection occurring after the commission of an error at frontocentral sites. The ERN has frequently been examined in the context of individual differences and has been proposed as a neurobehavioral risk marker. Given this, it is important to characterize the psychometric properties of the ERN across multiple tasks as a function of increasing trial numbers in order to establish task‐specific psychometric properties for efficient assessments in clinical or applied settings. The current study examines the internal reliability of the ERN across the flankers, Stroop, and go/no‐go tasks as a function of error number. Results suggest that although the tasks all elicit the ERN reliably, important psychometric differences emerged indicating that the flankers task might be prioritized when assessing the ERN.     

Error-Related Electrocortical Responses Are Enhanced in Children With Obsessive–Compulsive Behaviors

The error-related negativity (ERN or Ne) and positivity (Pe) are event-related potential components elicited during simple discrimination tasks after an error response. The ERN and Pe have a fronto-central scalp distribution and may be an indirect measure of anterior cingulate (AC) activity as it relates to performance monitoring. Brain imaging studies suggest that obsessive–compulsive disorder (OCD) is associated with exaggerated activity of the AC while electrophysiological studies have found an association between OCD and pronounced ERNs in adults. The present study explored the relation between obsessive–compulsive behaviors, the ERN, and the Pe in a sample of nonclinical 10-year-old children. It was found that more parent-reported obsessive–compulsive behaviors were associated with larger ERN and Pe components in the children. Results suggest unique contributions of the ERN and Pe in predicting obsessive–compulsive behaviors.     

Symptom presentation and outcome of cognitive-behavioral therapy for obsessive-compulsive disorder

Previous researchers have classified obsessive-compulsive disorder (OCD) patients by the themes of their obsessions and compulsions (e.g., washing, checking); however, mental compulsions have not been adequately assessed in these studies. The authors conducted 2 studies using a large sample of OCD patients (N=132). In the 1st study, they categorized patients on the basis of symptom presentation, giving adequate consideration to mental compulsions. Five patient clusters were identified: harming, contamination, hoarding, unacceptable thoughts, and symmetry. Mental compulsions were most prevalent among patients with intrusive, upsetting religious, violent, or sexual thoughts. In the 2nd study, they compared response to cognitive-behavioral therapy across symptom categories, finding poorer outcomes among patients with hoarding symptoms compared with those with other symptom themes.     

Chronic medication does not affect hyperactive error responses in obsessive‐compulsive disorder

Patients with obsessive‐compulsive disorder (OCD) show an increased error‐related negativity (ERN), yet previous studies have not controlled for medication use, which may be important given evidence linking performance monitoring to neurotransmitter systems targeted by treatment, such as serotonin. In an examination of 19 unmedicated OCD patients, 19 medicated OCD patients, 19 medicated patient controls without OCD, and 21 unmedicated healthy controls, we found greater ERNs in OCD patients than in controls, irrespective of medication use. Severity of generalized anxiety and depression was associated with ERN amplitude in controls but not patients. These data confirm previous findings of an exaggerated error response in OCD, further showing that it cannot be attributed to medication. The absence in patients of a relationship between ERN amplitude and anxiety/depression, as was found in controls, suggests that elevated error signals in OCD may be disorder‐specific.     

Saccadic abnormalities in psychotropic-naive obsessive-compulsive disorder without co-morbidity

BACKGROUND: Oculomotor studies have found saccadic abnormalities in obsessive-compulsive disorder (OCD), lending support for models postulating a central role for inhibition in OCD. Saccadic abnormalities in OCD may also be potential candidates for a biological marker, important for more endophenotype-oriented research. Saccadic abnormalities have not been examined in psychotropic-naive patients with OCD without co-morbidity. METHOD: We compared the error rates and latencies of 14 carefully selected adult psychotropic-naive patients with OCD with no co-morbid diagnosis and 14 pairwise matched healthy controls on a fixation task, on a prosaccade task and on an antisaccade task. RESULTS: Patients with OCD showed normal error rates on all tasks, but latencies on the antisaccade task were significantly increased. CONCLUSIONS: Our results indicate that patients with OCD have no gross impairment of oculomotor inhibitory capacities, but may have a disturbed capacity to deliberately initiate a saccade to an imagined target.     

Pharmacotherapy of compulsive hoarding

Compulsive hoarding is a common and potentially disabling disorder. This article reviews studies of the effects of hoarding on response to serotonin reuptake inhibitor (SRI) medications in patients with obsessive-compulsive disorder (OCD), as well as recent studies of pharmacotherapy specifically for patients with the compulsive hoarding syndrome. Taken together, the results of these studies indicate that the "conventional wisdom" that compulsive hoarding does not respond well to SRI treatment is wrong. SRIs appear to be as effective for compulsive hoarders as for nonhoarding OCD patients. A case is presented of a compulsive hoarding patient who responded well to pharmacotherapy with a novel agent. Symptom improvement from pharmacotherapy of compulsive hoarding appears to be at least as great as that resulting from cognitive-behavioral therapy (CBT). However, the combination of pharmacotherapy and CBT for compulsive hoarding is likely more effective than either treatment alone.     

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.     

Symptom Dimensions in OCD: Item-Level Factor Analysis and Heritability Estimates

To reduce the phenotypic heterogeneity of obsessive-compulsive disorder (OCD) for genetic, clinical and translational studies, numerous factor analyses of the Yale-Brown Obsessive Compulsive Scale checklist (YBOCS-CL) have been conducted. Results of these analyses have been inconsistent, likely as a consequence of small sample sizes and variable methodologies. Furthermore, data concerning the heritability of the factors are limited. Item and category-level factor analyses of YBOCS-CL items from 1224 OCD subjects were followed by heritability analyses in 52 OCD-affected multigenerational families. Item-level analyses indicated that a five factor model: (1) taboo, (2) contamination/cleaning, (3) doubts, (4) superstitions/rituals, and (5) symmetry/hoarding provided the best fit, followed by a one-factor solution. All 5 factors as well as the one-factor solution were found to be heritable. Bivariate analyses indicated that the taboo and doubts factor, and the contamination and symmetry/hoarding factor share genetic influences. Contamination and symmetry/hoarding show shared genetic variance with symptom severity. Nearly all factors showed shared environmental variance with each other and with symptom severity. These results support the utility of both OCD diagnosis and symptom dimensions in genetic research and clinical contexts. Both shared and unique genetic influences underlie susceptibility to OCD and its symptom dimensions.     

Associations of neural error-processing with symptoms and traits in a dimensional sample recruited across the obsessive–compulsive spectrum

The error-related negativity (ERN), a neural response to errors, has been associated with several forms of psychopathology and assumed to represent a neural risk marker for obsessive–compulsive disorder (OCD) and anxiety disorders. Yet, it is still unknown which specific symptoms or traits best explain ERN variation. This study investigated performance-monitoring in participants (N = 100) recruited across a spectrum of obsessive–compulsive characteristics (n = 26 patients with OCD; n = 74 healthy participants including n = 24 with low, n = 24 with medium, and n = 26 with high OC-characteristics). Several compulsivity- and anxiety-associated characteristics were assessed and submitted to exploratory principal axis factor analysis. Associations of raw measures and derived factors with ERN and correct-related negativity (CRN) were examined. Patients with OCD showed increased ERN amplitudes compared to healthy participants. The ERN was associated with a variety of traits related to anxiety and negative affect. Factor analysis results revealed a most prominent association of the ERN with a composite measure of anxiety and neuroticism, whereas the CRN was specifically associated with compulsivity. Results support differential associations for the ERN and CRN and demonstrate that a dimensional recruitment approach and use of composite measures can improve our understanding of characteristics underlying variation in neural performance monitoring.     

Neuropsychological and neural correlates of hoarding: a practice-friendly review

Hoarding can be a symptom of multiple neurological and psychiatric disorders, including obsessive-compulsive disorder (OCD). Recent evidence suggests that, in many cases, hoarding can also be a standalone problem that presents independently from other conditions; this has led to the proposal of a new diagnostic entity named hoarding disorder. This article reviews the neuropsychological and neuroimaging research on pathological hoarding. Most research in humans has been conducted in the context of individuals with brain damage, dementia, or OCD. Studies of well-characterized samples of individuals with hoarding disorder are extremely rare. Although not possible to establish firm conclusions at this stage, we conclude with a series of observations and recommendations for clinical practice.     

Psychometric properties of the error‐related negativity in children and adolescents

Error processing is frequently examined using the error‐related negativity (ERN), a negative‐going event‐related potential occurring after the commission of an error at frontal‐central sites, and has been suggested as a neural biomarker that may be useful in characterizing trajectories of risk for anxiety. While the ERN has been shown to have excellent psychometric properties in adults, few studies have examined psychometric properties of the ERN in children and adolescents. The current study examined the 2‐year test‐retest reliability of the ERN in a sample of children and adolescents, and the convergent validity of the ERN using a flanker and go/no‐go task. Results suggest that the ERN is both reliable and stable across 2 years and across tasks. However, results also indicate that the internal consistency obtained using the flanker task is greater than the internal consistency obtained using the go/no‐go task.