Yanni Liu

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.

Loss feedback negativity elicited by single- versus conjoined-feature stimuli.

Event-related brain potential studies show that negative feedback in guessing tasks elicits a medial frontal negativity. Most theory and experimentation concerning this feedback-related negativity (FRN) has assumed that the FRN has little relationship to the perceptual characteristics of the feedback. This study challenges this assumption. We used a single visual feature or a conjunction of features to indicate reward feedback in a gambling task. In the single-feature condition, losses elicited a larger FRN than gains; in the conjoined-feature condition, that difference was not observed. The results are consistent with the proposal that the FRN is modulated by the deviation of feedback stimuli from a perceptual template. Future studies must not confound the perceptual properties and the valence of reward feedback.

Perceptual properties of feedback stimuli influence the feedback‐related negativity in the flanker gambling task

A negative deflection in the event-related potential is enhanced following error- and loss-related feedback in decision-making and simple gambling tasks. Researchers have assumed that the perceptual properties of the feedback stimuli are unimportant in explaining these effects. This assumption was tested in the present study through a flanker gambling task, in which the perceptual properties of the feedback were manipulated. Consistent with previous studies, loss elicited a larger feedback-related negativity (FRN) than gain feedback. However, this FRN reward effect was modulated by the perceptual properties of the feedback stimuli. When gain and loss feedback were perceptually similar to each other, the enhancement of the FRN following the loss feedback was smaller compared to when the gain and loss feedback were different from each other. In addition, incongruent feedback elicited a larger FRN than congruent feedback; this FRN congruency effect was larger following gain than loss feedback. These results suggested that perceptual properties of the feedback stimuli play a role in the elicitation of the FRN.

Altered Relationship Between Electrophysiological Response to Errors and Gray Matter Volumes in an Extended Network for Error-Processing in Pediatric Obsessive-Compulsive Disorder

Pediatric patients with obsessive‐compulsive disorder (OCD) show an increased electrophysiological response to errors that is thought to be localized to the posterior medial prefrontal cortex (pMFC). However, the relation of this response, the error‐related negativity (ERN), to underlying brain structures remains unknown. In an examination of 20 pediatric OCD patients and 20 healthy youth, we found that more negative ERN amplitude was correlated with lower gray matter (GM) density in pMFC and orbital frontal cortex. The association of the ERN with pMFC gray matter volume was driven by the patient group. In addition, a group difference in the association of ERN with gray matter in right insula was observed, showing an association of these measures in healthy youth (more negative ERN amplitude was associated with lower GM density in insula), but not in patients. These findings provide preliminary evidence linking gray matter volumes in an extended network for error processing to the ERN, and suggest that structural alterations in this network may underlie exaggeration of the ERN in pediatric OCD. Hum Brain Mapp 35:1143–1153, 2014.

Trial-by-trial adjustments of cognitive control following errors and response conflict are altered in pediatric obsessive compulsive disorder

Background: Impairments of cognitive control have been theorized to drive the repetitive thoughts and behaviors of obsessive compulsive disorder (OCD) from early in the course of illness. However, it remains unclear whether altered trial-by-trial adjustments of cognitive control characterize young patients. To test this hypothesis, we determined whether trial-by-trial adjustments of cognitive control are altered in children with OCD, relative to healthy controls. Methods: Forty-eight patients with pediatric OCD and 48 healthy youth performed the Multi-Source Interference Task. Two types of trial-by-trial adjustments of cognitive control were examined: post-error slowing (i.e., slower responses after errors than after correct trials) and post-conflict adaptation (i.e., faster responses in high-conflict incongruent trials that are preceded by other high-conflict incongruent trials, relative to low-conflict congruent trials). Results: While healthy youth exhibited both post-error slowing and post-conflict adaptation, patients with pediatric OCD failed to exhibit either of these effects. Further analyses revealed that patients with low symptom severity showed a reversal of the post-conflict adaptation effect, whereas patients with high symptom severity did not show any post-conflict adaptation. Conclusion: Two types of trial-by-trial adjustments of cognitive control are altered in pediatric OCD. These abnormalities may serve as early markers of the illness.

The typical development of posterior medial frontal cortex function and connectivity during task control demands in youth 8-19 years old

To characterize the development of neural substrate for interference processing and task control, this study examined both linear and non-linear effects of age on activation and connectivity during an interference task designed to engage the posterior medial frontal cortex (pMFC). Seventy-two youth, ages 8-19years, performed the Multi-Source Interference Task (MSIT) during functional magnetic resonance imaging (fMRI). With increasing age, overall performance across high-interference incongruent and low-interference congruent trials became faster and more accurate. Effects of age on activation to interference- (incongruent versus congruent conditions), error- (errors versus correct trials during the incongruent condition) and overall task-processing (incongruent plus congruent conditions, relative to implicit baseline) were tested in whole-brain voxel-wise analyses. Age differentially impacted activation to overall task processing in discrete sub-regions of the pMFC: activation in the pre-supplementary motor area (pre-SMA) decreased with age, whereas activation in the dorsal anterior cingulate cortex (dACC) followed a non-linear (i.e., U-shaped) pattern in relation to age. In addition, connectivity of pre-SMA with anterior insula/frontal operculum (AI/FO) increased with age. These findings suggest differential development of pre-SMA and dACC sub-regions within the pMFC. Moreover, as children age, decreases in pre-SMA activation may couple with increases in pre-SMA-AI/FO connectivity to support gains in processing speed in response to demands for task control.

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

OBJECTIVE The pathophysiology of obsessive-compulsive disorder (OCD) involves increased activity in corticostriatal circuits connecting the anterior cingulate cortex with other brain regions. The error-related negativity (ERN) is a negative deflection in the event-related potential after an incorrect response that is believed to reflect anterior cingulate cortex activity. This study examined the relation of the ERN to OCD symptom dimensions and other childhood symptom dimensions. METHOD The ERN, correct response negativity, and accuracy were measured during a flanker task to assess performance monitoring in 80 youth with a lifetime diagnosis of OCD and 80 matched healthy comparison participants ranging from 8 to 18 years old. The relation of the ERN to OCD symptom dimension scores and Child Behavior Checklist Syndrome Scale scores was examined in multiple linear regression analyses. RESULTS Accuracy was significantly decreased and ERN amplitude was significantly increased in patients compared with controls. ERN amplitude in patients was significantly correlated with accuracy, but not with OCD symptom dimensions, severity, comorbidity, or treatment. In a multiple linear regression analysis using age, accuracy, OCD, and Child Behavior Checklist Syndrome Scale scores as predictors of ERN amplitude, the ERN had significant associations only with Withdrawn/Depressed Scale scores and accuracy. CONCLUSION An enlarged ERN is a neural correlate of pediatric OCD that is independent of OCD symptom expression and severity. The finding of lower accuracy in pediatric cases requires replication. The relation between an enhanced ERN and withdrawn/depressed behaviors warrants further research in youth with OCD and other internalizing disorders.

Development of Posterior Medial Frontal Cortex Function in Pediatric Obsessive-Compulsive Disorder

OBJECTIVE Abnormal engagement of the posterior medial frontal cortex (pMFC) occurs during performance monitoring in obsessive-compulsive disorder (OCD), including in pediatric patients. Yet, the development of pMFC function in OCD-affected youth remains poorly understood. METHOD A total of 69 patients with pediatric OCD and 72 healthy controls (HC), 8 to 19 years of age, were scanned during the Multisource Interference Task (MSIT). The effects of group, age, performance, and interactions on pMFC response to errors and interference were tested in the region of interest [ROI]) and whole-brain analyses. Secondary analyses considered bilateral anterior insula/frontal operculum (aI/fO), given the contribution of these regions with pMFC to a cingulo-opercular network (CON) for task control (e.g., error and interference processing). RESULTS Error-related pMFC activity was greater for OCD patients than for HC, increased with age in OCD patients, but decreased with age in HC. Greater pMFC activation associated with better performance in HC but not OCD patients. In the patients, greater pMFC activation to errors was associated with lower OCD severity. Altered error-related activation and performance associations were also observed in the right aI/fO in OCD patients, whereas the left aI/fO response to interference was associated with lower OCD severity. CONCLUSION Atypical increase in error-related pMFC activation with age in pediatric OCD suggests altered development of pMFC function during the early course of illness. Greater pMFC activation with better performance in HC, and with age and lower symptom severity in OCD patients, suggests an adaptive function of heightened pMFC response to errors that could be further enhanced (e.g., via cognitive training) to improve outcomes in OCD from the early course of illness.

Error-related brain activity in adolescents with obsessive-compulsive disorder and major depressive disorder

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).

Developmental Neuroimaging in Pediatric Obsessive-Compulsive Disorder

Purpose of reviewThis review examines emerging neuroimaging research in pediatric obsessive-compulsive disorder (OCD) and explores the possibility that developmentally sensitive mechanisms may underlie OCD across the lifespan.Recent findingsDiffusion tensor imaging (DTI) studies of pediatric OCD reveal abnormal structural connectivity within fronto-striato-thalamic circuity (FSTC). Resting-state functional magnetic resonance imaging (fMRI) studies further support atypical FSTC connectivity in young patients, but they also suggest altered connectivity within cortical networks for task control. Task-based fMRI studies show that hyperactivation and hypoactivation of task-control networks may depend on task difficulty in pediatric patients similar to recent findings in adults.SummaryThis review suggests that atypical neurodevelopmental trajectories may underlie the emergence and early course of OCD. Abnormalities of structural and functional connectivity may vary with age, while functional engagement during task may vary with age and task complexity. Future research should combine DTI, resting-state fMRI, and task-based fMRI methods and incorporate longitudinal designs to reveal developmentally sensitive targets for intervention.