Probing midbrain dopamine function in pediatric obsessive-compulsive disorder via neuromelanin-sensitive magnetic resonance imaging.

Obsessive-compulsive disorder (OCD) is an impairing psychiatric condition, which often onsets in childhood. Growing research highlights dopaminergic alterations in adult OCD, yet pediatric studies are limited by methodological constraints. This is the first study to utilize neuromelanin-sensitive MRI as a proxy for dopaminergic function among children with OCD. N = 135 youth (6-14-year-olds) completed high-resolution neuromelanin-sensitive MRI across two sites; n = 64 had an OCD diagnosis. N = 47 children with OCD completed a second scan after cognitive-behavioral therapy. Voxel-wise analyses identified that neuromelanin-MRI signal was higher among children with OCD compared to those without (483 voxels, permutation-corrected p = 0.018). Effects were significant within both the substania nigra pars compacta (p = 0.004, Cohen's d = 0.51) and ventral tegmental area (p = 0.006, d = 0.50). Follow-up analyses indicated that more severe lifetime symptoms (t = -2.72, p = 0.009) and longer illness duration (t = -2.22, p = 0.03) related to lower neuromelanin-MRI signal. Despite significant symptom reduction with therapy (p < 0.001, d = 1.44), neither baseline nor change in neuromelanin-MRI signal associated with symptom improvement. Current results provide the first demonstration of the utility of neuromelanin-MRI in pediatric psychiatry, specifically highlighting in vivo evidence for midbrain dopamine alterations in treatment-seeking youth with OCD. Neuromelanin-MRI likely indexes accumulating alterations over time, herein, implicating dopamine hyperactivity in OCD. Given evidence of increased neuromelanin signal in pediatric OCD but negative association with symptom severity, additional work is needed to parse potential longitudinal or compensatory mechanisms. Future studies should explore the utility of neuromelanin-MRI biomarkers to identify early risk prior to onset, parse OCD subtypes or symptom heterogeneity, and explore prediction of pharmacotherapy response.

Obsessive-Compulsive Symptoms: Baseline Prevalence, Comorbidity, and Implications in a Clinically Anxious Pediatric Sample.

Subclinical symptoms of obsessive-compulsive disorder (i.e., obsessive compulsive symptoms, or "OCS") cause functional impairment, including for youth without full-syndrome OCD. Further, despite high rates of OCS in youth with anxiety disorders, knowledge of OCS in the context of specific anxiety disorders is limited. The present study seeks to: (1) compare OCS in pediatric patients with anxiety disorders and healthy youth, (2) determine which categorical anxiety disorder(s) associate most with OCS, and (3) determine relationships between OCS with anxiety severity and impairment. Data on OCS, anxiety, and functional impairment were collected from 153 youth with anxiety disorders and 45 healthy controls, ages 7-17 years (M = 11.84, SD = 3.17). Findings indicated that patients had significantly more OCS than healthy controls. Among patients, GAD was a significant predictor of OCS as well as OCD risk. These results suggest that OCS should be a primary diagnostic and treatment consideration for youth who present in clinical settings with GAD.

Disorder-specific cingulo-opercular network hyperconnectivity in pediatric OCD relative to pediatric anxiety.

BACKGROUND: Prior investigation of adult patients with obsessive compulsive disorder (OCD) has found greater functional connectivity within orbitofrontal-striatal-thalamic (OST) circuitry, as well as altered connectivity within and between large-scale brain networks such as the cingulo-opercular network (CON) and default mode network (DMN), relative to controls. However, as adult OCD patients often have high rates of co-morbid anxiety and long durations of illness, little is known about the functional connectivity of these networks in relation to OCD specifically, or in young patients near illness onset. METHODS: In this study, unmedicated female patients with OCD (ages 8-21 years, n = 23) were compared to age-matched female patients with anxiety disorders (n = 26), and healthy female youth (n = 44). Resting-state functional connectivity was used to determine the strength of functional connectivity within and between OST, CON, and DMN. RESULTS: Functional connectivity within the CON was significantly greater in the OCD group as compared to the anxiety and healthy control groups. Additionally, the OCD group displayed greater functional connectivity between OST and CON compared to the other two groups, which did not differ significantly from each other. CONCLUSIONS: Our findings indicate that previously noted network connectivity differences in pediatric patients with OCD were likely not attributable to co-morbid anxiety disorders. Moreover, these results suggest that specific patterns of hyperconnectivity within CON and between CON and OST circuitry may characterize OCD relative to non-OCD anxiety disorders in youth. This study improves understanding of network dysfunction underlying pediatric OCD as compared to pediatric anxiety.

Real-Time fMRI Functional Connectivity Neurofeedback Reducing Repetitive Negative Thinking in Depression: A Double-Blind, Randomized, Sham-Controlled Proof-of-Concept Trial.

INTRODUCTION: Repetitive negative thinking (RNT) is a cognitive process focusing on self-relevant and negative experiences, leading to a poor prognosis of major depressive disorder (MDD). We previously identified that connectivity between the precuneus/posterior cingulate cortex (PCC) and right temporoparietal junction (rTPJ) was positively correlated with levels of RNT. OBJECTIVE: In this double-blind, randomized, sham-controlled, proof-of-concept trial, we employed real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) to delineate the neural processes that may be causally linked to RNT and could potentially become treatment targets for MDD. METHODS: MDD-affected individuals were assigned to either active (n = 20) or sham feedback group (n = 19). RNT was measured by the Ruminative Response Scale-brooding subscale (RRS-B) before and 1 week after the intervention. RESULTS: Individuals in the active but not in the sham group showed a significant reduction in the RRS-B; however, a greater reduction in the PCC-rTPJ connectivity was unrelated to a greater reduction in the RRS-B. Exploratory analyses revealed that a greater reduction in the retrosplenial cortex (RSC)-rTPJ connectivity yielded a more pronounced reduction in the RRS-B in the active but not in the sham group. CONCLUSIONS: RtfMRI-nf was effective in reducing RNT. Considering the underlying mechanism of rtfMIR-nf, the RSC and rTPJ could be part of a network (i.e., default mode network) that might collectively affect the intensity of RNT. Understanding the relationship between the functional organization of targeted neural changes and clinical metrics, such as RNT, has the potential to guide the development of mechanism-based treatment of MDD.

Self-regulation and Psychopathology in Young Children.

The current study examined concurrent relationships between children's self-regulation, measured behaviorally and by parent-report, and children's internalizing and externalizing symptoms. The aim was to distinguish which components of self-regulation (attention vs. inhibitory control, "hot" vs. "cool" regulation) best predict dimensional symptomatology and clinical disorders in young children. The participants were 120 children, ages 4-8 years old. Results showed that greater parent-reported attention was associated with fewer internalizing and externalizing symptoms. Behaviorally-measured hot inhibitory control related to fewer internalizing symptoms, whereas parent-reported inhibitory control related to fewer externalizing symptoms. Similar patterns emerged for clinical diagnoses, with parent-rated attention most strongly predicting disorders across domains. Results support prior evidence implicating self-regulatory deficits in externalizing problems, while also demonstrating that components of self-regulation are impaired with internalizing symptoms. Further, different sub-components of self-regulation relate to different dimensions of psychopathology in children. Interventions should target these areas in children at-risk for disorders.

Post-error slowing in anxiety and obsessive-compulsive disorders.

Altered brain response to errors in anxiety and obsessive-compulsive disorders (OCD) suggests cognitive control abnormalities across both types of illness, but behavioral metrics of cognitive control function have yet to be compared in patients selected from these different diagnostic categories. Thus, we examined post-error slowing (PES), a behavioral adjustment that typically occurs after a mistake, in children and adolescents with and without a primary anxiety disorder (N = 103 anxiety and N = 28 healthy controls) and adolescents and adults with and without OCD (N = 118 OCD and N = 60 healthy controls) using a go/no-go task. Primary analyses tested for differences in PES between diagnostic groups (anxiety, OCD, healthy), controlling for age, overall reaction time, and overall accuracy. Results indicated that patients with anxiety disorders exhibited more post-error slowing than both patients with OCD and healthy volunteers. In contrast, participants with OCD did not differ from healthy volunteers in post-error slowing. In subgroup analyses restricted to adolescent participants (ages 13-17 years), more post-error slowing was observed in the anxiety disorders group compared with either the OCD or healthy groups. These data suggest that excessive post-error slowing, an index of behavioral adjustment following errors, may uniquely characterize patients with anxiety disorders relative to healthy individuals and those with OCD.

Depression in Female Adolescents with Heavy Menstrual Bleeding.

OBJECTIVE: To assess the degree to which heavy menstrual bleeding is associated with depression, independent of hormonal contraception. STUDY DESIGN: We performed a retrospective cohort study of 1168 female adolescents 9-18 years old presenting to general pediatricians for heavy menstrual bleeding or well visits. Depression was the primary outcome and defined as a diagnosis in the health record. Univariable and multivariable regression models were fit to the data to identify factors associated with depression diagnosis. RESULTS: In total, 581 adolescents with heavy menstrual bleeding and 587 without heavy menstrual bleeding were included. Depression diagnoses occurred with greater frequency in youth with heavy menstrual bleeding compared with those without heavy menstrual bleeding (50.9% vs 24.2% P < .001; risk ratio 1.67, 95% CI 1.39-2.01) but did not significantly differ between those taking vs not taking hormonal contraception (risk ratio 0.99; 95% CI 0.84-1.17). Most patients with depression and heavy menstrual bleeding developed depression following or concurrent with heavy menstrual bleeding (261/296, 88%). Of these, 199 of 261 (76%) were treated with hormonal contraception, but the majority (168/199; 84%) were diagnosed with depression before initiation. CONCLUSIONS: Heavy menstrual bleeding is associated with depression diagnosis in female adolescents. The use of hormonal contraception was not associated with depression diagnosis in multivariable analysis, covarying heavy menstrual bleeding, age, body mass index, anxiety, sexual activity, and substance use. As hormonal contraception is often used to treat heavy menstrual bleeding, heavy menstrual bleeding may be partially driving previous reports of increased depression risk in those taking hormonal contraception.

Targeting cognitive control to reduce anxiety in very young children: A proof of concept study.

OBJECTIVE: Underdeveloped cognitive control (CC)-the capacity to flexibly adjust to changing environments-may predispose some children to early onset anxiety disorders and represents a promising intervention target. The current study established and pilot-tested "Camp Kidpower"-a novel group-based, interactive CC training intervention-and assessed its impacts on behavioral and neurophysiological indices of CC among preschool children with elevated anxiety symptoms. METHODS: Forty-four anxious children (4-6 years) were enrolled in Camp Kidpower, delivered in four sessions over 10 days. Before and after camp, children's capacity for CC was measured using well-validated, non-trained behavioral tasks and error-related negativity (ERN). Child anxiety symptoms were measured by parent report on the Spence Preschool Anxiety Scale. RESULTS: Thirty-two children completed the study, as defined by completion of pre- and follow-up assessments and at least three camp sessions. From baseline to after camp, performance on behavioral tests of CC improved, ERN amplitude increased, and anxiety symptoms decreased. CONCLUSION: Results provide initial evidence that play-based cognitive training targeted to behavioral and brain markers of CC reduces anxiety in preschoolers.

Exposure-Focused CBT Outperforms Relaxation-Based Control in an RCT of Treatment for Child and Adolescent Anxiety.

OBJECTIVE: The relative contribution of individual cognitive behavioral therapy (CBT) components to treatment outcomes for child anxiety disorders (CADs) is unclear. Recent meta-analyses suggest that exposure may be the primary active ingredient in CBT for CADs, and that relaxation may be relatively less effective. This brief report tests the hypothesis that exposure-focused CBT (EF-CBT) would outperform a relaxation-based active therapy control (Relaxation Mentorship Training; RMT) for the treatment of CADs. METHOD: Participants were 102 youth with CADs (mean age = 11.91, 26 males; 76.4% White, 14.7% Multiracial, 3.9% Black, 3.9% Asian, 0.9% other/do not wish to identify) as part of an ongoing neuroimaging randomized controlled trial. Participants were randomly assigned (ratio 2:1) to receive 12 sessions of EF-CBT (n = 70) or RMT (n = 32). Clinical improvement was measured at Week 12 (Clinical Global Impression - Improvement scale; CGI-I); treatment response was defined as receiving a rating of "very much" or "much improved" on the CGI-I. Anxiety severity was measured at Weeks 1, 6, 9, 12 (Pediatric Anxiety Rating Scale; PARS). Outcome measures were completed by an independent evaluator unaware of condition. RESULTS: EF-CBT exhibited 2.98 times higher odds of treatment completion than RMT; 13 treatment non-completers were included in analyses. Estimated treatment response rates were higher for EF-CBT (57.3%) than for RMT (19.2%). Longitudinal analyses indicated that EF-CBT was associated with faster and more pronounced anxiety reductions than RMT on the PARS (Hedges' g = .77). CONCLUSIONS: Results suggest that EF-CBT without relaxation is effective for CADs, and more effective than a relaxation-based intervention.

The moderating role of externalizing problems on the association between anxiety and the error-related negativity in youth.

The error-related negativity (ERN) is an event-related potential that reflects error monitoring. Enhanced ERN indicates sensitivity to performance errors and is a correlate of anxiety disorders. In contrast, youth with externalizing problems exhibit a reduced ERN, suggesting decreased error monitoring. Anxiety and externalizing problems commonly co-occur in youth, but no studies have tested how comorbidity might modulate the ERN. In a sample of youth (N = 46, ages 7-19) with and without anxiety disorders, this preliminary study examined the interactive effect of anxiety and externalizing problems on ERN. Results suggest that externalizing problems moderate the relation between anxiety symptoms and ERN in youth. Anxious youth with less externalizing problems exhibited enhanced ERN response to errors. Conversely, anxious youth with greater externalizing problems demonstrated diminished ERN in response to errors. The regions of significance and proportion affected tests indicated that the moderating the effect of externalizing problems was only significant for youth with anxiety disorders. Findings suggest that enhanced neural error sensitivity could be a specific neurophysiological marker for anxiety disorders, whereas anxious individuals with comorbid externalizing problems demonstrate reduced error monitoring, similar to those with primary externalizing pathology. Results underscore the utility of examining neural correlates of pediatric anxiety comorbidity subtypes.

Conducting EEG research in clinically anxious preschoolers: A pilot study and preliminary recommendations.

Electroencephalography (EEG) data collection can be challenging in preschoolers with anxiety who are often debilitated by fear of the unknown. Thus, we iteratively refined techniques for EEG collection in three cohorts of children with anxiety enrolled in our study of a novel intervention. Techniques involved directing child attention away from the EEG setup (Cohort 1, N = 18), open discussion of equipment and processes during setup (Cohort 2, N = 21), and a preparatory EEG-exposure session prior to data collection (Cohort 3, N = 6). Children (N = 45, 4-7 years) attempted a Time 1 EEG before intervention, and those who completed intervention (N = 28) were invited to a Time 2 EEG. The percentages who provided analyzable EEGs were assessed by cohort. Cohort 3 provided more Time 1 EEGs (83.3%) than Cohorts 1 or 2 (66.7% each), suggesting that the preparatory session supported first-time EEG collection. More children provided Time 2 EEG data across successive cohorts (Cohort 1: 66.7%, Cohort 2: 82%, Cohort 3: 100%), suggesting that more open communication facilitated repeat EEG collection. Ultimately, increased EEG exposure and child-friendly communication about procedures improved data acquisition in this sample of clinically anxious preschoolers. Detailed study procedures are shared to support future EEG research in young children with anxiety.

Startle to neutral, not negative stimuli: A neurophysiological correlate of behavioral inhibition in young children.

A putative biomarker of anxiety risk, the startle response is typically enhanced by negative compared to neutral emotion modulation in adults, but remains understudied in children. To determine the extent to which neutral, negative, and positively valenced emotional conditions modulate startle response in early life, a child-friendly film paradigm was used to vary emotion across these conditions during startle induction in sixty-four 4- to 7-year-old children. Association of emotion-modulated startle with parent-reported anxiety symptom severity and child behavioral inhibition, a risk factor for anxiety problems, were assessed. Analyses revealed no difference in startle magnitude during negative compared to neutral film clips. By contrast, startle during both negative and neutral conditions was greater than startle during the positive condition. Larger startle magnitude during the neutral condition associated with higher levels of child behavioral inhibition (BI). These results are consistent with possible immaturity of startle response in young children, and suggest that startle amplitude in more emotionally ambiguous, neutral conditions could serve as an early biomarker for anxiety risk.

Impact of pubertal timing and depression on error-related brain activity in anxious youth.

Anxiety disorders are associated with enhanced error-related negativity (ERN) across development but it remains unclear whether alterations in brain electrophysiology are linked to the timing of puberty. Pubertal timing and alterations of prefrontal and limbic development are implicated in risk for depression, but the interplay of these factors on the ERN-anxiety association has not been assessed. We examined the unique and interactive effects of pubertal timing and depression on the ERN in a sample of youth 10-19 years old with anxiety disorders (n = 30) or no history of psychopathology (n = 30). Earlier pubertal maturation was associated with an enhanced ERN. Among early, but not late maturing youth, higher depressive symptoms were associated with a reduced ERN. The magnitude of neural reactivity to errors is sensitive to anxiety, depression, and development. Early physical maturation and anxiety may heighten neural sensitivity to errors yet predict opposing effects in the context of depression.

Neural correlates of explicit and implicit emotion processing in relation to treatment response in pediatric anxiety.

BACKGROUND: Approximately 40%-45% of youth with anxiety disorders do not achieve remission (or a substantial reduction in symptoms) following treatment, highlighting the need to identify predictors of treatment response. Given the well-established link between attentional biases and anxiety disorders in youth and adults, this study examined the neural correlates of directing attention toward and away from emotional faces in relation to pediatric anxiety treatment response. METHOD: Prior to beginning treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline or cognitive behavior therapy (CBT), 37 youth (age 7-19 years) with generalized and/or social anxiety disorder completed a task with conditions that manipulated whether participants were instructed to match emotional faces (explicit emotion processing) or match shapes in the context of emotional face distractors (implicit emotion processing) during functional magnetic resonance imaging. RESULTS: Results revealed that reduced activation in superior frontal gyrus (SFG), encompassing the dorsal anterior cingulate cortex (ACC) and dorsomedial prefrontal cortex (PFC), during implicit processing of emotional faces predicted a greater reduction in anxiety severity pre-to-post treatment. Post hoc analyses indicated that effects were not significantly moderated by the type of treatment or anxiety type. CONCLUSIONS: Findings suggest that less recruitment of SFG, including the dorsal ACC and dorsomedial PFC, during implicit emotion processing predicts a greater reduction in youth anxiety symptoms pre-to-post treatment. Youth who exhibit reduced activation in these areas while matching shapes in the context of emotional face distractors may have more to gain from CBT and SSRI treatment due to preexisting deficits in attentional control. These findings suggest that neuroimaging may be a useful tool for predicting which youth are most likely to benefit from anxiety treatment.

Attenuated neural reactivity to happy faces is associated with rule breaking and social problems in anxious youth.

Pediatric anxiety is associated with comorbid externalizing behaviors and social problems, and these associations may be related to altered emotion processing. The late positive potential (LPP), an event-related potential component, is a neural marker of emotion processing, and there is evidence that anxious youth exhibits enhanced LPPs to threatening signals. It is unknown, however, if differences in the LPP are related to externalizing behaviors and social problems co-occurring with anxiety and if these associations are driven by altered processing of threatening (angry or fearful faces) or rewarding (happy faces) socio-emotional signals. Thus, in the present study, we examined, in a sample of 39 anxious youth, the association between LPPs, following socio-emotional signals and externalizing behaviors and social problems. Results indicated an association between attenuated LPPs in response to happy faces and greater rule-breaking and social problems. These findings suggest that differences in positive socio-emotional signal processing are related to heterogeneity in pediatric anxiety and that LPPs are a sensitive index of such heterogeneity.

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

Age-related changes in amygdala-frontal connectivity during emotional face processing from childhood into young adulthood.

The ability to process and respond to emotional facial expressions is a critical skill for healthy social and emotional development. There has been growing interest in understanding the neural circuitry underlying development of emotional processing, with previous research implicating functional connectivity between amygdala and frontal regions. However, existing work has focused on threatening emotional faces, raising questions regarding the extent to which these developmental patterns are specific to threat or to emotional face processing more broadly. In the current study, we examined age-related changes in brain activity and amygdala functional connectivity during an fMRI emotional face matching task (including angry, fearful, and happy faces) in 61 healthy subjects aged 7-25 years. We found age-related decreases in ventral medial prefrontal cortex activity in response to happy faces but not to angry or fearful faces, and an age-related change (shifting from positive to negative correlation) in amygdala-anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) functional connectivity to all emotional faces. Specifically, positive correlations between amygdala and ACC/mPFC in children changed to negative correlations in adults, which may suggest early emergence of bottom-up amygdala excitatory signaling to ACC/mPFC in children and later development of top-down inhibitory control of ACC/mPFC over amygdala in adults. Age-related changes in amygdala-ACC/mPFC connectivity did not vary for processing of different facial emotions, suggesting changes in amygdala-ACC/mPFC connectivity may underlie development of broad emotional processing, rather than threat-specific processing. Hum Brain Mapp 37:1684-1695, 2016. © 2016 Wiley Periodicals, Inc.

Age-related changes in emotional face processing across childhood and into young adulthood: Evidence from event-related potentials.

Socio-emotional processing is an essential part of development, and age-related changes in its neural correlates can be observed. The late positive potential (LPP) is a measure of motivated attention that can be used to assess emotional processing; however, changes in the LPP elicited by emotional faces have not been assessed across a wide age range in childhood and young adulthood. We used an emotional face matching task to examine behavior and event-related potentials (ERPs) in 33 youth aged 7-19 years old. Younger children were slower when performing the matching task. The LPP elicited by emotional faces but not control stimuli (geometric shapes) decreased with age; by contrast, an earlier ERP (the P1) decreased with age for both faces and shapes, suggesting increased efficiency of early visual processing. Results indicate age-related attenuation in emotional processing that may stem from greater efficiency and regulatory control when performing a socio-emotional task.

Error-processing abnormalities in pediatric anxiety and obsessive compulsive disorders.

Anxiety and obsessive compulsive disorders are among the earliest occurring psychopathology and may derive from atypical maturation of neural networks for error processing. Psychological models have alternately suggested that over-detection of errors, excessive caring about errors, or failure of errors to elicit regulatory control could associate with the expression of anxiety. In this review article, the potential relevance of error processing for anxiety and obsessive compulsive disorders is described in the context of neurophysiological and functional magnetic resonance imaging (fMRI) research demonstrating altered brain response to errors in pediatric and adult patients. Finally, hypotheses about developmentally sensitive mechanisms of anxiety and obsessive compulsive disorders are drawn from the extant literature, and avenues for clinical translation are discussed.

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.