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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cortical-subcortical hyperconnectivity related to affective-behavioral integration and cortical network hypoconnectivity related to cognitive control have been demonstrated in obsessive-compulsive disorder (OCD); the study objective was to examine whether these connectivity patterns predict treatment response. Adolescents (ages 12–17) and adults (ages 24–45) were randomly assigned to 12 sessions of exposure and response prevention (ERP) or stress management therapy (SMT), an active control. Before treatment, resting-state connectivity of ventromedial prefrontal cortical (vmPFC), cingulo-opercular, frontoparietal, and subcortical regions was assessed with functional MRI. OCD severity was assessed with the Yale-Brown Obsessive Compulsive Scale before, during, and after treatment. Usable fMRI and longitudinal symptom data were obtained from 116 patients (68 female; 54 adolescents; 60 medicated). ERP produced greater decreases in symptom scores than SMT. ERP was selectively associated with less vmPFC-subcortical (caudate and thalamus) connectivity in both age groups and primarily in unmedicated participants. Greater symptom improvement with both ERP and SMT was associated with greater cognitive-control (cingulo-opercular and frontoparietal) and subcortical (putamen) connectivity across age groups. Developmental specificity was observed across ERP and SMT treatments, such that greater improvements with ERP than SMT were associated with greater frontoparietal-subcortical (nucleus accumbens) connectivity in adolescents but greater connectivity between frontoparietal regions in adults. Comparison of response-predictive connections revealed no significant differences compared with a matched healthy control group. The results suggest that less vmPFC-subcortical connectivity related to affect-influenced behavior may be important for ERP engagement, whereas greater cognitive-control and motor circuit connectivity may generally facilitate response to psychotherapy. Finally, neural predictors of treatment response may differ by age. [ABSTRACT FROM AUTHOR]

Background: Schools increasingly provide mental health services to students, but often lack access to implementation strategies to support school-based (and school professional [SP]) delivery of evidence-based practices. Given substantial heterogeneity in implementation barriers across schools, development of adaptive implementation strategies that guide which implementation strategies to provide to which schools and when may be necessary to support scale-up. Methods: A clustered, sequential, multiple-assignment randomized trial (SMART) of high schools across Michigan was used to inform the development of a school-level adaptive implementation strategy for supporting SP-delivered cognitive behavioral therapy (CBT). All schools were first provided with implementation support informed by Replicating Effective Programs (REP) and then were randomized to add in-person Coaching or not (phase 1). After 8 weeks, schools were assessed for response based on SP-reported frequency of CBT delivered to students and/or barriers reported. Responder schools continued with phase 1 implementation strategies. Slower-responder schools (not providing ≥ 3 CBT components to ≥10 students or >2 organizational barriers identified) were re-randomized to add Facilitation to current support or not (phase 2). The primary aim hypothesis was that SPs at schools receiving the REP + Coaching + Facilitation adaptive implementation strategy would deliver more CBT sessions than SPs at schools receiving REP alone. Secondary aims compared four implementation strategies (Coaching vs no Coaching × Facilitation vs no Facilitation) on CBT sessions delivered, including by type (group, brief and full individual). Analyses used a marginal, weighted least squares approach developed for clustered SMARTs. Results: SPs (n = 169) at 94 high schools entered the study. N = 83 schools (88%) were slower-responders after phase 1. Contrary to the primary aim hypothesis, there was no evidence of a significant difference in CBT sessions delivered between REP + Coaching + Facilitation and REP alone (111.4 vs. 121.1 average total CBT sessions; p = 0.63). In secondary analyses, the adaptive strategy that offered REP + Facilitation resulted in the highest average CBT delivery (154.1 sessions) and the non-adaptive strategy offering REP + Coaching the lowest (94.5 sessions). Conclusions: The most effective strategy in terms of average SP-reported CBT delivery is the adaptive implementation strategy that (i) begins with REP, (ii) augments with Facilitation for slower-responder schools (schools where SPs identified organizational barriers or struggled to deliver CBT), and (iii) stays the course with REP for responder schools. Trial registration: ClinicalTrials.gov, NCT03541317, May 30, 2018. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Schools increasingly provide mental health services to students, but often lack access to implementation strategies to support school-based (and school professional [SP]) delivery of evidence-based practices. Given substantial heterogeneity in implementation barriers across schools, development of adaptive implementation strategies that guide which implementation strategies to provide to which schools and when may be necessary to support scale-up.Methods: A clustered, sequential, multiple-assignment randomized trial (SMART) of high schools across Michigan was used to inform the development of a school-level adaptive implementation strategy for supporting SP-delivered cognitive behavioral therapy (CBT). All schools were first provided with implementation support informed by Replicating Effective Programs (REP) and then were randomized to add in-person Coaching or not (phase 1). After 8 weeks, schools were assessed for response based on SP-reported frequency of CBT delivered to students and/or barriers reported. Responder schools continued with phase 1 implementation strategies. Slower-responder schools (not providing ≥ 3 CBT components to ≥10 students or >2 organizational barriers identified) were re-randomized to add Facilitation to current support or not (phase 2). The primary aim hypothesis was that SPs at schools receiving the REP + Coaching + Facilitation adaptive implementation strategy would deliver more CBT sessions than SPs at schools receiving REP alone. Secondary aims compared four implementation strategies (Coaching vs no Coaching × Facilitation vs no Facilitation) on CBT sessions delivered, including by type (group, brief and full individual). Analyses used a marginal, weighted least squares approach developed for clustered SMARTs.Results: SPs (n = 169) at 94 high schools entered the study. N = 83 schools (88%) were slower-responders after phase 1. Contrary to the primary aim hypothesis, there was no evidence of a significant difference in CBT sessions delivered between REP + Coaching + Facilitation and REP alone (111.4 vs. 121.1 average total CBT sessions; p = 0.63). In secondary analyses, the adaptive strategy that offered REP + Facilitation resulted in the highest average CBT delivery (154.1 sessions) and the non-adaptive strategy offering REP + Coaching the lowest (94.5 sessions).Conclusions: The most effective strategy in terms of average SP-reported CBT delivery is the adaptive implementation strategy that (i) begins with REP, (ii) augments with Facilitation for slower-responder schools (schools where SPs identified organizational barriers or struggled to deliver CBT), and (iii) stays the course with REP for responder schools.Trial Registration: ClinicalTrials.gov, NCT03541317 , May 30, 2018. [ABSTRACT FROM AUTHOR]

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. 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. 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). Results suggest that EF-CBT without relaxation is effective for CADs, and more effective than a relaxation-based intervention. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: The authors sought to examine whether brain activity is associated with treatment response to cognitive-behavioral therapy (CBT) in adolescents and adults with obsessive-compulsive disorder (OCD), and whether any associations are treatment specific relative to an active control psychotherapy (stress management therapy; SMT).Methods: Eighty-seven patients with OCD (age range 12-45 years; 57 female, 39 medicated) were randomly assigned to receive 12 weeks of CBT or SMT. Prior to treatment, functional MRI scans were conducted in patients performing an incentive flanker task, which probes brain activation to both cognitive control and reward processing. Voxelwise linear mixed-effects models examined whether baseline brain activation was differentially associated with change in scores on the Yale-Brown Obsessive Compulsive Scale (standard or Children's version) over the course of CBT or SMT treatment.Results: Within the CBT group, a better treatment response was significantly associated with greater pretreatment activation within the right temporal lobe and rostral anterior cingulate cortex during cognitive control and within the ventromedial prefrontal, orbitofrontal, lateral prefrontal, and amygdala regions during reward processing. In contrast, reduced pretreatment activation within a largely overlapping set of regions was significantly associated with a better treatment response to SMT.Conclusions: The study findings demonstrate that associations between brain activation and treatment response were treatment specific to CBT relative to a control psychotherapy and that these associations were stable from adolescence to mature adulthood. Such treatment-specific associations are important for the development of biomarkers to personalize treatment in OCD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Anxiety disorders are among the earliest emerging disorders and most common mental health problem across the lifespan. A common characteristic of individuals with anxiety is poor attentional and cognitive control. Therefore, researchers are interested in how cognitive functioning relates to anxiety in young children. In particular, research has demonstrated associations between anxiety and electrophysiological markers of cognitive control skills such as the error-related negativity (ERN). The nature of the anxiety-ERN relationship is not well understood, however. The purpose of the present study was to examine: 1) the association between the ERN and diagnostically-defined symptoms of different anxiety disorders; and 2) the extent to which disorder-specific symptoms of anxiety moderated the association between ERN and behavioral performance on a Go/No-Go task in a sample of 139 children 5-8 years of age (70 females and 69 males). Results suggest that more separation anxiety disorder (SAD) symptoms are associated with a smaller ΔERN, even after controlling for other anxiety disorder symptoms. Children with more SAD symptoms showed higher error rates and failed to exhibit the expected association between ΔERN and behavioral performance, suggesting ineffective error-monitoring in young children with SAD problems. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Although cognitive-behavioral psychotherapy (CBT) and pharmacotherapy are evidence-based treatments for pediatric anxiety, many youth with anxiety disorders fail to respond to these treatments. Given limitations of clinical measures in predicting treatment response, identifying neural predictors is timely. In this study, 35 anxious youth (ages 7-19 years) completed an emotional face-matching task during which the late positive potential (LPP), an event-related potential (ERP) component that indexes sustained attention towards emotional stimuli, was measured. Following the ERP measurement, youth received CBT or selective serotonin reuptake inhibitor (SSRI) treatment, and the LPP was examined as a predictor of treatment response. Findings indicated that, accounting for pre-treatment anxiety severity, neural reactivity to emotional faces predicted anxiety severity post- CBT and SSRI treatment such that enhanced electrocortical response to angry faces was associated with better treatment response. An enhanced LPP to angry faces may predict treatment response insofar as it may reflect greater emotion dysregulation or less avoidance and/or enhanced engagement with environmental stimuli in general, including with treatment. [ABSTRACT FROM AUTHOR]

The article presents a mega- and meta-analyses of data from obsessive-compulsive disorder (OCD). The meta-analysis showed that adult patients had larger pallidum volumes and smaller hippocampal volumes compared with adult controls. It revealed that the hippocampus and pallidum seem to be of significance in adult OCD, while the thalamus appears to be key in pediatric OCD.

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. [ABSTRACT FROM AUTHOR]

: 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. [ABSTRACT FROM AUTHOR]

Anxiety disorders are characterized by enhanced reactivity to threat, and event-related potentials (ERPs) are useful neural measures of the dynamics of threat processing. In particular, the late positive potential (LPP) is an ERP component that reflects sustained attention towards motivationally salient information. Previous studies in adults suggest that the LPP is enhanced to threatening stimuli in anxiety but blunted in depression; however, very little work has evaluated the LPP to threat in anxious youth. We measured the LPP during an emotional face-matching task in youth (age 7-19) with current anxiety disorders (n = 53) and healthy controls with no history of psychopathology (n = 37). We evaluated group differences, as well as the effect of depressive symptoms on the LPP. Youth with anxiety disorders exhibited enhanced LPPs to angry and fearful faces 1000-2000 ms after stimulus onset. Higher depressive symptoms were associated with reduced LPPs to angry faces across both groups. Enhanced LPPs to threatening faces were most apparent for social anxiety disorder, as opposed to generalized anxiety disorder or separation anxiety disorder. Results suggest the LPP may be a useful neural measure of threat reactivity in youth with anxiety disorders and highlight the importance of accounting for symptoms of both depression and anxiety when examining emotional processing. [ABSTRACT FROM AUTHOR]

Anxiety disorders are associated with abnormalities in amygdala function and prefrontal cortex–amygdala connectivity. The majority of functional magnetic resonance imaging studies have examined mean group differences in amygdala activation or connectivity in children and adolescents with anxiety disorders relative to controls, but emerging evidence suggests that abnormalities in amygdala function are dependent on the timing of the task and may vary across the course of a scanning session. The goal of the present study was to extend our knowledge of the dynamics of amygdala dysfunction by examining whether changes in amygdala activation and connectivity over scanning differ in pediatric anxiety disorder patients relative to typically developing controls during an emotion processing task. Examining changes in activation over time allows for a comparison of how brain function differs during initial exposure to novel stimuli versus more prolonged exposure. Participants included 34 anxiety disorder patients and 19 controls 7 to 19 years old. Participants performed an emotional face-matching task during functional magnetic resonance imaging scanning, and the task was divided into thirds in order to examine change in activation over time. Results demonstrated that patients exhibited an abnormal pattern of amygdala activation characterized by an initially heightened amygdala response relative to controls at the beginning of scanning, followed by significant decreases in activation over time. In addition, controls evidenced greater context-modulated prefrontal cortex–amygdala connectivity during the beginning of scanning relative to patients. These results indicate that differences in emotion processing between the groups vary from initial exposure to novel stimuli relative to more prolonged exposure. Implications are discussed regarding how this pattern of neural activation may relate to altered early-occurring or anticipatory emotion-regulation strategies and maladaptive later-occurring strategies in children and adolescents with anxiety disorders. [ABSTRACT FROM PUBLISHER]

Background Pediatric and adult anxiety disorder patients exhibit attention bias to threat and difficulty disengaging attention away from threat. Cognitive frameworks suggest that these patterns are associated with hyperactivation of regions associated with detecting threat, such as the amygdala, and hypoactivation of regions associated with regulating attention, including the lateral prefrontal cortex and rostral anterior cingulate cortex (rACC). The aim of the present study was to examine the neural correlates of these processes in children and adolescents with anxiety disorders. Methods Participants with an anxiety disorder 7 to 19 years old ( n = 34) and typically developing controls ( n = 35) underwent fMRI scanning. During scanning, they completed a task with conditions that manipulated whether participants were instructed to match emotional faces (direct emotion processing) or match shapes in the context of emotional face distractors (attentional control). Results Results revealed a significant difference in rACC activation during shape versus face matching, with controls evidencing greater rACC activation relative to patients. Conclusions This study identifies abnormalities in rACC activation as a potential neural mediator associated with pediatric anxiety disorders, which can inform frameworks for understanding their development and treatment. [ABSTRACT FROM AUTHOR]

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. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Obsessive-compulsive disorder (OCD) is often associated with pathological uncertainty regarding whether an action has been performed correctly or whether a bad outcome will occur, leading to compulsive 'evidence gathering' behaviors aimed at reducing uncertainty. The current study used event-related functional magnetic resonance imaging to investigate neural functioning in OCD patients and controls as subjective certainty was rated in response to sequential pieces of evidence for a decision. Uncertainty was experimentally manipulated so that some decisions were associated with no 'objective' uncertainty (all observed evidence pointed to one correct choice), whereas other decisions contained calculable but varying levels of objective uncertainty based on displayed probabilities. Results indicated that OCD patients differed from controls on decisions that contained no objective uncertainty, such that patients rated themselves as more uncertain. Patients also showed greater activation in a network of brain regions previously associated with internally-focused thought and valuation including ventromedial prefrontal cortex, parahippocampus, middle temporal cortex, as well as amygdala and orbitofrontal cortex/ventral anterior insula. In the patient group, a significantly greater number of positive intersubject correlations were found among several of these brain regions, suggesting that this network is more interconnected in patients. OCD patients did not differ from controls on decisions where task parameters led to uncertainty. These results indicate that OCD is associated with hyperactivation in a network of limbic/paralimbic brain regions when making decisions, which may contribute to the greater subjective experience of doubt that characterizes the disorder. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

According to the conflict monitoring model of cognitive control, reaction time (RT) in distracter interference tasks (e.g., the Stroop task) is a more precise index of response conflict than stimulus congruency (incongruent vs. congruent). The model therefore predicts that RT should be a reliable predictor of activity in regions of the posterior medial frontal cortex (pMFC) that are posited to detect response conflict. In particular, pMFC activity should be (a) greater in slow-RT than in fast-RT trials within a given task condition (e.g., congruent) and (b) equivalent in RT-matched trials from different conditions (i.e., congruent and incongruent trials). Both of these effects have been observed in functional magnetic resonance imaging (MRI) studies of adults. However, neither effect was observed in a recent study of healthy youth, suggesting that (a) the model does not accurately describe the relationship between RT and pMFC activity in this population or (b) the recent study was characterized by high variability due to a relatively small sample size. To distinguish between these possibilities, we asked a relatively large group of healthy youth (n = 28) to perform a distracter interference task - the multi-source interference task (MSIT) - while we recorded their brain activity with functional MRI. In this relatively large sample, both of the model’s predictions were confirmed. We conclude that the model accurately describes the relationship between pMFC activity and RT in healthy youth, but that additional research is needed to determine whether processes unrelated to response conflict contribute to this relationship. [ABSTRACT FROM AUTHOR]

Background 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. Methods 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. Results 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. Conclusions 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. [ABSTRACT FROM AUTHOR]

Background Anxiety disorders are commonly comorbid with bipolar disorder ( BP) and may worsen course of illness, but differential impact of specific anxiety disorders in men and women remains unknown. Methods We measured the impact of comorbid panic disorder ( PD), social phobia, specific phobia, and obsessive-compulsive disorder ( OCD) in 460 women and 276 men with Bipolar I Disorder ( BPI) or schizoaffective disorder, bipolar type from the National Institute of Mental Health Bipolar Genetics Initiative. We compared clinical characteristics in BPwith and without each anxiety disorder in men and women separately correcting for family relatedness. Results Comorbid PD, OCD, and specific phobia were more common in women with BPthan men. Comorbid social phobia correlated with increased risk of alcohol abuse in BPwomen, but not men. Women with comorbid PDattended fewer years of school. Comorbidity with OCDwas associated with earlier age at the onset of BPfor both genders. Comorbid PD, OCD, and specific phobia were associated with more antidepressant trials in BP, across both genders, compared to BPpatients without these anxiety disorders. Conclusion In BP, comorbid anxiety disorders are associated with increased risk for functional impairment, and women had differently associated risks than men. Clinicians should be aware of an increased risk for comorbid PD, OCD, and specific phobia in women with BP, and an increased risk of alcohol abuse in women with BDand comorbid social phobia. [ABSTRACT FROM AUTHOR]

Background: Obsessive-compulsive disorder (OCD) is characterized by an excessive focus on upsetting or disturbing thoughts, feelings, and images that are internally-generated. Internally-focused thought processes are subserved by the ''default mode network'' (DMN), which has been found to be hyperactive in OCD during cognitive tasks. In healthy individuals, disengagement from internally-focused thought processes may rely on interactions between DMN and a frontoparietal network (FPN) associated with external attention and task execution. Altered connectivity between FPN and DMN may contribute to the dysfunctional behavior and brain activity found in OCD. Methods: The current study examined interactions between FPN and DMN during rest in 30 patients with OCD (17 unmedicated) and 32 control subjects (17 unmedicated). Timecourses from seven fronto-parietal seeds were correlated across the whole brain and compared between groups. Results: OCD patients exhibited altered connectivity between FPN seeds (primarily anterior insula) and several regions of DMN including posterior cingulate cortex, medial frontal cortex, posterior inferior parietal lobule, and parahippocampus. These differences were driven largely by a reduction of negative correlations among patients compared to controls. Patients also showed greater positive connectivity between FPN and regions outside DMN, including thalamus, lateral frontal cortex, and somatosensory/motor regions. Conclusions: OCD is associated with abnormal intrinsic functional connectivity between large-scale brain networks. Alteration of interactions between FPN and DMN at rest may contribute to aspects of the OCD phenotype, such as patients' inability to disengage from internally-generated scenarios and thoughts when performing everyday tasks requiring external attention. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Individual variability in the location of neural activations poses a unique problem for neuroimaging studies employing group averaging techniques to investigate the neural bases of cognitive and emotional functions. This may be especially challenging for studies examining patient groups, which often have limited sample sizes and increased intersubject variability. In particular, medial frontal cortex (MFC) dysfunction is thought to underlie performance monitoring dysfunction among patients with schizophrenia, yet previous studies using group averaging to compare schizophrenic patients to controls have yielded conflicting results. To examine individual activations in MFC associated with two aspects of performance monitoring, interference and error processing, functional magnetic resonance imaging data were acquired while 17 patients with schizophrenia and 21 healthy controls (HCs) performed an event-related version of the multisource interference task. Comparisons of averaged data revealed few differences between the groups. By contrast, topographic analysis of individual activations for errors showed that control subjects exhibited activations spanning across both posterior and anterior regions of MFC while patients primarily activated posterior MFC, possibly reflecting an impaired emotional response to errors in schizophrenia. This discrepancy between topographic and group-averaged results may be due to the significant dispersion among individual activations, particularly in HCs, highlighting the importance of considering intersubject variability when interpreting the medial frontal response to error commission. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Making an error elicits activity from brain regions that monitor performance, especially the medial frontal cortex (MFC). However, uncertainty exists about whether the posterior or anterior/rostral MFC processes errors and to what degree affective responses to errors are mediated in the MFC, specifically the rostral anterior cingulate cortex (rACC). To test the hypothesis that rACC mediates a type of affective response, we conceptualized affect in response to an error as a reaction to loss and amplified this response with a monetary penalty. While subjects performed a cognitive interference task during functional magnetic resonance imaging, hemodynamic activity in the rACC was significantly greater when subjects lost money as a result of an error compared with errors that did not lead to monetary loss. A significant interaction between the incentive conditions and error events demonstrated that the effect was not merely attributable to working harder to win (or not lose) money, although an effect of motivation was noted in the mid-MFC. Activation foci also occurred in similar regions of the posterior MFC for error and interference processing, which were not modulated by the incentive conditions. However, at the level of the individual subject, substantial functional variability occurred along the MFC during error processing, including foci in the rostral/anterior extent of the MFC not appearing in the group analysis. The findings support the hypothesis that the rostral extent of the MFC (rACC) processes loss-related responses to errors, and individual differences may account for some of the reported variation of error-related foci in the MFC. [ABSTRACT FROM AUTHOR]

Background: A growing body of research has demonstrated associations between specific neurodevelopmental disorders and variation in DNA methylation (DNAm), implicating this molecular mark as a possible contributor to the molecular etiology of these disorders and/or as a novel disease biomarker. Furthermore, genetic risk variants of neurodevelopmental disorders have been found to be enriched at loci associated with DNAm patterns, referred to as methylation quantitative trait loci (mQTLs). Methods: We conducted two epigenome-wide association studies in individuals with attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) (aged 4–18 years) using DNA extracted from saliva. DNAm data generated on the Illumina Human Methylation 450 K array were used to examine the interaction between genetic variation and DNAm patterns associated with these disorders. Results: Using linear regression followed by principal component analysis, individuals with the most endorsed symptoms of ADHD or OCD were found to have significantly more distinct DNAm patterns from controls, as compared to all cases. This suggested that the phenotypic heterogeneity of these disorders is reflected in altered DNAm at specific sites. Further investigations of the DNAm sites associated with each disorder revealed that despite little overlap of these DNAm sites across the two disorders, both disorders were significantly enriched for mQTLs within our sample. Conclusions: Our DNAm data provide insights into the regulatory changes associated with genetic variation, highlighting their potential utility both in directing GWAS and in elucidating the pathophysiology of neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]