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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 fronto-parietal 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. 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. 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. 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.

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.

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.

Introduction The error‐related negativity (ERN) is a neural response that reflects error monitoring. Contradictorily, an enlarged (more negative) ERN has been cited as both a risk factor and a protective factor, which hinders its utility as a predictive indicator. The aim of the current study was to examine the associations between ERN measured in early childhood with the development of cognitive control (CC), emotion regulation, and internalizing/externalizing symptoms over 1–2 years. Methods When children were ages 5–7, EEG was collected during a Go/No‐Go task. A subset of the original participants (n = 30) were selected based on their baseline ERN in an extreme‐case design: half with high‐amplitude ERN, matched by age and sex with another group with low‐amplitude ERN. Results At follow‐up, children in the High‐Amplitude group showed better executive function, less self‐reported anxiety and depression, less affect dysregulation, more parent‐rated CC, less lability/negativity, and fewer parent‐reported externalizing problems. Many results held even when accounting for baseline levels. Further, emotion dysregulation mediated the relationship between the ERN and both anxiety and externalizing problems, while CC mediated the ERN's relationship with externalizing problems only. Conclusions These results can inform identification and intervention efforts for children at risk for psychopathology. High‐amplitude error‐related negativity (ERN), measured in early childhood, predicts better self‐control, including executive function and cognitive control and less affect dysregulation in middle childhood, and predicts fewer anxiety, depression, and externalizing symptoms over time. Emotion dysregulation mediated the relationship between the ERN and both anxiety and externalizing problems, while cognitive control mediated the ERN's relationship with externalizing problems only.

Background Subclinical obsessive–compulsive symptoms (OCS) are common in children, and increase risk for later onset of obsessive–compulsive disorder (OCD). In pediatric patients with OCD, neuroimaging research implicates altered neural mechanisms for error‐processing, but whether abnormal brain response occurs with subclinical OCS remains poorly understood. Methods Using functional magnetic resonance imaging (fMRI), 113 youth (8–18 years; 45 female) from a community sample were scanned during an error‐eliciting Go/No‐Go task. OCS were assessed dimensionally using the obsessive–compulsive subscale of the Child Behavior Checklist. The association between OCS scores and error‐related brain activity was examined at the whole‐brain level. Results Lower OCS scores associated with stronger response to errors in dorsal anterior cingulate cortex (dACC), caudate, putamen, thalamus, and occipital cortex. Additionally, lower OCS related to higher capacity for inhibitory control, as indexed by greater accuracy on No‐Go trials during fMRI scanning. The relationship between lower OCS and better accuracy on No‐Go trials was mediated by greater error‐related dACC activity. Conclusions The inverse relationship between OCS and error‐related activity in the dACC and extended cortical–striatal–thalamic circuitry may index an adaptive process by which subclinical OCS are minimized in youth. Further, these results identify an observable pattern of brain activity that tracks with subclinical OCS severity. Understanding the link between neural networks for error processing and the normal to abnormal range of OCS may pave the way for brain‐based strategies to identify children who are more likely to develop OCD and enable the targeting of preventive strategies to reduce risk. Graphical : This fMRI study examines the association of error‐related brain activity and dimensionally measured obsessive–compulsive symptoms (OCS) in a community sample of youth. Results showed that lower OCS was associated with greater error‐related activity of the dorsal anterior cingulate cortex (dACC), caudate, putamen and thalamus, as well as better task performance. This finding provides new information about error‐related brain activity in youth with OCS and sheds light on neural markers that might be relevant for the later development of OCD pathology.

Executive functions, such as working memory, must intersect with functions that determine value for the organism. Functional imaging work in humans and single-unit recordings in non-human primates provide evidence that PFC might integrate motivational context with working memory. With functional magnetic resonance imaging (fMRI), we addressed the question of motivation and working memory, using a trial-related design in an object-working memory task. The design permitted the analysis of BOLD signal at separate stages, corresponding to encoding, maintenance, and retrieval. Subjects were motivated by a financial incentive during the task, such that they could gain a high or a low reward. The two different levels of reward also entailed greater or lesser risk of losing money for incorrect responses. In the high, relative to the low, reward condition, subjects shifted response bias, and showed a trend to greater sensitivity. We found main effects in fMRI BOLD signal for reward, which overlapped with BOLD effects for maintenance of information, in the right superior frontal sulcus and bilateral intraparietal sulcus. We also found an interaction between reward and retrieval from working memory in the right dorsolateral prefrontal cortex. Main effects of load and reward occurred in adjacent regions of the ventrolateral PFC during retrieval. The data demonstrate that when subjects perform a simple working memory task, financial incentives motivate performance and interact with some of the same neural networks that process various stages of working memory. Areas of overlap and interaction may integrate information about value, or they may represent a general effect of motivation increasing neural effort.

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.

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.

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.