Developmentally specified characterization of the irritability spectrum at early school age: Implications for pragmatic mental health screening.

OBJECTIVES: Developmentally specified measures that identify clinically salient irritability are needed for early school-age youth to meaningfully capture this transdiagnostic risk factor for psychopathology. Thus, the current study modeled the normal:abnormal irritability spectrum and generated a clinically optimized screening tool for this population. METHODS: The irritability spectrum was modeled via the youth version of the Multidimensional Assessment Profile Scales-Temper Loss Scale (MAPS-TL-Youth) in children (n = 474; 6.0-8.9 years) using item response theory (IRT). Both cross-cutting core irritability items from the early childhood version and new developmentally specific items were included. Items uniquely associated with impairment were identified and used to derive a brief, clinically optimized irritability screener. Longitudinal data were then utilized to test the predictive utility of this clinically optimized screener in preadolescence (n = 348; 8.0-12.9 years). RESULTS: Most children exhibit irritability regularly, but daily occurrence was rare. Of the top 10 most severe items from the IRT analyses, 9 were from the developmentally specific items added for the MAPS-TL Youth version. Two items associated with concurrent impairment were identified for the clinically optimized irritability screener ("Become frustrated easily" and "Act irritable"). The MAPS-TL-Youth clinically optimized screener demonstrated good sensitivity (69%) and specificity (84%) in relation to concurrent DSM 5 irritability-related diagnoses. Youth with elevated scores on the screener at early school age (ESA) had more than 7x greater odds of irritability-related psychopathology at pre-adolescence. CONCLUSIONS: The MAPS-TL-Youth characterized the developmental spectrum of irritability at ESA and a clinically optimized screener showed promise at predicting psychopathology risk. Rigorous testing of clinical applications is a critical next step.

MAPping affective dimensions of behavior: Methodologic and pragmatic advancement of the Multidimensional Assessment Profiles scales.

Rigorous validation of the full developmentally sensitive normal:abnormal spectrum, including evaluating the incremental value of age-specific behaviors, is necessary for nuanced characterization of dimensional features of psychopathology. To maximize the clinical utility of transdiagnostic approaches to risk identification, derivation of psychometrically sound, pragmatic versions with empirically derived cutoffs is also key. This special section has a central focus on rigorous, developmentally-based measurement of irritability as an exemplar of this theory- and pragmatically-based approach. Elevated irritability is a robust transdiagnostic predictor of the common psychopathologies of childhood. The Multidimensional Assessment Profiles Temper Loss (MAPS-TL) Scales are the only irritability tool specifically designed to capture the normal:abnormal dimensional spectrum. These have been extensively investigated in preschool age but lack rigorous modeling at older and younger ages. In this special issue, (with three independent-and one longitudinal-set of samples), we test and improve measurement of irritability as a transdiagnostic phenotype of psychopathology risk as it unfolds across development, expanding the MAPS-TL scale in three important ways: (1) extending irritability dimensional modeling and the developmental specification approach to older ages, (2) advancing science to practice translation by generating pragmatic irritability screening tools across ages, and (3) extending the dimensional, developmental specification approach to other dimensions of behavior, that is, internalizing. Collectively, the special issue operationalizes and advances application of a neurodevelopmental, dimensional and transdiagnostic approach to psychopathology.

A pragmatic, clinically optimized approach to characterizing adolescent irritability: Validation of parent- and adolescent reports on the Multidimensional Assessment Profile Scales-Temper Loss Scale.

OBJECTIVES: Heightened irritability in adolescence is an impairing symptom that can lead to negative outcomes in adulthood, but effective screening tools are lacking. This study aimed to derive clinically-optimized cutoff scores using the Multidimensional Assessment Profile Scales-Temper Loss (MAPS-TL) to pragmatically identify adolescents with impairing irritability. METHODS: A diverse sample of 79 adolescents and their parents completed the MAPS-TL-Youth version. Stepwise logistic regression analyses were used to determine the items associated with impairment, and receiver operator characteristic (ROC) analyses were conducted to derive optimal cutoff scores. RESULTS: Three parent-report items (become frustrated easily, angry/irritable/grouchy throughout the day, difficulty calming down when angry) and two youth-report items (hit/shove/kick when lost temper, difficulty calming down when angry) were strongly associated with impairment. Optimal cutoff scores garnered very good sensitivity (91%, 73%) and specificity (77%, 75%) for the parent- and youth-report versions respectively. Scores above these cutoffs were associated with increased internalizing and externalizing problems and lower overall quality of life. CONCLUSIONS: The MAPS-TL clinically optimized irritability scores show preliminary validity for implementation in practical settings to efficiently identify adolescents who need additional evaluation and/or intervention. Further research is important to validate these cutoff scores with larger population-based samples and real-world settings.

Longitudinal Change in Adolescent Depression and Anxiety Symptoms from before to during the COVID-19 Pandemic.

This study aimed to examine changes in depression and anxiety symptoms from before to during the first 6 months of the COVID-19 pandemic in a sample of 1,339 adolescents (9-18 years old, 59% female) from three countries. We also examined if age, race/ethnicity, disease burden, or strictness of government restrictions moderated change in symptoms. Data from 12 longitudinal studies (10 U.S., 1 Netherlands, 1 Peru) were combined. Linear mixed effect models showed that depression, but not anxiety, symptoms increased significantly (median increase = 28%). The most negative mental health impacts were reported by multiracial adolescents and those under 'lockdown' restrictions. Policy makers need to consider these impacts by investing in ways to support adolescents' mental health during the pandemic.

Parental Factors That Confer Risk and Resilience for Remote Learning Outcomes During the COVID-19 Pandemic Among Children With and Without Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To test whether parental factors including internalizing symptoms, parenting style, and confidence in assisting with remote learning conferred risk/resilience for children with/without ADHD's learning and emotional outcomes during the COVID-19 pandemic. METHOD: 291 parents of children (ages 6-13; n = 180 males) with (n = 148) and without ADHD completed questionnaires online (April-July 2020). RESULTS: Structural equation modeling identified parental risk/resilience factors. Across groups, risk predicted greater difficulties with learning, internalizing and externalizing symptoms, while parent confidence in educating their child predicted better outcomes. A positive association was observed between parental involvement and child difficulties, which was stronger in families of children with ADHD. Children with/without ADHD did not differ in remote learning difficulties. CONCLUSION: Parent factors impacted child emotional and learning outcomes during the pandemic. With increases in remote learning practices, there is a need for improved understanding of how parent factors impact outcomes of children with/without ADHD.

A preliminary examination of key strategies, challenges, and benefits of remote learning expressed by parents during the COVID-19 pandemic.

Among the many impacts of the Coronavirus disease (COVID-19) pandemic, one of the most dramatic was the immediate closure of in-person schooling in March/April 2020 when parents were faced with much greater responsibility in supporting their children's learning. Despite this, few studies have examined parents' own perspectives of this experience. The aims of this preliminary study were to (a) identify challenges, benefits, and useful strategies related to remote learning and (b) examine differences in findings across two countries, between parents of youth with and without attention-deficit/hyperactivity disorder (ADHD), and between parents of children and adolescents. To address these aims, parent responses to open-ended questions on the Home Adjustment to COVID-19 Scale (HACS; Becker, Breaux, et al., 2020) were examined across three studies conducted in the United States and Australia (N = 606, children: 68.5% male, ages 6-17 years). The challenges most frequently expressed by parents included the child's difficulty staying on task (23.8% of parents), lack of motivation (18.3%), remote learning factors (17.8%), and lack of social interaction (14.4%). The most frequently expressed strategy related to using routines and schedules (58.2%) and the biggest benefit was more family time (20.3%). Findings were largely consistent across countries, ADHD status, and age, with a few notable group differences. Given that the most common challenges involved child- (e.g., difficulties with staying on task and motivation), parent- (e.g., balancing remote learning with work responsibilities), and school- (e.g., remote instruction difficulties) related factors, there is a need for improved support across these systems going forward. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Psychological, Academic, and Economic Impact of COVID-19 on College Students in the Epicenter of the Pandemic.

Initial research has indicated that college students have experienced numerous stressors as a result of the pandemic. The current investigation enrolled the largest and most diverse sample of college students to date (N = 4714) from universities in New York (NY) and New Jersey (NJ), the epicenter of the North American pandemic in Spring 2020. We described the impact on the psychological, academic, and financial health of college students who were initially most affected and examined racial/ethnic group differences. Results indicated that students' mental health was severely affected and that students of color were disproportionately affected by academic, financial, and COVID-related stressors. Worry about COVID-19 infection, stressful living conditions, lower grades, and loneliness emerged as correlates of deteriorating mental health. COVID-19's mental health impact on college students is alarming and highlights the need for public health interventions at the university level.

Decomposing complex links between the childhood environment and brain structure in school-aged youth.

Childhood experiences play a profound role in conferring risk and resilience for brain and behavioral development. However, how different facets of the environment shape neurodevelopment remains largely unknown. Here we sought to decompose heterogeneous relationships between environmental factors and brain structure in 989 school-aged children from the Adolescent Brain Cognitive Development Study. We applied a cross-modal integration and clustering approach called 'Similarity Network Fusion', which combined two brain morphometrics (i.e., cortical thickness and myelin-surrogate markers), and key environmental factors (i.e., trauma exposure, neighborhood safety, school environment, and family environment) to identify homogeneous subtypes. Depending on the subtyping resolution, results identified two or five subgroups, each characterized by distinct brain structure-environment profiles. Notably, more supportive caregiving and school environments were associated with greater myelination, whereas less supportive caregiving, higher family conflict and psychopathology, and higher perceived neighborhood safety were observed with greater cortical thickness. These subtypes were highly reproducible and predicted externalizing symptoms and overall mental health problems. Our findings support the theory that distinct environmental exposures are differentially associated with alterations in structural neurodevelopment. Delineating more precise associations between risk factors, protective factors, and brain development may inform approaches to enhance risk identification and optimize interventions targeting specific experiences.

Advances in the Conceptualization, Assessment, and Treatment of Pediatric Irritability.

Pediatric irritability is a functionally impairing transdiagnostic symptom underlying a substantial proportion of child mental health referrals. The past 20 years have witnessed a striking uptick in empirical work focused on pediatric irritability, with increasing recognition of its role across multiple internalizing and externalizing disorders. That said, it has only been in recent years that research has begun to make advances in understanding the natural course and neurobiological underpinnings of irritability across development; research directly informing effective clinical management of pediatric irritability has been limited. At this critical stage in the study of pediatric irritability, this special series brings together the latest work from leading experts across three interrelated domains: (a) progress in understanding the phenomenology and course of pediatric irritability; (b) advances in the assessment of pediatric irritability; and (c) innovations in the treatment of pediatric irritability. The papers in this special series collectively offer critical steps forward for better understanding pediatric irritability and improving proper assessment, classification, and clinical management.

Functional connectivity of the anterior insula associated with intolerance of uncertainty in youth.

Intolerance of uncertainty (IU) is a trait characteristic marked by distress in the face of insufficient information. Elevated IU has been implicated in the development and maintenance of anxiety disorders, particularly during adolescence, which is characterized by dramatic neural maturation and the onset of anxiety disorders. Previous task-based work implicates the bilateral anterior insula in IU. However, the association between anterior insula intrinsic functional connectivity (iFC) and IU has not been examined in adolescents. Fifty-eight healthy youth (mean age = 12.56; 55% boys) completed the Intolerance of Uncertainty Scale for Children (IUSC-12) and a 6-minute resting state fMRI scan. Group-level analyses were conducted using a random-effects, ordinary least-squares model, including IUSC-12 scores (Total, Inhibitory subscale, Prospective subscale), and three nuisance covariates (age, sex, and mean framewise displacement). IUSC-12 Inhibitory subscale scores were predictive of iFC between the left and right anterior insula and right prefrontal regions. IUSC-12 Prospective subscale scores significantly predicted iFC between the anterior insula and the anterior cingulate cortex. IUSC-12 total scores did not predict significant iFC of the bilateral anterior insula. Follow-up analyses, including anxiety (MASC Total Score) in the models, failed to find significant results. This could suggest that the associations found between IUSC-12 scores and anterior insula iFC are not unique to IU and, rather, reflect a broader anxiety-related connectivity pattern. Further studies with larger samples are needed to tease apart unique associations. These findings bear significance in contributing to the literature evaluating the neural correlates of risk factors for anxiety in youth.

The Neural Correlates of Emotional Lability in Children with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is exceptionally heterogeneous in both clinical and physiopathological presentations. Clinical variability applies to ASD-specific symptoms and frequent comorbid psychopathology such as emotional lability (EL). To date, the physiopathological underpinnings of the co-occurrence of EL and ASD are unknown. As a first step, we examined within-ASD inter-individual variability of EL and its neuronal correlates using resting-state functional magnetic resonance imaging (R-fMRI). We analyzed R-fMRI data from 58 children diagnosed with ASD (5-12 years) in relation to the Conners' Parent Rating Scale EL index. We performed both an a priori amygdala region-of-interest (ROI) analysis, and a multivariate unbiased whole-brain data-driven approach. While no significant brain-behavior relationships were identified regarding amygdala intrinsic functional connectivity (iFC), multivariate whole-brain analyses revealed an extended functional circuitry centered on two regions: middle frontal gyrus (MFG) and posterior insula (PI). Follow-up parametric and nonparametric ROI-analyses of these regions revealed relationships between EL and MFG- and PI-iFC with default, salience, and visual networks suggesting that higher-order cognitive and somatosensory processes are critical for emotion regulation in ASD. We did not detect evidence of amygdala iFC underpinning EL in ASD. However, exploratory whole-brain analyses identified large-scale networks that have been previously reported abnormal in ASD. Future studies should consider EL as a potential source of neuronal heterogeneity in ASD and focus on multinetwork interactions.

Distinct Functional Connectivities Predict Clinical Response with Emotion Regulation Therapy.

Despite the success of available medical and psychosocial treatments, a sizable subgroup of individuals with commonly co-occurring disorders, generalized anxiety disorder (GAD) and major depressive disorder (MDD), fail to make sufficient treatment gains thereby prolonging their deficits in life functioning and satisfaction. Clinically, these patients often display temperamental features reflecting heightened sensitivity to underlying motivational systems related to threat/safety and reward/loss (e.g., somatic anxiety) as well as inordinate negative self-referential processing (e.g., worry, rumination). This profile may reflect disruption in two important neural networks associated with emotional/motivational salience (e.g., salience network) and self-referentiality (e.g., default network, DN). Emotion Regulation Therapy (ERT) was developed to target this hypothesized profile and its neurobehavioral markers. In the present study, 22 GAD patients (with and without MDD) completed resting state MRI scans before receiving 16 sessions of ERT. To test study these hypotheses, we examined the associations between baseline patterns of intrinsic functional connectivity (iFC) of the insula and of hubs within the DN (anterior and dorsal medial prefrontal cortex [MPFC] and posterior cingulate cortex [PCC]) and treatment-related changes in worry, somatic anxiety symptoms and decentering. Results suggest that greater treatment linked reductions in worry were associated with iFC clusters in both the insular and parietal cortices. Greater treatment linked gains in decentering, a metacognitive process that involves the capacity to observe items that arise in the mind with healthy psychological distance that is targeted by ERT, was associated with iFC clusters in the anterior and posterior DN. The current study adds to the growing body of research implicating disruptions in the default and salience networks as promising targets of treatment for GAD with and without co-occurring MDD.

Age-related changes in the intrinsic functional connectivity of the human ventral vs. dorsal striatum from childhood to middle age.

The striatum codes motivated behavior. Delineating age-related differences within striatal circuitry can provide insights into neural mechanisms underlying ontogenic behavioral changes and vulnerabilities to mental disorders. To this end, a dual ventral/dorsal model of striatal function was examined using resting state intrinsic functional connectivity (iFC) imaging in 106 healthy individuals, ages 9-44. Broadly, the dorsal striatum (DS) is connected to prefrontal and parietal cortices and contributes to cognitive processes; the ventral striatum (VS) is connected to medial orbitofrontal and anterior cingulate cortices, and contributes to affective valuation and motivation. Findings revealed patterns of age-related changes that differed between VS and DS iFCs. We found an age-related increase in DS iFC with posterior cingulate cortex (pCC) that stabilized after the mid-twenties, but a decrease in VS iFC with anterior insula (aIns) and dorsal anterior cingulate cortex (dACC) that persisted into mid-adulthood. These distinct developmental trajectories of VS vs. DS iFC might underlie adolescents' unique behavioral patterns and vulnerabilities to psychopathology, and also speaks to changes in motivational networks that extend well past 25 years old.

Clinical features of young children referred for impairing temper outbursts.

OBJECTIVE: In light of the current controversy about whether severe temper outbursts are diagnostic of mania in young children, we conducted a study to characterize such children, focusing on mania and other mood disorders, emotion regulation, and parental psychiatric history. METHODS: Study participants included 51 5-9-year-old children with frequent, impairing outbursts (probands) and 24 non-referred controls without outbursts. Parents completed a lifetime clinical interview about their child, and rated their child's current mood and behavior. Teachers completed a behavior rating scale. To assess emotion regulation, children were administered the Balloons Game, which assesses emotion expressivity in response to frustration, under demands of high and low regulation. Parental lifetime diagnoses were ascertained in blind clinical interviews. RESULTS: No child had bipolar disorder, bipolar disorder not otherwise specified (NOS), or major depression (MDD). The most prevalent disorder was oppositional defiant disorder (88.2%), followed by attention-deficit/hyperactivity disorder (74.5%), anxiety disorders (49.0%), and non-MDD depressive disorders (33.3%). Eleven probands (21.6%) met criteria for severe mood dysregulation. During the Balloons Game, when there were no demands for self-regulation, children with severe outbursts showed reduced positive expressivity, and also showed significant deficits in controlling negative facial expressions when asked to do so. Anxiety disorders were the only diagnoses significantly elevated in probands' mothers. CONCLUSIONS: Overall, young children with severe temper outbursts do not present with bipolar disorder. Rather, disruptive behavior disorders with anxiety and depressive mood are common. In children with severe outbursts, deficits in regulating emotional facial expressions may reflect deficits controlling negative affect. This work represents a first step towards elucidating mechanisms underlying severe outbursts in young children.

Intrinsic functional connectivity of amygdala-based networks in adolescent generalized anxiety disorder.

OBJECTIVE: Generalized anxiety disorder (GAD) typically begins during adolescence and can persist into adulthood. The pathophysiological mechanisms underlying this disorder remain unclear. Recent evidence from resting state functional magnetic resonance imaging (R-fMRI) studies in adults suggests disruptions in amygdala-based circuitry; the present study examines this issue in adolescents with GAD. METHOD: Resting state fMRI scans were obtained from 15 adolescents with GAD and 20 adolescents without anxiety who were group matched on age, sex, scanner, and intelligence. Functional connectivity of the centromedial, basolateral, and superficial amygdala subdivisions was compared between groups. We also assessed the relationship between amygdala network dysfunction and anxiety severity. RESULTS: Adolescents with GAD exhibited disruptions in amygdala-based intrinsic functional connectivity networks that included regions in medial prefrontal cortex, insula, and cerebellum. Positive correlations between anxiety severity scores and amygdala functional connectivity with insula and superior temporal gyrus were also observed within the GAD group. There was some evidence of greater overlap (less differentiation of connectivity patterns) of the right basolateral and centromedial amygdala networks in the adolescents with, relative to those without, GAD. CONCLUSIONS: These findings suggest that adolescents with GAD manifest alterations in amygdala circuits involved in emotion processing, similar to findings in adults. In addition, disruptions were observed in amygdala-based networks involved in fear processing and the coding of interoceptive states.

Adolescents' risk-taking behavior is driven by tolerance to ambiguity.

Adolescents engage in a wide range of risky behaviors that their older peers shun, and at an enormous cost. Despite being older, stronger, and healthier than children, adolescents face twice the risk of mortality and morbidity faced by their younger peers. Are adolescents really risk-seekers or does some richer underlying preference drive their love of the uncertain? To answer that question, we used standard experimental economic methods to assess the attitudes of 65 individuals ranging in age from 12 to 50 toward risk and ambiguity. Perhaps surprisingly, we found that adolescents were, if anything, more averse to clearly stated risks than their older peers. What distinguished adolescents was their willingness to accept ambiguous conditions--situations in which the likelihood of winning and losing is unknown. Though adults find ambiguous monetary lotteries undesirable, adolescents find them tolerable. This finding suggests that the higher level of risk-taking observed among adolescents may reflect a higher tolerance for the unknown. Biologically, such a tolerance may make sense, because it would allow young organisms to take better advantage of learning opportunities; it also suggests that policies that seek to inform adolescents of the risks, costs, and benefits of unexperienced dangerous behaviors may be effective and, when appropriate, could be used to complement policies that limit their experiences.

Durable effects of cognitive restructuring on conditioned fear.

Studies of cognitive reappraisal have demonstrated that reinterpreting a stimulus can alter emotional responding, yet few studies have examined the durable effects associated with reinterpretation-based emotion regulation strategies. Evidence for the enduring effects of emotion regulation may be found in clinical studies that use cognitive restructuring (CR) techniques in cognitive-behavioral therapy (CBT) to alleviate anxiety. These techniques are based on cognitive theories of anxiety that suggest these disorders arise from biased cognitions; therefore, changing a person's thoughts will elicit durable changes in an individual's emotional responses. Despite the considerable success of CBT for anxiety disorders, durable effects associated with emotion regulation have not been thoroughly examined in the context of a laboratory paradigm. The goal of this study was to determine whether CR, a technique used in CBT and similar to cognitive reappraisal, could attenuate conditioned fear responses, and whether the effect would persist over time (24 hr). We conditioned participants using images of snakes or spiders that were occasionally paired with a mild shock to the wrist while we obtained subjective fear reports and electrodermal activity (EDA). After conditioning, half of the participants were randomly assigned to CR training aimed at decreasing their emotional response to the shock and the conditioned stimuli, while the other half received no such training. All participants returned 24 hr later to repeat the conditioning session. Compared with control participants, CR participants demonstrated a reduction in fear and EDA across sessions. These findings suggest that CR has durable effects on fear responding.

Your resting brain CAREs about your risky behavior.

BACKGROUND: Research on the neural correlates of risk-related behaviors and personality traits has provided insight into mechanisms underlying both normal and pathological decision-making. Task-based neuroimaging studies implicate a distributed network of brain regions in risky decision-making. What remains to be understood are the interactions between these regions and their relation to individual differences in personality variables associated with real-world risk-taking. METHODOLOGY/PRINCIPAL FINDINGS: We employed resting state functional magnetic resonance imaging (R-fMRI) and resting state functional connectivity (RSFC) methods to investigate differences in the brain's intrinsic functional architecture associated with beliefs about the consequences of risky behavior. We obtained an individual measure of expected benefit from engaging in risky behavior, indicating a risk seeking or risk-averse personality, for each of 21 participants from whom we also collected a series of R-fMRI scans. The expected benefit scores were entered in statistical models assessing the RSFC of brain regions consistently implicated in both the evaluation of risk and reward, and cognitive control (i.e., orbitofrontal cortex, nucleus accumbens, lateral prefrontal cortex, dorsal anterior cingulate). We specifically focused on significant brain-behavior relationships that were stable across R-fMRI scans collected one year apart. Two stable expected benefit-RSFC relationships were observed: decreased expected benefit (increased risk-aversion) was associated with 1) stronger positive functional connectivity between right inferior frontal gyrus (IFG) and right insula, and 2) weaker negative functional connectivity between left nucleus accumbens and right parieto-occipital cortex. CONCLUSIONS/SIGNIFICANCE: Task-based activation in the IFG and insula has been associated with risk-aversion, while activation in the nucleus accumbens and parietal cortex has been associated with both risk seeking and risk-averse tendencies. Our results suggest that individual differences in attitudes toward risk-taking are reflected in the brain's functional architecture and may have implications for engaging in real-world risky behaviors.

The intolerance of uncertainty scale for children: a psychometric evaluation.

Intolerance of uncertainty (IU) has contributed to our understanding of excessive worry and adult anxiety disorders, but there is a paucity of research on IU in child samples. This gap is due to the absence of a psychometrically sound measure of IU in youth. The present study adapted parallel child- and parent-report forms of the Intolerance of Uncertainty Scale (IUS) and examined the internal consistency, convergent validity, and classification properties of these forms in youth aged 7-17 (M = 11.6 years, SD = 2.6). Participating youth (N = 197; 100 girls, 97 boys) either met diagnostic criteria for an anxiety disorder (n = 73) or were nonreferred community participants (n = 124). The child-report form (i.e., IUS for Children, or IUSC), and to a lesser extent the parent-report form, demonstrated strong internal consistency and convergent validity, evidenced by significant associations with anxiety and worry (and reassurance-seeking in the case of the child-report form). Children diagnosed with anxiety disorders scored higher than nonreferred community youth on both forms. Receiver operating characteristic (ROC) analysis demonstrated acceptable overall utility in distinguishing the 2 groups of youth. Findings provide preliminary support for use of the IUSC for continuous measurement of children's ability to tolerate uncertainty.

Regional variation in interhemispheric coordination of intrinsic hemodynamic fluctuations.

Electrophysiological studies have long demonstrated a high degree of correlated activity between the left and right hemispheres, however little is known about regional variation in this interhemispheric coordination. Whereas cognitive models and neuroanatomical evidence suggest differences in coordination across primary sensory-motor cortices versus higher-order association areas, these have not been characterized. Here, we used resting-state functional magnetic resonance imaging data acquired from 62 healthy volunteers to examine interregional correlation in spontaneous low-frequency hemodynamic fluctuations. Using a probabilistic atlas, we correlated probability-weighted time series from 112 regions comprising the entire cerebrum. We then examined regional variation in correlated activity between homotopic regions, contrasting primary sensory-motor cortices, unimodal association areas, and heteromodal association areas. Consistent with previous studies, robustly correlated spontaneous activity was noted between all homotopic regions, which was significantly higher than that between nonhomotopic (heterotopic and intrahemispheric) regions. We further demonstrated substantial regional variation in homotopic interhemispheric correlations that was highly consistent across subjects. Specifically, there was a gradient of interhemispheric correlation, with highest correlations across primary sensory-motor cortices (0.758, SD=0.152), significantly lower correlations across unimodal association areas (0.597, SD=0.230) and still lower correlations across heteromodal association areas (0.517, SD=0.226). These results demonstrate functional differences in interhemispheric coordination related to the brain's hierarchical subdivisions. Synchrony across primary cortices may reflect networks engaged in bilateral sensory integration and motor coordination, whereas lower coordination across heteromodal association areas is consistent with functional lateralization of these regions. This novel method of examining interhemispheric coordination may yield insights regarding diverse disease processes as well as healthy development.