Responding to threat: Associations between neural reactivity to and behavioral avoidance of threat in pediatric anxiety.

BACKGROUND: Despite broad recognition of the central role of avoidance in anxiety, a lack of specificity in its operationalization has hindered progress in understanding this clinically significant construct. The current study uses a multimodal approach to investigate how specific measures of avoidance relate to neural reactivity to threat in youth with anxiety disorders. METHODS: Children with anxiety disorders (ages 6-12 years; n = 65 for primary analyses) completed laboratory task- and clinician-based measures of avoidance, as well as a functional magnetic resonance imaging task probing neural reactivity to threat. Primary analyses examined the ventral anterior insula (vAI), amygdala, and ventromedial prefrontal cortex (vmPFC). RESULTS: Significant but distinct patterns of association with task- versus clinician-based measures of avoidance emerged. Clinician-rated avoidance was negatively associated with right and left vAI reactivity to threat, whereas laboratory-based avoidance was positively associated with right vAI reactivity to threat. Moreover, left vAI-right amygdala and bilateral vmPFC-right amygdala functional connectivity were negatively associated with clinician-rated avoidance but not laboratory-based avoidance. LIMITATIONS: These results should be considered in the context of the restricted range of our treatment-seeking sample, which limits the ability to draw conclusions about these associations across children with a broader range of symptomatology. In addition, the limited racial and ethnic diversity of our sample may limit the generalizability of findings. CONCLUSION: These findings mark an important step towards bridging neural findings and behavioral patterns using a multimodal approach. Advancing understanding of behavioral avoidance in pediatric anxiety may guide future treatment optimization by identifying individual-specific targets for treatment.

Extinction Learning Across Development: Neurodevelopmental Changes and Implications for Pediatric Anxiety Disorders.

Alterations in extinction learning relate to the development and maintenance of anxiety disorders across the lifespan. While exposure therapy, based on principles of extinction, can be highly effective for treating anxiety, many patients do not show sufficient improvement following treatment. In particular, evidence suggests that exposure therapy does not work sufficiently for up to 40% of children who receive this evidence-based treatment.Importantly, fear learning and extinction, as well as the neural circuitry supporting these processes, undergo dynamic changes across development. An improved understanding of developmental changes in extinction learning and the associated neural circuitry may help to identify targets to improve treatment response in clinically anxious children and adolescents. In this chapter, we provide a brief overview of methods used to study fear learning and extinction in developmental populations. We then review what is currently known about the developmental changes that occur in extinction learning and related neural circuitry. We end this chapter with a discussion of the implications of these neurodevelopmental changes for the characterization and treatment of pediatric anxiety disorders.

Family accommodation in pediatric anxiety: Relations with avoidance and self-efficacy.

Pediatric anxiety disorders are common, impairing, and chronic when not effectively treated. A growing body of research implicates family accommodation in the maintenance of pediatric anxiety. The present study aimed to quantify previously untested relations among family accommodation and two theoretically linked constructs: avoidance and self-efficacy. Eighty youths between ages 8 and 17 (53 with anxiety disorders, 27 non-anxious controls) completed measures of family accommodation and self-efficacy. In addition, avoidance was assessed using two distinct measures of avoidance: a clinician rating of real-world behaviors and a laboratory task-based index. As predicted, youths with anxiety disorders reported greater family accommodation than non-anxious controls. Across the sample, greater family accommodation was associated with greater avoidance, as measured using both clinician rating and the laboratory task, as well as with lower self-efficacy. In an exploratory mediation model, self-efficacy partially mediated the relation between family accommodation and clinician-rated avoidance; however, it did not mediate the relation between family accommodation and task-based avoidance. Considering the robust association between family accommodation and anxiety in youths, this addition to our understanding of related cognitive and behavioral factors provides important preliminary insight, which can guide future research on potential targets for early identification and intervention for pediatric anxiety.

Reliability of task-evoked neural activation during face-emotion paradigms: Effects of scanner and psychological processes.

Assessing and improving test-retest reliability is critical to efforts to address concerns about replicability of task-based functional magnetic resonance imaging. The current study uses two statistical approaches to examine how scanner and task-related factors influence reliability of neural response to face-emotion viewing. Forty healthy adult participants completed two face-emotion paradigms at up to three scanning sessions across two scanners of the same build over approximately 2 months. We examined reliability across the main task contrasts using Bayesian linear mixed-effects models performed voxel-wise across the brain. We also used a novel Bayesian hierarchical model across a predefined whole-brain parcellation scheme and subcortical anatomical regions. Scanner differences accounted for minimal variance in temporal signal-to-noise ratio and task contrast maps. Regions activated during task at the group level showed higher reliability relative to regions not activated significantly at the group level. Greater reliability was found for contrasts involving conditions with clearly distinct visual stimuli and associated cognitive demands (e.g., face vs. nonface discrimination) compared to conditions with more similar demands (e.g., angry vs. happy face discrimination). Voxel-wise reliability estimates tended to be higher than those based on predefined anatomical regions. This work informs attempts to improve reliability in the context of task activation patterns and specific task contrasts. Our study provides a new method to estimate reliability across a large number of regions of interest and can inform researchers' selection of task conditions and analytic contrasts.

Leveraging big data to map neurodevelopmental trajectories in pediatric anxiety.

Anxiety disorders are the most prevalent psychiatric condition among youth, with symptoms commonly emerging prior to or during adolescence. Delineating neurodevelopmental trajectories associated with anxiety disorders is important for understanding the pathophysiology of pediatric anxiety and for early risk identification. While a growing literature has yielded valuable insights into the nature of brain structure and function in pediatric anxiety, progress has been limited by inconsistent findings and challenges common to neuroimaging research. In this review, we first discuss these challenges and the promise of 'big data' to map neurodevelopmental trajectories in pediatric anxiety. Next, we review evidence of age-related differences in neural structure and function among anxious youth, with a focus on anxiety-relevant processes such as threat and safety learning. We then highlight large-scale cross-sectional and longitudinal studies that assess anxiety and are well positioned to inform our understanding of neurodevelopment in pediatric anxiety. Finally, we detail relevant challenges of 'big data' and propose future directions through which large publicly available datasets can advance knowledge of deviations from normative brain development in anxiety. Leveraging 'big data' will be essential for continued progress in understanding the neurobiology of pediatric anxiety, with implications for identifying markers of risk and novel treatment targets.

Evaluating the Role of a Socially Assistive Robot in Children's Mental Health Care.

Socially assistive robots (SARs) present a promising intervention for addressing the increasing prevalence of childhood stress. This innovative technology has become increasingly common in practical implementation. However, empirical support has not kept pace with the robots' growing popularity. The present study set out to provide an empirical test of the stress-buffering capability of this technology. We examined the effects of the presence of an SAR on self-reported measures of stress in a community sample of 70 children (40 girls, 30 boys) between the ages of 7 and 10 years old. Child participants were randomly assigned to either a robot-present or a robot-absent condition during the Trier Social Stress Test for Children. Contrary to our predictions, we did not detect a stress-buffering effect of the presence of the robot. Instead, the primary analysis showed that the robot's presence led to a larger decrease in positive affect following the task. However, further analyses found no significant difference in positive affect when accounting for baseline group differences. Exploratory analyses of the nature of children's interactions with the SAR during the stressful task found that higher levels of parent-reported social anxiety were associated with greater prosocial behaviors towards the SAR, thus signifying a potential target for future interventions. Further work on SARs is needed to determine the optimal timing and robotic specifications that would maximize the potential of this developing technology to improve children's mental health care.

Influences of early-life stress on frontolimbic circuitry: Harnessing a dimensional approach to elucidate the effects of heterogeneity in stress exposure.

Early-life stress confers profound and lasting risk for developing cognitive, social, emotional, and physical health problems. The effects of stress on the developing brain contribute to this risk, with frontolimbic circuitry particularly susceptible to early experiences, possibly due to its innervation with glucocorticoid receptors and the timing of frontolimbic circuit maturation. To date, the majority of studies on stress and frontolimbic circuitry have employed a categorical approach, comparing stress-exposed versus non-stress-exposed youth. However, there is vast heterogeneity in the nature of stress exposure and in outcomes. Recent forays into understanding the psychobiological effects of stress have employed a dimensional approach focused on experiential, environmental, and temporal factors that influence the association between stress and subsequent vulnerability. This review highlights empirical findings that inform a dimensional approach to understanding the effects of stress on frontolimbic circuitry. We identify the timing, type, severity, controllability, and predictability of stress, and the degree to which a caregiver is involved, as specific features of stress that may play a substantial role in differential outcomes. We propose a framework for the effects of these features of stress on frontolimbic development that may partially determine how heterogeneity in stress exposure influences this circuitry and, ultimately, mental health.

Comparing neural correlates of conditioned inhibition between children with and without anxiety disorders - A preliminary study.

Cognitive-behavioral therapy (CBT), a first-line treatment for pediatric anxiety disorders, is based on principles of threat learning and extinction. However, CBT does not work sufficiently for up to 40% of clinically anxious youth. The neural and behavioral correlates of conditioned inhibition might provide promising targets for attempts to improve CBT response. During conditioned inhibition, threat and safety cues appear together, forming a safety compound. Here, we test whether this safety compound elicits a reduced fear response compared to pairing the threat cue with a novel cue (novel compound). The current pilot study compares behavioral, physiological, and neural correlates of conditioned inhibition between children with (n = 17, Mage = 13.09, SDage = 3.05) and without (n = 18, Mage = 14.49, SDage = 2.38) anxiety disorders. Behavioral and physiological measures did not differ between children with and without anxiety disorders during fear acquisition. During testing, children with anxiety disorders showed overall higher skin conductance response and expected to hear the aversive sound following the novel compound more often than children without anxiety disorders. Children with anxiety disorders showed more activity in the right ventromedial prefrontal cortex (vmPFC) to the safety versus novel compound. Children without anxiety disorders showed the opposite pattern - more right vmPFC activity to the novel versus safety compound (F(1,31) = 5.40, p = 0.03). No group differences manifested within the amygdala, dorsal anterior cingulate cortex, or hippocampus. These pilot findings suggest a feasible approach for examining conditioned inhibition in pediatric anxiety disorders. If replicated in larger samples, findings may implicate perturbed conditioned inhibition in pediatric anxiety disorders and provide targets for CBT.

The Influence of Interactions with Dogs on Affect, Anxiety, and Arousal in Children.

Interactions with animals represent a promising way to reduce the burden of childhood mental illness on a large scale. However, the specific effects of child-animal interactions are not yet well-established. This study provides a carefully controlled demonstration that unstructured interactions with dogs can improve clinically relevant symptoms in children. Seventy-eight children (55.1% female, 44.9% male) ages 10 to 13 (M = 12.01, SD = 1.13) completed the Trier Social Stress Test for Children, followed by (a) interaction with a dog, (b) a tactile-stimulation control condition, or (c) a waiting control condition. The Positive and Negative Affect Schedule for Children, Short Form and the State/Trait Anxiety Inventory for Children were completed at baseline and posttest, and salivary cortisol was assessed at 5 time points. Adjusting for baseline scores, participants in the experimental condition showed higher scores on the Positive Affect scale than participants in both control conditions and lower scores on the State/Trait Anxiety Inventory for Children than participants in the waiting control condition at posttest. Negative affect was not assessed reliably, and we detected no effect of the interactions on salivary cortisol, as measured by area under the curve with respect to ground. Brief, unstructured interactions with dogs boosted children's positive emotions and reduced anxiety. Additional research is needed to further clarify which features of the interactions produce these benefits and the extent to which interactions with animals offer benefits that exceed the effects of other common coping strategies, activities, and interventions.