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Altered Prefrontal Cortex Function Marks Heightened Anxiety Risk in Children.

ABSTRACT: Anxiety disorders are prevalent and cause substantial disability. An important risk factor for anxiety disorders is inhibited temperament, the tendency to be shy and to avoid new situations. Inhibited adults have heightened amygdala activation and less flexible engagement of the prefrontal cortex (PFC); however, it remains unknown whether these brain alterations are present in inhibited children before the onset of anxiety disorders.A total of 37 children (18 inhibited and 19 uninhibited), 8 to 10 years of age, completed a task testing anticipation and viewing of threat stimuli and social stimuli in the magnetic resonance imaging (MRI) scanner. Brain activation and functional connectivity were measured.During the anticipation of threat stimuli, inhibited children failed to show the robust PFC engagement observed in the uninhibited children. In contrast, when viewing social stimuli, inhibited children had increased medial PFC and dorsolateral PFC activation. Connectivity analyses revealed a pattern of reduced connectivity between prefrontal and limbic regions and among distinct PFC regions in the inhibited group. The medial PFC emerged as a key hub of the altered PFC circuitry in inhibited children.This study provides new evidence of a neural signature of vulnerability to anxiety disorders. By investigating both anticipation and response to images, we identified that high-risk, inhibited children have widespread alterations in PFC function and connectivity, characterized by an inability to proactively prepare for social threat combined with heightened reactivity to social stimuli. Thus, children at high risk for anxiety show significantly altered prefrontal cortical function and connectivity before the onset of anxiety disorders.

SUBMITTER: Clauss JA

PROVIDER: S-EPMC5003319 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Altered Prefrontal Cortex Function Marks Heightened Anxiety Risk in Children.

Clauss Jacqueline Alexandra JA Benningfield Margaret M MM Rao Uma U Blackford Jennifer Urbano JU

Journal of the American Academy of Child and Adolescent Psychiatry 20160701 9

<h4>Objective</h4>Anxiety disorders are prevalent and cause substantial disability. An important risk factor for anxiety disorders is inhibited temperament, the tendency to be shy and to avoid new situations. Inhibited adults have heightened amygdala activation and less flexible engagement of the prefrontal cortex (PFC); however, it remains unknown whether these brain alterations are present in inhibited children before the onset of anxiety disorders.<h4>Method</h4>A total of 37 children (18 inh ...[more]

PMID: 27566122

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Project description:BackgroundAnxiety and stress reactivity are risk factors for the development of affective disorders. However, the behavioral and neurocircuit mechanisms that potentiate maladaptive emotion regulation are poorly understood. Neuroimaging studies have implicated the amygdala and dorsolateral prefrontal cortex (DLPFC) in emotion regulation, but how anxiety and stress alter their context-specific causal circuit interactions is not known. Here, we use computational modeling to inform affective pathophysiology, etiology, and neurocircuit targets for early intervention.MethodsForty-five children (10-11 years of age; 25 boys) reappraised aversive stimuli during functional magnetic resonance imaging scanning. Clinical measures of anxiety and stress were acquired for each child. Drift-diffusion modeling of behavioral data and causal circuit analysis of functional magnetic resonance imaging data, with a National Institute of Mental Health Research Domain Criteria approach, were used to characterize latent behavioral and neurocircuit decision-making dynamics driving emotion regulation.ResultsChildren successfully reappraised negative responses to aversive stimuli. Drift-diffusion modeling revealed that emotion regulation was characterized by increased initial bias toward positive reactivity during viewing of aversive stimuli and increased drift rate, which captured evidence accumulation during emotion evaluation. Crucially, anxiety and stress reactivity impaired latent behavioral dynamics associated with reappraisal and decision making. Anxiety and stress increased dynamic casual influences from the right amygdala to DLPFC. In contrast, DLPFC, but not amygdala, reactivity was correlated with evidence accumulation and decision making during emotion reappraisal.ConclusionsOur findings provide new insights into how anxiety and stress in children impact decision making and amygdala-DLPFC signaling during emotion regulation, and uncover latent behavioral and neurocircuit mechanisms of early risk for psychopathology.

Dataset Information

Altered Prefrontal Cortex Function Marks Heightened Anxiety Risk in Children.

Publications

Altered Prefrontal Cortex Function Marks Heightened Anxiety Risk in Children.

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