Neurocognitive Predictors of Anxiety Risk Among Behaviorally Inhibited Children

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The temperament of behavioral inhibition (BI) is seen in approximately 10-15% of infants and it is among the earliest and strongest predictors of later anxiety. Nevertheless, around 50% of toddlers with high BI do not manifest anxiety problems in childhood or adolescence. Preliminary evidence suggests that cognitive control moderates BI-related anxiety risk, with higher risk among youth who rely more on reactive control strategies than on proactive control strategies. To date, work examining BI youth has largely measured cognitive control and anxiety concurrently, limiting the ability to predict future clinical outcomes. Moreover, the neural mechanisms underlying proactive and reactive control remain underspecified, partly because these two types of control may involve overlapping brain regions. This K23 application presents a research and training program that will support the applicant on a path toward becoming an NIH-funded independent investigator focused on neurocognitive mechanisms that moderate the early-life risk for emotional difficulties such as anxiety. The activities in this application build on the candidate’s prior training and are set in a resource-rich environment that will foster the development of expertise in 1) advanced neuroimaging analytic methods such as fMRI-constrained source localization of EEG, and 2) design, statistical analysis, and interpretation of longitudinal research to study changes in functioning over time. The current research proposal uses an accelerated longitudinal design and combines EEG and fMRI measures in a sample of 100 9- to 11-year-olds with and without a history of high BI. Proactive control, reactive control, and anxiety will each be assessed twice, 1 year apart. This design will allow the candidate to 1) test cross-sectional associations between neural measures of proactive/reactive control and child anxiety at baseline, 2) identify commonalities in neural substrates of cognitive control as measured across EEG and fMRI, and 3) test for temporal precedence of proactive and reactive control over anxiety. The overarching hypothesis is that, specifically among children with high BI, high reliance on reactive control and low reliance on proactive control prospectively predict worsening anxiety difficulties. This training and research program will facilitate the candidate’s transition to an independent research career, will inform the assessment and identification of youth at particularly high risk for future anxiety problems, and provide viable target mechanisms for early prevention efforts. RELEVANCE: The novel combined application of fMRI and EEG to the study of cognitive control will shed light on the unique contributions of proactive and reactive control on anxiety risk among youth with BI. This, coupled with a prospective longitudinal design, will help enhance prediction of anxiety outcomes among BI youth. In the long term, results may be used to inform: 1) the identification of BI youth at particularly elevated risk for future anxiety, and 2) the development of novel therapeutics to prevent or treat anxiety in this population.