Abstract
<h3>Background</h3> Threat anticipation engages neural circuitry that has evolved to promote defensive behaviours; perturbations in this circuitry could generate excessive threat-anticipation response, a key characteristic of pathological anxiety. Research into such mechanisms in youth faces ethical and practical limitations. Here, we use thermal stimulation to elicit pain-anticipatory psychophysiological response and map its correlates to brain structure among youth with anxiety and healthy youth. <h3>Methods</h3> Youth with anxiety (<i>n</i> = 25) and healthy youth (<i>n</i> = 25) completed an instructed threat-anticipation task in which cues predicted nonpainful or painful thermal stimulation; we indexed psychophysiological response during the anticipation and experience of pain using skin conductance response. High-resolution brain-structure imaging data collected in another visit were available for 41 participants. Analyses tested whether the 2 groups differed in their psychophysiological cue-based pain-anticipatory and pain-experience responses. Analyses then mapped psychophysiological response magnitude to brain structure. <h3>Results</h3> Youth with anxiety showed enhanced psychophysiological response specifically during anticipation of painful stimulation (<i>b</i> = 0.52, <i>p</i> = 0.003). Across the sample, the magnitude of psychophysiological anticipatory response correlated negatively with the thickness of the dorsolateral prefrontal cortex (<i>p</i><i><sub>FWE</sub></i> < 0.05); psychophysiological response to the thermal stimulation correlated positively with the thickness of the posterior insula (<i>p</i><i><sub>FWE</sub></i> < 0.05). <h3>Limitations</h3> Limitations included the modest sample size and the cross-sectional design. <h3>Conclusion</h3> These findings show that threat-anticipatory psychophysiological response differentiates youth with anxiety from healthy youth, and they link brain structure to psychophysiological response during pain anticipation and experience. A focus on threat anticipation in research on anxiety could delineate relevant neural circuitry.
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