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1. Context. Vigilance to threat is a key feature of generalized anxiety disorder (GAD). The amygdala and ventrolateral prefrontal cortex comprise a neural circuit that is responsible for detection of threats. Disturbed interactions between these structures may underlie pediatric anxiety. To date, no study has selectively examined responses to briefly-presented threats (e.g. less than 50 msec) in GAD or in pediatric anxiety.

2. Objective. To investigate amygdala and ventrolateral prefrontal cortex activation during processing of briefly-presented threats in pediatric GAD.

3. Design. Case-control study.

4. Setting. Government clinical research institute.

5. Participants. Youth volunteers, 17 with GAD and 12 diagnosis-free.

6. Main Outcome Measures. We used functional magnetic resonance imaging to measure blood oxygenation level-dependent signal. During imaging, subjects performed an attention orienting task with rapidly presented (17 msec), masked emotional (angry or happy) and neutral faces.

7. Results. When viewing masked angry faces, GAD youth, relative to comparison subjects, showed greater right amygdala activation that positively correlates with anxiety disorder severity. Moreover, in a functional connectivity (psychophysiological interaction) analysis, right amygdala and right ventrolateral prefrontal cortex showed strong negative coupling specifically to masked angry faces. This negative coupling tended to be weaker in GAD youth than in comparisons.

Conclusions. GAD youth have hyper-activation of the amygdala to briefly-presented, masked threats. The presence of threat-related negative connectivity between the right ventrolateral prefrontal cortex and amygdala suggests that the prefrontal cortex modulates amygdala response to threat. In pediatric GAD, hyper-amygdala response occurs in the absence of a compensatory increase in modulation by ventrolateral prefrontal cortex.


Published as:

Monk, C.S., Telzer, E.H., Mogg, K., Bradley, B. P., Xiaoqin, M., McClure-Tone, E.B., Ernst, M., & Pine, D.S., (2008). Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. Archives of General Psychiatry, 65(5), 568-576. DOI: 10.1001/archpsyc.65.5.568

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