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Monk CS, Telzer EH, Mogg K, Bradley BP, Mai XQ, Louro HMC et al. Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. Arch Gen Psychiat 65: 568-576

Department of Psychology, University of Michigan, 530 Church St, Ann Arbor, MI 48109-1043, USA.
Archives of general psychiatry (Impact Factor: 13.75). 06/2008; 65(5):568-76. DOI: 10.1001/archpsyc.65.5.568
Source: PubMed

ABSTRACT Vigilance for threat is a key feature of generalized anxiety disorder (GAD). The amygdala and the ventrolateral prefrontal cortex constitute 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 in GAD or in pediatric anxiety.
To investigate amygdala and ventrolateral prefrontal cortex activation during processing of briefly presented threats in pediatric GAD.
Case-control study.
Government clinical research institute.
Youth volunteers, 17 with GAD and 12 without a psychiatric diagnosis.
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 milliseconds) masked emotional (angry or happy) and neutral faces.
When viewing masked angry faces, youth with GAD relative to comparison subjects showed greater right amygdala activation that positively correlated with anxiety disorder severity. Moreover, in a functional connectivity (psychophysiological interaction) analysis, the right amygdala and the right ventrolateral prefrontal cortex showed strong negative coupling specifically to masked angry faces. This negative coupling tended to be weaker in youth with GAD than in comparison subjects.
Youth with GAD have hyperactivation of the amygdala to briefly presented masked threats. The presence of threat-related negative connectivity between the right ventrolateral prefrontal cortex and the amygdala suggests that the prefrontal cortex modulates the amygdala response to threat. In pediatric GAD, amygdala hyperresponse occurs in the absence of a compensatory increase in modulation by the ventrolateral prefrontal cortex.

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    • "during early, rapid processing of emotions (Monk et al., 2008; Nomura et al., 2004). Aberrant automatic processing of emotional faces (e.g., angry, happy faces) may contribute to the mood dysregulation and interpersonal difficulties in irritable youth. "
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    ABSTRACT: Reproducibility of results is important in improving the robustness of conclusions drawn from research, particularly in fMRI. In this study, we aim to replicate a previous study on the neural correlates of face emotion processing above and below awareness level using an independent sample of youth with severe mood dysregulation (SMD) and healthy volunteers (HV). We collected fMRI data in 17 SMD and 20 HV, using an affective priming paradigm with masked (17ms) and unmasked (187ms) faces (angry, happy, neutral, blank oval). When processing masked and unmasked angry faces, SMD patients exhibited increased activation in the parahippocampal gyrus and superior temporal gyrus relative to HV. When processing masked and unmasked happy faces, SMD patients showed decreased activation in the insula, parahippocampal gyrus, and thalamus compared to HV. During masked face processing in general across emotions, youth with SMD showed greater ventromedial prefrontal cortex (vmPFC) activation relative to HV. Perturbed activation in emotion processing areas (e.g., insula, parahippocampal gyrus, superior temporal gyrus, thalamus) manifest as hyper-sensitivity towards negative emotions and hypo-sensitivity towards positive emotions may be important in the etiology and maintenance of irritability, aggression, and depressive symptoms in SMD. vmPFC dysfunction may mediate over-reactivity to face emotions associated with irritability. Published by Oxford University Press 2015. This work is written by US Government employees and is in the public domain in the US.
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    • "many features of early stress models that make them amenable to translation across species . Specifically , neural circuits that are affected by early stress , and those which support fear learning and attachment , are highly preserved across different species ( e . g . , rodents and primates ; Lissek et al . , 2005 ; Milad et al . , 2008 , 2009 ; Monk et al . , 2008 ) . Also , the infant - caregiver relationship is critical for infant survival in all altricial mammals ( due to complete dependence upon the caregiver at birth ) , suggesting that maternal - deprivation / separation and abuse represent ecologically valid models of disruption in exposure to a species - expected stimulus ."
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    Developmental Psychobiology 12/2014; 56(8). DOI:10.1002/dev.21260 · 3.16 Impact Factor
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    • "Functional neuroimaging studies of pediatric patients with GAD suggest dysfunction within the anterior limbic network, a collection of subcortical and cortical structures involved in the modulation and expression of complex affective states (Beesdo et al., 2009; McClure et al., 2007; Monk et al., 2006, 2008; Strawn, Wehry, et al., 2012; Strawn et al., in press). Specifically, this research suggests hyperactivation of amygdala (Beesdo et al., 2009; Monk et al., 2008) as well as ventrolateral prefrontal cortex (Beesdo et al., 2009; Guyer, Lau, & McClure-Tone, 2008; McClure et al., 2007; Strawn, Bitter, et al., 2012) and ventromedial prefrontal cortex (Strawn, Bitter, et al., 2012) in addition to altered functional connectivity among these structures (McClure et al., 2007; Strawn, Bitter, et al., 2012). In parallel, neurostructural studies of the circuits that subserve emotional processing have identified abnormalities in structures within (De Bellis et al., 2000, 2002; Milham et al., 2005; Mueller et al., 2013) and beyond the anterior limbic network (Strawn, Wehry, et al., 2013). "
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