Amygdala and Ventrolateral Prefrontal Cortex Activation to Masked Angry Faces in Children and Adolescents With Generalized Anxiety Disorder

Abstract

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.

Future Directions in Emotion Dysregulation and Youth Psychopathology

“…Thus, consistent with a primary theme of this article, effective emotion regulation requires top-down, prefrontal inhibition of subcortical structures that generate affective experiences (e.g., Ochsner & Gross, 2005). As previously noted, and similar to findings reported among adults, a limited number of neuroimaging studies indicate that children and adolescents with anxiety disorders exhibit less functional connectivity in amygdalar-prefrontal connections than controls (e.g., Monk et al, 2008) and that adolescents with externalizing disorders exhibit less functional connectivity in striatal-prefrontal connections than controls (e.g., Shannon et al, 2009). Of interest, anxiety-disordered adults also require greater PFC involvement than controls to effectively regulate negative emotion (e.g., Campbell-Sills et al, 2011).…”

“…Volitional regulation of anxiety occurs through lateral prefrontal inhibition of amygdalar activity and reactivity, whereas volitional regulation of impulsivity occurs through orbitofrontal and dorsolateral prefrontal inhibition of striatal activity and reactivity (see Davidson, 2002;Heatherton, 2011;Heatherton & Wagner, 2011). Children and adolescents with anxiety disorders exhibit less functional connectivity in amygdalar-ventrolateral prefrontal connections than controls (e.g., Monk et al, 2008), and adolescents with externalizing disorders exhibit less functional connectivity in striatal-anterior cingulate connections than controls (e.g., Shannon, Sauder, Beauchaine, & Gatzke-Kopp, 2009). Deficient top-down control of the amygdala by the medial PFC, and reduced functional connectivity between the amygdala and the orbitofrontal cortex, are implicated in emotional lability and deficient self-regulation (see Churchwell, Morris, Heurtelou, & Kesner, 2009;Hilt, Hanson, & Pollak, 2011).…”

Activation of GABAA receptors in the medial prefrontal cortex produces an anxiolytic-like response

“…A study on anxious youth using selective imaging of the amygdala showed that patients showed greater response to threat-related facial expressions and increased amygdala activation and abnormal ventral PFC responses. These neural abnormalities may be responsible for regulatory processes of anxietyrelated behaviours (4,31). Only the role of GABA receptors in the mPFC has been evaluated in the present study.…”

Introduction to the Special Issue: Understanding the Role of Attentional Control in the Development of Anxiety in Childhood, Adolescence and across the Lifespan

“…Developmental research has found enhanced sensitivity in the amygdala in children who experience elevated anxiety and in the context of threat or uncertainty (e.g., Williams et al, 2015). Other studies have found reduced functional connectivity between the amygdala with the PFC associated with elevated trait anxiety in adolescents (Hare et al, 2008;Monk et al, 2008; review by Lau & Pine, 2008) and in young children who meet the diagnostic criteria for an anxiety disorder (Carpenter et al, 2015).…”