Neurocircuitry of Generalized Anxiety Disorder in Adolescents: A Pilot Functional Neuroimaging and Functional Connectivity Study

Abstract

In addition to increased activation of the medial prefrontal cortex and right VLPFC, we observed altered connectivity between the amygdala or VLPFC and regions, which subserve mentalization (e.g. posterior cingulate cortex, precuneus, and medial prefrontal cortex). This suggests that structures that regulate emotion and affect interact abnormally with key structures that are involved in mentalization, a process known to be disrupted in GAD.

Neural Function Before and After Mindfulness-Based Cognitive Therapy in Anxious Adolescents at Risk for Developing Bipolar Disorder

“…Subjects completed the fMRI session in which whole-brain images (volumes) were acquired every 2 seconds while they were performing the continuous processing task with emotional and neutral distracters (CPT-END) (Yamasaki et al 2002) using a T2*-weighted gradient-echo echoplanar imaging (EPI) pulse sequence. The CPT-END, which has been utilized in pediatric patients with anxiety disorders (Strawn et al 2012a), utilizes a visual oddball paradigm in which 70% of the cues are simple, colored squares, 10% are simple colored circles (targets), 10% are emotionally neutral pictures, and 10% are emotionally unpleasant pictures, with the neutral and emotional distractors (fear and disgust-evoking images) that originated from the International Affective Picture System (University of Florida, Gainesville, Florida). In response to each visual cue, participants provided a unique response: Button 2 when presented with a colored circle (target) and button 1 when presented with the other stimuli.…”

“…In this task, subjects distinguished targets from frequent background shapes and interspersed novel images varied for emotional valence. Consequently, the CPT-END is an ideally suited cognitive-emotional probe for studying treatment-associated changes in pediatric patients with anxiety disorders (Strawn et al 2012a). Anatomic and fMRI data were co-registered and fMRI data were motion corrected.…”

“…Specifically, regression analyses were performed for PARS score and BOLD signal (in response to emotional images) in regions of interest (ROIs) based on regions in which significant treatment-related differences were observed in the more conservative voxelwise analysis. The ROI activation in response to emotional images was extracted from measurements obtained from the neuroanatomic scans using semiautomatic segmentation (gray and white matter) and volumetric analyses performed as previously described (Strakowski et al, 2011;Strawn et al 2012a). Findings were considered statistically significant at the p < 0.05 level.…”

“…anxiety symptoms, suggesting a compensatory role for this structure in anxiety (Strawn et al 2012a). This finding is consistent with one prior study of mindfulness training in marines who demonstrated training-associated changes in anterior insula and ACC activation during loaded breathing, a paradigm that assesses responsiveness to aversive stimuli, suggesting modification of a neural substrate for the processing of aversive and interoceptive stimuli (Haase et al 2014), at least in young adults.…”

“…These two structures were examined given their central role in the pathophysiology of anxiety. In this regard, most fMRI studies of youth with anxiety disorders suggest increased activation of the VLPFC (Monk et al 2006;McClure et al 2007;Guyer et al 2008;Monk et al 2008;Beesdo et al 2009;Strawn et al 2012a) and also suggest structural deficits in this region in children and adolescents with anxiety disorders . The VLPFC subserves a number of regulatory functions, including modulation of amygdala activity (Monk et al 2008) and is responsible for conscious regulation of affect (Phillips et al 2008).…”