Of ‘Disgrace’ and ‘Pain’ – Corticolimbic Interaction Patterns for Disorder-Relevant and Emotional Words in Social Phobia

Abstract

Limbic hyperactivation and an impaired functional interplay between the amygdala and the prefrontal cortex are discussed to go along with, or even cause, pathological anxiety. Within the multi-faceted group of anxiety disorders, the highly prevalent social phobia (SP) is characterized by excessive fear of being negatively evaluated. Although there is widespread evidence for amygdala hypersensitivity to emotional faces in SP, verbal material has rarely been used in imaging studies, in particular with an eye on disorder-specificity. Using functional magnetic resonance imaging (fMRI) and a block design consisting of (1) overall negative, (2) social-phobia related, (3) positive, and (4) neutral words, we studied 25 female patients with social phobia and 25 healthy female control subjects (HC). Results demonstrated amygdala hyperactivation to disorder-relevant but not to generally negative words in SP patients, with a positive correlation to symptom severity. A functional connectivity analysis revealed a weaker coupling between the amygdala and the left middle frontal gyrus in patients. Symptom severity was negatively related to connectivity strength between the amygdala and the ventromedial prefrontal and orbitofrontal cortex (Brodmann Area 10 and 11). The findings clearly support the view of a hypersensitive threat-detection system, combined with disorder-related alterations in amygdala-prefrontal cortex connectivity in pathological anxiety.

White matter integrity in brain networks relevant to anxiety and depression: evidence from the human connectome project dataset

“…With regard to the salience and error detection network (CON), the WM between the anterior PFC (BA 10) and amygdala showed reduced integrity in relation to anxiety-depression. Here, our findings are consistent with reduced fronto-limbic connectivity found in generalized anxiety disorder (Etkin et al 2009), lower functional coupling between amygdala and BA 10 with increasing social phobia severity (Laeger et al 2014), and weaker functional connectivity between BA 10 and amygdala elicited by negative stimuli with increasing severity of depression and anxiety in patients with major depression (Friedel et al 2009). Etkin et al (2009) speculate that reduced connectivity between the amygdala and the CON might be associated with dysfunctions in the modulation of the autonomic nervous system.…”

Oxytocin Receptor Gene Methylation: Converging Multilevel Evidence for a Role in Social Anxiety

“…A total of 25 female patients (age ¼ 28.8 þ 8.3 years þ SD) with current SAD according to DSM-IV criteria (SCID-I) constituting a subsample of the overall sample of SAD patients described above also took part in an fMRI experiment assessing amygdala responsiveness to social phobia-relevant verbal stimuli in relation to OXTR methylation status. This patient subsample and the fMRI task have been described elsewhere (Laeger et al, 2014a), with patients showing greater amygdala responsiveness to social phobiarelated words than to generally negative words when compared with healthy controls. All patients fulfilled the inclusion/exclusion criteria mentioned above for the overall sample and did not take any psychotropic medication including benzodiazepines.…”

Repeated noninvasive stimulation of the ventromedial prefrontal cortex reveals cumulative amplification of pleasant compared to unpleasant scene processing: A single subject pilot study

“…More precisely, the vmPFC shows increased activation patterns specifically for stimuli with pleasant content in comparison to unpleasant or neutral stimuli [3][4][5][6][7][8]. Furthermore, several psychiatric disorders were shown to be linked-amongst others-to dysfunctional processing in vmPFC regions [9][10][11][12][13].…”