Atypical modulation of medial prefrontal cortex to self-referential comments in generalized social phobia

Abstract

Generalized social phobia (GSP) involves the fear of being negatively evaluated. Previous work suggests that self-referentiality, mediated by medial prefrontal cortex (MFPC), plays an important role in the disorder. However, it is not clear whether this anomalous MPFC response to selfrelated information in patients with GSP concerns an increased representation of their own or others' opinions. In this paper we examined whether GSP is associated with increased response to own (1 st person) or other individuals' (2 nd person) opinions relative to healthy individuals. Unmedicated individuals with GSP (n=15) and age, IQ, and gender-matched comparison individuals (n=15) read 1 st (e.g., I'm ugly), and 2 nd (e.g., You're ugly) person viewpoint comments during fMRI. We observed significant group-by-viewpoint interactions within ventral MPFC. Whereas the healthy comparison individuals showed significantly increased (or less decreased) BOLD responses to 1 st relative to 2 nd person viewpoints, the patients showed significantly increased responses to 2 nd relative to 1 st person viewpoints. The reduced BOLD responses to 1 st person viewpoint comments shown by the patients correlated significantly with severity of social anxiety symptom severity. These results underscore the importance of dysfunctional selfreferential processing and MPFC in GSP. We believe that these data reflect a reorganization of self-referential reasoning in the disorder with a self-concept perhaps atypically related to the view of others.

Fear of negative evaluation is associated with altered brain function in nonclinical subjects

“…The self-referential network has been associated with the inhibition or extinction of excessive corticolimbic activity (LeDoux, 1998) and altered self-reference in SAD (Blair et al, 2011;Liao et al, 2010). As there is a prominent cognitive behavioral model of SAD, which hypothesizes a tendency toward increased self-awareness and monitoring as a response to fear of being observed and evaluated by others (Liao et al, 2010;Rapee and Heimberg, 1997), our results indicated alteration of self-referential processing, even in nonclinical populations.…”

Learning from other people's fear: amygdala-based social reference learning in social anxiety disorder

“…Previous work has shown that this population shows heightened medial frontal cortical responses to self-relevant material (Blair et al . 2008 a , 2010, 2011 b ; Goldin & Gross, 2010). Moreover, self-referential processing has been shown to recruit the cortical midline structure from ventromedial and rostral regions to the posterior cingulate cortex (Amodio & Frith, 2006; Northoff et al .…”

Impaired self-awareness in human addiction: deficient attribution of personal relevance

“…In another dissociation, healthy controls and individuals with social phobia (who fear being negatively evaluated by others) were exposed to evaluative phrases that were presented either in the first person (e.g., “I’m ugly”) or in the second person (e.g., “You’re ugly”). Healthy controls had higher vmPFC activity during first- versus second-person phrases, whereas individuals with social phobia had higher vmPFC activity during the reverse contrast (23) – presumably of high personal relevance to this psychopathology.…”