Abnormal brain activation and connectivity to standardized disorder-related visual scenes in social anxiety disorder

Abstract

Our understanding of altered emotional processing in social anxiety disorder (SAD) is hampered by a heterogeneity of findings, which is probably due to the vastly different methods and materials used so far. This is why the present functional magnetic resonance imaging (fMRI) study investigated immediate disorder-related threat processing in 30 SAD patients and 30 healthy controls (HC) with a novel, standardized set of highly ecologically valid, disorder-related complex visual scenes. SAD patients rated disorder-related as compared with neutral scenes as more unpleasant, arousing and anxiety-inducing than HC. On the neural level, disorder-related as compared with neutral scenes evoked differential responses in SAD patients in a widespread emotion processing network including (para-)limbic structures (e.g. amygdala, insula, thalamus, globus pallidus) and cortical regions (e.g. dorsomedial prefrontal cortex (dmPFC), posterior cingulate cortex (PCC), and precuneus). Functional connectivity analysis yielded an altered interplay between PCC/precuneus and paralimbic (insula) as well as cortical regions (dmPFC, precuneus) in SAD patients, which emphasizes a central role for PCC/precuneus in disorder-related scene processing. Hyperconnectivity of globus pallidus with amygdala, anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) additionally underlines the relevance of this region in socially anxious threat processing. Our findings stress the importance of specific disorder-related stimuli for the investigation of altered emotion processing in SAD. Disorder-related threat processing in SAD reveals anomalies at multiple stages of emotion processing which may be linked to increased anxiety and to dysfunctionally elevated levels of self-referential processing reported in previous studies.

Keywords: amygdala; default-mode-network; globus pallidus; precuneus; psychophysiological interaction; self-referential processing; social phobia.

Figure 1

Mean valence, arousal and anxiety ratings for disorder‐related and neutral scenes in patients suffering from social anxiety disorder (SAD) and healthy controls (HC). Asterisks mark significant differences (P ≤ 0.0125). [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 2

Differential brain activations during disorder‐related versus neutral scene processing in patients suffering from social anxiety disorder (SAD) as compared with healthy controls (HC). Statistical parametric maps are overlaid on a T1 scan (P < 0.005 uncorrected, P < 0.05 corrected; radiological convention: left (L) = right (R)). SAD patients display enhanced activation in corticomedial amygdala (y = 5), insula (y = 9), thalamus (x = −5), globus pallidus (z = 2), dorsomedial prefrontal cortex (dmPFC) (x = 5), posterior cingulate cortex (PCC)/precuneus (x = −10), left precuneus (x = −10) and right precuneus (x = 6). Diagrams show contrasts of parameter estimates (disorder‐related versus neutral; mean ± SE). [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 3

Differential psychophysiological interactions in patients suffering from social anxiety disorder (SAD) and healthy controls (HC) seeded from posterior cingulate cortex (PCC)/precuneus with findings (all SAD > HC) in insula (y = −18), left precuneus (x = −4) and right precuneus (x = 7), as well as seeded from dorsomedial prefrontal cortex (dmPFC) with a finding (HC > SAD) in PCC/precuneus (x = −4). Statistical parametric maps are overlaid on a T1 scan (P < 0.005 uncorrected, P < 0.05 corrected; radiological convention: left (L) = right (R)). Diagrams show contrasts of parameter estimates (disorder‐related versus neutral; mean ± SE). [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 4

Differential psychophysiological interactions in patients suffering from social anxiety disorder (SAD) and healthy controls (HC) seeded from globus pallidus with findings (all SAD > HC) in basolateral amygdala (y = −4), anterior cingulate cortex (ACC; x = 5) and medial prefrontal cortex (mPFC; x = 3). Statistical parametric maps are overlaid on a T1 scan (P < 0.005 uncorrected, P < 0.05 corrected; radiological convention: left (L) = right (R)). Diagrams show contrasts of parameter estimates (disorder‐related versus neutral; mean ± SE). [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]