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.

Aberrant pulvinar effective connectivity in generalized social anxiety disorder

“…Heightened functional reactivity of thalamus was also reported in several studies in which subjects with gSAD performed emotionally laden visual processing tasks. [23–25] In a resting-state fMRI functional connectivity analysis by Arnold Anteraper et al, [26] hyperconnectivity of thalamus was detected with the precuneus, interior temporal, and parahippocampal regions. Findings of our study expand on the literature of thalamus dysfunction in gSAD by focusing on a more specific anatomical part of thalamus, pulvinar, and applying directed (effective) connectivity method for investigating causal dynamics of involved brain regions that to the best of our knowledge has not been used to investigate thalamus or pulvinar causal network behavior in generalized social anxiety disorder.…”

Reward Prediction Error Signaling during Reinforcement Learning in Social Anxiety Disorder is altered by Social Observation

“…Earlier studies have reported aberrant functional connectivity (FC) in SAD in DMPFC. Heitmann et al (2016) identified hyperconnectivity of globus pallidus with DMPFC during presentation of disorder-related scenes. Gimenez et al (2014) also reported differences in FC between SAD and HC in regions of medial frontal cortex.…”

“…As RPEs are a likely candidate mechanism for the modulation of connection strength between regions (den Ouden et al, 2011), another aim of the present study was to assess differences in effective connectivity between SAD and HC. In an earlier study, Heitmann et al (2016) identified aberrant functional connectivity in both DMPFC and VS in SAD. Based on their findings, we used Dynamic Causal Modelling to model dependencies between the mentalizing network and the reward network.…”

“…DMPFC has also been shown to respond to the perception of scrutiny (Gimenez et al, 2012, Becker et al, 2014). In SAD, socially evaluative contexts trigger differential responses in VS (Becker, Simon, et al, 2017) as well as in regions of medial prefrontal cortex (MPFC, Pujol et al, 2013), and alter functional connectivity patterns (Gimenez et al, 2012, Heitmann et al, 2016). In particular, performance feedback given to SAD patients during social observation (Becker et al, 2017) has been linked to these alterations in network activation.…”

“…We expected observation to modulate RPEs in SAD patients. Analogous to the socio-emotional hypersensitivity they typically exhibit in evaluative social situations and based on findings from several lines of research, we expected SAD patients to show hypersensitive response signatures in medial prefrontal cortex (Voegeler et a., 2019; Bas-Hogendam et al, 2019, Heitmann et al, 2016). Based on these studies’ coordinates, we hypothesized an interaction of observation and PEs would recruit Area 9 of DMPFC.…”