Cognitive Neural Mechanism of Social Anxiety Disorder: A Meta-Analysis Based on fMRI Studies

Background: Social anxiety disorder (SAD) is a prevalent and disabling mental health condition, characterized by excessive fear and anxiety in social situations. Resting-state functional magnetic resonance imaging (fMRI) paradigms have been increasingly used to understand the neurobiological underpinnings of SAD in the absence of threat-related stimuli. Previous studies have primarily focused on the role of the amygdala in SAD. However, the amygdala consists of functionally and structurally distinct subregions, and recent studies have highlighted the importance of investigating the role of these subregions independently. Method: Using multiband fMRI, we analyzed resting-state data from 135 participants (42 SAD, 93 healthy controls). By employing voxel-wise permutation testing, we examined group differences of fMRI connectivity and associations between fMRI connectivity and social anxiety symptoms to further investigate the classification of SAD as a categorical or dimensional construct. Results: Seed-to-whole brain functional connectivity analysis using multiple seeds including the amygdala and its subregions and the precuneus, revealed no statistically significant group differences. However, social anxiety severity was significantly negatively correlated with functional connectivity of the precuneus - perigenual anterior cingulate cortex and positively correlated with functional connectivity of the amygdala (specifically the superficial subregion) - parietal/cerebellar areas. Conclusion: Our findings demonstrate clear links between symptomatology and brain connectivity in the absence of diagnostic differences, with evidence of amygdala subregion-specific alterations. The observed brain-symptom associations did not include disturbances in the brains fear circuitry (i.e., disturbances in connectivity between amygdala - prefrontal regions) likely due to the absence of threat-related stimuli.

Social anxiety disorder (SAD) is a mental disorder characterized by excessive anxiety in social situations. This study aimed to examine the alteration of resting-state functional connectivity in SAD patients related to the virtual reality-based self-training (VRS) which enables exposure to social situations in a controlled environment. Fifty-two SAD patients were randomly assigned to the experimental group who received the VRS, or the control group who did not. Self-report questionnaires and resting-state functional magnetic resonance imaging (fMRI) were performed to assess clinical symptoms and analyze the resting-state network properties, respectively. Significant decrease in social anxiety and an increase in self-esteem was found in the experimental group. From the resting-state fMRI analysis, alteration of local network properties in the left dorsolateral prefrontal gyrus (-10.0%, p = 0.025), left inferior frontal gyrus (-32.3%, p = 0.044), left insula (-17.2%, p = 0.046), left Heschl's gyrus (-21.2%, p = 0.011), bilateral inferior temporal gyrus (right: +122.6%, p = 0.045; left:−46.7%, p = 0.015), and right calcarine sulcus (+17.0%, p = 0.010) were found in the experimental group. Average shortest path length (+8.3%, p = 0.008) and network efficiency (-7.6%, p = 0.011) are found to be altered from the global network property analysis. In addition, the experimental group displayed more positive and more negative changes in the correlation trend of average shortest path length (p = 0.004) and global network efficiency (p = 0.014) with the severity of social anxiety, respectively. These results suggest potential effectiveness of the VRS, which is possibly related to the change of aberrant processing and control of visual and auditory linguistic stimuli and the adaptive change in rumination pattern.

Social anxiety disorder (SAD) is a prevalent and disabling mental health condition, characterized by excessive fear and anxiety in social situations. Resting-state functional magnetic resonance imaging (fMRI) paradigms have been increasingly used to understand the neurobiological underpinnings of SAD in the absence of threat-related stimuli. Previous studies have primarily focused on the role of the amygdala in SAD. However, the amygdala consists of functionally and structurally distinct subregions, and recent studies have highlighted the importance of investigating the role of these subregions independently. Using multiband fMRI, we analyzed resting-state data from 135 participants (42 SAD, 93 healthy controls). By employing voxel-wise permutation testing, we examined group differences of fMRI connectivity and associations between fMRI connectivity and social anxiety symptoms to further investigate the classification of SAD as a categorical or dimensional construct. Seed-to-whole brain functional connectivity analysis using multiple ‘seeds’ including the amygdala and its subregions and the precuneus, revealed no statistically significant group differences. However, social anxiety severity was significantly negatively correlated with functional connectivity of the precuneus - perigenual anterior cingulate cortex and positively correlated with functional connectivity of the amygdala (specifically the superficial subregion) - parietal/cerebellar areas. Our findings demonstrate clear links between symptomatology and brain connectivity in the absence of diagnostic differences, with evidence of amygdala subregion-specific alterations. The observed brain-symptom associations did not include disturbances in the brain’s fear circuitry (i.e., disturbances in connectivity between amygdala - prefrontal regions) likely due to the absence of threat-related stimuli.