Resting-State Amygdala Subregion and Precuneus Connectivity Provide Evidence for a Dimensional Approach to Studying Social Anxiety Disorder

Abstract

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.

Informing the treatment of social anxiety disorder with computational and neuroimaging data

“…1C ), this method also demonstrates low replicability (Ashar et al ., 2021 ) reflecting issues concerning the reliability of fMRI measures (Noble et al ., 2019 ) and the heterogeneity of mental health disorders (Forbes et al ., 2023 ). As one example, significant within-group differences observed in precuneus and amygdala rsFC among individuals with SAD, in the absence of any group-level difference with healthy controls (Mizzi et al ., 2024 ), further necessitates an approach accounting for patient heterogeneity when employing a predictive (neural) model (Talmon et al ., 2021 ).…”