Precuneus-related regional and network functional deficits in social anxiety disorder: A resting-state functional MRI study

Abstract

BackgroundNeuroimaging findings suggest that social anxiety disorder (SAD) may be correlated with changes in regional- or network-level brain function. However, few studies have explored alterations in intrinsic resting cerebral function in patients with SAD at both the regional and network levels, particularly focusing on the theory of mind (ToM)-related regions. This study was performed to investigate changes in neural activity and functional connectivity (FC) in ToM-related regions during the resting state in SAD patients and to determine how these alterations are correlated with the clinical symptoms of SAD. MethodsForty-three SAD patients and 43 matched healthy controls underwent resting-state functional magnetic resonance imaging (rsfMRI) scans. First, the amplitude of low-frequency fluctuation (ALFF) approach was used to explore regional activity. Then, the ToM-related region, i.e., the left precuneus, which showed altered ALFF values, was adopted as a seed for further FC analyses to assess network-level alterations in SAD. Between-group differences were compared using voxel-based two-sample t-tests (P<0.05, with Gaussian random field correction). Pearson's correlation analyses were performed to examine relationships between alterations in ALFF and FC and clinical symptoms. ResultsCompared with the healthy controls, SAD patients showed decreased ALFF in the bilateral putamen (PUT) and left supplementary motor area (SMA) and increased ALFF in the right inferior parietal lobule (IPL), left precuneus and right cerebellar posterior lobe. Moreover, SAD patients exhibited lower connectivity between the left precuneus and the cerebellar posterior lobe, right inferior temporal gyrus (ITG), right parahippocampal gyrus (PHG) and left medial prefrontal cortex (mPFC). The altered ALFF values in the left precuneus and the hypoconnectivity between the left precuneus and left cerebellar posterior lobe were correlated with the patients' clinical symptoms (P<0.05). ConclusionThe precuneus, a ToM-related region, was altered at both the regional and network level in patients with SAD. Pathological fear and avoidance in SAD were correlated with abnormal regional function in the precuneus, whereas depression and anxiety were primarily correlated with functional deficits in the precuneus-related network. The altered FC within the precuneus-cerebellar region may reflect an imbalance in the neuromodulation of anxiety and depressive symptoms in SAD. These findings may facilitate a greater understanding of potential SAD neural substrates and could be used to identify potential targets for further treatment.