Functional and morphological alterations associated with working memory dysfunction in patients with generalized anxiety disorder

Background Generalized anxiety disorder (GAD) has been related to functional brain activities and structural brain abnormalities. Purpose To investigate the neural mechanism on working memory dysfunction in patients with GAD in terms of the combined functional and morphological brain abnormalities. Material and Methods Patients with GAD and healthy controls matched for age, sex, and education level underwent high-resolution T1-weighted (T1W) magnetic resonance imaging (MRI) and functional MRI (fMRI). In this study, fMRI and voxel-based morphometry (VBM) were used for assessing the differential brain activation patterns, as well as for comparing the morphological alterations between the two groups. Results In response to the neutral distractors, the patients showed significantly lower activities in the regions of the fusiform gyrus (FuG), superior parietal gyrus (SPG), precuneus (PCu), superior occipital gyrus (SOG), lingual gyrus (LiG), cuneus (Cun), calcarine cortex (CaC), parahippocampal gyrus (PHG) and cerebellar cortex (Cb) compared to the controls. In response to the anxiety-inducing distractors, the patients showed significantly higher activity in the hippocampus and lower activities in the regions of the dorsolateral prefrontal cortex (DLPFC), FuG, SPG, PCu, SOG, and Cb. Also, the patients showed a significant reduction of the white matter volumes in the DLPFC, anterior limb of the internal capsule (ALIC) and midbrain. Conclusion This study provides the first evidence for the association between the morphometric alterations and functional deficit in the working memory processing with the neutral and anxiety-inducing distractors in GAD patients. These findings would be helpful to understand the neural mechanisms on working memory impairment in connection with GAD symptoms.