Altered brain function in treatment-resistant depression patients: A resting-state functional magnetic resonance imaging study

Background: It has been established that there are functional changes in the brain of treatment-resistant depression (TRD) patients, but previous studies of functional connectivity (FC) usually involved selection of regions of interest based on accumulated a priori knowledge of the disorder. In this study, we combine amplitude of low-frequency fluctuation (ALFF) and FC; this approach, based on the abnormal ALFF, may provide some insights into the neural basis of the disease in terms of fMRI signals of low-frequency fluctuations. Methods: A total of 16 TRD patients, who visited the Qingdao Mental Health Center, Shandong Province, China between March 2023 and January 2024, along with 16 normal subjects, were enrolled into this study for functional imaging. In this study, we first explored the ALFF changes of TRD patients at a baseline resting state. Second, we selected the regions that were significantly changed in the ALFF as seeds and calculated the regional activity and functional connectivity (FC) of these regions using a seed-based approach. We also calculated correlations between the percent change in the PDQ-5D scores and ALFF values in brain regions with differing activity for TRD patients. Results: During the baseline resting state, by using the ALFF, we found a significantly decreased or increased ALFF in the TRD patients relative to the controls. These regions were located in the left/right postcentral gyrus (PoCG. L/PoCG.R), right cuneus(CUN.R). We found that the ALFF values of the right hippocampus (HIP.R) in the TRD group were negatively correlated with the PDQ-5D score. Then, we selected these brain regions as seeds to investigate the FC changes in brains of TRD patients. We found abnormal functional connectivity in left/right middle frontal gyrus(MFG.L/MFG.R), the right Inferior frontal gyrus, opercular part (IFGoperc.R), the left/right Anterior cingulate and paracingulate gyri (ACC.L/ACC.R), the right supramarginal gyrus (SMG.R), and the right Calcarine fissure and surrounding cortex (CAL.R). Conclusion: We found a larger range of altered brain regions in TRD patients compared to healthy controls, especially in the central executive network (CEN), salience network (SN) and default mode network (DMN).