<p>The aim of this study was to investigate the functional connectivity of resting-state networks in patients with temporal lobe epilepsy (TLE) with and without comorbid depression. Resting-state fMRI and the XCP-D software package were used to assess functional connectivity between the nodes of the main resting-state neural networks: the default mode network (DMN), the salience network (SN), the dorsal attention network (DAN), the sensorimotor network (SMN), and the frontoparietal control network (FPCN). The study included 77 patients with TLE (36 with and 41 without depression) and 48 healthy subjects. Patients with TLE and depression showed reduced functional connectivity between key nodes of the SN, DAN, and DMN as compared with patients with TLE without depression and the control group. In contrast, those with TLE without depression showed an increase in connectivity between individual nodes of different resting-state networks, i.e., the DMN, SNS, and FPCN, and a decrease in connectivity within one resting-state network, the DMN. A common feature for both groups of patients with TLE was an increase in connectivity between the prefrontal nodes of the DMN and FPCN. The results indicate the existence of different mechanisms underlying the reorganization of neural networks in TLE depending on the presence of comorbid depression and emphasize the importance of an integrated approach to the study of epilepsy using neuroimaging methods.</p>