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Objective Reduced deactivation within the default mode network (DMN) is common in individuals with primary affective disorders relative to healthy volunteers (HVs). It is unknown whether similar network abnormalities are present in temporal lobe epilepsy (TLE) patients with a history of affective psychopathology. Methods 17 TLE patients with a lifetime affective diagnosis, 31 TLE patients with no formal psychiatric history and 30 HVs were included. We used a visuospatial 'n-back' paradigm to compare working memory (WM) network activation between these groups. Post hoc analyses included voxel-based morphometry and diffusion tensor imaging. The Beck Depression Inventory- Fast Screen and Beck Anxiety Inventory were completed on the day of scanning. Findings Each group activated the fronto-parietal WM networks and deactivated the typical DMN in response to increasing task demands. Group comparison revealed that TLE patients with lifetime affective morbidity showed significantly greater deactivation in subgenual anterior cingulate cortex (sACC) than either the TLE-only or the HVs (p<0.001). This effect persisted after covarying for current psychotropic medication and severity of current depressive/anxiety symptoms (all p<0.001). Correlational analysis revealed that this finding was not driven by differences in task performance. There were no significant differences in grey matter volume or structural connectivity between the TLE groups. Conclusions Our results provide novel evidence suggesting that affective psychopathology in TLE has a neurobiological correlate, and in this context the sACC performs differently compared with network activity in primary affective disorders. [ABSTRACT FROM AUTHOR]