BACKGROUND: It is known that the abnormal neural activity in epilepsy may be associated to the reorganization of neural circuits and brain plasticity in various ways. On that basis, we hypothesized that changes in neuronal circuitry due to epilepsy could lead to measurable variations in patterns of both EEG and BOLD signals in patients performing some cognitive task as compared to what would be obtained in normal condition. Thus, the aim of this study was to compare the cerebral areas involved in EEG oscillations versus fMRI signal patterns during a working memory (WM) task in normal controls and patients with refractory mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS). The study included six patients with left MTLE-HS (left-HS group) and seven normal controls (control group) matched to the patients by age and educational level, both groups undergoing a blocked design paradigm based on Sternberg test during separated EEG and fMRI sessions. This test consisted of encoding and maintenance of a variable number of consonant letters on WM. RESULTS: EEG analysis for the encoding period revealed the presence of theta and alpha oscillations in the frontal and parietal areas, respectively. Likewise, fMRI showed the co-occurrence of positive and negative BOLD signals in both brain regions. As for the maintenance period, whereas EEG analysis revealed disappearance of theta oscillation, fMRI showed decrease of positive BOLD in frontal area and increase of negative BOLD in the posterior part of the brain. CONCLUSIONS: Generally speaking, these patterns of electrophysiological and hemodynamic signals were observed for both control and left-HS groups. However, the data also revealed remarkable differences between these groups that are consistent with the hypothesis of reorganization of brain circuitry associated with epilepsy.