RATIONALE: Reproducible direct measurement of neuronal electrical activity using MRI signal changes due to local magnetic field perturbations would represent a step change in neuroimaging methods. While some previous studies using experiments based on evoked and spontaneous activity provided encouraging results no clear demonstration of neuronal current-related MR changes in the human brain has emerged to date. The availability of simultaneously acquired EEG-fMRI in patients with frequent interictal epileptic discharges (IED), which have significantly greater amplitude than evoked potentials, offers the opportunity to further investigate the phenomenon. METHODS: We re-analysed simultaneously acquired EEG-fMRI data in 6 epilepsy patients with very frequent focal IED and a well-localised generator. A model of MRI signal changes due to fast activity and BOLD signal changes was used to identify fast MR signal changes, potentially directly reflecting neuronal activity. Simultaneously-acquired EEG allowed the comparison of electrical source localisation (ESI), clinical epilepsy localisation and BOLD signal changes with the fast MR signal changes. RESULTS: Clusters of IED-related fast MR signal change were observed in all cases. Spatial correspondence between the IED-related fast MR, BOLD, ESI clusters and irritative zone (IZ) was observed in one slice of a single dataset. The other IED-related fast MR clusters were remote from electro-clinically determined generators of interictal activity. The sign and magnitude of the fast MR signal changes varied across regions and subjects. CONCLUSION: The observed fast MR changes cannot be confidently attributed to the direct effect of neuronal currents due to lack of spatial concordance with generators of interictal activity, IED-related BOLD clusters and ESI estimates.