Epilepsia, 47(Suppl. 5):52–58, 2006 Blackwell Publishing, Inc. C  International League Against Epilepsy EEG/fMRI Study of Ictal and Interictal Epileptic Activity: Methodological Issues and Future Perspectives in Clinical Practice ∗ Carlo Di Bonaventura, ∗ Anna E. Vaudano, †§Marco Carn` ı, ∗ Patrizia Pantano, ∗ Valter Nucciarelli, †‡§Girolamo Garreffa, †§Bruno Maraviglia, ∗ Massimiliano Prencipe, ∗ Luigi Bozzao, ∗ ‡Mario Manfredi, and ∗ Anna T. Giallonardo ∗ Department of Neurological Sciences, †Department of Physics, and ‡Neuromed Institute at Pozzilli, University of Rome “La Sapienza,” Rome; and §Enrico Fermi Center, Rome, Italy Summary: Purpose: Electroencephalography/functional mag- netic resonance imaging (EEG/fMRI) has been proposed re- cently as a tool to study electrophysiological activity and, conse- quently, detect brain regions activated during epileptiform EEG abnormalities. The purpose of the study was to review our two- year experience with studying ictal and interictal activities in patients with epilepsy. Methods: Using EEG/fMRI, we studied hemodynamic changes associated with ictal and interictal EEG abnormalities in 43 patients with partial (31 cases) or generalized (12 cases) epilepsy. Using two different paradigms (block design and event- related design), we studied several forms of EEG activity consist- ing of (i) interictal abnormalities constantly elicitable by specific stimulation (8 cases); (ii) focal and generalized interictal activity, such as focal spikes or typical and atypical generalized spike- and-wave discharges (18 cases); and (iii) focal and generalized ictal electro-clinical activity, such as tonic seizures or pseudo- absences in frontal lobe epilepsy, typical absences in idiopathic generalized epilepsy, complex partial seizures in temporal lobe epilepsy, and perisylvian seizures in special syndromes (17 patients). Results: EEG/fMRI revealed clear hemodynamic changes re- lated to EEG abnormalities in 21 patients. In 18 of these patients, the changes were highly concordant with electro-clinical find- ings. In the remaining 22 patients, fMRI analysis data failed to show activation or deactivation clusters, probably owing either to lack or inadequate amount of temporal distribution of abnormal EEG activity, or to intrinsic methodological problems. Conclusions: By defining the electro-clinical and hemody- namic correlates of EEG activity, fMRI may shed light on the neurophysiological mechanisms underlying epileptic phe- nomena. However, as several methodological issues have yet to be addressed, further studies are warranted to assess the reliability and usefulness of EEG/fMRI in clinical practice. Key Words: EEG—fMRI—Interictal epileptiform activity— Ictal epileptiform activity. Functional magnetic resonance imaging (fMRI) is a powerful, noninvasive method that can be used to detect brain regions in which there is a variation in the level of neuronal activity during an experimental condition com- pared with a control condition. The variation in the level of neuronal activity is accompanied by a change in the ratio of oxy- and deoxy-hemoglobin in the blood. This change can be measured by means of the blood oxygen level de- pendent (BOLD) effect. Recently, simultaneous electroen- cephalography (EEG) and fMRI recording (EEG/fMRI) has been used to study hemodynamic correlates of ictal and interictal EEG abnormalities, thereby shedding light on the neurophysiological mechanisms underlying epilep- Address correspondence and reprint requests to Carlo Di Bonaven- tura, M.D., Epilepsy Unit, Department of Neurological Sciences, “La Sapienza” University of Rome, Viale dell’Universit` a 30, 00185 Rome, Italy. E-mail: c dibonaventura@yahoo.it doi: 10.1111/j.1528-1167.2006.00878.x tic phenomena (Salek-Haddadi et al., 2003a; Gotman et al., 2004, 2005). We describe results obtained in the last two years us- ing EEG/fMRI to study ictal or interictal EEG activity in patients with various forms of epilepsy. METHODS Patients The study was conducted in 43 patients with epilepsy (13 male, 30 female, mean age 31.7 years) who underwent continuous EEG/fMRI monitoring. All patients were re- cruited from the Epilepsy Unit of the Department of Neu- rological Sciences, “La Sapienza” University of Rome, and were selected according to the following criteria: (a) well-defined, documented epileptic syndrome; (b) pres- ence of easily recognizable, stereotyped focal/generalized EEG activity, with “ideal” amount and temporal distribu- tion (“neither too little nor too much”); (c) in case of ictal 52