Spatiotemporal Brain Imaging of Visual-Evoked Activity Using Interleaved EEG and fMRI Recordings G. Bonmassar, 1 D. P. Schwartz,* A. K. Liu, K. K. Kwong, A. M. Dale, and J. W. Belliveau NMR Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129; and *Laboratoire SIM, Universite de Rennes I, Rennes, France Received April 7, 2000 Combined analysis of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) has the potential to provide higher spatiotem- poral resolution than either method alone. In some situations, in which the activity of interest cannot be reliably reproduced (e.g., epilepsy, learning, sleep states), accurate combined analysis requires simulta- neous acquisition of EEG and fMRI. Simultaneous measurements ensure that the EEG and fMRI record- ings reflect the exact same brain activity state. We took advantage of the spatial filtering properties of the bipolar montage to allow recording of very short (125–250 ms) visual-evoked potentials (VEPs) during fMRI. These EEG and fMRI measurements are of suf- ficient quality to allow source localization of the cor- tical generators. In addition, our source localization approach provides a combined EEG/fMRI analysis that does not require any manual selection of fMRI activations or placement of source dipoles. The source of the VEP was found to be located in the occipital cortex. Separate analysis of EEG and fMRI data dem- onstrated good spatial overlap of the observed acti- vated sites. As expected, the combined EEG/fMRI anal- ysis provided better spatiotemporal resolution than either approach alone. The resulting spatiotemporal movie allows for the millisecond-to-millisecond dis- play of changes in cortical activity caused by visual stimulation. These data reveal two peaks in activity corresponding to the N75 and the P100 components. This type of simultaneous acquisition and analysis al- lows for the accurate characterization of the location and timing of neurophysiological activity in the hu- man brain. © 2001 Academic Press Key Words: fMRI; visual-evoked potentials; VEPs; source localization; inverse problem; forward prob- lem; weighted minimum norm; bipolar montage; checkerboard; Hall effect. INTRODUCTION Functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) detect two fundamen- tally different physiological phenomena reflecting brain activity. fMRI typically measures changes in the blood oxygenation due to neuronal activity (Kwong et al., 1992; Ogawa et al., 1992), whereas EEG measures the electric potential directly generated by neuronal activity (Berger, 1929; Regan, 1989). The fMRI (hemo- dynamic) and EEG (electromagnetic) measurements are complementary in their spatiotemporal resolu- tions. fMRI has high spatial resolution, typically on the order of millimeters (Belliveau et al., 1991; Moonen and Bandettini, 1999), whereas EEG has millisecond temporal resolution (Regan, 1989). Although separate measurements of fMRI and EEG will be adequate for many situations, simultaneous acquisition is necessary when the activity of interest cannot be easily reproduced. In epilepsy patients, for example, spontaneous interictal activity (epileptiform activity between seizures) may vary from spike to spike, which may reflect different cortical generators. Simultaneous EEG/fMRI recordings (Huang-Hellinger et al., 1995; Warach et al., 1996; Seeck et al., 1998; Krakow et al., 1999) have been used to measure the interictal activity with the hypothesis that interictal epileptiform discharges are likely to produce a focal change measurable by fMRI (Ives et al., 1993). These studies recorded interleaved EEG and fMRI to monitor for the presence of interictal activity without, however, localizing the EEG activity. Other studies have combined the analysis of hemo- dynamic and electrophysiological data that were col- lected separately. These studies include (a) positron emission tomography (PET) and EEG (Heinze et al., 1994; Snyder et al., 1995; Heinze et al., 1998), (b) fMRI and EEG (Menon et al., 1997; Opitz et al., 1999), (c) fMRI and magnetoencephalography (MEG) (George et al., 1995; Ahlfors et al., 1999; Korvenoja et al., 1999), (d) fMRI, MEG and EEG (Belliveau, 1993; Belliveau et al., 1993; Morioka et al., 1995), (e) fMRI, EEG, and 1 To whom correspondence should be addressed at Building 149, 13th Street, Charlestown, MA 02129. Fax: (617) 726 7422. E-mail: giorgio@nmr.mgh.harvard.edu. NeuroImage 13, 1035–1043 (2001) doi:10.1006/nimg.2001.0754, available online at http://www.idealibrary.com on 1035 1053-8119/01 $35.00 Copyright © 2001 by Academic Press All rights of reproduction in any form reserved.