Epilepsia, 48(2):305–314, 2007 Blackwell Publishing, Inc. C  2007 International League Against Epilepsy Cortical Activation Mapping of Epileptiform Activity Derived from Interictal ECoG Spikes ∗ Yuan Lai, †Wim van Drongelen, †Kurt Hecox, ‡David Frim, †Michael Kohrman, and ∗ Bin He ∗ Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota; and †Department of Pediatrics and ‡Surgery, University of Chicago, Chicago, Illinois, U.S.A. Summary: Purpose: To develop and evaluate a new cortical activation mapping (CAM) method to obtain the neuronal acti- vation sequences from the cortical potential distributions. Methods: Interictal electrocorticogram (ECoG) recordings were analyzed for eight pediatric epilepsy patients to find the cortical activation maps, which were compared with the patients’ seizure-onset zones identified from ictal ECoG recordings. Vari- ous relations between the local activation time and cortical poten- tial were assumed. The most effective relation was determined by accessing their capability to predict the seizure-onset zone. Computer simulations using a moving dipole source model were also conducted to test the present approach in imaging the prop- agated cortical activity. Results: In both clinical data analysis and computer simula- tions, the maximal amplitude proved to be the most effective criterion with which to determine the local cortical activation time. The present method successfully predicted the seizure- onset zone in seven of eight patients by the CAM analysis of ECoG-recorded interictal spikes (IISs). For patients with mul- tiple seizure foci, each focus can be revealed by analyzing IISs with different spatial patterns. Conclusions: The time difference between spike peaks of the interictal events in the leading channel and other channels can be effectively defined as the local cortical activation time. The cortical activation mapping method based on this time latency can be used to predict the seizure-onset zones, suggesting that the present CAM method is useful to assist the presurgical evaluation for the epilepsy patients. Key Words: Cortical activation mapping—Interictal spike— Electroencephalography—ECoG—Neuronal propagation— Activation time—Seizure-onset zone—Cortical potential distribution—Epilepsy—Source localization. The interictal spike (IIS) is often used to locate epilep- tiform activity and thus is clinically important. It is usu- ally assumed that regions displaying the largest amplitude of spikes are within the epileptogenic zone, and conse- quently, such regions should be resected if possible to render the patients seizure free (Tsai et al., 1993a, 1993b; Kanazawa et al., 1996). However, the IISs may propa- gate from their initial sites by uncertain neural pathways (Alarcon et al., 1994, 1997; Ebersole, 2000; Ulbert et al., 2004). Therefore one cannot conclude that the potential amplitude distribution at the spike peak best represents the character of the spike source unless the distribution does not change with temporal evolution of the interictal discharge. The distinction between primary and propagated spikes was introduced as early as 1950s (Penfield and Jasper, 1954). Recent studies suggest rapid propagation of IISs Accepted September 13, 2006. Address correspondence and reprint requests to Dr. B. He at Uni- versity of Minnesota, Department of Biomedical Engineering, 7-105 Hasselmo Hall, 312 Church Street SE, Minneapolis, MN 55455, U.S.A. E-mail: binhe@umn.edu doi: 10.1111/j.1528-1167.2006.00936.x during the discharges (Sutherling and Barth, 1989; Alar- con et al., 1994, 1997; Emerson et al., 1995; Merlet et al., 1996; Merlet and Gotman, 1999; Leal et al., 2002; Lantz et al., 2003; Asano et al., 2003). Thus it is important to discern where the IIS starts and how it propagates to lo- cate its generators accurately. It has been shown that the identification of brain regions initiating the epileptiform activities can be potentially used to reduce the necessary resection area (Alarcon et al., 1997). Both human and animal experiments have been de- signed to study the initiation and propagation of the epilep- tiform activity (Alarcon et al., 1994; Tsau et al., 1999; Ulbert et al., 2004). Alarcon et al. (1994) used both depth and surface electrodes to record the interictal discharges, where the results regarding latency and spatial distribu- tion suggest that relatively large areas of neocortex and archicortex can be simultaneously or consecutively acti- vated through fast association fibers or propagation along the cortex during interictal activities. Tsau et al. (1999) found that spontaneous epileptiform activity could be ini- tiated in various cortical layers on neocortical slices har- vested from rats. The activations were found to start from a small area (less than 0.04 mm 3 ) and spread smoothly 305