SummaryThe authors report the use of dense two-dimensional microelectrode array recordings to characterize fine resolution electrocortical activity ("μEEG") in epileptogenic human cortex. A 16-mm 2 96 microelectrode array with 400-μm interelectrode spacing was implanted in five patients undergoing invasive EEG monitoring for medically refractory epilepsy. High spatial resolution data from the array were analyzed in conjunction with simultaneously acquired data from standard intracranial electrode grids and strips. μEEG recorded from within the epileptogenic zone demonstrates discharges resembling both interictal epileptiform activity ("microdischarges") and electrographic seizures ("microseizures") but confined to cortical regions as small as 200 μm 2 . In two patients, this activity appeared to be involved in the initiation or propagation of electrographic seizures. The authors hypothesize that microdischarges and microseizures are generated by small cortical domains that form the substrate of epileptogenic cortex and play important roles in seizure initiation and propagation. KeywordsMultichannel extracellular recording; Epilepsy; Intracranial EEG; Epileptiform EEG discharges Recent findings of small (<1 mm 2 ) foci of high frequency oscillations in both human epilepsy (Bragin et al., 1999 and animal models of epilepsy (Bragin et al., 2000(Bragin et al., ,2003(Bragin et al., , 2005 suggest that seizures may be initiated in regions comparable in size with basic cortical functional units. It is not known whether epileptiform activity under 40 Hz (i.e., in the frequency range of standard clinical EEG) exhibits similar focality. Although intracranial EEG (iEEG) recordings in patients with intractable epilepsy (Engel et al., 1990;Tonini et al., 2004) afford higher spatial resolution than scalp EEG (Pacia and Ebersole, 1997;Tao et al., 2005), the electrodes used, typically 3 to 5 mm in diameter, effectively sum the electrical potentials generated in large regions of underlying cortex and so cannot register spatial signal patterns at a submillimeter scale. High resolution (∼100 μm) recordings spanning cortical layers have been obtained in epilepsy patients using linear array multielectrodes (Ulbert et al., 2004a, Copyright © 2008 (Schroeder and Seto, 1995) or even microcolumns (Lakatos et al., 2007) but only from one site at a time. High spatiotemporal resolution data from epilepsy patients have also been obtained using bundles of flexible microwires incorporated in a clinical depth electrode with a 1.5-mm tip-to-tip span (Bragin et al., 1999(Bragin et al., ,2003Worrell et al., 2008), but recording sites are not precisely constrained and spatial resolution is limited. We report results from a twodimensional, 96-microelectrode array (MEA) in epileptic patients to record neuroelectric signals at high spatial resolution. Our findings demonstrate epileptic abnormalities at a submillimeter scale, including highly focal ictal-appearing events, and provide new insights into the nature of electrophysiological disturbance...