Abstracts

Rationale: Disturbances of cerebral activity associated with epilepsy and seizures have been well characterized at low spatial resolutions. Less information, however, is available concerning corresponding disturbances at submillimeter resolution. We report the use of a 2D microelectrode array (MEA) to provide new details of electrophysiological disturbances in human epileptogenic cortex in vivo.Methods: A 4mm square MEA (96 microelectrodes in a 10 x 10 grid, 400 micron spacing, 1 mm long, 3-5 micron diameter recording tips) (NeuroPort™ , Cyberkinetics Neurotechnology Systems, Foxboro, MA) was implanted in patients with medically intractable focal epilepsy undergoing intracranial EEG (iEEG) monitoring at the Columbia University Medical Center and chronic recordings were obtained. Signals were sampled at 30 kHz/channel (0.1-7.5 kHz bandpass), then downsampled offline to 500 Hz/channel after 125 Hz anti-alias filtering to obtain high spatial resolution signals in the frequency range of standard EEG (“µEEG”). Clinical iEEG was acquired at 500 Hz/channel (0.5 – 125 Hz bandpass) using an XLTek system (XLTek Inc., Oakville, Ontario, Canada). Epidural references were used for both recordings. The two recordings were synchronized using a pulse-coded timing signal, then merged offline for combined viewing with spatially organized, referential montages.Results: MEA recordings were obtained from five patients, two men and three women, between July of 2006 and January of 2007. In four patients, the µEEG contained waveforms (“focal µEDs”) that resembled interictal discharges, but were topographically restricted to areas spanning 4 mm2 or less, and were not evident in the iEEG. In three patients, the µEEG contained similarly highly localized patterns that were otherwise analogous electrographic seizures in conventional EEG, with repetitive sharp waveforms or rhythmic activity evolving in frequency, amplitude, and morphology. We refer to these as “micro-ictal appearing discharges”, or ΜIDs. In each of these patients, MIDs exhibited behaviors that implicated them with generation or propagation of clinical seizuresConclusions: MEA recordings in patients with focal epilepsy provide unprecedented resolution of microphysiological features of epileptogenic cortex. As both focal µEDs and MIDs are spatially restricted, recordings with relatively large subdural electrodes or sparse sampling with microelectrodes are unlikely to have detected them. Our findings suggest that MIDs are specific markers of epileptogenic cortex. We speculate that the epileptogenic zone has a heterogenous structure, with multiple domains perhaps as small as single cortical columns interspersed within areas of normal tissue; these epileptogenic domains can give rise to focal electrophysiologic disturbances and may also induce cognitive dysfunction. Further, we speculate that clinical seizures result from a MID developing either individually or as part of a distributed network, then spreading to adjacent non-epileptogenic domains.