Abstracts

Rationale: The spatiotemporal scales characterizing epileptic brain and the generation of focal seizures (ictogenesis) in humans are not known. While focal seizures appear to start abruptly and unpredictably on low spatial resolution clinical intracranial EEG (iEEG) recordings, we report evidence from 19 patients that seizures organize over spatial and temporal scales not probed by clinical iEEG. Methods: We obtained wide bandwidth iEEG from hybrid electrodes containing macro (clinical) and microelectrode arrays in epileptic and non-epileptic regions from patients undergoing evaluation for epilepsy surgery, and in control brain from patients implanted with subdural electrodes for motor cortex stimulation for intractable facial pain. Results: A total of 2544 hours of continuous iEEG were recorded from 616 macroelectrodes during which time 57 clinical and electrographic seizures were recorded. In epileptic brain, seizure-like events, hereafter called microseizures, were observed on sub-millimeter spatial scales, isolated to single microelectrodes, and not seen on clinical macroelectrodes. Microseizures showed a range of spectral dynamics and occurred asynchronously in non-contiguous regions within epileptic brain. Microseizures were increased in brain regions generating seizures (82.8 microseizure-seconds/hour), rare in brain regions not generating seizures (4.5), and absent in control brain from patients without a history of seizures (0.0; Kruskal-Wallis p<0.001). We observed microseizures that evolved directly into large-scale seizures detectable on clinical macroelectrodes and were ultimately associated with clinical symptoms. Conclusions: Based on these findings, we propose that epileptic brain is topographically fractured and composed of pathological microciruits generating microseizures that are involved in the generation of seizures.