Running Head: High Frequency Synchronization During Seizures

26 Pathological synchronization of neuronal firing is considered to be an inherent property of 27 epileptic seizures. However, it remains unclear if the synchrony increases for the high frequency 28 activity as well as for the local field potentials. We present spatio-temporal analysis of 29 synchronization during epileptiform activity using wide band (up to 2000 Hz) spectral analysis 30 of multi-electrode array recordings at up to 60 locations throughout the mouse hippocampus in 31 vitro. Our study revealed a prominent structure of LFP profiles during epileptiform discharges, 32 triggered by elevated extracellular potassium, with characteristic distribution of current sinks and 33 sources with respect to anatomical structure. The cross-coherence of high frequency activity 34 (500-2000 Hz) across channels was reduced during epileptic bursts compared to baseline 35 activity, and showed the opposite trend for lower frequencies. Furthermore, the magnitude of 36 cross-coherence during epileptiform activity was dependent on distance; electrodes closer to the 37 epileptic foci showed increased cross-coherence and electrodes further away showed reduced 38 cross-coherence for high frequency activity. These experimental observations were recreated and 39 supported in a computational model. Our study suggests that different intrinsic and synaptic 40 processes can mediate paroxysmal synchronization at low, medium and high frequencies. 41