Abstracts

Rationale: Mechanism of epileptic seizure has been an essential issue both in clinical and basic neuroscience. The prevailing view of seizure generation was imbalance between excitatory and inhibitory neuronal activities due to structural or functional problems within the brain. Recent report described heterogeneity and sparsity of activation of neurons. In addition, neurons even outside seizure onset zone showed significant spiking rate change minutes before seizure onset. Another report mentioned the activity of small subset of neurons result in epileptic seizure by examining spatial relationship of multi unit activity in mesial temporal lobe. Thus activity of neurons in peri-ictal state has not been fully understood yet. Methods: Thirteen seizures from eleven patients with intractable epilepsy participated in this study. They were implanted microelectrodes together with clinical macroelectrodes in multiple sites bilaterally to localize the epileptic foci. Recorded neuronal spike firings were classified into putative pyramidal cells and interneurons using cluster analysis. Unit firing of peri-ictal state was analyzed in two ways comparing between preictal and ictal states with respect to the seizure onset zone (SOZ). One is modulation of unit firing rate. Another is the change of functional connectivity between neuron pairs. Results: Four hundreds and sixty-eight unit activities were extracted from 378 microwires. Clustering analysis resulted in 217 putative pyramidal cells and 49 interneurons, including significant differences in mean firing rate, burst ISI, and spike waveform duration. Number of sites with multi-unit activity was 212. With respect to the SOZ, heterogeneity of neuronal spike firing change was observed in peri-ictal state. The number of sites where multi-unit spike firing increased during seizures was significantly larger inside the SOZ and fewer outside the SOZ. The result suggests that the increased spike firing inside the SOZ likely reflects activity from principal cells rather than interneurons since there were a significantly greater proportion of putative pyramidal cells, but not presumed interneurons, which increased spike firing during seizures. Furthermore, connectivity analysis indicated that greater synchrony of discharges between single neurons outside the SOZ than inside the SOZ during preictal states. However, during ictal states, there was a 46% reduction in synchrony of discharges outside the SOZ, while there was a 188% increase in synchrony inside the SOZ. Conclusions: Results propose mechanisms that tightly regulated principal cell spike firing and synchrony of discharges during interictal states result in seizure generation. In transition to ictus, abnormal external and/or internal impulses to principal cell networks overcome these local mechanisms that generates hyper-excitability and -synchrony, whereas feedforward mechanisms are engaged to restrict ictal spread.