Propagating Interictal Spikes in the neocortex: Relationship to Inactivated Action Potentials, and implications for Epileptogenesis

Interictal spikes - transient bursts of neuronal depolarization observed between epileptic seizures - are typically regarded as a sign of epilepsy and have been used in the localization of seizure onsets. Interictal spikes are thought to arise primarily from large excitatory postsynaptic potentials (EPSPs), although not much is known about the precise role they play in epilepsy. Here the in vivo spatiotemporal dynamics of sequences of interictal spikes in a small (4mm x 4mm) patch of the cortex of a patient with intractable epilepsy is studied. In conjunction with this, the impact on action potential generation and firing of local voltage changes due to paroxysmal depolarizations similar to interictal spikes was also evaluated in vitro using resected neural tissue from an epileptic human neocortex. Sequences of interictal spikes were found to consistently propagate in a direction-specific manner across the neocortex. In addition to this, bursts of action potentials from the ex vivo samples underwent variable degrees of depolarization-induced inactivation. Intracellular recordings in neocortical slices of human brain tissue confirmed that bursts of inactivated action potentials occurred during spontaneous paroxysmal depolarization shifts. These ex vivo findings showed inactivated action potentials being generated by large depolarizations. The results suggest the existence of an aberrantly strong synchronization among neuronal populations in the epileptic cortex, triggered or enhanced by interictal spike depolarization and propagation. This supports a key element in the hypothesis that interictal spikes, and the associated alteration of action potential firing patterns, may alter the electrical environment of the brain and contribute to the progression of the underlying idiopathic seizure disorder.