Interictal spikes in focal epileptogenesis

Area of Science:

• Neuroscience
• Epileptology
• Computational Neuroscience

Background:

• Interictal electroencephalography (EEG) potentials in focal epilepsies are linked to neuronal hyperexcitability.
• The prevailing belief is that interictal spikes (IS) predispose to ictal discharges, but experimental evidence is limited.

Purpose of the Study:

• To investigate the relationship between interictal spikes (IS) and ictal discharges in focal epilepsy.
• To elucidate the cellular and network mechanisms underlying IS generation and their impact on seizure activity.

Main Methods:

• Analysis of human pre-surgical studies.
• Recordings from chronic and acute animal models of focal epilepsy.
• Examination of cellular and network mechanisms, including synaptic and non-synaptic communication.

Main Results:

• IS and ictal discharges originate from distinct neuronal populations via different mechanisms.
• The region generating IS (irritative zone) differs from the ictal-onset zone.
• IS frequency does not increase before seizures; it is enhanced post-ictally.
• Spike suppression precedes ictal discharges, while enhanced IS suppresses seizures.
• IS induces a prolonged refractory period due to inhibition and ionic changes.

Conclusions:

• IS generation involves complex synaptic and non-synaptic neuronal communication.
• The refractory period following IS, characterized by inhibition and ionic shifts, plays a crucial role in seizure protection.
• Post-spike depression may govern the periodicity of interictal spiking.
• Strong inhibition following IS acts as a protective mechanism against ictal discharges in hyperexcitable neuronal networks.