A1 Epilepsy (hyperexcitability, synchronous discharges)

Topic

The cortical network maintains normal activity thanks to a balance between excitation and inhibition that limits the collective firing rate of its neurons. In epilepsy, the cortical network loses a portion of this inhibition, causing it to shift toward a regime of sustained or unstable activity; the greater the loss of inhibition, the further the network drifts from its original equilibrium point. This shift can be predicted using a stability analysis derived from the Wilson-Cowan model—the same model that describes the cortical network itself. This analysis examines how the network responds to small perturbations around its equilibrium: if these perturbations are dampened, the balance between excitation and inhibition is preserved, but if they grow unchecked, that growth signals the network's transition to an ictal state.

Within the cortical network, individual neurons contribute to this shift through changes in their own ionic currents: a reduction in potassium conductance and the emergence of sustained sodium currents—extensions of the ionic conductance model describing neuronal firing—lower the neuron's firing threshold. The lower the potassium conductance, the lower the threshold becomes; the stronger the sustained sodium current, the more likely the neuron is to fire repeatedly rather than firing once and stopping. When multiplied across all neurons in the cortical network, this propensity for repetitive firing underpins the network-level hyperexcitability described in the previous paragraph.

This cortical network hyperexcitability does not manifest as an epileptic seizure until neuronal discharges become synchronized. This pathological synchronization of the cortical network is summarized by a synchronization indicator—derived from the framework used to describe the synchronization of coupled oscillator networks—that measures the fraction of the cortical network firing in unison; the more neurons that fire simultaneously, the higher the synchronization indicator rises, and when this indicator crosses a critical threshold, that crossing marks the clinical onset of the epileptic seizure.

Once the epileptic seizure is triggered at a point within the cortical network, the discharge does not remain localized; instead, it propagates physically through the network as an advancing front—analogous to the type of propagation front seen in neuronal migration—where activity in a synchronized zone drives synchronization in the neighboring zone, which in turn drives the next. This expanding-front propagation transforms the epileptic seizure from a local phenomenon into one that involves extensive regions of the cortical network.

Following the seizure, the cortical network does not remain trapped in a hyperexcitable state; rather, its excitability recovers exponentially during the post-ictal period. This recovery gradually restores the balance between excitation and inhibition that characterized the network prior to the episode, thereby closing the cycle that gave rise to the seizure. Understanding this sequence—from the initial loss of inhibition to post-ictal recovery—makes it possible to anticipate when the cortical network is approaching the transition to the ictal state and to determine the time required for the network to regain the excitation-inhibition balance necessary for normal functioning.

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