Focal brain cooling has been extensively studied in the past decade as an alternative therapeutic treatment for medically intractable epilepsy. It has shown consistent success in animal studies and also preliminarily in an intraoperative study with a surgical patient. However, precise mechanism of how cooling suppresses or terminates epileptic discharge activity remains unclear. In this study, we utilized a computational approach in understanding the mechanisms of focal brain cooling for thermal modulation of epileptic discharges.
In the first part of this study, we formulated temperature dependence in a neural mass model of epileptic discharges. Based from experimental evidences on the effect of cooling on synaptic dynamics of neurons, we assumed a mean-field attenuation of post-synaptic potential by using a Q10 factor in the post-synaptic impulse response function of the neural mass model. Simulated activity showed that a low attenuation could already result in reduction of frequency of discharges but with no significant decrease in magnitude and termination could be achieved with further attenuation. We conjectured that a concomitant mechanism opposes reduction in the average firing frequency and integrated it in the model by adding a reciprocal Q10 factor in the firing response function. Using both mechanisms, the effect of cooling on epileptic discharges as observed from in vivo experiments were reproduced.
The second part of the study considers the case of a spreading seizure activity and investigates whether focal cooling can stop the spread. A coupling model was proposed to simulate the propagation of brain activity between two brain regions. We identified a minimum coupling strength that is required to propagate an epileptic discharge activity from one brain region to another brain region. Using the temperature-dependent model, focal cooling was found to be effective by increasing this minimum coupling strength; nevertheless, it may not be sufficient to stop the propagation of seizure activity.