Abstract
Experiments with drug-induced epilepsy in rat brains and epileptic human brain region reveal that focal cooling can suppress epileptic discharges without affecting the brain’s normal neurological function. Findings suggest a viable treatment for intractable epilepsy cases via an implantable cooling device. However, precise mechanisms by which cooling suppresses epileptic discharges are still not clearly understood. Cooling experiments in vitro presented evidence of reduction in neurotransmitter release from presynaptic terminals and loss of dendritic spines at post-synaptic terminals offering a possible synaptic mechanism. We show that termination of epileptic discharges is possible by introducing a homogeneous temperature factor in a neural mass model which attenuates the post-synaptic impulse responses of the neuronal populations. This result however may be expected since such attenuation leads to reduced post-synaptic potential and when the effect on inhibitory interneurons is less than on excitatory interneurons, frequency of firing of pyramidal cells is consequently reduced. While this is observed in cooling experiments in vitro, experiments in vivo exhibit persistent discharges during cooling but suppressed in magnitude. This leads us to conjecture that reduction in the frequency of discharges may be compensated through intrinsic excitability mechanisms. Such compensatory mechanism is modelled using a reciprocal temperature factor in the firing response function in the neural mass model. We demonstrate that the complete model can reproduce attenuation of both magnitude and frequency of epileptic discharges during cooling. The compensatory mechanism suggests that cooling lowers the average and the variance of the distribution of threshold potential of firing across the population. Bifurcation study with respect to the temperature parameters of the model reveals how heterogeneous response of epileptic discharges to cooling (termination or suppression only) is exhibited. Possibility of differential temperature effects on post-synaptic potential generation of different populations is also explored.
Highlights
The World Health Organization identifies epilepsy as one of the most common neurological diseases affecting approximately 50 million people across all ages across the world [1]
Our model involves a synaptic mechanism that results in a reduced frequency of discharges and an intrinsic excitability mechanism that compensates such reduction in frequency of discharges resulting in persistent discharges during cooling but suppressed in magnitude
Exploration of the model shows that EEG recordings from the animal model of epilepsy used in the study is best explained by high average fast inhibitory gain GFIN and low average slow inhibitory gain GSIN (Table 2)
Summary
The World Health Organization identifies epilepsy as one of the most common neurological diseases affecting approximately 50 million people across all ages across the world [1]. Because of the risks involved with unanticipated seizures, treatment of the disease is required to improve long-term quality-of-life of the patients. Antiepileptic drugs such as anticonvulsants are usually given as first line treatment after being diagnosed with epilepsy. The success rate of surgical treatment is high, limitation in indication and cost significantly hinder intractable epilepsy patients in acquiring it. Another increasingly attractive treatment option involves electrical neurostimulation of specific neural region such as vagus nerve stimulation and deep brain stimulation [11, 12]
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