Feasibility of focal brain cooling for partial epilepsy with secondary generalization: A computational study.

Experiments with animal models of epilepsy have consistently shown that focal cooling of epilepsy-induced brain region reversibly suppresses or terminates epileptic discharge activity. Recently, we formulated a physiologically plausible temperature dependence in a neural mass model that can reproduce the effect of focal cooling on epileptic discharge activity. This can be used to implement a temperature control in an implantable cooling device for thermal neuromodulation of the epileptogenic zone in patients with partial epilepsy when seizure activity is detected. However, there have been no experiments that looked into the effect of focal cooling in animal models of epilepsy with secondary generalization in which the seizure activity spreads from the pathologic region to other regions of the brain. Using the temperature-dependent neural mass model and a physiological coupling model, we show that focal cooling stops the propagation of low-frequency discharge activity; on the other hand, it increases the amount of coupling required to propagate high-frequency discharge activity. Moreover, discharge activities that are propagated with cooling are lower in both magnitude and frequency compared to those propagated without cooling. These results suggest the feasibility of focal cooling as an effective alternative therapeutic treatment for medically intractable partial epilepsy even with secondary generalization.Clinical Relevance- The computational study establishes focal cooling of the brain region with partial epilepsy not only suppresses epileptic discharges but can also prevent its generalization to other brain regions.

Application of SsVGMM to medical data - classification with novelty detection.

There is a huge demand to apply classification in medical analysis. A traditional classifier requires having training samples from each class. However, in reality, it is possible that the testing set may include classes that are not in the training set. This inevitably causes an issue: data from a undefined class will be assigned to a predefined classes. To tackle this, we propose a semi-supervised variational Gaussian mixture model to perform multi-class classification with novelty detection. Comparing to some popular novelty detection methods, we demonstrate that it gets better performance on a thyroid disease data, by generating the distribution of predefined classes and undefined class, without explicitly setting a threshold.

Differential temperature sensitivity of synaptic and firing processes in a neural mass model of epileptic discharges explains heterogeneous response of experimental epilepsy to focal brain cooling.

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.