Summary: Researchers have developed a computer model that provides insight into how cooling specific areas of the brain could help to treat epilepsy.
Using computer simulation techniques, scientists have gained new insights into the mechanism by which lowering the temperature of specific brain regions could potentially treat epileptic seizures. The results are published in PLOS Computational Biology.
About 50 million people worldwide deal with sudden, recurring seizures that are the hallmark of epilepsy. Treatment with medication or surgery does not work for some patients, so scientists have been investigating a potential alternative called focal cooling, in which a device would be implanted in the brain to suppress the electrical signals–discharges–that characterize epileptic seizures.
In the new study, Jaymar Soriano of Nara Institute of Science and Technology (NAIST), Japan, and colleagues, sought to better understand the mechanism by which focal cooling operates. So far, the technique has been tested only temporarily in epilepsy patients as intraoperative studies, while it has shown consistent success in rats. However, focal cooling sometimes slightly increases the frequency of epileptic discharges in rats, even while suppressing their strength.
To investigate how focal cooling suppresses epileptic discharges with possible increase in frequency, the research team took a computational approach. They employed a model of the rat brain that allowed them to simulate different mechanisms underlying the effects of a focal cooling device on epileptic discharges.
Using data from laboratory and rat studies, the researchers first simulated a mechanism by which focal cooling reduces activity at connections between neurons, resulting in less frequent discharges. However, with this mechanism alone, the model could not accurately reproduce electrical activity patterns previously observed in focal brain cooling experiments on rats with drug-induced epilepsy.
To compensate for the first mechanism, the researchers devised a second mechanism in which cooling resulted in discharges that were persistent but weaker. Incorporating both mechanisms into the model allowed the team to successfully reproduce results from previous rat experiments.
“Focal brain cooling could be an alternative treatment for epileptic seizures with lower risk of irreversible functional loss compared to surgery,” says study co-author Takatomi Kubo. “Our study attempts to start an initiative on thermal neuromodulation of brain activity using a computational approach that can elucidate its mechanism and complement animal experiments and clinical tests.”
Further investigation and laboratory studies could help the researchers refine their model and better understand the mechanisms that underpin focal cooling.
Funding: This study was supported in part by grant 15H05719 from The Japan Society for the Promotion of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Source: Takatomi Kubo – PLOS
Image Source: NeuroscienceNews.com image is credited to Soriano et al.
Original Research: Full open access research for “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” by Jaymar Soriano, Takatomi Kubo, Takao Inoue, Hiroyuki Kida, Toshitaka Yamakawa, Michiyasu Suzuki, and Kazushi Ikeda in PLOS Computational Biology. Published online October 5 2017 doi:10.1371/journal.pcbi.1005736
[cbtabs][cbtab title=”MLA”]PLOS “Simulating a Brain-Cooling Treatment That Could One Day Ease Epilepsy.” NeuroscienceNews. NeuroscienceNews, 5 October 2017.
<https://neurosciencenews.com/brain-cooling-epilepsy-7674/>.[/cbtab][cbtab title=”APA”]PLOS (2017, October 5). Simulating a Brain-Cooling Treatment That Could One Day Ease Epilepsy. NeuroscienceNews. Retrieved October 5, 2017 from https://neurosciencenews.com/brain-cooling-epilepsy-7674/[/cbtab][cbtab title=”Chicago”]PLOS “Simulating a Brain-Cooling Treatment That Could One Day Ease Epilepsy.” https://neurosciencenews.com/brain-cooling-epilepsy-7674/ (accessed October 5, 2017).[/cbtab][/cbtabs]
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.
“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” by Jaymar Soriano, Takatomi Kubo, Takao Inoue, Hiroyuki Kida, Toshitaka Yamakawa, Michiyasu Suzuki, and Kazushi Ikeda in PLOS Computational Biology. Published online October 5 2017 doi:10.1371/journal.pcbi.1005736