Low-frequency brain stimulation inhibits seizures in mice with temporal lobe epilepsy

It is difficult to quantify epileptic activity that originated from one or more brain regions in the temporal lobe. Many patients with such temporal lobe epilepsy often do not respond to treatment with anti-epileptic drugs, so the affected brain areas need to be removed with surgery. Unfortunately, this approach only gives about one-third of patients freedom of attachment, so the development of therapeutic treatments is of paramount importance.

Scientists led by neurobiologist Dr. Dr. Carola Haas, head of the research group at the Department of Neurosurgery at the Medical Center – University of Freiburg and BrainLinks-BrainTools research center, has explored a new therapeutic approach to prevent epileptic seizures in temporal lobe epilepsy.

They showed in mice that low-frequency stimulation of specific brain areas could stop epileptic activity completely. Instead of using an electric current, the researchers stimulated the cells with light. To do this, they had introduced light-sensitive molecules into the cells that allow specific precision stimulation. They published the results in December 2020 in the scientific journal elife.

“As soon as we stimulated the brain region with a frequency of one hertz, the epileptic seizures disappeared. This effect was stable over several weeks,” Haas says. Cultivation did not occur, which can happen with drug therapy. The brain region was stimulated for an hour each day.

Circuits and cells marked

In temporal lobe epilepsy, the hippocampus is often pathologically altered and usually represents a focus called epileptic activity. Previous studies have used detailed genetic labeling techniques to map the fibrous system and the synaptic connections between the temporal lobe and hippocampus, which are commonly preserved in temporal lobe epilepsy.

The researchers used this fibrous system to manipulate hippocampal activity in a specific and temporary manner using light-dependent proteins. Brain wave measurements showed that the rhythmic activity of the infected hippocampus at a low frequency of one hertz inhibited epileptic activity and prevented it from spreading.

Haas and her colleagues showed that the anti-epileptic effect is largely due to the re-activation of surviving granule cells in the focus of the seizure. Single-cell studies confirmed the hypothesis that granule cells are so excitable due to their stimulation, making the epileptic seizure less likely to spread.

It is also possible that we have a wide network effect as the stimulus can spread through the hippocampal circulation. “

Prof. Dr. Carola Haas, Department of Non-Surgery at the Medical Center, University of Freiburg

In the future, the team, along with the medical physics department at the Medical Center – University of Freiburg, would like to use magnetic resonance imaging to observe the entire brain during stimulation. This method could be used to identify additional brain regions that are affected by the stimulus. Corresponding results to these could provide information on how they are linked and what the additional effect of stimulation is.

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Magazine Reference:

Paschen, E., et al. (2021) Low-frequency hippocampal stimulation inhibits seizure generation in a mouse model of temporal lobe epilepsy. eLife. doi.org/10.7554/eLife.54518.

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