The Effect of Deep Brain Stimulation on High Frequency Oscillations in a Chronic Epilepsy Model

Abstract

Abstract Temporal lobe epilepsy (TLE) is a severe neurological disease which is often pharmacoresistant. Deep brain stimulation (DBS) is a novel method for treating epilepsy; however, its mechanism of action is not fully understood. We aimed to study the effect of amygdala DBS in the pilocarpine model of TLE. Status epilepticus was induced by pilocarpine in male Wistar rats, and spontaneous seizures occurred after a latency period. A stimulating electrode was inserted into the left basolateral amygdala and two recording electrodes into the left and right hippocampus. A stimulus package consisted of 0.1 ms-long biphasic pulses applied regularly at 4 Hz for 50 seconds. This package was repeated four times a day, with 5-minute pauses, for 10 days. We also used an age-matched healthy control group of stimulated animals and another one of sham-operated rats. From the hippocampal local field potentials high frequency oscillations (HFOs) were analyzed as these are promising epilepsy biomarkers. HFOs are short oscillatory events between 80-600 Hz which were detected offline using an open-source application of MATLAB, the RIPPLELAB system. We found that the HFO rate was significantly higher in pilocarpine-treated rats compared to the control groups (0.41 ± 0.14 HFO/min vs. 0.006 ± 0.003 in the stimulated control group and no HFO in the sham-operated group). In the pilocarpine group an instantaneous decrease in HFO rate was observed while the stimulation was on (0.44 ± 0.15 HFO/min vs 0.07 ± 0.03 HFO/min, p=0.017). The effect was short-lived because the frequency of HFOs did not change significantly in the time windows between stimulus packages or during the ten-day stimulation period. The difference of HFO rates between epileptic and control groups could be used in the electrographic assessment of epilepsy. The decreased frequency of HFOs during stimulation may be useful to study the efficacy of DBS.