Abstracts

Rationale: Drug-resistant epilepsy affects approximately 1 million people in the United States. Neurostimulation devices provide an alternative treatment option for refractory seizures, but they are generally less effective than surgical resection. This difference may be due to suboptimal device settings, electrode placement, or other patient factors. The most common refractory focal epilepsy in adults is temporal lobe epilepsy, which is often treated with neurostimulation of the hippocampus. There is some clinical evidence for regional differences in the clinical response to hippocampal neurostimulation, which could be taken advantage of by directional neurostimulation electrodes. However, the optimal target for hippocampal electrode placement, directionality, and stimulation settings are unknown.

Methods: Temporal and spatial dynamics of neurostimulation were investigated in the intrahippocampal kainate mouse model of acute seizures. Mice were anesthetized, and kainic acid was stereotactically injected via a small cranial window into the dentate gyrus. Screw electrode Electrocorticography was recorded and processed using a bandpass filter. Ictal spiking activity was quantified in an automated pipeline analysis using wavelet decomposition (PyWavelet toolbox) and Savitzky–Golay filtering. Animals developed persistent seizure activity, during which neurostimulation settings were tested: (temporal) 1-Hz low and 100-Hz high-frequency settings, and (spatial) corpus callosum, CA1, CA3, and DG locations.

Results: Temporal: High-frequency stimulation of the CA1 region resulted in a reduction in seizure activity when comparing spike rates before (3.5 spikes/sec) and during (1.8 spikes/sec) stimulation (p< 0.01). Low-frequency stimulation had no apparent qualitative or quantitative effect. Spatial: Preliminary results suggest that CA1 stimulation is most effective in reducing spike frequency.

Conclusions: These results demonstrate spatial and temporal variability between regions of the hippocampus when using direct hippocampal stimulation. High-frequency stimulation of the CA1 hippocampal region resulted in the suppression of KA-induced seizure activity. These findings describe spatial and temporal aspects of intrahippocampal neurostimulation in an acute animal model of temporal lobe epilepsy, which may have important clinical implications in treating refractory epilepsy.

Funding: Please list any funding that was received in support of this abstract.: ICTS JIT#747 (Internal Funding, Washington University School of Medicine).