Abstracts

While electrical stimulation of the brain emerges as a potential therapy for intractable epilepsy, an interest in closed-loop stimulation has developed. Currently in clinical trials, the fully implantable Responsive Neurostimulator (RNS[trade]) device (Neuropace, Inc.) is capable of customizable EEG event detection, continuous event-triggered stimulation and storage of recorded electrocorticograms (ECoGs) for analysis. We demonstrate chronic use of the RNS in a rodent model of temporal lobe epilepsy to 1) investigate acute suppression of interictal epileptiform activity in the hippocampus with closed-loop stimulation of the hippocampal circuit and 2) test the hypothesis that stimulation parameters can be manipulated to achieve optimal suppression. Bipolar electrodes (Pt/Ir, 100[mu]m diameter) were implanted bilaterally in the posterior dentate gyrus (DG) and perforant path (PP) of the spontaneously seizing pilocarpine rat. Electrodes were connected to an implanted RNS[trade] device, resulting in a fully subcutaneous system functional for at least 3 months. Half-wave (HW) and Area algorithms were configured to detect interictal spike and seizure events, respectively. When responsive therapy was enabled, HW event-triggered stimulations were delivered bilaterally to PP or DG at a range of parameter (pulse frequency, amplitude, pulse duration, pulse width) combinations and anode/cathode configurations. ECoGs containing baseline activity, detected seizures and responsive stimulations were stored for analysis. For quantification of suppression, the Area and Line Length (LL) of the EEG signal were calculated (MATLAB) during 2s time windows pre- and post-detection, ignoring an intervening 2s window to avoid stimulation artifact. Ratios of pre- and post-detection window values were calculated to quantify suppression. Event-triggered stimulations of PP (200Hz, 560mA, 100ms pulse duration, n = 415) resulted in significantly reduced LL and Area ratios in the left and right DG (p [lt] .01) compared to non-stimulated event detections (n = 110). Event-triggered stimulations (n = 51) of DG (200Hz, 420mA, 100ms pulse duration) resulted in significantly reduced LL and Area ratios in the left and right DG (p [lt] .01), with exception of the LL ratio in the left DG (p [lt] = .362), when compared to non-stimulated event detections (n = 36). These initial observations demonstrate that spike-triggered stimulation to PP and DG via an implantable neurostimulator can acutely suppress epileptiform EEG. Effects of parameter variations on efficacy will be discussed. (Supported by NSF IGERT Neuroengineering Training Grant DGE-9972802, Neuropace, Inc.)