Abstracts

Rationale: Several methods for stimulatory neuromodulation are available or under study for treatment of refractory epilepsy, including vagus nerve stimulation, responsive neurostimulation, or deep brain stimulation. Presently, the precise neurological substrate(s) and mechanism of seizure initiation and termination within the human hippocampus are poorly understood. We have developed a novel method of analyzing epileptiform activity at high spatiotemporal resolution from epileptogenic human hippocampal slices resected from patients who have undergone amygdalahippocampectomy for drug-resistant mesial temporal lobe epilepsy.Methods: Patients with drug-resistant temporal lobe epilepsy who completed a standard presurgical workup and were deemed surgical candidates were offered participation in this IRB approved study (HS-10–00162). En bloc amygdalahippocampectomy was performed and 500u thick slices were prepared with a vibratome. Before conducting electrophysiological recordings, slices were immersed in artificial CSF (aCSF) for at least 1 h to permit maximal recovery from surgery, slicing, and transportation. Electrophysiology data were collected through an MEA1060-Inv extracellular, multi-electrode array recording system with 60 input channels (Fig 1). Spatio-temporal inter-ictal activity from human hippocampal slices was recorded in high-potassium (8 mM), low-magnesium (0.25 mM) aCSF with additional 100 μM 4-aminopyridine.Results: Spiking activity varied considerably between subjects, and could be recorded from different hippocampal subregions including dentate, CA1 and subiculum. In addition, four different patterns of spiking activity were observed: (1) brief bursts, (2) prolonged bursts, (3) low frequency firing, and (4) high frequency firing (Fig 2).Conclusions: We present a novel technique for the in vitro study of epileptogenic human hippocampal slices demonstrating that epileptiform spiking can be recorded from different hippocampal subregions, and that such spiking varies in both frequency and burst pattern. Further study is needed to correlate specific hippocampal spiking patterns with neuroimaging and/or clinical features. Improved understanding of these correlations may guide future strategies for neurostimulation platforms.