Abstracts

Rationale: Despite the recent clinical adoption of both open and closed loop deep brain stimulation strategies, poor understanding of the mechanisms underlying the effects of electrical stimulation on seizure networks remains a significant barrier to improving efficacy. A modified clinical DBS hardware platform was recently described (PC+S) that allows long-term recording of electrical brain activity such that the acute and chronic effects of DBS on neural networks can be examined. In this study, idiopathic epilepsy was characterized for the first time in a nonhuman primate (NHP) implanted with the PC+S device, and the effect of various stimulation paradigms on local field potential (LFP) activity and seizure frequency was examined. Methods: Clinical DBS electrodes were implanted in the hippocampus bilaterally in an NHP with idiopathic epilepsy. Baseline LFP recordings were collected for seizure characterization using the PC+S device. The effects of variable DBS stimulation paradigms delivered acutely under ketamine anesthesia were examined, and this data was used to predict settings for subsequent chronic testing in the awake, normally behaving state. The effect of chronic stimulation (2wk) paradigms on seizure frequency was then assessed. Results: Real-time automatic detection of ictal events was demonstrated using the PC+S device and validated by concurrent visual observation of seizure behavior. Seizures consisted of large-amplitude 8-25Hz oscillations originating from the right hemisphere and quickly generalizing, with an average duration of 55.3 ± 2.0 seconds and occurrence of 1.0 ± 0.2 seizures per day. The timing and spectral content of ictal events was similar to seizures observed in human temporal lobe epilepsy (TLE), as illustrated in Figure 1, which shows an example of bilateral hippocampal recording traces and spectrograms from a human left TLE case (A) and the epileptic NHP (B). Variable stimulation parameters resulted in either suppression of local neural activity or seizure induction, during stimulation under ketamine anesthesia. Chronic stimulation in the awake animal was studied to evaluate the effects of predicted therapeutic stimulation configurations on seizure activity. Stimulation conditions tested thus far have not resulted in a decrease in seizure frequency, although chronic stimulation was found to alter the time-course of inter-hemispheric coherence of LFPs during seizures. Conclusions: This is the first electrophysiological characterization of idiopathic epilepsy using a next-generation clinical DBS system that offers the ability to record and analyze neural signals from the stimulating electrode. These and future results will inform further development of this technology, especially with regard to the modulation of ictogenic biomarkers through chronic stimulation, and should ultimately provide insight into therapeutic mechanisms of DBS for epilepsy.