title: Sensing-enabled hippocampal deep brain stimulation in idiopathic nonhuman primate epilepsy.
abstract: Epilepsy is a debilitating condition affecting 1% of the population worldwide. Medications fail to control seizures in at least 30% of patients, and deep brain stimulation (DBS) is a promising alternative treatment. A modified clinical DBS hardware platform was recently described (PC+S) allowing long-term recording of electrical brain activity such that effects of DBS on neural networks can be examined. This study reports the first use of this device to characterize idiopathic epilepsy and assess the effects of stimulation in a nonhuman primate (NHP). Clinical DBS electrodes were implanted in the hippocampus of an epileptic NHP bilaterally, and baseline local field potential (LFP) recordings were collected for seizure characterization with the PC+S. Real-time automatic detection of ictal events was demonstrated and validated by concurrent visual observation of seizure behavior. Seizures consisted of large-amplitude 8- to 25-Hz oscillations originating from the right hemisphere and quickly generalizing, with an average occurrence of 0.71 ± 0.15 seizures/day. Various stimulation parameters resulted in suppression of LFP activity or in seizure induction during stimulation under ketamine anesthesia. Chronic stimulation in the awake animal was studied to evaluate how seizure activity was affected by stimulation configurations that suppressed broadband LFPs in acute experiments. This is the first electrophysiological characterization of epilepsy using a next-generation clinical DBS system that offers the ability to record and analyze neural signals from a chronically implanted stimulating electrode. These results will direct further development of this technology and ultimately provide insight into therapeutic mechanisms of DBS for epilepsy.
authors.affiliation: Brain Modulation Lab, Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors.forename: W J
authors.initials: WJ
authors.lastname: Lipski
authors.affiliation: Brain Modulation Lab, Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors.forename: V J
authors.initials: VJ
authors.lastname: DeStefino
authors.affiliation: Medtronic Neuromodulation, Minneapolis, Minnesota;
authors.forename: S R
authors.initials: SR
authors.lastname: Stanslaski
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors.forename: A R
authors.initials: AR
authors.lastname: Antony
authors.affiliation: Brain Modulation Lab, Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors.forename: D J
authors.initials: DJ
authors.lastname: Crammond
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: J L
authors.initials: JL
authors.lastname: Cameron
authors.affiliation: Brain Modulation Lab, Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania; Center for the Neural Basis of Cognition and McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania richardsonrm@upmc.edu.
authors.forename: R M
authors.initials: RM
authors.lastname: Richardson
mesh_terms: D000818:Animals; D058256:Brain Waves; D046690:Deep Brain Stimulation; D004829:Epilepsy, Generalized / Q000503:physiopathology* / Q000628:therapy; D006624:Hippocampus / Q000503:physiopathology*; D008253:Macaca mulatta; D008297:Male
keywords: deep brain stimulation; hippocampus; local field potential; temporal lobe epilepsy