Asynchronous Distributed Multielectrode Microstimulation Reduces Seizures in the Dorsal Tetanus Toxin Model of Temporal Lobe Epilepsy

• Type of Material: Article
• Authors: Sharanya Arcot Desai, Georgia Institute of Technology; John D. Rolston, University of California San Francisco; Courtney E. McCracken, Emory University; Steve Potter, Emory University; Robert Gross, Emory University
• Language: English
• Date: 2016-01-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.brs.2015.08.008
• Title of Journal or Parent Work: Brain Stimulation
• Volume: 9
• Issue: 1
• Start Page: 86
• End Page: 100
• Grant/Funding Information: This work was supported by the CURE Foundation, NSF EFRI 1238097, the Wallace H. Coulter Foundation, and NIH NS05480.; The Schlumberger Faculty for the Future fellowship supported Sharanya Arcot Desai.
• Keywords: Theta oscillations; Life Sciences & Biomedicine; ELECTRICAL-STIMULATION; Science & Technology; Multielectrode array; LONG-TERM CHANGES; HIPPOCAMPUS; Multi site stimulation; Epilepsy; CULTURES; Microstimulation; MECHANISMS; BRAIN-STIMULATION; DEEP BRAIN; Neurosciences & Neurology; HIGH-FREQUENCY OSCILLATIONS; THETA OSCILLATIONS; RATS; Clinical Neurology; Neurosciences
• Research Categories: Engineering, Biomedical; Biology, Neuroscience

Abstract

Background Electrical brain stimulation has shown promise for reducing seizures in drug-resistant epilepsy, but the electrical stimulation parameter space remains largely unexplored. New stimulation parameters, electrode types, and stimulation targets may be more effective in controlling seizures compared to currently available options. Hypothesis We hypothesized that a novel electrical stimulation approach involving distributed multielectrode microstimulation at the epileptic focus would reduce seizure frequency in the tetanus toxin model of temporal lobe epilepsy. Methods We explored a distributed multielectrode microstimulation (DMM) approach in which electrical stimulation was delivered through 15 33-μm-diameter electrodes implanted at the epileptic focus (dorsal hippocampus) in the rat tetanus toxin model of temporal lobe epilepsy. Results We show that hippocampal theta (6-12 Hz brain oscillations) is decreased in this animal model during awake behaving conditions compared to control animals (p < 10-4). DMM with biphasic, theta-range (6-12 Hz/electrode) pulses delivered asynchronously on the 15 microelectrodes was effective in reducing seizures by 46% (p < 0.05). When theta pulses or sinusoidal stimulation was delivered synchronously and continuously on the 15 microelectrodes, or through a single macroelectrode, no effects on seizure frequency were observed. High frequency stimulation (>16.66 Hz/per electrode), in contrast, had a tendency to increase seizure frequency. Conclusions These results indicate that DMM could be a new effective approach to therapeutic brain stimulation for reducing seizures in epilepsy.