title: Brain stimulation for epilepsy--local and remote modulation of network excitability.
abstract: BACKGROUND
  The use of Deep Brain Stimulation (DBS) as a potential therapy for treatment resistant epilepsy remains an area of active clinical investigation. We recently reported the first chronic evaluation of an implantable, clinical-grade system that permits concurrent stimulation and recording, in a large animal (ovine) model developed to study DBS for epilepsy.
  
  
  OBJECTIVE
  In this study we extended this work to compare the effects of remote (anterior thalamic) and direct (hippocampal) stimulation on local field potential (LFP) activity and network excitability, and to assess closed-loop stimulation within this neural network.
  
  
  METHODS
  Following anesthesia and 1.5T MRI acquisition, unilateral anterior thalamic and hippocampal DBS leads were implanted in three subjects using a frameless stereotactic system. Chronic, awake recordings of evoked potentials (EPs) and LFPs in response to thalamic and hippocampal stimulation were collected with the implanted device and analyzed off-line.
  
  
  RESULTS
  Consistent with earlier reports, thalamic DBS and direct stimulation of the hippocampus produced parameter-dependent effects on hippocampal activity. LFP suppression could be reliably induced with specific stimulation parameters, and was shown to reflect a state of reduced network excitability, as measured by effects on hippocampal EP amplitudes and after-discharge thresholds. Real-time modulation of network excitability via the implanted device was demonstrated using hippocampal theta-band power level as a control signal for closed-loop stimulation.
  
  
  CONCLUSIONS
  The results presented provide evidence of network excitability changes induced by stimulation that could underlie the clinical effects that have been reported with both thalamic and direct cortical stimulation.
authors.affiliation: Medtronic Neuromodulation, 7000 Central Avenue NE, Minneapolis, MN 55432, USA. Electronic address: paul.stypulkowski@medtronic.com.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Stypulkowski
authors.affiliation: Medtronic Neuromodulation, 7000 Central Avenue NE, Minneapolis, MN 55432, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Stanslaski
authors.affiliation: Medtronic Neuromodulation, 7000 Central Avenue NE, Minneapolis, MN 55432, USA.
authors.forename: Randy M
authors.initials: RM
authors.lastname: Jensen
authors.affiliation: Medtronic Neuromodulation, 7000 Central Avenue NE, Minneapolis, MN 55432, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Denison
authors.affiliation: Medtronic Neuromodulation, 7000 Central Avenue NE, Minneapolis, MN 55432, USA.
authors.forename: Jonathon E
authors.initials: JE
authors.lastname: Giftakis
mesh_terms: D000465:Algorithms; D000818:Animals; D001931:Brain Mapping / Q000379:methods; D046690:Deep Brain Stimulation / Q000379:methods*; D004567:Electrodes, Implanted; D004827:Epilepsy / Q000628:therapy*; D005071:Evoked Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D016571:Neural Networks, Computer; D012756:Sheep; D013238:Stereotaxic Techniques; D013788:Thalamus / Q000502:physiology*; D013997:Time Factors
keywords: Deep brain stimulation; Epilepsy; Excitability; Hippocampus; Local field potentials