title: Investigation of mechanisms of vagus nerve stimulation for seizure using finite element modeling.
abstract: While the efficacy of vagus nerve stimulation (VNS) to reduce seizures in pharmaco-resistant patients is clinically proven, its efficacy and side effects mechanisms are not fully understood. Our goals were 1) to use a finite element model (FEM) and axon models to examine different fiber activation and blocking thresholds and 2) examine fiber activation and blocking in three fiber groups likely to be responsible for efficacy and side effects.
  
  
  
  Using FEM, we examined the field potential along axons within a vagus nerve model with fascicles. These data were input to a computational fiber model to estimate numbers of axons activated across all diameters. We estimated numbers of activated and blocked fibers by diameter.
  
  
  
  1) At the low end of VNS amplitudes, little efficacy for seizure control is appreciated while large Aβ fibers associated with the recurrent laryngeal nerve are recruited. As amplitudes are increased, Aβ fibers can produce hoarseness, and next recruited are fast B fibers associated with the aortic fascicle. We hypothesize these B fibers are the source of efficacy in treating seizure. As amplitudes are further increased, coughing may occur, possibly due to recruitment of smaller and deeper pulmonary fibers. 2) Clinical parameters are in a range that could cause inadvertent blocking at the cathode and activation at the anode. Conversely, innovative approaches to field shape and charge-balancing can allow controlled fiber activation at the cathode for maximum activation of the fibers responsible for efficacy, and possibly blocking at the anode to minimize side effects and expand therapeutic range. In design and operation, the cathode and anode can each be approached as a band pass filter.
  
  
  
  The B fiber group is necessary and possibly sufficient to produce VNS efficacy in epilepsy. This group may emanate from aortic baroreceptors that, via synapses in the solitary tract nucleus, stimulate the locus coeruleus, hypothalamus and other influential targets such as the hippocampus. Responder rates may be increased with a lead that fully encircles the nerve. With better identification of the fiber groups involved in VNS, efficacy, side effects, therapeutic range and responder rates can be optimized.
authors.affiliation: Department of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, MA, United States; Department of Neurosurgery, Harvard Medical School, Boston, MA, United States; Department of Neurosurgery, Mount Auburn Hospital, Cambridge, MA, United States.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Arle
authors.affiliation: Department of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, MA, United States. Electronic address: kwcarlso@bidmc.harvard.edu.
authors.forename: Kristen W
authors.initials: KW
authors.lastname: Carlson
authors.affiliation: Department of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, MA, United States.
authors.forename: Longzhi
authors.initials: L
authors.lastname: Mei
mesh_terms: D001369:Axons / Q000502:physiology*; D003198:Computer Simulation; D000069279:Drug Resistant Epilepsy / Q000503:physiopathology / Q000628:therapy; D005260:Female; D020342:Finite Element Analysis; D006801:Humans; D008875:Middle Aged; D008959:Models, Neurological; D012640:Seizures / Q000503:physiopathology* / Q000628:therapy*; D017552:Solitary Nucleus / Q000503:physiopathology; D014630:Vagus Nerve / Q000503:physiopathology; D055536:Vagus Nerve Stimulation / Q000009:adverse effects
keywords: Epilepsy; Finite element modeling; Nucleus tractus solitarius; Seizure; Vagus nerve; Vagus nerve stimulation