title: In vivo modulation of hippocampal epileptiform activity with radial electric fields.
abstract: OBJECTIVE
  Electric field stimulation can interact with brain activity in a subthreshold manner. Electric fields have been previously adaptively applied to control seizures in vitro. We report the first results from establishing suitable electrode geometries and trajectories, as well as stimulation and recording electronics, to apply this technology in vivo.
  
  
  METHODS
  Electric field stimulation was performed in a rat kainic acid injection seizure model. Radial electric fields were generated unilaterally in hippocampus from an axial depth electrode. Both sinusoidal and multiphasic stimuli were applied. Hippocampal activity was recorded bilaterally from tungsten microelectrode pairs. Histologic examination was performed to establish electrode trajectory and characterize lesioning.
  
  
  RESULTS
  Electric field modulation of epileptiform neural activity in phase with the stimulus was observed in five of six sinusoidal and six of six multiphasic waveform experiments. Both excitatory and suppressive modulation were observed in the two experiments with stimulation electrodes most centrally placed within the hippocampus. Distinctive modulation was observed in the period preceding seizure-onset detection in two of six experiments. Short-term histologic tissue damage was observed in one of six experiments associated with high unbalanced charge delivery.
  
  
  CONCLUSIONS
  We demonstrated in vivo electric field modulation of epileptiform hippocampal activity, suggesting that electric field control of in vivo seizures may be technically feasible. The response to stimulation before seizure could be useful for triggering control systems, and may be a novel approach to define a preseizure state.
authors.affiliation: Krasnow Institute Department of Physics and Astronomy, George Mason University, Fairfax, Virginia 22030-4444, USA.
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Richardson
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Gluckman
authors.forename: Steven L
authors.initials: SL
authors.lastname: Weinstein
authors.forename: Caryn E
authors.initials: CE
authors.lastname: Glosch
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Moon
authors.forename: Ryder P
authors.initials: RP
authors.lastname: Gwinn
authors.forename: Karen
authors.initials: K
authors.lastname: Gale
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Schiff
mesh_terms: D000669:Amplifiers, Electronic; D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004599:Electric Stimulation Therapy / Q000295:instrumentation / Q000379:methods*; D004567:Electrodes, Implanted; D004582:Electronics, Medical / Q000295:instrumentation / Q000379:methods; D004827:Epilepsy / Q000503:physiopathology / Q000628:therapy*; D006624:Hippocampus / Q000033:anatomy & histology / Q000503:physiopathology*; D006801:Humans; D007608:Kainic Acid; D007696:Kindling, Neurologic / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008839:Microelectrodes; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013238:Stereotaxic Techniques
chemical_list: D007608:Kainic Acid