title: Timing of high-frequency cortical stimulation in a genetic absence model.
abstract: BACKGROUND
  Seizure control is one of the ultimate aims of epileptology: here acute and prolonged effects of closed loop high-frequency stimulation of the somatosensory cortex on the expression of spontaneously occurring spike-wave discharges (SWD) were investigated in a genetic absence model. Effects of closed loop stimulation in the experimental group were compared with a yoked control group allowing to investigate the effect of timing related to SWD occurrence, while controlling for amount and intensity of stimulation.
  
  
  METHODS
  WAG/Rij rats were implanted with stimulation electrodes in the deep layers of the somatosensory cortex, and recording electrodes in the cortex and thalamus. Closed-loop and yoked stimulation (1 sec trains, biphasic 0.4 msec pulses, 130 Hz) sessions lasted 24h. The stimulation sessions were preceded and followed by baseline and post stimulation 24-h recordings.
  
  
  RESULTS
  Closed-loop stimulation interrupted SWD and duration of SWD was shortened. Both types of stimulation resulted in a reduction in SWD number during stimulation sessions. Closed-loop stimulation also resulted in less SWD during the last eight hours of the post-stimulation recording session. Sometimes yoked stimulation induced low-frequency afterdischarges.
  
  
  CONCLUSIONS
  SWD can be aborted by closed-loop stimulation of the somatosensory cortex, and at the same time the number of SWD was reduced. It can be regarded as a relatively safe neuromodulatory technique without habituation. The reduction of SWD during yoked stimulation session might be caused by 3 Hz afterdischarges. The reduction of SWD on the stimulation and post-stimulation sessions demonstrates the critical relevance of timing for the induction of longer lasting neuromodulatory effects: it suggests that absence seizures themselves might be involved in their reoccurrence.
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Donders Centre for Cognition, Radboud University, Nijmegen, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: van Heukelum
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Donders Centre for Cognition, Radboud University, Nijmegen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Kelderhuis
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Donders Centre for Cognition, Radboud University, Nijmegen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Janssen
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Donders Centre for Cognition, Radboud University, Nijmegen, The Netherlands. Electronic address: g.vanluijtelaar@donders.ru.nl.
authors.forename: G
authors.initials: G
authors.lastname: van Luijtelaar
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Donders Centre for Cognition, Radboud University, Nijmegen, The Netherlands; Institute of Physiology I, Westfälische Wilhelms University Münster, Münster, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Lüttjohann
mesh_terms: D000818:Animals; D046690:Deep Brain Stimulation / Q000379:methods*; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy*; D058542:Implantable Neurostimulators; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology; D055647:Rats, Transgenic; D013003:Somatosensory Cortex / Q000503:physiopathology*; D013788:Thalamus / Q000503:physiopathology*
keywords: WAG/Rij rats; deep brain stimulation; neuroplasticity; somatosensory cortex; spike-wave discharges; yoked control stimulation