title: Rapid brief feedback intracerebral stimulation based on real-time desynchronization detection preceding seizures stops the generation of convulsive paroxysms.
abstract: OBJECTIVE
  To investigate the abortion of seizure generation using "minimal" intervention in hippocampi using two rat models of human temporal lobe epilepsy.
  
  
  METHODS
  The recording or stimulation electrodes were implanted into both hippocampi (CA1 area). Using the kainic acid (chronic: experiment duration 24 days) and the 4-aminopyridine (acute: experiment duration 2 h) models of paroxysms in rats, a real-time feedback stimulation paradigm was implemented, which triggered a short periodic electrical stimulus (5 Hz for 5 s) upon detecting a seizure precursor. Our seizure precursor detection algorithm relied on the monitoring of the real-time phase synchronization analysis, and detected/anticipated electrographic seizures as early as a few seconds to a few minutes before the behavioral and electrographic seizure onset, with a very low false-positive rate of the detection.
  
  
  RESULTS
  The baseline mean seizure frequencies were 5.39 seizures per day (chronic) and 13.2 seizures per hour (acute). The phase synchrony analysis detected 88% (434 of 494) of seizures with a mean false alarm of 0.67 per day (chronic) and 83% (86 of 104) of seizures with a mean false alarm of 0.47 per hour (acute). The feedback stimulation reduced the seizure frequencies to 0.41 seizures per day (chronic) and 2.4 seizures per hour (acute). Overall, the feedback stimulation paradigm reduced seizure frequency by a minimum of 80% to a maximum of 100% in 10 rats, with 83% of the animals rendered seizure-free.
  
  
  CONCLUSIONS
  This approach represents a simple and efficient manner for stopping seizure development. Because of the short on-demand stimuli, few or no associated side effects are expected in clinical application in patients with epilepsy. Abnormal synchrony patterns are common features in epilepsy and other neurologic and psychiatric syndromes; therefore, this type of feedback stimulation paradigm could be a novel therapeutic modality for use in various neurologic and psychiatric disorders.
authors.affiliation: Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Muhammad T
authors.initials: MT
authors.lastname: Salam
authors.affiliation: Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Hossein
authors.initials: H
authors.lastname: Kassiri
authors.affiliation: Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Roman
authors.initials: R
authors.lastname: Genov
authors.affiliation: Neuroscience & Mental Health Programme and Division of Neurology, Hospital for Sick Children, Institute of Medical Science and Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Perez Velazquez
mesh_terms: D015761:4-Aminopyridine / Q000633:toxicity; D000818:Animals; D056547:CA1 Region, Hippocampal; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004569:Electroencephalography; D058407:Electroencephalography Phase Synchronization; D004833:Epilepsy, Temporal Lobe; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007608:Kainic Acid / Q000633:toxicity; D058765:Neurofeedback; D026902:Potassium Channel Blockers / Q000633:toxicity; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000628:therapy*
chemical_list: D018690:Excitatory Amino Acid Agonists; D026902:Potassium Channel Blockers; D015761:4-Aminopyridine; D007608:Kainic Acid
keywords: Electrical stimulation; Epilepsy; Feedback stimulation; In vivo; Phase synchrony