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Seizure entrainment with polarizing low-frequency electric fields in a chronic animal epilepsy model

Sridhar Sunderam1, Nick Chernyy1, Nathalia Peixoto2, Jonathan P Mason1, Steven L Weinstein3, Steven J Schiff1,4,5 and Bruce J Gluckman1,4,6

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Neural activity can be modulated by applying a polarizing low-frequency (Lt100 Hz) electric field (PLEF). Unlike conventional pulsed stimulation, PLEF stimulation has a graded, modulatory effect on neuronal excitability, and permits the simultaneous recording of neuronal activity during stimulation suitable for continuous feedback control. We tested a prototype system that allows for simultaneous PLEF stimulation with minimal recording artifact in a chronic tetanus toxin animal model (rat) of hippocampal epilepsy with spontaneous seizures. Depth electrode local field potentials recorded during seizures revealed a characteristic pattern of field postsynaptic potentials (fPSPs). Sinusoidal voltage-controlled PLEF stimulation (0.5–25 Hz) was applied in open-loop cycles radially across the CA3 of ventral hippocampus. For stimulated seizures, fPSPs were transiently entrained with the PLEF waveform. Statistical significance of entrainment was assessed with Thomson's harmonic F-test, with 45/132 stimulated seizures in four animals individually demonstrating significant entrainment (p < 0.04). Significant entrainment for multiple presentations at the same frequency (p < 0.01) was observed in three of four animals in 42/64 stimulated seizures. This is the first demonstration in chronically implanted freely behaving animals of PLEF modulation of neural activity with simultaneous recording.


PACS

87.80.-y Biophysical techniques (research methods)

87.19.L- Neuroscience

87.19.X- Diseases

87.19.R- Mechanical and electrical properties of tissues and organs

Subjects

Instrumentation and measurement

Medical physics

Biological physics

Dates

Issue 4 (6 August 2009)

Received 29 January 2009, accepted for publication 3 June 2009

Published 15 July 2009



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