Distinct temporal patterns of electrical stimulation influence neural recruitment during PTZ infusion: an fMRI study

Prog Biophys Mol Biol. 2011 Mar;105(1-2):109-18. doi: 10.1016/j.pbiomolbio.2010.10.005. Epub 2010 Oct 31.


Our working hypothesis is that constant inter-pulse interval (IPI) electrical stimulation (ES) would resonate with endogenous epileptogenic reverberating circuits, favoring seizure, while random inter-interval ES protocol would promote desynchronization of such neural networks, interfering with the abnormal recruitment of neural structures. Male Wistar rats were stereotaxically implanted with a monopolar ES carbon-fiber electrode (minimizing fMRI artifact) in the amygdala. A 7T fMRI scanner was used to evaluate brain activity during ES, fixed four pulses per second ratio, using either a periodic IPI (ES-P) or random IPI (non-periodic ES-NP) stimulation paradigm. Appropriate imaging protocols were used to compare baseline BOLD (blood oxygen level dependent) MRI with scans during ES. A second series of experiments, both without stimuli and under the same ES paradigms, were evaluated during continuous infusion of pentylenetetrazole (PTZ, 4 mg/ml/min) through an i.v. catheter. Our results show that temporal lobe activation during ES-P or ES-NP did not present any statistical differences during ES. However, during PTZ infusion, PTZ-P facilitated recruitment of the temporal lobe ipsilateral to ES while PTZ-NP showed significantly less activation ipsilateral to ES and, in turn, less inter-hemispheric differences. Altogether, our results support the hypothesis of reverberating circuits being synchronized by ES-P and desynchronized by ES-NP. Time-coded low frequency stimulation may be an interesting alternative treatment for patients with refractory epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / physiology
  • Animals
  • Brain Mapping
  • Electric Stimulation / methods*
  • Electroencephalography / methods
  • Epilepsy / physiopathology
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Pentylenetetrazole
  • Rats
  • Rats, Wistar
  • Recruitment, Neurophysiological / physiology*
  • Seizures / chemically induced
  • Seizures / physiopathology*
  • Seizures / therapy*
  • Stereotaxic Techniques / instrumentation


  • Pentylenetetrazole