Epileptogenesis-induced changes of hippocampal-piriform connectivity

Mark D. Skopin, Arezou Bayat, Lalitha Kurada, Mithilesh Siddu, Sweta Joshi, Christina M. Zelano, Mohamad Z. Koubeissi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Objective: Tissue remodeling has been described in brain circuits that are involved in the generation and propagation of epileptic seizures. Human and animal studies suggest that the anterior piriform cortex (aPC) is crucial for seizure expression in focal epilepsies. Here, we investigate the effect of kainic-acid (KA)-induced seizures on the effective connectivity of the aPC with bilateral hippocampal CA3 regions using cerebro-cerebral evoked potentials (CCEPs). Methods: Adult male Sprague-Dawley rats were implanted with a tripolar electrode in the left aPC for stimulation and recording, and with unipolar recording electrodes in bilateral CA3 regions. Single pulse stimulations were given to the aPC and CCEPs were averaged before KA injections and after the emergence of spontaneous recurrent seizures (SRS). Similar recordings at equivalent time intervals were obtained from animals that received saline injections instead of KA (controls). Results: In the experimental group, the percentage change of increased amplitude of the contralateral (but not ipsilateral) CA3 CCEPs between pre-KA injection and after the emergence of SRS was significantly greater than in controls. No significant single-pulse-induced spectral change responses were observed in either epileptic or control rats when comparing pre- and post-stimulus time intervals. Also, we found no correlation between seizure frequency and the extent of amplitude changes in the CCEPs. Conclusions: In the KA model, epileptogenesis results in plastic changes that manifest as an amplification of evoked potential amplitudes recorded in the contralateral hippocampus in response to single-pulse stimulation of the aPC. These results suggest epileptogenesis-induced facilitation of interhemispheric connectivity between the aPC and the hippocampus. Since the amplitude increase of the contralateral CCEP is a possible in vivo biomarker of epilepsy, any intervention (e.g. neuromodulatory) that can reverse this phenomenon may hold a potential antiepileptic efficacy.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
StatePublished - Oct 2020


  • Anterior piriform cortex (aPC)
  • Biomarker
  • Cerebro-cerebral evoked potentials (CCEPs)
  • Low-frequency stimulation (LFS)
  • Spontaneous recurrent seizures (SRS)

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Epileptogenesis-induced changes of hippocampal-piriform connectivity'. Together they form a unique fingerprint.

Cite this