Abstracts

Rationale: Whether interictal spikes (IIS) arise from the ictal onset zone (IOZ) or the extended epileptic network as well as the etiology and function of IIS are widely debated. This debate has great clinical implications as IIS initiation sites are used to locate surgical targets for treatment of intractable seizure disorders. Here we use electrophysiology and calcium imaging to examine the relationship between IIS initiation site and excitatory state in the cortex. Methods: After performing a whole-hemispheric craniotomy and convection enhanced delivery of 8uM of OGB-1 calcium dye, an ictal focus was created via local unilateral injection of 4aminopyradine (4AP, 500nl, 15mM) in adult SD rats under isoflurane anesthesia. Ictal events and IIS were recorded through bilateral LFP measurements and simultaneous wide-field calcium imaging. Results: We found that after 4AP injection, 93.65% of IIS initiated from the contralateral hemisphere (mirror focus). After focal blockade of inhibition with local injection of bicuculline methiodide (BMI, 500nL, 5mM), a GABA antagonist, into the contralateral mirror focus the IIS initiation site switched from the contralateral mirror focus to the 4AP IOZ, with 91.43% of IIS now occurring ipsilaterally. In a separate group of animals, we injected BMI ipsilaterally ~4mm posterior to the 4AP injection site, after which we observed that the majority (95.23%) of IIS once again initiated from the contralateral mirror focus. Conclusions: Consequently, our results suggest that IIS initiation is mediated by GABAergic cells in the epileptic network. Suppression of network interactions creates an environment for IIS to arise from the IOZ. This finding suggests that under certain circumcstances, IIS arise not from the IOZ but from the epileptic network, particularly from the contralateral hemisphere. Funding: This project was supported by the National Science Foundation, NSF-1264948 (H. M. and T. H. S.).