Abstracts

Rationale: Neuromodulation is an effective therapy for patients with medically intractable focal epilepsy (MIFE). Inhibitory effects of high and low frequency electric cortical stimulation (ECS) have been previously reported (Durand et al. 2001). On the other hands, ECS can be pro-epileptic and can induce electrographic seizure (Khatoun et al. 2017). Thus the mechanism of ECS on ictogenesis needs to be further investigated. Cortico-cortical evoked potentials (CCEPs), have been utilized to electrically trace cortico-cortical connections in vivo, to evaluate the cortico-cortical networks and to evaluate cortical excitability associated with epileptogenicity (Matsumoto et al. 2017). The aim of this study is to investigate how CCEPs modulate the interictal epileptiform discharges in the epileptic zone (EZ) in relation to the effective connectivity measured using CCEPs.  Methods: We investigated 2 out of a planned 32 MIFE patients who underwent CCEP stimulation during the pre-surgical evaluation by stereoelectroencephalography (SEEG). These patients are seizure free following epilepsy surgery. SEEG contacts were co-registered to the post-operative MRI and SEEG contacts within the resected cortex were identified. The EZ was defined as SEEG contacts that were part of the resected cortex. Cortical excitability was quantified by using numbers of interictal spikes. CCEP stimulation of two SEEG contact pairs outside the EZ were selected per patient based on their connectivity with the EZ. Contacts were categorized as high connectivity (HC) or low connectivity (LC) contacts based on CCEPs to the EZ. Spike frequency at the EZ contacts to low frequency stimulation of HC and LC contact were estimated.  Results: Patient 1 was a 22-year-old man with left neocortical temporal lobe epilepsy. The HC contacts were located at the anterior planum polare and LC contacts were located at the temporal pole. There was no statistically significant difference (p>0.26) in number of spike with low frequency stimulation of LC or HC contact for the stimulation amplitude of 4 to 8 mA. Patient 2 was a 54-year-old woman with right perisylvian epilepsy. The HC contacts were located in the uncus and amygdala and LC contacts were located at the parietal operculum. Stimulation of HC areas generated statistically significant and lower number of spikes (p<0.03) when compared to LC area for stimulation amplitude of 4 and 8 mA. Stimulation of HC areas generated statistically significant and higher number of spikes (p=0.0018) when compared to LC area for a stimulation amplitude of 6 mA.  Conclusions: Preliminary results from the study suggest that cortical excitability could be influenced by the amplitude of electrical stimulation and spatial location of stimulation electrode. Extension of the study to a larger group of patients can help identifying optimal stimulation targets and parameters for neuromodulatory therapy in MIFE.  Funding: NIH RO1 Grant (RO1NS089212A_A7886P1)Brain Atlas for Mapping Connectivity in Focal Epilepsy