Abstracts

Rationale: The responsive neurostimulation (RNS) is the first closed-loop neuromodulatory therapy used as an adjunctive therapy for patients with medically intractable focal epilepsy. Although the demand of RNS is increasing, the appropriate stimulus sites of RNS have not been elucidated. Cortico-cortical evoked potentials (CCEPs), the responses by direct single-pulse electrical stimulation (SPES) on cerebral cortex, have been investigated to electrically trace cortico-cortical connections in vivo, although limited to epilepsy or tumor patients who undergo invasive presurgical evaluation. CCEPs have been extensively employed to evaluate the cortico-cortical networks associated with various normal brain functions and to evaluate cortical excitability associated with epileptogenicity. We aim to explore whether CCEPs can be used to guide cortical targeting for RNS therapy. Methods: We reviewed 12 patients with medically intractable epilepsy who underwent CCEP recordings during the presurgical evaluation by stereoelectroencephalography (SEEG) and had RNS implanted. Repetitive SPES (1 Hz, 4 mA, alternating polarity) was applied to a pair of two adjacent electrodes in the cortex and CCEPs were recorded from the cortical contacts. The contact locations of SEEG and RNS were precisely reconstructed and confirmed in each patient by using the MRI before SEEG implantation and the CTs after SEEG and RNS implantation. In order to standardize across patient, we focused on the CCEPs on the middle temporal gyrus (MTG) and superior temporal gyrus (STG), which were the common anatomical locations across 12 patients. In the process of CCEP analysis, we used the functional anatomically-guided stacked-area-graph (FAST graph) we originally created, which presents the sum of the responses at the MTG or STG of each stimulus site. We preformed sign permutation test to extract a statistically significant CCEP and its significant time points for each stimulus site. We classified the time points of CCEP after SPES into the 3 responses based on its latency: early response (ER) between 10-60 ms, late response (LR) between 60-250 ms, and very late response (VLR) between 250-600 ms. Results: We classified the 12 patients into the 4 epilepsy types based on the ictal onset pattern in the SEEG evaluation: 3 with mesial temporal lobe epilepsy (TLE), 7 with neocortical TLE, 1 with temporo-parietal epilepsy, and 1 with occipital lobe epilepsy. There was a slight tendency that significant CCEPs for ER, LR, and VLR were observed in patients with TLE. Four patients with hyperperfusion on MTG or STG in subtraction ictal SPECT co-registered with MRI (SISCOM) tended to show significant CCEPs compared with the other 8 patients without hyperperfusion on the areas. Stimulus sites with distances of 0-5 mm to the closest RNS contacts presented more significant ERs than those with distances more than 10 mm to the closest RNS contacts. Conclusions: CCEPs focused on MTG and STG in this evaluation seemed to have correlations with the hyperperfusion in SISCOM. The RNS contacts were placed mainly based on the ictal onset patterns. However, the propagation network as determined by CCEPs, seemed to correlate with the type of epilepsy, in this case temporal lobe epilepsy. Understanding the ictal onset as well as the propagation network maybe helpful in guiding the placement of electrodes for RNS therapy. Funding: No funding