Stimulation better targets fast ripple generating networks in super-responders to the responsive neurostimulator system (RNS)

Objective How responsive neurostimulation (RNS) decreases seizure frequency is unclear. Stimulation may alter epileptic networks during inter-ictal epochs. Since fast ripples (FR) may be a substrate of the epileptic network, we examined whether stimulation of FR generating networks differed in RNS super- and intermediate-responders. Methods In 10 patients, we detected FR during sleep from stereo EEG (SEEG) contacts during the pre-surgical evaluation in patients with subsequent RNS placement. The normalized coordinates of the SEEG contacts were compared with that of the eight RNS contacts, and RNS stimulated SEEG contacts were defined as within 1.5 cm 3 of the RNS contacts. We compared the post-RNS placement seizure outcome to 1) the ratio of stimulated SEEG contacts in the seizure-onset zone (SOZ SR); 2) the ratio of FR events on stimulated contacts (FR SR); and 3) the global efficiency of the FR temporal correlational network on stimulated contacts (FR SGe). Results We found that the SOZ SR (p=0.18) and FR SR (p=0.06) did not differ in the RNS super- and intermediate-responders, but the FR SGe did (p=0.02). In super-responders highly active desynchronous sites of the FR network were stimulated. Significance RNS that better targets FR networks, as compared to the SOZ, may reduce epileptogenicity more. Short summary Responsive neurostimulation (RNS) may reduce seizures by altering the epileptic network. Fast ripples (FR) may be a substrate of the epileptic network. We investigated, in 10 patients, if RNS stimulation of FR generating brain differed in RNS super-responders and intermediate-responders. The RNS stimulated brain sites were defined as contacts in the pre-surgical stereo EEG implant within 1.5 cm 3 of the subsequently placed RNS stimulation contacts. FR events were more highly active and temporally desynchronous (p<0.05) on the stimulated contacts in the RNS super-responders. We show RNS that better targets FR networks, as compared to the seizure onset zone, may reduce epileptogenicity more.