T103. The connectivity index: A novel metric to grade epileptogenicity

Abstract

To investigate the performance of a metric of functional connectivity to classify and grade excitable brain regions based on cortical-evoked potentials to single pulse electrical stimulation (SPES) compared to non-epileptic sites. Patients who received 1-Hz frequency stimulation in 2003–2014 at Yale, were included. The stimulated contacts were classified as seizure onset zone (SOZ), irritative zone (IZ, frequent or periodic spiking, and early ictal propagation within 5 s of seizure onset) or control. Stimulation intensities ranged 9–12 mA (or lower if not tolerated or if auras were triggered) and pulse width of 250–300 μs. Evoked responses were reproduced at least once and averaged from 45–110 single pulse stimulations. Response contacts were classified as seizure onset zone (SOZ), active interictal (IZ), quiet or other when data did not indicate whether a contact was involved in an epileptic activity or not. The normalized number of responses was defined as the number of contacts with any evoked responses divided by the total number of contacts, and the normalized distance is the ratio of the average distances between the site of stimulation and sites of evoked responses to all other recording contacts. A new metric we labeled the connectivity index (Ci) is defined as the product of the two values. Fifty-seven stimulation sessions in 22 patients were analyzed. Stimulation of SOZ contacts evoked cortical potentials at significantly higher rates than control sites (medians 0.72 vs. 0.26, respectively p 0.0003). These differences were even stronger when normalized to the average distance of recorded responses from the stimulation site i.e. metric we labeled connectivity index Ci (median 0.74 vs. 0.16, respectively, p 0.0002). The evoked cortical potentials after stimulation of SOZ were seen at a further distance from the site of stimulation (median of normalized distance 0.96 vs. 0.62, p 0.0005). It was 1.8 times more likely to record an evoked response from the SOZ than non-epileptic contacts after stimulation of a remote-control site. Habitual partial seizures or auras were triggered in 27% of the patients and 35% of the SOZ contacts that were stimulated (median stimulation intensity 4 mA) but in none of the control or IZ contacts. Non-SOZ contacts in multifocal or poor surgical outcome cases had a higher (Ci) than those in localizable onsets (medians Ci of 0.5 vs. 0.12, p 0.04). There was a correlation between the stimulation current intensity and the normalized number of evoked responses (r = + 0.49, p 0.01) but not with distance (r = + 0.1, p 0.64). The SOZ has an enhanced connectivity with more distant sites compared to non-epileptic contacts. The responses evoked by stimulation of the SOZ have longer average latencies and durations. Auras and seizures provoked by SPES are predictive of brain sites involved in seizure generation. There was a correlation between the Ci of non-SOZ contacts and the duration of epilepsy.