Seizure Onset Zone Electrodes Research Articles

Quantifying trial-by-trial variability during cortico-cortical evoked potential mapping of epileptogenic tissue.

Measuring cortico-cortical evoked potentials (CCEPs) is a promising tool for mapping epileptic networks, but it is not known how variability in brain state and stimulation technique might impact the use of CCEPs for epilepsy localization. We test the hypotheses that (1) CCEPs demonstrate systematic variability across trials and (2) CCEP amplitudes depend on the timing of stimulation with respect to endogenous, low-frequency oscillations. We studied 11 patients who underwent CCEP mapping after stereo-electroencephalography electrode implantation for surgical evaluation of drug-resistant epilepsy. Evoked potentials were measured from all electrodes after each pulse of a 30 s, 1Hz bipolar stimulation train. We quantified monotonic trends, phase dependence, and standard deviation (SD) of N1 (15-50 ms post-stimulation) and N2 (50-300 ms post-stimulation) amplitudes across the 30 stimulation trials for each patient. We used linear regression to quantify the relationship between measures of CCEP variability and the clinical seizure-onset zone (SOZ) or interictal spike rates. We found that N1 and N2 waveforms exhibited both positive and negative monotonic trends in amplitude across trials. SOZ electrodes and electrodes with high interictal spike rates had lower N1 and N2 amplitudes with higher SD across trials. Monotonic trends of N1 and N2 amplitude were more positive when stimulating from an area with higher interictal spike rate. We also found intermittent synchronization of trial-level N1 amplitude with low-frequency phase in the hippocampus, which did not localize the SOZ. These findings suggest that standard approaches for CCEP mapping, which involve computing a trial-averaged response over a .2-1Hz stimulation train, may be masking inter-trial variability that localizes to epileptogenic tissue. We also found that CCEP N1 amplitudes synchronize with ongoing low-frequency oscillations in the hippocampus. Further targeted experiments are needed to determine whether phase-locked stimulation could have a role in localizing epileptogenic tissue.

0147 Electrophysiologic Localization of Pathological Brain Tissue Is Accomplished with Intracranial Sleep Staging

0147 Electrophysiologic Localization of Pathological Brain Tissue Is Accomplished with Intracranial Sleep Staging

Factors correlated with intracranial interictal epileptiform discharges in refractory epilepsy.

This study was undertaken to evaluate the influence that subject-specific factors have on intracranial interictal epileptiform discharge (IED) rates in persons with refractory epilepsy. One hundred fifty subjects with intracranial electrodes performed multiple sessions of a free recall memory task; this standardized task controlled for subject attention levels. We utilized a dominance analysis to rank the importance of subject-specific factors based on their relative influence on IED rates. Linear mixed-effects models were employed to comprehensively examine factors with highly ranked importance. Antiseizure medication (ASM) status, time of testing, and seizure onset zone (SOZ) location were the highest-ranking factors in terms of their impact on IED rates. The average IED rate of electrodes in SOZs was 34% higher than the average IED rate of electrodes outside of SOZs (non-SOZ; p<.001). However, non-SOZ electrodes had similar IED rates regardless of the subject's SOZ location (p=.99). Subjects on older generation (p<.001) and combined generation (p<.001) ASM regimens had significantly lower IED rates relative to the group taking no ASMs; newer generation ASM regimens demonstrated a nonsignificant association with IED rates (p=.13). Of the ASMs included in this study, the following ASMs were associated with significant reductions in IED rates: levetiracetam (p<.001), carbamazepine (p<.001), lacosamide (p=.03), zonisamide (p=.01), lamotrigine (p=.03), phenytoin (p=.03), and topiramate (p=.01). We observed a nonsignificant association between time of testing and IED rates (morning-afternoon p=.15, morning-evening p=.85, afternoon-evening p=.26). The current study ranks the relative influence that subject-specific factors have on IED rates and highlights the importance of considering certain factors, such as SOZ location and ASM status, when analyzing IEDs for clinical or research purposes.

Physiological and pathological high frequency oscillations in focal epilepsy.

ObjectiveThis study investigates high‐frequency oscillations (HFOs; 65–600 Hz) as a biomarker of epileptogenic brain and explores three barriers to their clinical translation: (1) Distinguishing pathological HFOs (pathHFO) from physiological HFOs (physHFO). (2) Classifying tissue under individual electrodes as epileptogenic (3) Reproducing results across laboratories.MethodsWe recorded HFOs using intracranial EEG (iEEG) in 90 patients with focal epilepsy and 11 patients without epilepsy. In nine patients with epilepsy putative physHFOs were induced by cognitive or motor tasks. HFOs were identified using validated detectors. A support vector machine (SVM) using HFO features was developed to classify tissue under individual electrodes as normal or epileptogenic.ResultsThere was significant overlap in the amplitude, frequency, and duration distributions for spontaneous physHFO, task induced physHFO, and pathHFO, but the amplitudes of the pathHFO were higher (P < 0.0001). High gamma pathHFO had the strongest association with seizure onset zone (SOZ), and were elevated on SOZ electrodes in 70% of epilepsy patients (P < 0.0001). Failure to resect tissue generating high gamma pathHFO was associated with poor outcomes (P < 0.0001). A SVM classified individual electrodes as epileptogenic with 63.9% sensitivity and 73.7% specificity using SOZ as the target.InterpretationA broader range of interictal pathHFO (65–600 Hz) than previously recognized are biomarkers of epileptogenic brain, and are associated with SOZ and surgical outcome. Classification of HFOs into physiological or pathological remains challenging. Classification of tissue under individual electrodes was demonstrated to be feasible. The open source data and algorithms provide a resource for future studies.

F05. Neurophysiological effects of chronic subthreshold cortical stimulation for focal epilepsy: Spike and spontaneous ECoG activity

Neurostimulation is a treatment option for drug-resistant focal epilepsy. Chronic subthreshold cortical stimulation (CSCS) is a novel, promising technique that directly targets the seizure onset zone (SOZ) with continuous electrical stimulation. Prior retrospective analyses have shown reduced seizure frequencies and improved quality of life. Here, we investigate underlying neurophysiological changes induced by CSCS in order to gain an insight into the mechanism underlying the clinical effect of chronic electrical stimulation in focal epilepsy. We examined intracranial EEG data from seven patients with drug-resistant focal epilepsy and SOZs located in eloquent cortex who underwent continuous stimulation during their hospitalization. Subdural grid electrodes were implanted, and after the SOZ was localized to eloquent cortex, 2 Hz electrical stimulation was applied to contacts targeting the SOZ. Ninety minutes of intracranial EEG from a 4 × 4 electrode grid was analyzed before and during stimulation. Electrophysiological parameters were estimated for both pre-stimulation and stimulation data. Power spectrum and coherence of background activity was analysed together with spiking activity characteristics including spike rate, spike amplitude, and spike duration. Cortical stimulation resulted in a marked reduction of the amplitudes of background activity across all channel types for frequencies 5–40 Hz, particularly over SOZ electrodes. During cortical stimulation there was increased coherence between all electrodes and a decrease in spike rate, greatest over SOZ (p < 0.001). Spike-rate coherence was greatest within and between SOZ for pre-stimulation recordings and showed a significant decrease with cortical stimulation for electrodes near SOZ (p < 0.001). No such effect was seen for the other electrodes. Analysis of spike amplitudes showed that cortical stimulation resulted in a clear reduction of spikes over SOZ electrodes (p < 0.001) and only minor reductions for other electrodes (p < 0.001). Moreover, stimulation onset resulted in minor changes in the distribution of spike durations over all electrodes (p < 0.001). Spike-rate and power of background activity showed a significant correlation (p < 0.01). These results show changes in cortical electrophysiology during CSCS over the SOZ where reduction in interictal spikes is correlated with an attenuation of background activity. This suggests a possible causal relationship between background activity and interictal spikes and with seizure frequency rate. With an improved understanding of chronic electrical stimulation better stimulation paradigms might be developed for improved suppression of seizure frequency.