Intracranial Grid Research Articles

Modeling intracranial electrodes. A simulation platform for the evaluation of localization algorithms.

IntroductionIntracranial electrodes are implanted in patients with drug-resistant epilepsy as part of their pre-surgical evaluation. This allows the investigation of normal and pathological brain functions with excellent spatial and temporal resolution. The spatial resolution relies on methods that precisely localize the implanted electrodes in the cerebral cortex, which is critical for drawing valid inferences about the anatomical localization of brain function. Multiple methods have been developed to localize the electrodes, mainly relying on pre-implantation MRI and post-implantation computer tomography (CT) images. However, they are hard to validate because there is no ground truth data to test them and there is no standard approach to systematically quantify their performance. In other words, their validation lacks standardization. Our work aimed to model intracranial electrode arrays and simulate realistic implantation scenarios, thereby providing localization algorithms with new ways to evaluate and optimize their performance.ResultsWe implemented novel methods to model the coordinates of implanted grids, strips, and depth electrodes, as well as the CT artifacts produced by these. We successfully modeled realistic implantation scenarios, including different sizes, inter-electrode distances, and brain areas. In total, ∼3,300 grids and strips were fitted over the brain surface, and ∼850 depth electrode arrays penetrating the cortical tissue were modeled. Realistic CT artifacts were simulated at the electrode locations under 12 different noise levels. Altogether, ∼50,000 thresholded CT artifact arrays were simulated in these scenarios, and validated with real data from 17 patients regarding the coordinates’ spatial deformation, and the CT artifacts’ shape, intensity distribution, and noise level. Finally, we provide an example of how the simulation platform is used to characterize the performance of two cluster-based localization methods.ConclusionWe successfully developed the first platform to model implanted intracranial grids, strips, and depth electrodes and realistically simulate thresholded CT artifacts and their noise. These methods provide a basis for developing more complex models, while simulations allow systematic evaluation of the performance of electrode localization techniques. The methods described in this article, and the results obtained from the simulations, are freely available via open repositories. A graphical user interface implementation is also accessible via the open-source iElectrodes toolbox.

Risk of seizure clusters and status epilepticus following rapid and ultra-rapid medication discontinuation during intracranial EEG monitoring

ObjectiveAnti-seizure medications (ASMs) are discontinued in the course of intracranial EEG (iEEG) monitoring for presurgical evaluation. The ASM withdrawal facilitates an emergence of seizures but may also precipitate seizure clusters (SC) and status epilepticus (SE). The aim of this study was to compare the rates of SC and SE during the ultra-rapid withdrawal (URW) and rapid withdrawal (RW) of ASMs during iEEG. MethodsWe performed a retrospective observational study of all consecutive patients with drug resistant epilepsy who completed iEEG at our comprehensive epilepsy center from 2012-2018. SC was defined as three or more seizures in 24 h with a return to baseline between the events. SE was defined as ≥ 5 min of clinical seizure or ≥ 10 min of ictal electrographic activity or series of seizures with no return to the neurological baseline between the events. ResultsOf 107 patients who completed iEEG with intracranial grid or strip electrodes, 46 (43%) were male. Median age at the time of iEEG was 35.4 years (interquartile range [IQR], 26.4 - 44.9). Ninety patients (84.1%) had all AEDs held on admission, while 16 patients (15%) underwent a rapid taper. The median time to first seizure was 15.1 (8.2 - 22.6) h. Sixty-two patients (57.9%) developed SC, while 10 (9.4%) developed SE. Twenty-six patients (36.1%) with these complications required intravenous lorazepam or other rescue ASMs, while the remaining patients had spontaneous resolution of seizures; intubations were not required. While there were differences in the proportions in patients who experienced SC, SE, or neither in the URW and RW groups, these differences were not significant at the 0.05 alpha level. SignificanceUltra-rapid and rapid ASM withdrawal are accompanied by SC and SE the majority of which terminate spontaneously. These data support the use of either approach of the medication taper for seizure provocation in iEEG.

Method of invasive monitoring in epilepsy surgery and seizure freedom and morbidity: A systematic review.

Invasive monitoring is sometimes necessary to guide resective surgery in epilepsy patients, but the ideal method is unknown. In this systematic review, we assess the association of postresection seizure freedom and adverse events in stereoelectroencephalography (SEEG) and subdural electrodes (SDE). We searched three electronic databases (MEDLINE, Embase, and CENTRAL [Cochrane Central Register of Controlled Trials]) from their inception to January 2018 with the keywords "electroencephalography," "intracranial grid," and "epilepsy." Studies that presented primary quantitative patient data for postresection seizure freedom with at least 1year of follow-up or complication rates of SEEG- or SDE-monitored patients were included. Two trained investigators independently collected data from eligible studies. Weighted mean differences (WMDs) with 95% confidence interval (CIs) were used as a measure of the association of SEEG or SDE with seizure freedom and with adverse event outcomes. Of 11462 screened records, 48 studies met inclusion criteria. These studies reported on 1973 SEEG patients and 2036 SDE patients. Our systematic review revealed SEEG was associated with 61.0% and SDE was associated with 56.4% seizure freedom after resection (WMD = +5.8%, 95% CI = 4.7-6.9%, P=.001). Furthermore, SEEG was associated with 4.8% and SDE was associated with 15.5% morbidity (WMD = -10.6%, 95% CI = -11.6 to -9.6%, P=.001). SEEG was associated with 0.2% mortality and SDE was associated with 0.4% mortality (WMD = -0.2%, 95% CI = -0.3 to -0.1%, P=.001). In this systematic review of SEEG and SDE invasive monitoring techniques, SEEG was associated with fewer surgical resections yet better seizure freedom outcomes in those undergoing resections. SEEG was also associated with lower mortality and morbidity than SDE. Clinical studies directly comparing these modalities are necessary to understand the relative rates of seizure freedom, morbidity, and mortality associated with these techniques.

Concurrent recording of neurometabolic changes and local field potential in the central nervous system of awake-behaving rodent models of epilepsy

Introduction: Temporal lobe epilepsy (TLE) is a form of acquired epilepsy characterized as an electro-clinical syndrome in which seizures emanate from the limbic system [1,2]. TLE is particularly disabling due to the unpredictable and recurrent nature of seizures and incidence of antiepileptic drug resistance [3] many times an indication for resection surgery [4,5]. Pre-surgical identification of the seizure onset zone relies on multimodal methods based on different pathophysiological principles. The golden standard technique is long-term intracranial electroencephalogram (EEG) [6] combined neuroimaging techniques, which explore brain hemodynamics as a surrogate signal for brain activity [7,8]. To date, no single sensor approach allows simultaneous and seamless recording of electrical and hemodynamic responses. Materials and methods: We used multisite ceramic-based Pt microelectrode arrays (MEAs) to perform high-frequency amperometric recording of pO2 and local field potential (LFP)-related currents in the CNS of chronically implanted freely-moving rats during pilocarpine-evoked status epilepticus. Using fast Fourier transform (FFT) filtering of the raw electrochemical signal we separated into the low frequency component (<1 Hz), corresponding to the electrochemical reduction of O2 and high (>1 Hz) frequency component, corresponding to the LFP currents. Results: We determined the mean resting level of pO2 in two subregions of the hippocampus as well as in the striatum and the cortex of freely moving rats. The hippocampal DG showed lowest (p < 0.01) resting pO2 level (6.6 ± 0.7 μM) when compared to CA1 (22.1 ± 3.4 μM), striatum (17.2 ± 1.7 μM), and cortex (22.1 ± 4.9 μM). Evoked changes in interstitial pO2 in vivo we performed a 5 min tail pinch stress paradigm test, which induced a transient increase pO2 in the hippocampus of 15 ± 4% from baseline, corresponding to an average Δ[O2] of 3.7 ± 0.6 μM. Induction of status epilepticus induced biphasic changes in pO2 in the hippocampus. The initial dip at seizure onset (−4.5 ± 0.7 µM) was followed by a prolonged hyperoxygenation phase (+10.4 ± 2.9 µM). Analysis of high-frequency component of the amperometric signal allowed the simultaneous monitoring LFP at the site of pO2 recording. This has high potential for translation into the clinical setting supported on intracranial grid or strip electrodes. Discussion and conclusions: This strategy revealed that a single sensor can simultaneously report chemical (pO2) and electrophysiological (LFP currents) information, allowing concurrent monitoring of electrical and neurovascular/neurometabolic activities.

Combined in Vivo Amperometric Oximetry and Electrophysiology in a Single Sensor: A Tool for Epilepsy Research.

Seizures are paroxysmal events in which increased neuronal activity is accompanied by an increase in localized energetic demand. The ability to simultaneously record electrical and chemical events using a single sensor poses a promising approach to identify seizure onset zones in the brain. In the present work, we used ceramic-based platinum microelectrode arrays (MEAs) to perform high-frequency amperometric recording of local pO2 and local field potential (LFP)-related currents during seizures in the hippocampus of chronically implanted freely moving rats. Resting levels of O2 in the rodent brain varied between 6.6 ± 0.7 μM in the dentate gyrus (DG) region of the hippocampus and 22.1 ± 4.9 μM in the cerebral cortex. We also observed an expected increase in hippocampal pO2 (15 ± 4% from baseline) in response to tail pinch stress paradigm. Finally, induction of status epilepticus by intrahippocampal injection of pilocarpine induced biphasic changes in pO2 in the hippocampus. The initial dip at seizure onset (ΔO2 = -4.5 ± 0.7 μM) was followed by a prolonged hyperoxygenation phase (ΔO2 = +10.4 ± 2.9 μM). By acquiring the amperometry signal with a high sampling rate of 100 Hz we decomposed the raw signal in an oximetry recording (<1 Hz) and LFP recording (>1 Hz), demonstrating that each individual Pt site can simultaneously report changes in local pO2 and LFP-related currents during pilocarpine-induced seizure activity. This has high potential for translation into the clinical setting supported on intracranial grid or strip electrodes.

Reduced complications from intracranial grid insertion by using a small grid size and a precise protocol during monitoring

A study of the risk factors associated with complications during intracranial EEG monitoring led to a change in protocol for monitoring and implantation at our centres. We conducted a study to identify any reduction in complications following the changed protocols involving the use of smaller subdural electrode arrays, continuous ICP monitoring, use of a central line, and intake of prophylactic antibiotics and dexamethasone. We prospectively collected data on patient outcomes between 2005 and 2012 (group B) compared with patients between 1988 and 2004 (group A) before the protocol changes. Seventy-one patients in group A and 58 patients in group B underwent intracranial electrode implantation. Complications directly related to grids occurred in 25 % of group A vs. 8.6 % in group B (p < 0.05) and those indirectly related to grids were 11.2 % in group A vs. none in group B. The rate of transient complications requiring no treatment was 12.5 % in group A versus 1.7 % in group B. The rate of transient complications requiring treatment was 10 % in group A and 6.9 % in group B. There were two deaths in group A. The infection rate was higher in group B than group A (5.2 % vs. 2.8 %; p = 0.90). Since 2008 there have been no infective complications. Complications directly related to intracranial EEG monitoring were significantly reduced using the revised protocol (p < 0.05). Regression analysis identifying only the size of the grids (≤4 × 8 grid arrays) implanted was an independent predictor of more complications in group A (P < 0.05). Complication rates following intracranial implantation decreased following the use of a small grid size and adherence to a stringent protocol.

Use of interictal 18F-fluorodeoxyglucose (FDG)-PET and magnetoencephalography (MEG) to localize epileptogenic foci in non-lesional epilepsy in a cohort of 16 patients

We assessed the efficacy of interictal 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and magnetoencephalography (MEG) for localizing the epileptogenic foci in a small cohort of patients with non-lesional epilepsy. Sixteen patients, aged 8–32years, with non-lesional epilepsy underwent MRI, continuous scalp video-electroencephalography (EEG) monitoring, interictal (FDG)-PET and MEG at our institution. Each patient subsequently underwent intracranial grid placement. The data from the intracranial grids was correlated with the previous studies to determine the efficacy of FDG-PET and MEG in localizing the epileptogenic zone. Of the 16 patients, the epileptogenic zone was accurately localized in 8 (50%) using FDG-PET and in 12 patients (75%) using MEG. Of the 11 patients with a temporal hypometabolism, only 4 were ultimately confirmed as temporal lobe epilepsy via intracranial grids and 2 additional patients were found to have extra-temporal lobe epilepsy. Compared to interictal FDG-PET, MEG appears to be more sensitive to detection of the epileptogenic zone in this small cohort of non-lesional epilepsy patients though provided more diffuse foci. Our findings can help in determining the surgical eligibility of a patient especially when MRI or video-EEG monitoring are non-localizing, and can help with placement of subdural grids and strips for EEG studies.

Commentary: Epilepsia's Wada survey.

The potential equivalence of non-invasive approaches for establishing language and memory representation to invasive methods (e.g., Wada testing, cortical simulation mapping) in epilepsy surgery candidates is an important topic of discussion, and we thank the editors of EPILEPSIA for the opportunity to present our rationale as to why we consider it premature to make broad pronouncements that invasive approaches should be abandoned. Our comments were intended to be balanced, acknowledging the differences in backgrounds and skills across epilepsy surgery programs, and thus were couched in probabilistic rather than absolute terms to reflect this variability. We recognize that the readership poll on the initial controversy dialogue was never intended to be scientific, and indeed, the sample size is insufficient to allow any broad generalizations. The goals of such polls, however, are to encourage greater participation of EPILEPSIA readers on topics for which there is a lack of consensus, and the equivalence of invasive and non-invasive measures of language and memory during preoperative evaluation is such a topic. No exchanges will convince persons with strongly held beliefs to abandon them, although commentary and dialogue are important to articulate the clinical rationale behind choice of methods. From our perspective, the survey questions addressing the persuasiveness of our clinical rationale could be improved upon, and perhaps future EPILEPSIA controversy authors could supply several questions similar to what is typically necessary in continuing education courses. For example, neither Papanicolaou nor our manuscript directly addressed the necessity of Wada testing as part of the evaluation for temporal lobe epilepsy, but rather, discussed whether existing non-invasive approaches to language and memory provide information that is sufficiently equivalent to Wada results so that Wada testing itself becomes unnecessary, a comparison that was explicitly probed regarding MEG and fMRI vs. intracranial grids. That over half of responders indicated intracranial grids are still necessary for cortical localization despite MEG and fMRI is a valuable data point reflecting diverse clinical practice. It would be interesting to have included a question as to whether MEG and fMRI were sufficiently developed so that Wada testing should be fully abandoned across all epilepsy programs. While we never argued whether Wada testing should or should not be performed on all temporal lobe epilepsy surgical candidates, the survey findings that no European responders felt that the Wada is necessary reflects the greater emphasis of using fMRI to minimize Wada testing by epilepsy clinicians in Europe in the epilepsy literature. We reassert our belief, though, that it is premature to develop position statements asserting that the Wada test (or stimulation mapping) is unnecessary due to the availability of non-invasive measures of language and memory fMRI or MEG since non-invasive approaches have important limitations that are not always fully appreciated or acknowledged by non-expert users, and that such a position does not reflect the opinion of many clinicians who actively manage and follow epilepsy patients to optimize their epilepsy care.

Subdural to subgaleal EEG signal transmission: The role of distance, leakage and insulating affectors

ObjectiveTo estimate the area of cortex affecting the extracranial EEG signal. MethodsThe coherence between intra- and extracranial EEG channels were evaluated on at least 10min of spontaneous, awake data from seven patients admitted for epilepsy surgery work up. ResultsCortical electrodes showed significant extracranial coherent signals in an area of approximately 150cm2 although the field of vision was probably only 31cm2 based on spatial averaging of intracranial channels taking into account the influence of the craniotomy and the silastic membrane of intracranial grids. Selecting the best cortical channels, it was possible to increase the coherence values compared to the single intracranial channel with highest coherence. The coherence seemed to increase linearly with an accumulation area up to 31cm2, where 50% of the maximal coherence was obtained accumulating from only 2cm2 (corresponding to one channel), and 75% when accumulating from 16cm2. ConclusionThe skull is an all frequency spatial averager but dominantly high frequency signal attenuator. SignificanceAn empirical assessment of the actual area of cerebral sources generating the extracranial EEG provides better opportunities for clinical electroencephalographers to determine the location of origin of particular patterns in the EEG.

Focal Peak Activities in Spread of Interictal-Ictal Discharges in Epilepsy with Beamformer MEG: Evidence for an Epileptic Network?

Non-invasive studies to predict regions of seizure onset are important for planning intracranial grid locations for invasive cortical recordings prior to resective surgery for patients with medically intractable epilepsy. The neurosurgeon needs to know both the seizure onset zone (SOZ) and the region of immediate cortical spread to determine the epileptogenic zone to be resected. The immediate zone of spread may be immediately adjacent, on a nearby gyrus, in a different lobe, and sometimes even in the contralateral cerebral hemisphere. We reviewed consecutive simultaneous EEG/MEG recordings on 162 children with medically intractable epilepsy. We analyzed the MEG signals in the bandwidth 20–70 Hz with a beamformer algorithm, synthetic aperture magnetometry, at a 2.5 mm voxel spacing throughout the brain (virtual sensor locations, VSLs) with the kurtosis statistic (g2) to determine presence of excess kurtosis (γ2) consistent with intermittent increased high frequency spikiness of the background. The MEG time series was reconstructed (virtual sensor signals) at each of these VSLs. The VS signals were further examined with a relative peak amplitude spike detection algorithm. The time of VS spike detection was compared to the simultaneous EEG and MEG sensor signals for presence of conventional epileptiform spike morphology in the latter signals. The time of VS spike detection was compared across VSLs to determine earliest and last VSL to show a VS spike. Seven subjects showed delay in activation across VS locations detectable on visual examination. We compared the VS locations that showed earliest and later VS spikes with the locations on intracranial grid locations by electrocorticography (ECoG) that showed spikes and both onset and spread of seizures. We compared completeness of resection of VS locations to postoperative outcome. The VS locations for spike onset and spread were similar to locations for ictal onset and spread by ECoG.

Technical Tips: Verification of Accurate Placement and Labeling of 10–10 Scalp Electrodes and Intracranial Grid/Strip Electrodes Using Documentation Tools

ABSTRACT.In some instances, evaluation of seizure activity may require the addition of 10–10 scalp electrodes or the placement of intracranial grids and strips. At any given time, different technologists may be responsible for placement, addition, and the care of electrodes for the same patient. The presence of extra surface electrodes or extensive coverage of brain with intracranial electrodes increases the risk of incorrect placement and labeling which can cause treatment errors based on inaccurate reading of EEG recordings. Procedures should be put into place with documentation tools to correctly place, label, and hook-up extra 10–10 scalp and intracranial electrodes without errors. By using written processes and documentation tools, staff are more capable of acquiring safe and accurate patient data which increase good patient outcomes. The processes for placement and hook up of 10–10 scalp electrodes and intracranial grid and strip electrodes are different and require separate procedures and documentation tools to ensure accuracy. For 10–10 scalp electrode placement, the use of a 10–10 map, labeled tape, and non-duplicating adjacent electrode colors reduces risk of error. Documentation of intracranial grid/strip electrodes includes placement map, list of electrode locations in amplifier, and a table of cables and corresponding grid/strips with colors. Accurate hook-up is verified by the technologist and the epileptologist and is documented on recording. With the use of documentation tools and verification procedures, the quality of patient outcomes increases while the potential for recording errors is reduced.

Roles for the pre-supplementary motor area and the right inferior frontal gyrus in stopping action: Electrophysiological responses and functional and structural connectivity

Both the pre-supplementary motor area (preSMA) and the right inferior frontal gyrus (rIFG) are important for stopping action outright. These regions are also engaged when preparing to stop. We aimed to elucidate the roles of these regions by harnessing the high spatio-temporal resolution of electrocorticography (ECoG), and by using a task that engages both preparing to stop and stopping outright. First, we validated the task using fMRI in 16 healthy control participants to confirm that both the preSMA and the rIFG were active. Next, we studied a rare patient with intracranial grid coverage of both these regions, using macrostimulation, diffusion tractography, cortico-cortical evoked potentials (CCEPs) and task-based ECoG. Macrostimulation of the preSMA induced behavioral motor arrest. Diffusion tractography revealed a structural connection between the preSMA and rIFG. CCEP analysis showed that stimulation of the preSMA evoked strong local field potentials within 30 ms in rIFG. During the task, when preparing to stop, there was increased high gamma amplitude (~70-250 Hz) in both regions, with preSMA preceding rIFG by ~750 ms. For outright stopping there was also a high gamma amplitude increase in both regions, again with preSMA preceding rIFG. Further, at the time of stopping, there was an increase in beta band activity (~16 Hz) in both regions, with significantly stronger inter-regional coherence for successful vs. unsuccessful stop trials. The results complement earlier reports of a structural/functional action control network between the preSMA and rIFG. They go further by revealing between-region timing differences in the high gamma band when preparing to stop and stopping outright. They also reveal strong between-region coherence in the beta band when stopping is successful. Implications for theories of action control are discussed.

Local epileptogenic networks in tuberous sclerosis complex: A case review

Objective Cortical tubers are a pathognomonic finding in some patients with tuberous sclerosis complex (TSC), and are believed to be epileptogenic foci. Surgery is an effective option in selected patients with TSC who are refractory to medical therapy. This article describes three patients with TSC who underwent three-stage epilepsy surgery at our center, with the intention of examining local electrophysiological changes after each stage of the procedure. Methods Magnetic resonance images were obtained after initial implantation of electrodes and after resection and electrode reimplantation. These images were co-registered and overlaid. The intracranial grids were overlaid in a similar procedure and manually traced, and then added to the volumetric image. Mean spike counts were obtained for each patient and expressed in spikes per minute. Statistical analysis was performed on spike counts prior to and after resection. Results All three patients displayed intense spiking in the regions around the dominant epileptogenic tuber. On tuber removal, spike counts diminished significantly. In each case, new areas of spiking emerged in regions remote from the tuber periphery after tuber resection, with the emergence of secondary ictal onset zones in the resection margin. Conclusion This retrospective study highlights some common electrophysiological features among the patients examined. The observed epileptogenic activity and regions of ictal onset suggest that it may be the region of brain tissue surrounding the tuber that is responsible for the majority of epileptogenic activity in these patients.

Multimodality image-guided surgery for the treatment of medically refractory epilepsy.

The aim of this study was to review seizure outcome, imaging modalities used, and complications following surgery in patients with epilepsy who had undergone multimodality image-guided surgery at our institution. Data from patients with epilepsy who had undergone surgery between April 1999 and October 2001 were reviewed. During this time period, 116 operations were performed in 109 patients with medically refractory epilepsy. Among these patients, 22 were selected to undergo multimodality image-guided surgery primarily on the basis of whether they had no lesion visible on conventional magnetic resonance (MR) imaging sequences, multiple lesions, or one very large lesion that could not be completely resected without the risk of significant postoperative morbidity. A fourth group of patients in whom there was a single lesion in the eloquent cortex, a location associated with a significant risk of postoperative morbidity, was also included in the analysis. This latter group was assessed with the aid of intracranial grid electrodes that were coregistered to the MR image and were used intraoperatively to minimize electrode position error. Other imaging modalities used included positron emission tomography (PET), fluid-attenuated inversion recovery (FLAIR) MR imaging, and subtracted ictal-interictal single-photon positron emission computerized tomography (SPECT) coregistered with MR imaging (SISCOM). After coregistration, images were then downloaded onto an image-guided surgical system and the epileptogenic area was then resected. The mean patient age was 33 years (range 17-46 years), and there was a mean follow up of 27 months (range 14-41 months). Multimodality coregistrations used were as follows: nine PET scans, seven subdural electrode grids, four SISCOM studies, one FLAIR MR image, and one combined PET/subdural grid. Seizure outcome was excellent in 17 patients (77%) and not excellent in five (23%), or favorable in 19 (86%) and unfavorable in three (14%). Six patients (27%) had a transient neurological deficit, one patient (5%) a permanent major deficit, and three patients (15%) a permanent minor deficit. Five patients (24%) had a transient psychiatric problem postoperatively. Multimodality image-guided surgery offers a new perspective in surgery for epilepsy. Functional imaging modalities previously lateralized and often localized a seizure focus, but did not provide enough anatomical information to resect the epileptogenic zone confidently and safely. The coregistration of these modalities to a volumetric MR image and their incorporation into an image-guided system has allowed surgeons to offer surgery to patients who may not previously have been considered eligible, with outcomes comparable to those in patients with more straightforward lesional epilepsy.

Improved cortical MRI segmentation of brains with intracranial grid electrodes

Improved cortical MRI segmentation of brains with intracranial grid electrodes