Electroencephalographic source localization (ESL) relies on an accurate model representing the human head for the computation of the forward solution. In this head model, the skull is of utmost importance due to its complex geometry and low conductivity compared to the other tissues inside the head. We investigated the influence of using different skull modeling approaches on ESL. These approaches, consisting in skull conductivity and geometry modeling simplifications, make use of X-ray computed tomography (CT) and magnetic resonance (MR) images to generate seven different head models. A head model with an accurately segmented skull from CT images, including spongy and compact bone compartments as well as some air-filled cavities, was used as the reference model. EEG simulations were performed for a configuration of 32 and 128 electrodes, and for both noiseless and noisy data. The results show that skull geometry simplifications have a larger effect on ESL than those of the conductivity modeling. This suggests that accurate skull modeling is important in order to achieve reliable results for ESL that are useful in a clinical environment. We recommend the following guidelines to be taken into account for skull modeling in the generation of subject-specific head models: (i) If CT images are available, i.e., if the geometry of the skull and its different tissue types can be accurately segmented, the conductivity should be modeled as isotropic heterogeneous. The spongy bone might be segmented as an erosion of the compact bone; (ii) when only MR images are available, the skull base should be represented as accurately as possible and the conductivity can be modeled as isotropic heterogeneous, segmenting the spongy bone directly from the MR image; (iii) a large number of EEG electrodes should be used to obtain high spatial sampling, which reduces the localization errors at realistic noise levels.
Epilepsy surgery is the most efficient treatment option for patients with refractory epilepsy. Before surgery, it is of utmost importance to accurately delineate the seizure onset zone (SOZ). Non-invasive EEG is the most used neuroimaging technique to diagnose epilepsy, but it is hard to localize the SOZ from EEG due to its low spatial resolution and because epilepsy is a network disease, with several brain regions becoming active during a seizure. In this work, we propose and validate an approach based on EEG source imaging (ESI) combined with functional connectivity analysis to overcome these problems. We considered both simulations and real data of patients. Ictal epochs of 204-channel EEG and subsets down to 32 channels were analyzed. ESI was done using realistic head models and LORETA was used as inverse technique. The connectivity pattern between the reconstructed sources was calculated, and the source with the highest number of outgoing connections was selected as SOZ. We compared this algorithm with a more straightforward approach, i.e. selecting the source with the highest power after ESI as the SOZ. We found that functional connectivity analysis estimated the SOZ consistently closer to the simulated EZ/RZ than localization based on maximal power. Performance, however, decreased when 128 electrodes or less were used, especially in the realistic data. The results show the added value of functional connectivity analysis for SOZ localization, when the EEG is obtained with a high-density setup. Next to this, the method can potentially be used as objective tool in clinical settings.
Electrical source imaging (ESI) from interictal scalp EEG is increasingly validated and used as a valuable tool in the presurgical evaluation of epilepsy as a reflection of the irritative zone. ESI of ictal scalp EEG to localize the seizure onset zone (SOZ) remains challenging. We investigated the value of an approach for ictal imaging using ESI and functional connectivity analysis (FC). Ictal scalp EEG from 111 seizures in 27 patients who had Engel class I outcome at least 1 year following resective surgery was analyzed. For every seizure, an artifact-free epoch close to the seizure onset was selected and ESI using LORETA was applied. In addition, the reconstructed sources underwent FC using the spectrum-weighted Adaptive Directed Transfer Function. This resulted in the estimation of the SOZ in two ways: (i) the source with maximal power after ESI, (ii) the source with the strongest outgoing connections after combined ESI and FC. Next, we calculated the distance between the estimated SOZ and the border of the resected zone (RZ) for both approaches and called this the localization error ((i) LEpow and (ii) LEconn respectively). By comparing LEpow and LEconn, we assessed the added value of FC. The source with maximal power after ESI was inside the RZ (LEpow = 0 mm) in 31% of the seizures and estimated within 10 mm from the border of the RZ (LEpow ≤ 10 mm) in 42%. Using ESI and FC, these numbers increased to 72% for LEconn = 0 mm and 94% for LEconn ≤ 10 mm. FC provided a significant added value to ESI alone (p < 0.001). ESI combined with subsequent FC is able to localize the SOZ in a non-invasive way with high accuracy. Therefore it could be a valuable tool in the presurgical evaluation of epilepsy.
SummaryObjectiveWe investigated the performance of automatic spike detection and subsequent electroencephalogram (EEG) source imaging to localize the epileptogenic zone (EZ) from long‐term EEG recorded during video‐EEG monitoring.MethodsIn 32 patients, spikes were automatically detected in the EEG and clustered according to their morphology. The two spike clusters with most single events in each patient were averaged and localized in the brain at the half‐rising time and peak of the spike using EEG source imaging. On the basis of the distance from the sources to the resection and the known patient outcome after surgery, the performance of the automated EEG analysis to localize the EZ was quantified.ResultsIn 28 out of the 32 patients, the automatically detected spike clusters corresponded with the reported interictal findings. The median distance to the resection in patients with Engel class I outcome was 6.5 and 15 mm for spike cluster 1 and 27 and 26 mm for cluster 2, at the peak and the half‐rising time of the spike, respectively. Spike occurrence (cluster 1 vs. cluster 2) and spike timing (peak vs. half‐rising) significantly influenced the distance to the resection (p < 0.05). For patients with Engel class II, III, and IV outcomes, the median distance increased to 36 and 36 mm for cluster 1. Localizing spike cluster 1 at the peak resulted in a sensitivity of 70% and specificity of 100%, positive prediction value (PPV) of 100%, and negative predictive value (NPV) of 53%. Including the results of spike cluster 2 led to an increased sensitivity of 79% NPV of 55% and diagnostic OR of 11.4, while the specificity dropped to 75% and the PPV to 90%.SignificanceWe showed that automated analysis of long‐term EEG recordings results in a high sensitivity and specificity to localize the epileptogenic focus.
The mechanism of action of vagus nerve stimulation (VNS) is yet to be elucidated. To that end, the effects of VNS on the brain of epileptic patients were studied. Both when VNS was switched "On" and "Off", the brain activity of responders (R, seizure frequency reduction of over 50%) was compared to the brain activity of nonresponders (NR, seizure frequency reduction of less than 50%). Using EEG recordings, a significant increase in P300 amplitude for R and a significant decrease in P300 amplitude for NR were found. We found biomarkers for checking the efficacy of VNS with accuracy up to 94%. The results show that P300 features recorded in nonmidline electrodes are better P300 biomarkers for VNS efficacy than P300 features recorded in midline electrodes. Using source localization and connectivity analyses, the activity of the limbic system, insula and orbitofrontal cortex was found to be dependent on VNS switched "On" versus "Off" or patient group (R versus NR). The results suggest an important role for these areas in the mechanism of action of VNS, although a larger patient study should be done to confirm the findings.
Objective Electric source imaging (ESI) of interictal epileptiform discharges (IEDs) has shown significant yield in numerous studies; however, its implementation at most centers is labor‐ and cost‐intensive. Semiautomatic ESI analysis (SAEA) has been proposed as an alternative and has previously shown benefit. Computer‐assisted automatic spike cluster retrieval, averaging, and source localization are carried out for each cluster and are then reviewed by an expert neurophysiologist, to determine their relevance for the individual case. Here, we examine its yield in a prospective single center study. Method Between 2017 and 2022, 122 patients underwent SAEA. Inclusion criteria for the current study were unifocal epilepsy disorder, epilepsy surgery with curative purpose, and postoperative follow‐up of 2 years or more. All patients (N=40) had continuous video‐electroencephalographic (EEG) monitoring with 37 scalp electrodes, which underwent SAEA. Forty patients matched our inclusion criteria. Results Twenty patients required intracranial monitoring; 13 were magnetic resonance imaging (MRI)‐negative. Mean duration of analyzed EEG was 4.3 days (±3.1 days), containing a mean of 12 749 detected IEDs (±22 324). The sensitivity, specificity, and accuracy of SAEA for localizing the epileptogenic focus of the entire group were 74.3%, 80%, and 75%, respectively, leading to an odds ratio (OR) of 11.5 to become seizure‐free if the source was included in the resection volume (p < .05). In patients with extratemporal lobe epilepsy, our results indicated an accuracy of 68% (OR=11.7). For MRI‐negative patients (n = 13) and patients requiring intracranial EEG (n = 20), we found a similarly high accuracy of 84.6% (OR=19) and 75% (OR = 15.9), respectively. Significance In this prospective study of SAEA of long‐term video‐EEG, spanning several days, we found excellent localizing information and a high yield, even in difficult patient groups. This compares favorably to high‐density ESI, most likely due to marked improved signal‐to‐noise ratio of the averaged IEDs. We propose including ESI, or SAEA, in the workup of all patients who are referred for epilepsy surgery.
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