This work was supported by the National Institute of Neurological Disorders and Stroke (R01NS104116; R01NS134944; Principal Investigator: Christos Papadelis).

Integrating MEG and HD-EEG in Pediatric Epilepsy Localization

The authors report no disclosures.

In this study, we illustrate the experimental setup to record simultaneous MEG and HD-EEG in children with DRE while resting/sleeping, performing a task, or receiving stimuli, and propose a methodological framework for localizing the irritative zone, SOZ, and eloquent brain areas using EMSI, as well as individual MSI and ESI. We further provide technical recommendations for merging MEG and HD-EEG data from different commercially available products that present unique features. We present data from three cases to enhance the clinical utility of EMSI in the localization of epileptogenic and eloquent brain areas. The findings here indicate that EMSI results outperform those obtained by either modality alone, most likely due to the additive value of the complementary properties of MEG and EEG signals in the combined solution and possibly due to the increased number of sensors used for recording the data (&#62;550 sensors). Particularly, EMSI noninvasively localized the irritative and SOZs with concordant findings as ESI on iEEG gold standard, which confirmed the clinical observations.
The proposed methodology includes the following critical steps: (i) high-quality acquisition of simultaneous MEG and HD-EEG (i.e., high SNR) recordings with high spatial sampling of sensors (&#62;550 sensors) covering the entire brain of interictal and ictal activities, as well as visual-, motor-, auditory-, and somatosensory-evoked fields and potentials, from children with DRE (steps 3.1-3.2); (ii) temporal synchronization and spatial co-registration of MEG and HD-EEG signals recorded with different acquisition systems (step 3.12); (iii) careful preprocessing and selection of data portions containing interictal activity (steps 4.1.1-4.1.7), ictal onset activity (steps 4.2.1-4.2.7), and event-related responses (steps 4.3.1-4.3.6), respectively; and (iv) accurate source localization of the irritative zone, SOZ, and eloquent brain areas of interest using reliable source localization methods (e.g., ECDs with clustering and dSPM) (steps 4.1.8-4.1.9, 4.2.8-4.2.9, and 4.3.7-4.3.9, respectively).
The most critical step when performing simultaneous MEG and HD-EEG recordings is to spatially (alignment between coordinate spaces) and temporally (correction of the linear clock drift) synchronize the data recorded by the two acquisition systems. Such synchronization is crucial to ensure the correct identification of interictal, ictal, and visual/motor/auditory/tactile events that simultaneously occur in the MEG and HD-EEG signals. Errors in the timepoint selection of these events may affect the source localization results and identify areas of the brain that are not necessarily involved in the generation of these events.
MEG systems often offer compatible 32-, 64-, and 128-channel EEG systems incorporated into the product for performing simultaneous MEG and EEG measurements. In these cases, there is no need to temporally synchronize the data by sending common trigger signals. Similarly, most EEG systems are nowadays compatible with all MEG systems. Despite these advances in hardware, only few epilepsy centers perform simultaneous MEG and HD-EEG recordings as part of the presurgical evaluation. Here, we took advantage of such integrability and combined the 306-channel MEG and 256-channel EEG systems to simultaneously record the brain activity with &#62;550 sensors covering the subject&#39;s head. So far, few software for advanced analysis of MEG, HD-EEG, and iEEG data (e.g., Brainstorm, CURRY, EEGLab, FieldTrip, MNE, or NUTMEG) are available. Future studies are therefore necessary to validate the proposed methodology with new neuroimaging analysis software. Finally, the combination of MSI and ESI into a unique solution (EMSI) increased the computational complexity of the data analysis.
The described method presents a few limitations that should be addressed in future studies. We manually selected IEDs occurring on both MEG and HD-EEG data of two representative patients while ignoring interictal spikes that occurred in only one of the two signals (either MEG or EEG). Manual selection of spikes can be a time-consuming and subjective approach that can be simplified using automated approaches for detecting IEDs developed during the last decades57,58,59. However, visual inspection is always recommended for careful analysis and refined detection of each IED. Furthermore, we used the SOZ as an approximator of the EZ. Yet, the SOZ does not always predict surgical outcomes60,61,62,63. Future studies can, therefore, use the surgical outcome as ground truth for more precise delineation of the EZ13,14,15,16,17,19,20. Although seizures can be successfully captured using simultaneous MEG and EEG and localized using appropriate source localization techniques44,64, it is relatively rare to record such ictal events in clinical practice, especially from outpatients on ASMs. This is mostly due to the limited duration of MEG recordings and the excessive body movements occurring during seizures (e.g., the patient&#39;s head slipped out the dewar), which may cause biological artifacts that can severely affect source localization findings. In a recent review, Stefan et al. reported the occurrence of seizures during MEG recordings in 7%-24% of patients, with an average recording time of 30 minutes up to 5.7 h across different studies65.&#160;At CCMC, 18 out of 89 (20.2%) patients had ictal events captured during simultaneous MEG and HD-EEG recordings performed within the past ~2 years. However, only 8 out of the 18 (44.4%) patients were successfully analyzed. In cases where interictal MEG recordings show normal or inconclusive findings, ictal MEG or HD-EEG may be used to localize the EZ with high precision. Yet, technical and logistical requirements for these recordings should be addressed. In addition, the representative data for the eloquent cortex localization via EMSI were not compared with any gold standards for localization of these functional brain areas, such as noninvasive fMRI or intraoperative electrocortical stimulation. Further investigations may, therefore, integrate EMSI and fMRI towards a multimodal noninvasive imaging tool to improve the localization accuracy of these eloquent brain areas in children with DRE. This work may also be extended to localize other functional brain areas, such as the language-eloquent regions. Localization of language functions is of critical importance during the presurgical evaluation of patients with DRE to determine their surgical candidacy, plan the extent of surgical resection, and prevent permanent postoperative functional deficits66. Several noninvasive studies have shown that language mapping using MEG can provide concordant results, similar to the invasive Wada test, which is often regarded as the gold standard for identifying the dominant language hemisphere67,68,69,70. A recent study has proposed a multimodal approach in which the combination of different techniques (i.e., cortical stimulation mapping, high-gamma electrocorticography, fMRI, and transcranial magnetic stimulation) can provide mutual, confirmatory, and complementary information for presurgical language mapping71. Despite these advantages, mapping language areas is still challenging in pediatric patients who have cognitive, intellectual, and language barriers due to their age. Thus, more age-specific tasks and child-friendly setups should be developed in the near future. In this work, we analyzed MEG and HD-EEG data using software that is not certified for clinical purposes. Although these tools have been proven to be valuable and effective, they carry liability issues that should be considered when reporting presurgical evaluation findings for clinical use. Here, we describe procedures for HD-EEG recordings using only sponge-based EEG electrode systems. Alternative systems using gel-based EEG electrodes are widely used in both clinical and research settings. Although they provide higher SNR EEG recordings, they required longer preparation time (~40-60 min) and thus are less suitable for pediatric use. Alternatively, several laboratories use low-density gel-based EEG systems during the MEG recordings, which are advantageous in terms of preparation time (compared to HD-EEG systems), but they offer significantly lower spatial resolution due to the reduced number of electrodes covering the entire scalp12,16,72,73.
At present, the localization of the epileptogenic brain areas in patients with epilepsy is still mainly achieved with iEEG monitoring. Moreover, the methodology for the precise localization of eloquent brain areas is poorly defined, and the experiment setups currently used in MEG laboratories are inappropriate for pediatric patients, while the use of HD-EEG for this purpose is very limited. Accurate localization of these areas may facilitate the presurgical evaluation and augment the surgical planning for either resection or iEEG electrode placement. So far, several studies investigated the contribution of either ESI or MSI in the presurgical evaluation of patients with DRE and focal epilepsies for the identification of the EZ12,13,14,15,16,17,18,19&#160;and eloquent areas of the somatosensory cortex41, respectively. Few studies have shown better source localization results and outcome prediction performance using EMSI compared to either MSI or ESI alone13,31,42. Despite these findings, recording of MEG and EEG is rarely performed simultaneously, and MSI and ESI are implemented in only a few epilepsy centers worldwide. To our best knowledge, this is the first study that provides suggestions for collecting and analyzing simultaneous MEG and HD-EEG data, as well as performing EMSI in pediatric epilepsy for the noninvasive identification of the irritative zone, SOZ, and eloquent brain areas, namely primary visual, motor, auditory, and somatosensory cortices.
Here, we performed EMSI on interictal spikes and ictal events detected on simultaneous noninvasive data from two patients with DRE (Cases 1 and 2) and achieved a source localization error of ~9 mm and ~12 mm from the SOZ, respectively, in line with previous studies42. Impressively, such a method achieved a localization accuracy comparable to the intracranial findings (i.e., ESI on iEEG data), with clustered dipoles localized in the brain area pinpointed as epileptogenic by the clinical observations (Figure 3C and Figure 4B). Using noninvasive data from a third representative patient with DRE (Case 3), we also performed EMSI on visual-, motor-, auditory-, and somatosensory-evoked activities and found prominent source activation patterns in the corresponding eloquent brain areas (i.e., visual, motor, auditory, and somatosensory cortices) (Figure 5C, Figure 6C, Figure 7C, and Figure 8C).
Our results were derived from the fusion of complementary information captured from MEG and EEG modalities that may improve localization accuracy. EEG is well known to reflect all intracranial currents, whereas MEG is mostly sensitive to tangential sources and blind to deep brain sources29,74. As shown in this study, combining MEG and EEG can, therefore, overcome the limitations of each modality, provide superior localization results, and identify epileptogenic and eloquent brain areas that either ESI or MSI may have missed if used alone. Moreover, we present an alternative noninvasive approach for mapping eloquent brain areas using EMSI in those patients who did not undergo fMRI during their presurgical evaluation.
The localization of epileptogenic and eloquent brain areas using noninvasive techniques, such as simultaneous MEG and EEG, is an essential step during the presurgical evaluation of children with DRE for complete removal or disconnection of the EZ while preserving eloquent cortical areas. The proposed methodology offers a detailed description of the acquisition and analysis of simultaneous MEG and EEG data that supports its application not only in the presurgical epilepsy evaluation but also in cognitive neurosciences for exploring physiological functions of the healthy brain in both typically developing children as well as healthy adults, as well as morphological and functional brain changes associated with epilepsy or other neurological disorders. Future studies investigating epileptogenic brain networks may also assess whether network hubs (i.e., highly connected brain regions) estimated noninvasively using EMSI on simultaneous MEG and HD-EEG data can more accurately localize the EZ in children with DRE than those estimated using MSI and/or ESI alone75,76,77. Furthermore, the noninvasive mapping of spatiotemporal propagations of spikes and ripples (i.e., high-frequency oscillations, &#62;80 Hz), estimated through EMSI, can help to better understand the pathophysiological mechanisms of propagating epileptiform activity and noninvasively assess the onset generator of these propagations that is a precise biomarker of the EZ78,79. The presented protocol may help to further investigate the complementarity of MEG and EEG systems by examining the sensitivity of MEG and EEG sensor arrays to sources of different orientations. Such analysis may provide insights into the electrophysiological properties of the brain while performing simultaneous MEG and HD-EEG.

Epilepsy is one of the most common and disabling neurological disorders characterized by recurrent and unprovoked seizures that can be either focal or generalized in nature. Despite the availability of several effective pharmacologic therapies (e.g., antiseizure medications [ASMs]), about 20-30% of these patients are unable to control their seizures and suffer from drug-resistant epilepsy (DRE)1. For these patients, epilepsy surgery is the most effective treatment to eliminate seizures; a successful surgery can be achieved through the complete resection (or ablation/disconnection) of the epileptogenic zone (EZ), defined as the minimal area indispensable for the generation of seizures2. Accurate delineation and resection (or ablation/disconnection) of the EZ while preserving the eloquent cortex are crucial factors in ensuring seizure freedom. To establish surgical candidacy, several noninvasive diagnostic tools are used by a multidisciplinary team to define different cortical areas (i.e., irritative zone, seizure onset zone [SOZ], functional deficit zone, and epileptogenic lesion), which serve as indirect approximators of the EZ3. Extra-operative monitoring with intracranial EEG (iEEG) is required when none of these methods unequivocally identify the EZ. The role of iEEG is to define precisely the EZ by localizing the SOZ (i.e., the brain area where clinical seizures generate) and map eloquent brain areas. Yet, it presents serious limitations due to its invasiveness4,5,6, it offers limited spatial coverage, and it needs a clear presurgical localization hypothesis7. As a result, the actual focus and extent of the SOZ may be missed, leading to unsuccessful surgery. Also, its interpretation requires the recording of multiple stereotyped clinical seizures during several days of hospitalization, which increases the chances of complications (e.g., infection and/or bleeding)5. Hence, there is an unmet need to develop reliable and noninvasive localization methods that can provide clinically useful information and overall improve the presurgical evaluation of children with DRE.
Over the last decades, electric and magnetic source imaging (ESI and MSI) have been increasingly utilized in the presurgical evaluation of patients with DRE for the delineation of epileptogenic as well as functional brain areas. Particularly, ESI and MSI allow the reconstruction of neural sources from noninvasive recordings, such as high-density EEG (HD-EEG) and magnetoencephalography (MEG), to help guide surgical planning or iEEG electrode placement. ESI and MSI can be applied for localizing either interictal epileptiform discharges (IEDs), such as spikes and sharp waves, or ictal (seizure) activity. It may further be used for the localization of different functional brain areas involved in sensory, motor, auditory, and cognitive functions. The reconstruction of electrophysiological events, such as IEDs and seizures, allows the identification of the irritative zone (i.e., the brain area where IEDs originate) and the SOZ, respectively, which are considered a valid surrogate for the EZ localization. The localization of the eloquent cortex (i.e., the brain areas indispensable for defined cortical functions)3 allows instead to map the location and extent of eloquent areas with respect to the planned resection and, therefore, reduce in advance potential functional deficits that may be expected from epilepsy surgery8,9,10,11. Several studies investigated the clinical utility of ESI and/or MSI in the presurgical evaluation of epilepsy, and they showed promising findings in the delineation of the EZ12,13,14,15,16,17,18,19. For example, Mouthaan et al.14 performed an extensive meta-analysis using noninvasive data of 11 prospective and retrospective epilepsy studies and reported that these source localization techniques can overall identify the EZ with high sensitivity (82%) and low specificity (53%). Other studies also showed that MSI and ESI can correctly localize the epileptic focus within the resected area in epileptic patients having a normal magnetic resonance imaging (MRI)19,20,21. These localization results are particularly important for those patients who are ineligible for epilepsy surgery due to inconclusive clinical or imaging findings. In summary, ESI and MSI can contribute significantly to the presurgical mapping of epileptogenic as well as functional brain areas in patients with DRE.
Despite these encouraging findings, such techniques are currently performed in only a few tertiary epilepsy centers on a regular basis and are often underutilized in pediatric populations. Moreover, HD-EEG and MEG are rarely recorded simultaneously, although they provide both confirmatory and complementary information. MEG is sensitive to detect superficial sources with tangential orientation but is blind to radially oriented sources located at the gyri or deeper areas of the brain22,23,24,25,26. Furthermore, MEG provides better spatial resolution (millimeters) compared to EEG16,22,25. Unlike EEG signals, MEG signals are reference-free and are essentially unaffected by different conductivities of brain tissues (i.e., meninges, cerebrospinal fluid, skull, and scalp)25,27 providing undistorted measurements of the magnetic fields produced by the brain. On the other hand, EEG can detect sources of all orientations, but it offers lower spatial resolution than MEG and is more susceptible to artifacts26,28. Due to these complementary sensitivities to source orientation and depth, approximately 30% of the epileptiform activity (e.g., IEDs) can only be recorded on MEG but not on EEG, and vice versa26,29,30,31,32. Contrary to EEG, which allows prolonged recordings, capturing clinical seizures with MEG is challenging due to the restricted recording time that is usually insufficient to record ictal events in most patients. Furthermore, artifacts caused by seizure-related head movements can often interfere with the quality of MEG recordings29,33,34,35. On the other hand, MEG recordings are faster and easier compared to EEG, especially in children since there is no need to attach sensors over the children&#39;s head35.
Advances in hardware have made it possible to record simultaneously MEG and HD-EEG data with a high number of sensors (over 550 sensors) covering the whole head. Moreover, modern developments in EEG technologies have minimized the preparation time for HD-EEG to less than a quarter of an hour36. This is particularly important for pediatric populations with challenging behaviors who are unable to stay still for prolonged periods. Furthermore, advancements in software technologies have allowed the combination of ESI and MSI into a single solution, namely electromagnetic source imaging (EMSI), performed on simultaneous HD-EEG and MEG recordings. Several theoretical and empirical studies reported higher source localization accuracy with EMSI than either modality alone13,30,31,37,38,39,40,41. Using different source localization approaches to reconstruct the activity in response to sensory stimuli, Sharon et al.37 found that EMSI had consistently better localization results than either ESI or MSI alone compared to functional MRI&#160;(fMRI), which serves as noninvasive benchmark of precise localization accuracy. The authors suggested that this improved localization is due to the increased number of sensors for solving the inverse solution and the different sensitivity patterns of the two imaging modalities37. Similarly, Yoshinaga et al.31 performed dipole analysis on simultaneous EEG and MEG data of patients with intractable localization-related epilepsy and showed that EMSI provided information that would be not obtainable by using only one modality alone and led to successful localization for epilepsy surgery in one of the patients analyzed. In a prospective blinded study, Duez et al.13 showed that EMSI achieved a significantly higher odds ratio (i.e., probability of becoming seizure-free) compared to ESI and MSI, a localization accuracy &#8805;52%, and a concordance &#8805;53% and &#8805;36% with the irritative and SOZ, respectively. A more recent study from our group42 has shown that EMSI provided superior localization estimates and better outcome prediction performance than either ESI or MSI alone, with localization errors from resection and SOZ of ~8 mm and ~15 mm, respectively. Despite these promising findings, there is a lack of studies that provide the methodological framework regarding EMSI in children with DRE.
This study illustrates the experimental setup for performing simultaneous MEG and HD-EEG recordings as well as the methodological framework for analyzing these data aiming to localize the irritative zone, SOZ, and eloquent brain areas in children with DRE. More specifically, the experimental setups are presented for (i) recording and localizing interictal and ictal epileptiform activity during sleep and (ii) recording visual-, motor-, auditory-, and somatosensory-evoked responses and mapping relevant eloquent brain areas (i.e., visual, motor, auditory, and somatosensory) during a visuomotor task, as well as auditory and somatosensory stimulations. Detailed steps of the data analysis pipeline are further presented for performing EMSI as well as individual ESI and MSI using equivalent current dipole (ECD) and dynamic statistical parametric mapping (dSPM).

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>AIRSTIM unit</td>
			<td>SD Instruments</td>
			<td>N/A</td>
			<td>The SDI AIRSTIM system is an alternative unconditioned stimulus to shock</td>
		</tr>
		<tr>
			<td>Baby Shampoo&#160;</td>
			<td>Johnson&#39;s</td>
			<td>N/A</td>
			<td>Baby Shampoo is as gentle to the eyes as pure water and is specially designed to gently cleanse baby&#8217;s delicate hair and scalp.&#160;</td>
		</tr>
		<tr>
			<td>Control III disinfectant cleaning solution</td>
			<td>Maril Products, Inc.</td>
			<td>http://www.controlthree.com/</td>
			<td>Disinfectant and germicide solution formulated for hospitals</td>
		</tr>
		<tr>
			<td>Elekta Neuromag</td>
			<td>TRIUX</td>
			<td>NM24132A</td>
			<td>Comprehensive bioelectromagnetic measurement system characterized by 306-channel neuromagnetometer for functional brain studies</td>
		</tr>
		<tr>
			<td>FASTRAK</td>
			<td>Polhemus technology</td>
			<td>NS-7806</td>
			<td>Using A/C electromagnetic technology, FASTRAK delivers accurate position and orientation data, with virtually no latency. With a single magnetic source, FASTRAK delivers data for up to four sensors. The source emits an electromagnetic field, sensors within the field of range are tracked in full 6DOF (6 Degrees-Of-Freedom). Setup is simple and intuitive, with no user calibration required.</td>
		</tr>
		<tr>
			<td>Genuine Grass Reusable Cup EEG Electrodes</td>
			<td>Natus Medical, Inc.</td>
			<td>N/A</td>
			<td>Each Genuine Grass EEG Electrode undergoes rigorous mechanical and electrical testing to assure long life for unsurpassed recording clarity and dependability.</td>
		</tr>
		<tr>
			<td>Geodesic Sensor Net</td>
			<td>Electrical Geodesics, Inc.</td>
			<td>S-MAN-200-GSNR-001</td>
			<td>32 to 256 electrodes to place on the human head to aquire dense-array electroencephalography data</td>
		</tr>
		<tr>
			<td>GeoScan Sensor Digitization System</td>
			<td>Electrical Geodesics, Inc.</td>
			<td>8100550-03</td>
			<td>Handheld Scanner and Software for 3D electrode position registration</td>
		</tr>
		<tr>
			<td>Natus Xltek NeuroWorks</td>
			<td>Natus Medical, Inc.</td>
			<td>https://natus.com/</td>
			<td>The Natus NeuroWorks platform simplifies the process of collecting, monitoring and managing data for routine EEG testing, ambulatory EEG, long-term monitoring, ICU monitoring, and research studies.</td>
		</tr>
		<tr>
			<td>Natus NeuroWorks EEG Software</td>
			<td>Natus Medical, Inc.</td>
			<td>https://natus.com/neuro/neuroworks-eeg-software/</td>
			<td>NeuroWorks EEG software simplifies the process of collecting, monitoring, trending and managing EEG testing data, allowing care providers to save time and focus on delivering the best care.</td>
		</tr>
		<tr>
			<td>ROSA ONE Brain</td>
			<td>Zimmer Biomet</td>
			<td>https://www.zimmerbiomet.com/en/products-and-solutions/zb-edge/robotics/rosa-brain.html</td>
			<td>ROSA ONE Brain is a robotic solution to assist surgeons in planning and performing complex neurosurgical procedures through a small drill hole in the skull.&#160;</td>
		</tr>
		<tr>
			<td>Ten20 Conductive Paste</td>
			<td>Weaver and company</td>
			<td>N/A</td>
			<td>Ten20 contains the right balance of adhesiveness and conductivity, enabling the electrodes to remain in place while allowing the transmittance of electrical signals.</td>
		</tr>
	</tbody>
</table>

electromagnetic source imaging in presurgical evaluation of children with drug-resistant epilepsy

For children with drug-resistant epilepsy (DRE), seizure freedom relies on the delineation and resection (or ablation/disconnection) of the epileptogenic zone (EZ) while preserving the eloquent brain areas. The development of a reliable and noninvasive localization method that provides clinically useful information for the localization of the EZ is, therefore, crucial to achieving successful surgical outcomes. Electric and magnetic source imaging (ESI and MSI) have been increasingly utilized in the presurgical evaluation of these patients showing promising findings in the delineation of epileptogenic as well as eloquent brain areas. Moreover, the combination of ESI and MSI into a single solution, namely electromagnetic source imaging (EMSI), performed on simultaneous high-density electroencephalography (HD-EEG) and magnetoencephalography (MEG) recordings has shown higher source localization accuracy than either modality alone. Despite these encouraging findings, such techniques are performed in only a few tertiary epilepsy centers, are rarely recorded simultaneously, and are underutilized in pediatric cohorts. This study illustrates the experimental setup for recording simultaneous MEG and HD-EEG data as well as the methodological framework for analyzing these data aiming to localize the irritative zone, the seizure onset zone, and eloquent brain areas in children with DRE. More specifically, the experimental setups are presented for (i) recording and localizing interictal and ictal epileptiform activity during sleep and (ii) recording visual-, motor-, auditory-, and somatosensory-evoked responses and mapping relevant eloquent brain areas (i.e., visual, motor, auditory, and somatosensory) during visuomotor task, as well as auditory and somatosensory stimulations. Detailed steps of the data analysis pipeline are further presented for performing EMSI as well as individual ESI and MSI using equivalent current dipole (ECD) and dynamic statistical parametric mapping (dSPM).

Author Spotlight: Advancing Pediatric Epilepsy Surgery in Children Through Novel Biomarkers and Enhanced Localization

Electromagnetic Source Imaging in Presurgical Evaluation of Children with Drug-Resistant Epilepsy

Our main goal of research is to develop novel biomarkers of epilepsy that augment the presurgical evaluation process and improve the surgical outcome of children suffering from drug-resistant epilepsy. We're trying to investigate whether non-invasive methods can precisely localize brain areas that correspond to the epileptogenic tissue. The most recent developments in our field are the ability to record MEG and high-density EEG data simultaneously with a high number of sensors, new EG technologies offering minimal preparation time, which is critical in children, and advanced algorithms that combine electric and magnetic source imaging into a unique solution.We present evidence that combined electric and magnetic source imaging on simultaneous MEG and high-density EEG recordings outperform either modality alone in terms of localized accuracy. This is most likely due to the complementary and confirmatory sensitivity profiles of MEG and easy signals, and the increased number of sensors. We demonstrate a state-of-the-art setup that allows the simultaneous recording of magnetic and electric brain activity with more than 500 sensors covering the entire head.With the setup, we demonstrate the non-invasive localization of interictal and ictal epileptiform activity and the mapping of the local areas so as not to resect during surgery. Our findings will help us understand the complementary and confirmatory information that magnetoencephalography and high-density electroencephalography recordings provide in different clinical scenarios where the localization of the epileptogenic focus is challenging due to the deep location of the source or its radial orientation with respect to the patient's cortical surface.

Magnetoencephalography (MEG) and high-density electroencephalography (HD-EEG) are rarely recorded simultaneously, although they yield confirmatory and complementary information. Here, we illustrate the experimental setup for recording simultaneous MEG and HD-EEG and the methodology for analyzing these data aiming to localize epileptogenic and eloquent brain areas in children with drug-resistant epilepsy.

For children with drug-resistant epilepsy (DRE), seizure freedom relies on the delineation and resection (or ablation/disconnection) of the epileptogenic ...

electromagnetic-source-imaging-presurgical-evaluation-children-with

Research

JoVE Journal

Neuroscience

Simultaneous Magnetoencephalography (MEG) and Electroencephalography (EEG) Recording in Children with Drug-Resistant Epilepsy

To begin, have the subject in a hospital gown sitting comfortably on a wooden chair. Measure the subject's head circumference to select the appropriate EEG net size. Soak the correct size EEG net for five minutes in a solution of warm tap water, electrolytes, and baby shampoo.Using micropore paper tape, place five magnet coils, serving as head position indicators, or HPI, at known locations directly on the scalp. To record the subject's heartbeat, place two ECG electrodes on the right and left side of the chest below the collarbones respectively. For vertical eye movements, or blinks recording.Place two EOG electrodes on the upper and lower side of the right eye respectively. Tape two pairs of non-disposable cup electrodes on the first dorsal interosseous and abductor pollicis brevis of each hand to measure muscle activity during the visuomotor task. Place the reference receiver through the plastic goggles on the subject's head.Through the primary stylus receiver, locate the fiducial anatomical landmarks, the five HPI coils position, and uniformly sample additional scalp points. Before applying the EEG net, put both hands inside the net and spread it. Place the stretched net on the subject's head and adjust its position.Using an EEG impedance meter, ensure that all scalp electrode impedances are in the 0 to 50 kiliohm range. To determine the three dimensional positions of the EEG electrodes, ask the subject to sit comfortably and look straight ahead. On the optical scanner software, select the sensor template that matches the EEG sensor layout used during the recordings and initiate the scanning process.Slowly move the scanner around the subject's head following arced swaths from the top to the bottom to record the physical locations of all sensors. Next, probe the fiducial points and four alignment sensors using the wireless optical probe to align the three dimensional sensors cloud to the selected sensor template. For the resting or sleeping data, set the gantry of the MEG system to the supine position.Transfer the subject inside the magnetically shielded room, or MSR, and assist to sit on the edge of the bed and lie down on it. Gently move the subject's head until it touches the inside of the helmet. Plug the HPI coils, ECG, and EOG electrodes on the corresponding panels of the MEG system.Connect the EEG net to the amplifier unit until it is inside the MSR. Check the measurements of the head's coordinates from the acquisition workstation outside the MSR. For the visuomotor task, set the gantry of the MEG system to the upright position and arrange the MEG chair so that the subject's head is under the gantry.Assist the subject to sit on the non-magnetic and compatible chair. Plug the HPI coils, ECG, EOG, first dorsal, interosseous, and abductor pollicis brevis electrodes on the right panel of the MEG machine. Connect the EEG net to the amplifier unit inside the MSR.Raise the chair using the elevation pedal until the subject's head lightly touches the inside of the helmet. Place the projection screen in front of the subject, and instruct the subject to tap their index finger on the table only when the visual stimulus appears on the screen. Use the same setup for auditory stimulation, and help the subject wear headphones.While listening to the sound trigger, instruct the subject to fixate on the stimuli projected on the screen. For the somatosensory stimulation, attach thin elastic membranes directly to the distal volar parts of three digits of both hands for tactile stimulation. Ask the subject about their video preference to watch on the projector screen.Before starting the recording, close the door of the MSR. Through the voice intercom system, confirm the comfort of the subject inside the MSR, and instruct the subject to maintain a still position for approximately 30 seconds before starting the task. For each recording session, press the recording button on the EEG data acquisition software to begin the EEG recording.Then, press the recording button on the MEG data acquisition software to begin the MEG recording. Finally, press the start button on the stimulation computer software to display the visual stimuli. Record approximately one hour of simultaneous MEG and EEG signals for resting or sleeping data.Similarly, record MEG and EEG signals during the visuomotor task for approximately one hour. For auditory stimulations, record about 20 minutes, and for somatosensory stimulation, record about 14 minutes of simultaneous MEG and EEG data. After recording, ask the subject to sit on a chair outside the MSR.Pull out the EEG net from the subject's head with both hands until it is completely peeled away. On Brainstorm, import the simultaneous MEG and HD EEG signal. Using the standard display setting of 10 seconds per page, mark the negative peak of each IED that occurs on both MEG and EEG recordings, as well as on each modality alone.Localize the underlying generators of the selected interictal spikes using the unconstrained ECD method on the MEG, EEG, and combined MEG and EEG sensors arrays separately. Mark the negative peak of each burst of epileptiform discharges occurring during the ictal event on MEG and EEG, as well as on each modality alone. Similarly, localize the underlying generators of the selected ictal discharges using the unconstrained ECD method on the MEG, EEG, and combined MEG and EEG sensors array separately.For motor cortex mapping, mark the tapping event of the left hand by selecting the first peak of muscle activation different from the baseline on the FDI pair electrode. Next, apply the average reference montage, and estimate the average across stimuli to obtain the event evoked fields and potentials. For each event evoked field and potential, compute the cortical sources on the averaged events using DSPM for the MEG, EEG, and combined MEG and EEG sensors array separately.For a 10-year-old female, EMSI indicated focal clusters of dipoles at the bilateral frontotemporal regions in line with ESI performed on benchmark IEEG. For a 13-year-old male, EMSI revealed localization of the ictal onset within the temporal lobe concordant with ESI on benchmark IEEG. In a 15-year-old female, EMSI performed on the averaged visual, motor, auditory, and somatosensory evoked responses showed maximal cortical activation at the eloquent regions involved.

1.5K Views.  Cook Children’s Health Care System.  Magnetoencephalography (MEG) and high-density electroencephalography (HD-EEG) are rarely recorded simultaneously, although they yield confirmatory and complementary information. Here, we illustrate the experimental setup for recording simultaneous MEG and HD-EEG and the methodology for analyzing these data aiming to localize epileptogenic and eloquent brain areas in children with drug-resistant epilepsy.

Integrating MEG and HD-EEG in Pediatric Epilepsy Localization

Summary