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Source localization for clinical magnetoencephalography recordings is challenging, and many methods have been developed to solve this inverse problem. The most well-studied and validated tool for localization of the epileptogenic zone is the equivalent current dipole. However, it is often difficult to summarize the richness of the magnetoencephalography data with one or a few point sources. A variety of source localization algorithms have been developed to more fully explain the complexity of clinical magnetoencephalography data used to define the epileptogenic network. In this review, various clinically available source localization methods are described and their individual strengths and limitations are discussed.

Introduction: This study describes development of a novel language mapping approach using high-γ modulation in electrocorticograph (ECoG) during spontaneous conversation, and its comparison with electrical cortical stimulation (ECS) in childhood-onset drug-resistant epilepsy., Methods: Patients undergoing invasive pre-surgical monitoring and able to converse with the investigator were eligible. ECoG signals and synchronized audio were acquired during quiet baseline and during natural conversation between investigator and the patient. Using Signal Modeling for Real-time Identification and Event Detection (SIGFRIED) procedure, a statistical model for baseline high-γ (70-116 Hz) power, and a single score for each channel representing the probability that the power features in the experimental signal window belonged to the baseline model, were calculated. Electrodes with significant high-γ responses (HGS) were plotted on the 3D cortical model. Sensitivity, specificity, positive and negative predictive values (PPV, NPV), and classification accuracy were calculated compared to ECS., Results: Seven patients were included (4 males, mean age 10.28 ± 4.07 years). Significant high-γ responses were observed in classic language areas in the left hemisphere plus in some homologous right hemispheric areas. Compared with clinical standard ECS mapping, the sensitivity and specificity of HGS mapping was 88.89% and 63.64%, respectively, and PPV and NPV were 35.29% and 96.25%, with an overall accuracy of 68.24%. HGS mapping was able to correctly determine all ECS+ sites in 6 of 7 patients and all false-sites (ECS+, HGS- for visual naming, n = 3) were attributable to only 1 patient., Conclusions: This study supports the feasibility of language mapping with ECoG HGS during spontaneous conversation, and its accuracy compared to traditional ECS. Given long-standing concerns about ecological validity of ECS mapping of cued language tasks, and difficulties encountered with its use in children, ECoG mapping of spontaneous language may provide a valid alternative for clinical use., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: Magnetoencephalography (MEG) is used to guide intracranial electroencephalography (ICEEG) monitoring and determine areas for resection. The purpose of this retrospective cross-sectional study was to report our experience using dipole modeling/dipole scanning, current density reconstructions, and beam-forming methods in a large cohort of pediatric patients with intractable epilepsy., Methods: Source localization results for each algorithm and seizure-onset zone, defined by ICEEG, were described by three blinded reviewers according to five location criteria. The accuracy of each algorithm was then compared to ICEEG. The relationships between the accuracy of these algorithms (discordant, lobar concordant, sublobar concordant) and long-term seizure outcome was calculated using positive and negative predictive values., Results: Thirty-two patients (mean age ± SD, 10.8 ± 5 years) were included in this retrospective review. No algorithms had sublobar concordance with ICEEG in all patients, including when algorithms were grouped by type (dipole modeling/dipole scanning, current density reconstruction, beam forming). Synthetic aperture magnetometry (SAM) with excess kurtosis tended to be the most accurate, but there were no significant differences between algorithms. When comparing the source modeling with ICEEG findings, significantly more patients with a seizure-free outcome were found to have lobar or sublobar concordance of multiple signal classification (MUSIC) (61.1%) and standardized low resolution brain electromagnetic tomography (sLORETA) (52.9%). Positive predictive values were highest for MUSIC (61.9%) and equivalent current dipole (ECD) (57.1%). Negative predictive values were highest for SAM(g2 )-VS (83%), minimum norm estimate (MNE) (75%), MUSIC (73.7%), and ECD (73.5%)., Significance: This study describes the use of multiple MEG source estimation techniques and demonstrates that all algorithms have similar rates of concordance with ICEEG. Also, the concordance or discordance of MUSIC with ICEEG was the best predictor of long-term seizure outcome., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

SIGFRIED (SIGnal modeling For Real-time Identification and Event Detection) software provides real-time functional mapping (RTFM) of eloquent cortex for epilepsy patients preparing to undergo resective surgery. This study presents the first application of paradigms used in functional magnetic resonance (fMRI) and electrical cortical stimulation mapping (ESM) studies for shared functional cortical mapping in the context of RTFM. Results from the 3 modalities are compared. A left-handed 13-year-old male with intractable epilepsy participated in functional mapping for localization of eloquent language cortex with fMRI, ESM, and RTFM. For RTFM, data were acquired over the frontal and temporal cortex. Several paradigms were sequentially presented: passive (listening to stories) and active (picture naming and verb generation). For verb generation and story processing, fMRI showed atypical right lateralizing language activation within temporal lobe regions of interest and bilateral frontal activation with slight right lateralization. Left hemisphere ESM demonstrated no eloquent language areas. RTFM procedures using story processing and picture naming elicited activity in the right lateral and basal temporal regions. Verb generation elicited strong right lateral temporal lobe activation, as well as left frontal lobe activation. RTFM results confirmed atypical language lateralization evident from fMRI and ESM. We demonstrated the feasibility and usefulness of a new RTFM stimulation paradigm during presurgical evaluation. Block design paradigms used in fMRI may be optimal for this purpose. Further development is needed to create age-appropriate RTFM test batteries.

Purpose: Implantation of subdural grids and invasive electroencephalography (EEG) monitoring is important to define the ictal-onset zone and eloquent cortex in selected patients with medically refractory epilepsy. The objective of this systematic review is to summarize data about adverse events related to this procedure., Methods: English-language studies published up to July 2012, reporting such adverse events were reviewed. Outcome measures included demographic variables; surgical protocol including number of subdural electrodes implanted per patient, duration of monitoring, antibiotic, and steroid prophylaxis; and adverse events., Key Findings: Twenty-one studies were identified including a total of 2,542 patients. The reported mean number of electrodes per patient and duration of monitoring varied from 52 to 95 and 5 to 17 days, respectively. There is a trend toward more uniform use of antibiotics and steroids in the perioperative period. Neurologic infections (pooled prevalence 2.3%, 95% confidence interval 1.5-3.1), superficial infections (3.0%, 1.9-4.1), intracranial hemorrhage (4.0%, 3.2-4.8), and elevated intracranial pressure (2.4%, 1.5-3.3) were found to be the most common adverse events. Up to 3.5% of patients required additional surgical procedure(s) for management of these adverse events. Increased number of electrodes (≥67) was found to be independently associated with increased incidence of adverse events., Significance: Although providing critical information for patients with medically refractory epilepsy, subdural grids implantation and invasive EEG monitoring entails risks of infection, hemorrhage, and elevated intracranial pressure. The prevalence estimates, likely to be conservative due to selective reporting, are expected to be helpful in counseling patients., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Purpose: Magnetoencephalography (MEG) has been shown a useful diagnostic tool for presurgical evaluation of pediatric medically intractable partial epilepsy as MEG source localization has been shown to improve the likelihood of seizure onset zone (SOZ) sampling during subsequent evaluation with intracranial EEG (ICEEG). We investigated whether ictal MEG onset source localization further improves results of interictal MEG in defining the SOZ., Methods: We identified 20 pediatric patients with one habitual seizure during MEG recordings between October 2007 and April 2011. MEG was recorded with sampling rates of 600Hz and 4000Hz for 10 and 2min respectively. Continuous head localization (CHL) was applied. Source localization analyses were applied using multiple algorithms, both at the beginning of ictal onset and for interictal MEG discharges. Ictal MEG onsets were identified by visual inspection and power spectrum using short-time Fourier transform (STFT). Source localizations were compared with ICEEG, surgical procedure and outcome., Key Findings: Eight patients met all inclusion criteria. Five of the 8 patients (63%) had concordant ictal MEG onset source localization and interictal MEG discharge source localizations in the same lobe, but the source of ictal MEG onset was closer to the SOZ defined by ICEEG., Significance: Although the capture of seizures during MEG recording is challenging, the source localization for ictal MEG onset proved to be a useful tool for presurgical evaluation in our pediatric population with medically intractable epilepsy., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: A high prevalence of nonconvulsive status epilepticus (NCSE) has been reported in critically ill adults and neonates. Recent prospective pediatric studies focus on critically ill children and show wide variability in the frequency of NCSE. This study examines prevalence of pediatric NCSE regardless of inpatient setting and retrospectively identifies risk factors indicating a need for urgent continuous EEG., Methods: Medical records from patients aged 3 months to 21 years were identified either by (1) searching a clinical EEG database (n = 18) or (2) consecutive inpatient EEG referrals for NCSE over an 8-month period (n = 57)., Results: Seventy-five children, mean age of 7.8 years, were studied. NCSE was identified in 26 patients (35%) and in 8 of 57 (14%) patients referred for possible NCSE. More than half of the patients referred were outside of the ICU. A witnessed clinical seizure was observed in 24 of 26 (92%) patients with NCSE. Acute cortical neuroimaging abnormalities were significantly more frequent in patients with NCSE. The presence of clinical seizures and acute neuroimaging abnormality was associated with an 82% probability of NCSE. All but 1 patient with NCSE had electrographic or electroclinical seizures within the first hour of monitoring., Conclusions: A high prevalence of NCSE was observed, comparable to adult studies, but within a wider range of inpatient settings. Children with acute encephalopathy should undergo continuous EEG. This evaluation is more urgent if certain clinical risk factors are present. Optimal duration of monitoring and the effect of NCSE on prognosis should be studied.

In recent years, there has been a growing interest on the role of gamma band (>30 Hz) neural oscillations in motor control, although the function of this activity in motor control is unknown clearly. With the goal of discussing the high frequency sources non-invasively and precisely during unilateral index finger movement, we investigated gamma band oscillations in 20 right-handed normal adults with magnetoencephalography (MEG). The results showed that gamma band activity appeared only during finger movement. Nineteen subjects displayed consistently contralateral event-related synchronization (C-ERS) within high gamma band (70-150 Hz) in primary motor cortex (M1) of both hemispheres. Interestingly, 15 subjects displayed ipsilateral event-related desynchronization (I-ERD) and C-ERS within broad gamma band (30-150 Hz). The locations of the broad gamma band I-ERD and C-ERS revealed hemispherical symmetry in M1. These findings demonstrate that there are consistent high gamma C-ERS and inconsistent low gamma I-ERD during a simple finger movement in the motor cortex. This study provides new evidence for the use of high gamma frequency oscillations as biomarkers in the analyses of functional brain activity and the localization of the motor cortex., (Copyright 2009 Elsevier B.V. All rights reserved.)

Purpose: Invasive intracranial recordings have suggested that high-frequency oscillation is involved in epileptogenesis and is highly localized to epileptogenic zones. The aim of the present study is to characterize the frequency and spatial patterns of high-frequency brain signals in childhood epilepsy using a non-invasive technology., Methods: Thirty children with clinically diagnosed epilepsy were studied using a whole head magnetoencephalography (MEG) system. MEG data were digitized at 4,000 Hz. The frequency and spatial characteristics of high-frequency neuromagnetic signals were analyzed using continuous wavelet transform and beamformer. Three-dimensional magnetic resonance imaging (MRI) was obtained for each patient to localize magnetic sources., Results: Twenty-six patients showed high-frequency (100-1,000 Hz) components (26/30, 86%). Nineteen patients showed more than one high-frequency component (19/30, 63%). The frequency range of high-frequency components varied across patients. The highest frequency band was identified around 910 Hz. The loci of high-frequency epileptic activities were concordant with the lesions identified by magnetic resonance imaging for 21 patients (21/30, 70%). The MEG source localizations of high-frequency components were found to be concordant with intracranial recordings for nine of the eleven patients who underwent epilepsy surgery (9/11, 82%)., Conclusion: The results have demonstrated that childhood epilepsy was associated with high-frequency epileptic activity in a wide frequency range. The concordance of MEG source localization, MRI and intracranial recordings suggests that measurement of high-frequency neuromagnetic signals might provide a novel approach for clinical management of childhood epilepsy.

Background: Reports have suggested that abnormal cortical excitability may be associated with acute migraines. The present study quantitatively assesses the degree of cortical excitability in chronic migraine as compared to acute migraine and healthy controls within the pediatric population. Methods: We investigated 27 children suffering from chronic migraine, 27 children suffering from acute migraine, and 27 healthy controls using a magnetoencephalography (MEG) system, recording at a sampling rate of 6000 Hz. All groups were age-matched and gender-matched. Neuromagnetic brain activation was elicited by a finger-tapping motor task. The spatiotemporal and spectral signatures of MEG data within a 5-2884 Hz range were analyzed using Morlet wavelet transform and beamformer analyses. Results: Compared with controls, the chronic migraine group showed (1) significantly prolonged latencies of movement-elicited magnetic fields (MEFs) between 5 and 100 Hz; (2) increased spectral power between 100 and 200 Hz, and between 2200 and 2800 Hz; and (3) a higher likelihood of neuromagnetic activation in the ipsilateral sensorimotor cortices, supplementary motor area, and occipital regions. Compared with acute migraine group, chronic migraine patients showed (1) significantly higher odds of having strong MEFs after 150 ms; and (2) significantly higher odds of having neuromagnetic activation from the deep brain areas. Conclusions: Results demonstrated that chronic migraine subjects were not only different from the healthy controls, but also different from acute migraine subjects. The chronification of migraines may be associated with elevated cortical excitability, delayed and spread neural response, as well as aberrant activation from deep brain areas. [ABSTRACT FROM AUTHOR]

Purpose: Intracranial electroencephalography (EEG) is performed as part of an epilepsy surgery evaluation when noninvasive tests are incongruent or the putative seizure-onset zone is near eloquent cortex. Determining the seizure-onset zone using intracranial EEG has been conventionally based on identification of specific ictal patterns with visual inspection. High-frequency oscillations (HFOs, >80 Hz) have been recognized recently as highly correlated with the epileptogenic zone. However, HFOs can be difficult to detect because of their low amplitude. Therefore, the prevalence of ictal HFOs and their role in localization of epileptogenic zone on intracranial EEG are unknown. Methods: We identified 48 patients who underwent surgical treatment after the surgical evaluation with intracranial EEG, and 44 patients met criteria for this retrospective study. Results were not used in surgical decision making. Intracranial EEG recordings were collected with a sampling rate of 2,000 Hz. Recordings were first inspected visually to determine ictal onset and then analyzed further with time-frequency analysis. Forty-one (93%) of 44 patients had ictal HFOs determined with time-frequency analysis of intracranial EEG. Key Findings: Twenty-two (54%) of the 41 patients with ictal HFOs had complete resection of HFO regions, regardless of frequency bands. Complete resection of HFOs (n = 22) resulted in a seizure-free outcome in 18 (82%) of 22 patients, significantly higher than the seizure-free outcome with incomplete HFO resection (4/19, 21%). Significance: Our study shows that ictal HFOs are commonly found with intracranial EEG in our population largely of children with cortical dysplasia, and have localizing value. The use of ictal HFOs may add more promising information compared to interictal HFOs because of the evidence of ictal propagation and followed by clinical aspect of seizures. Complete resection of HFOs is a favorable prognostic indicator for surgical outcome. [ABSTRACT FROM AUTHOR]

The discontinuous patterns in neonatal magnetoencephalographic (MEG) data are quantified with a novel Hilbert phase (HP) based approach. The expert neurologists' scores were used as the gold standard. The performance of this approach was analyzed using a receiver operating characteristic (ROC) curve, and it was compared with two other approaches, namely spectral ratio (SR) and discrete wavelet transform (DWT) that have been proposed for the detection of discontinuous patterns in neonatal EEG. The area under the ROC curve (AUC) was used as a performance measure. AUCs obtained for SR, HP, and DWT were 0.87, 0.80, and 0.56, respectively. Although the performance of HP was lower than SR, it carries information about the frequency content of the signal that helps to distinguish brain patterns from artifacts such as cardiac residuals. Based on this property, the HP approach was extended to fetal MEG data. Further, using the frequency property of the HP approach, burst duration and interburst interval were computed for the discontinuous patterns detected and they are in agreement with reported values. [ABSTRACT FROM AUTHOR]

We compared the magnetic cerebral activity of 10 fetal subjects at two different gestational ages. Spontaneous cerebral activity was recorded with a large array magnetometer specially designed to conform to the maternal gravid abdomen during the third trimester of pregnancy. We recorded each fetal subject at least twice: first at less than 36 weeks and again after 36 weeks gestational age. Pervasive signal artifacts of maternal magnetocardiogram (MCG), respiration, uterine wall contractions, and fetal magnetocardiogram were removed with special filtering that preserved fetal cerebral signals. We used ultrasound to locate the fetal head immediately before and after the magnetic recordings. Auditory and visual evoked responses were also recorded for each fetal subject. The calculated origin for the spontaneous cerebral signals was verified to be at the ultrasound location for the fetal head and to be similar to the calculated locations for the cerebral evoked responses. The recordings for each fetal subject at less than and greater than 36 weeks gestational age were compared to the expected EEG findings for premature infants at comparable post conceptual ages. [Copyright &y& Elsevier]

Purpose There is wide variation in clinical practice regarding the role of electrocorticography immediately after resection (post-resection ECoG) for pediatric epilepsy surgery. Results can guide further resection of potentially epileptogenic tissue. We hypothesized that post-resection ECoG spiking represents a biomarker of the epileptogenic zone and predicts seizure outcome in children undergoing epilepsy surgery. Methods We retrospectively identified 124 children with post-resection ECoG performed on the margins of resection. ECoG records were scored in a blinded fashion based on presence of frequent spiking. For patients identified as having additional resection based on clinical post-resection ECoG interpretation, these “second-look” ECoG results were re-reviewed for ongoing discharges or completeness of resection. Frequent spike populations were grouped using a standard scoring system into three ranges: 0.1–0.5 Hz, 0.5–1 Hz, >1 Hz. Seizure outcomes were determined at minimum 12-month followup. Results Of 124 patients who met inclusion criteria, 60 (48%) had an identified spike population on post-resection ECoG. Thirty (50%) of these had further resection based on clinical interpretation. Overall, good outcome (ILAE 1) was seen in 56/124 (45%). Completeness of resection of spiking (absence of spiking on initial post-resection ECoG or resolution of spiking after further resection) showed a trend toward good outcome (OR 2.03, p = 0.099). Patients with completeness of resection had good outcome in 41/80 (51%) of cases; patients with continued spikes had good outcome in 15/44 (35%) of cases. Conclusions Post-resection ECoG identifies residual epileptogenic tissue in a significant number of children. Lower frequency or absence of discharges on initial recording showed a trend toward good outcome. Completeness of resection demonstrated on final ECoG recording did not show a significant difference in outcome. This suggests that post-resection discharges represent a prognostic marker rather than a remediable biomarker of the epileptogenic zone in all patients. Resecting residual spike-generating cortex may be beneficial in selected patients, including children with tumors. [ABSTRACT FROM AUTHOR]