Localization of language-specific cortex by using magnetic source imaging and electrical stimulation mapping.

Magnetic source imaging (MSI) is used routinely in epilepsy presurgical evaluation and in mapping eloquent cortex for surgery. Despite increasing use, the diagnostic yield of MSI is uncertain, with reports varying from 5% to 35%. To add benefit, a diagnostic technique should influence decisions made from other tests, and that influence should yield better outcomes. We report preliminary results of an ongoing, long-term clinical study in epilepsy, where MSI changed surgical decisions. We determined whether MSI changed the surgical decision in a prospective, blinded, crossover-controlled, single-treatment, observational case series. Sixty-nine sequential patients diagnosed with partial epilepsy of suspected neocortical origin had video-EEG and imaging. All met criteria for intracranial EEG (ICEEG). At a surgical conference, a decision was made before and after presentation of MSI. Cases where MSI altered the decision were noted. MSI gave nonredundant information in 23 patients (33%). MSI added ICEEG electrodes in 9 (13%) and changed the surgical decision in another 14 (20%). Based on MSI, 16 patients (23%) were scheduled for different ICEEG coverage. Twenty-eight have gone to ICEEG, 29 to resection, and 14 to vagal nerve stimulation, including 17 where MSI changed the decision. Additional electrodes in 4 patients covered the correct: hemisphere in 3, lobe in 3, and sublobar ictal onset zone in 1. MSI avoided contralateral electrodes in 2, who both localized on ICEEG. MSI added information to ICEEG in 1. Magnetic source imaging (MSI) provided nonredundant information in 33% of patients. In those who have undergone surgery to date, MSI added useful information that changed treatment in 6 (9%), without increasing complications. MSI has benefited 21% who have gone to surgery.

To gain information on the predictive and prognostic value of magnetic source imaging (MSI), 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG-PET), and ictal single-photon emission computed tomography (SPECT) as compared with intracranial electroencephalography (ICEEG) localization in epilepsy surgery. This work was part of a cohort study of epilepsy surgery candidates not sufficiently localized with noninvasive studies. Of 160 patients enrolled over 4 years, 77 completed ICEEG seizure monitoring. Sensitivity, specificity, and predictive values relative to ICEEG were computed for each modality. Seizures were not captured in five patients. Of the 72 diagnostic ICEEG studies, seizure localization results were 74% localized, 10% multifocal, and 17% nonlocalized. Sixty-one percent were localized to neocortical regions. Depending on patient subgroup pairs, sensitivity ranged from 58 to 64% (MSI), 22 to 40% (PET), and 39 to 48% (SPECT); specificity ranges were 79 to 88% (MSI), 53 to 63% (PET), and 44 to 50% (SPECT). Gains in diagnostic yield were seen only with the combination of MSI and PET or MSI and ictal SPECT. Localization concordance with ICEEG was greatest with MSI, but a significant difference was demonstrated only between MSI and PET. Moderate redundancy was seen between PET and ictal SPECT (kappa = 0.452; p = 0.011). Conclusively positive MSI has a high predictive value for seizures localized with ICEEG. Diagnostic gain may be achieved with addition of either PET or ictal SPECT to MSI. Diagnostic values for imaging tests are lower than "true values" because of the limitations of ICEEG as a gold standard.

Objective To evaluate the value of magnetic source imaging(MSI) in localizing the epileptic foci of patients with histologically proved grey matter heterotopia(GMH) and seizure. Methods MSI examinations were performed on 8 patients with GMH and seizure. The location of the epileptic foci defined by MSI was compared with the results of the ECoG. After imaging examinations, all patients received operation with 13-48 months follow up to observe the effectiveness of the operation. Results Among the 8 patients, 1 had hippocampal sclerosis,2 had focal cortical dysplasiaof type Ⅰ B and 1 had focal cortical dysplasia of type Ⅱ B. MRI showed normal findings in 2 cases, subcortical heterotopia in 4 cases, and nodulor heterotopia in 2 cases with one having schizencephaly. The epileptic foci defined by MSI were at right temporal lobe in 2 cases, left frontal lobe in 2 cases, biparietal lobe in1 case, left parietal lobe in 1 case, left temporal lobe in 1 case, and left frontal-parietal lobe in 1 case. The epileptic foci defined by MSI were completely overlaid with area of GMH in 4 cases, closely behind the area of GMH in case, and partly overlaid with area of GMH in 1 cases with size larger than that of the latter. One patient showed two epileptic foci with one located within the area of GMH and the other one 2 centimeters anterior to the area of GMH.One case's epileptic focus located 2 centimeters posteolateral to the area of GMH . The locations of the epileptic foci defined by MSI showed no difference with those defined by ECoG in all patients. According to Engel classification of treatment effect of epilepsy, 6 patients achieved Engle class Ⅰ ( seizure free after operation ), and 2 patients Engel class Ⅳ ( no changes in the frequcenty of occurrence of seizures before and after operation ). Conclusion MSI can noninvasively and precisely localize the epileptic foci before operation in patients with GMH and seizure. Key words: Epilepsy; Magnetoencephalography; Magnetic resonance imging

Preoperative localization of seizure onset zones (SOZs) is an evolving field in the treatment of refractory epilepsy. Both magnetic source imaging (MSI), and the more recent EEG-correlated functional MRI (EEG-fMRI), have shown applicability in assisting surgical planning. The purpose of this study was to evaluate the capability of each method and their combination in localizing the seizure onset lobe (SL). The study included 14 patients who underwent both MSI and EEG-fMRI before undergoing implantation of intracranial EEG (icEEG) as part of the presurgical planning of the resection of an epileptogenic zone (EZ) during the years 2012-2018. The estimated location of the SL by each method was compared with the location determined by icEEG. Identification rates of the SL were compared between the different methods. MSI and EEG-fMRI showed similar identification rates of SL locations in relation to icEEG results (88% ± 31% and 73% ± 42%, respectively; p = 0.281). The additive use of the coverage lobes of both methods correctly identified 100% of the SL, significantly higher than EEG-fMRI alone (p = 0.039) and nonsignificantly higher than MSI (p = 0.180). False-identification rates of the additive coverage lobes were significantly higher than MSI (p = 0.026) and EEG-fMRI (p = 0.027). The intersecting lobes of both methods showed the lowest false identification rate (13% ± 6%, p = 0.01). Both MSI and EEG-fMRI can assist in the presurgical evaluation of patients with refractory epilepsy. The additive use of both tests confers a high identification rate in finding the SL. This combination can help in focusing implantation of icEEG electrodes targeting the SOZ.

The current procedures that are used to evaluate candidates for epilepsy surgery are time-consuming, costly, and often invasive. Magnetic source imaging (MSI), the combination of magnetoencephalography and anatomic imaging modalities, has shown promise as an efficient noninvasive means of localizing and characterizing seizure sources for possible resection. However, MSI has been limited by the inability to conduct simultaneous bilateral monitoring. In this study, a newly developed dual-magnetometer system was employed to record bilaterally the interictal activity in 30 candidates for epilepsy surgery. A standard monitoring protocol that included concurrent electroencephalographic recording and required a 2- to 3-hour examination period for each patient was developed. As a first step in a series of studies, the resultant MSI indications were compared with the information available from standard magnetic resonance imaging and concurrent electroencephalographic results. In 83% of the cases, this MSI protocol provided new information about the location of interictal epileptic activity that could be directive for subsequent patient care. Based on these results, it seems that MSI may become a cost-effective early step in epilepsy surgery evaluation. To continue the development on this basis, a study intended to validate the accuracy of MSI indicated by comparison with invasive electroencephalography has been initiated.

Electromagnetic Source Imaging in Presurgical Workup of Patients With Epilepsy: A Prospective Study.Duez L, Tankisi H, Hansen PO, et al. Neurology. 2019;92(6):e576-e586. doi:10.1212/WNL.0000000000006877. Epub 2019 Jan 4. PMID: 30610090Objective:To determine the diagnostic accuracy and clinical utility of electromagnetic source imaging (EMSI) in presurgical evaluation of patients with epilepsy.Methods:We prospectively recorded magnetoencephalography (MEG) simultaneously with electroencephalogram (EEG) and performed EMSI, comprising electric source imaging, magnetic source imaging, and analysis of combined MEG-EEG data sets, using 2 different software packages. As reference standard for irritative zone (IZ) and seizure onset zone (SOZ), we used intracranial recordings and for localization accuracy outcome 1 year after operation.Results:We included 141 consecutive patients. Electromagnetic source imaging showed localized epileptiform discharges in 94 (67%) patients. Most (72%) of the epileptiform discharge clusters were identified by both modalities, 15% only by EEG, and 14% only by MEG. Agreement was substantial between inverse solutions and moderate between software packages. Electromagnetic source imaging provided new information that changed the management plan in 34% of the patients, and these changes were useful in 80%. Depending on the method, EMSI had a concordance of 53% to 89% with IZ and 35% to 73% with SOZ. Localization accuracy of EMSI was between 44% and 57% which was not significantly different from magnetic resonance imaging (49%-76%) and PET (54%-85%). Combined EMSI achieved significantly higher odds ratio compared to electric source imaging and magnetic source imaging.Conclusion:Electromagnetic source imaging has accuracy similar to established imaging methods and provides clinically useful, new information in 34% of the patients.Classification of evidence:This study provides class IV evidence that EMSI had a concordance of 53% to 89% and 35% to 73% (depending on analysis) for the localization of epileptic focus when compared to intracranial recordings (IZ and SOZ), respectively.

This chapter outlines the basic features and applications of Magnetic Source Imaging (MSI) as a tool for studying the functional organization of the brain circuits that support phonological decoding and word recognition. MSI provides temporal resolution in the order of milliseconds and adequate spatial resolution in order to (a) determine if the degree, peak latency, and temporal progression of regional activity vary systematically with individual differences in reading ability, and (b) identify cortical regions where activity predicts reading achievement scores. A series of small and larger-scale studies are described utilizing clinically validated source-parameter estimation techniques as well as minimum norm estimation procedures which permit modeling of distributed cortical magnetic sources. Results demonstrate that reading-impaired children show reduced activation of posterior temporal and inferior parietal regions during late stages of stimulus processing, mainly in the left hemisphere. Specific task demands, i.e. lexical characteristics and memory involvement may determine additional features of brain activation profiles, including hemispheric distribution of group effects, and the degree of prefrontal involvement in the reading process. These effects are present regardless of comorbidity with attention deficit hyperactivity disorder (ADHD), and also highlight the importance of early activity in the left fusiform gyrus for both word and pseudoword reading ability. The key role of these regions into the developing brain mechanism for reading receives further support from intervention studies, demonstrating “normalizing” changes in the degree and latency of regional activation.

The view of brain activity is determined by the method used, for example, conventional scalp electroencephalography (EEG) provides a blurred vision, subdural invasive electrodes a view like a magnifying lens, and intracerebral electrodes, a tunnel view. The development of sophisticated algorithms for source localization of magnetoencephalography (MEG) and EEG provides a new approach to recognize and localize source attributes. Intracellular and extracellular currents are the sources of electric/magnetic fields. The intracellular current (primary current) is surrounded by a magnetic field, whereas extracellular currents are due to passive volume conduction induced by the electric field. EEG and MEG are complementary recording techniques because both methods have certain advantages and disadvantages. MEG has some favorable characteristics for source localizations; for example, secondary volume currents are in general not so important and the modeling of the conductivities of the different brain tissues (gray–white matter, skull, scalp) do not play a major role. Modern MEG–multichannel systems with up to 300 channels provide a fast and contact-less measurement of the predominantly tangential components of the brain activity. On the other hand, EEG records both radial and tangential components, but secondary volume conduction plays a significant role and must be considered adequately by a realistic head model (Boundary Element Model, Finite Element Model). For source localization, special electroanatomic and physical characteristics have to be considered, because the solution of the inverse problem is not unique. Therefore, additional assumptions have to be made for the source model and the allowed source space. Very often the equivalent current dipole (ECD), which describes the center of gravity of the electrical activity, is used for the description of focal epileptic activity. This model provides in many cases a good estimation of the underlying source but a careful evaluation of the results with respect to stability and reproducibility have to be considered. In addition to the ECD, more elaborate source models, for example, multiple dipoles, beam former, or current density analysis can be used. In addition, the coherence analysis provides a better understanding of the brain dynamics. As in all functional imaging methods, the extension of activity and noise artifacts require special consideration. The depth resolution of MEG recordings depends on technical conditions such as the use of gradiometers or magnetometers. In addition to scalp EEG/MEG recordings, also simultaneously recorded electrocorticography (ECoG) and MEG recordings can be performed offering a better three-dimensional view of deeper localized epileptic activities. Source localization aims to detect focal epileptic activity within the interictal or even ictal onset of the epileptic network. In addition to the localization of epileptic activity, its spatial relationship to functional important areas (e.g., motor/speech) is a major task with regard to surgical planning. For this task a multimodal coregistration of MEG/EEG and functional magnetic resonance imaging (fMRI) as well as tractography by means of diffusion tensor imaging (DTI) can be used (Fig. 1). (A) Streamtube visualization of the right optic radiation based on diffusion tensor imaging (DTI). (B) For navigation, a three-dimensional object representing the optic radiation (wrapping the individual fibers) and two distinct magnetic source imaging (MSI) foci (red) are generated. (C) Relation of optic radiation (visualized as streamlines) to MSI foci. (D–F) Sagittal/coronal (axial view of T1-weighted images with registered DTI. Localization of focal epileptic activity is below the optic tract. (Stefan et al., 2006). The sensitivity of MEG for specific epileptic activity is approximately 70%. The MEG, compared to video-EEG monitoring and MRI, provided additional information during presurgical evaluation in 35% (Stefan et al., 2003). In patients, for whom interictal and focal epileptic seizures during long-term scalp EEG recordings were inconclusive (25 of 105 patients) MEG was able to localize in the lobe, which has been resected later on, in 44%. All these patients had an improvement of seizure frequency postoperatively (six patients were seizure-free; five patients had a reduction >50%) (Paulini et al., 2007). When comparing noninvasive magnetic source imaging and invasive seizure-onset localization, a positive predictive value of magnetic source imaging (MSI) for seizure localization was 82–90% (Knowlton et al., 2006). MEG predicted outcome following surgery for intractable epilepsy in children with normal or nonfocal MRI findings (RamachandranNair et al., 2007). There are special situations during presurgical evaluation in which MSI is helpful: for example, patients after surgery, multiple stage surgery, patients with missing cooperation for prolonged invasive recordings or contraindications for invasive recordings. Furthermore, presurgical invasive recordings can be guided by MEG and in some cases might be even omitted. The combined multimodal use of MEG/EEG, MRI, fMRI, single photon emission computed tomography (SPECT), and functional neuronavigation can be used for functional preservation in epilepsy surgery (Ganslandt et al., 1999). The author has no conflict of interest to disclose.

This review outlines the rationale for the use of magnetoencephalography (MEG) or magnetic source imaging (MSI), a noninvasive functional imaging technique, and the features that any imaging method should display to make a substantial contribution to cognitive neuroscience. After a brief discussion of the basic experimental approach used in the authors' studies, the use of early sensory components of brain magnetic responses is reviewed to address issues of the functional organization of the primary sensory cortices, followed by a comment on the clinical use of these components. Second, normative studies focusing on the late components of magnetic responses for establishing the validity and reliability of MSI maps of the language-specific cortex in normal subjects are reviewed. Third, the authors' investigations of fine spatiotemporal features of brain activation maps, specific to receptive language and to reading, are reviewed. Fourth, experience with presurgical mapping of the language-specific cortex in neurosurgery candidates and in patients undergoing the "Wada" procedure is summarized followed by a comment on the perfect agreement of the MSI maps with those derived by more direct invasive brain mapping procedures. Fifth. MSI-derived evidence of often dramatic, functional reorganization of brain areas subserving both simple sensory and linguistic functions is summarized along with comments on the use of MSI as a means for investigating brain plasticity. Finally, in the sixth section of this review, the authors relate their experience with the use of MSI in deriving brain activation profiles during silent reading of real words and pseudowords that are specific to dyslexic children. The review concludes with a discussion on the further use of MSI in assessing, among other issues, the effectiveness of intervention strategies designed to improve reading fluency in dyslexic children.

Intracranial language localization with electrical stimulation mapping (ESM) and high-gamma modulation (HGM) mapping relies on artificial, repetitive tasks, requiring sustained cooperation from patients. Herein, we tested the validity of unstructured, interpersonal, naturalistic conversation for language localization, using a novel methodology: Behavior-iEEG-Spectral-Power correlation (BESPoC). We first validated BESPoC against ESM, HGM, and neuropsychological outcomes using well-established language tasks, then demonstrated the validity of naturalistic conversation. We included 134 patients (59 females), aged 2-29 years, undergoing standard-of-care stereo-electroencephalography monitoring who engaged in picture naming, auditory naming, story listening, and conversed with a family member. ESM and HGM analysis were performed using established methods. BESPoC methodology quantified correlation between stereo-electroencephalography spectral power from task recordings, obviating the need for any trial-based epochs, and behavioral markers. The large sample size allowed mixed-effects modeling to compare BESPoC with HGM and ESM. BESPoC showed high specificity (0.79-0.83) and sensitivity (0.64-0.86) for localizing HGM language sites across the tasks. BESPoC also compared well with HGM across all language tasks for localizing ESM speech/language sites. With conventional tasks, BESPoC was superior to HGM for modeling neuropsychological deficits seen, despite preserving ESM speech/language sites. Naturalistic conversation compared well with standard tasks for localization of HGM and ESM language sites, and determined neuropsychological outcomes better than conventional tasks. Using BESPoC methodology naturalistic conversation is shown to produce valid cortical language maps of both expressive and receptive language, and determine neuropsychological outcomes after epilepsy surgery. ANN NEUROL 2025;98:1096-1110.

The goal was to determine whether magnetic source imaging could identify a signature for cortical involvement in patients with amyotrophic lateral sclerosis (ALS), and to determine whether the method might provide insight into functional abnormalities associated with the disease process. Spontaneous brain activity recordings from whole-head 148-channel magnetoencephalography (MEG) were employed to look for localized dipolar sources of focal delta-theta (1-7 Hz) discharges in patients with ALS without dementia. Localized slow wave dipoles were mapped and counted by anatomic brain region, defined by MRI, and correlated against the revised ALS functional rating scale (a functional measure of ALS disability). In a substudy, defects in cortical activations mediating purposeful movement were investigated in an ALS patient with probable motor apraxia of an upper limb. MEG revealed localized slow wave dipole sources in 7/7 ALS patients, including two recently diagnosed patients (0/8 age-similar controls). Systematic brain mapping of dipole source generators was possible in all seven ALS patients. The slow wave bursts were being generated from frontal, temporal, and parietal cortices, but not from occipital areas. The density of slow wave dipoles in cingulate gyrus correlated with the severity of upper-extremity disability as judged by the functional ALS measure. Further magnetic source imaging in the substudy patient with unilateral limb apraxia revealed abnormal central processing of purposeful movement with absent M2 in the contralateral secondary motor areas generating slow waves. This exploratory study documents widespread cortical dysfunction in patients with ALS, including those with recent onset of their disease. MEG is likely to be a powerful new tool for researching the contribution of cortical dysfunction to the motor disability that characterizes the disease process.

A patient in whom a variety of abnormal EEG findings can be elicited by elimination of central vision and fixation demonstrates fixation-off sensitivity. The underlying mechanisms of fixation-off sensitivity and its relationship with alpha rhythm remain unclear. To obtain a better understanding of this issue, we used a whole-head magnetoencephalograph to study an epileptic child with fixation-off sensitivity resulting in a 3-Hz, large-amplitude oscillation (300 microV) over the occipital regions on the EEG. Magnetic source localization revealed alpha activity around the calcarine fissure and surrounding parieto-occipital areas. Magnetic sources of abnormalities relating to fixation-off sensitivity, however, usually were located deeper in the brain, suggesting more extensively distributed sources, with involvement of the cingulate gyrus and the basomesial occipitotemporal region. Distributions of the sources of both types of activities show independent clusters but also an appreciable domain of overlap. Our findings indicate that abnormalities related to fixation-off sensitivity can emerge in thalamocortical networks, with larger and more anterior cortical distribution than those that generate alpha rhythm. Transition in the type of oscillation appears not only to depend on a change in cellular dynamics but also to be reflected in a different spatial distribution of the underlying neuronal networks.

Combined use of magnetoencephalography (MEG), functional magnetic resonance imaging (f-MRI), and motor evoked potentials (MEPs) was carried out on one patient in an attempt to localise precisely a structural lesion to the central sulcus. A small cyst in the right frontoparietal region was thought to be the cause of generalised seizures in an otherwise asymptomatic woman. First the primary sensory cortex was identified with magnetic source imaging (MSI) of somatosensory evoked magnetic fields using MEG and MRI. Second, the motor area of the hand was identified using f-MRI during hand-squeezing. Then transcranial magnetic stimulation localised the hand motor area on the scalp, which was mapped onto the MRI. There was a good agreement between MSI, f-MRI and MEP as to the location of the sensorimotor cortex and its relationship to the lesion. Multimodality mapping techniques may thus prove useful in the precise localisation of cortical lesions, and in the preoperative determination of the best treatment for peri-rolandic lesions.

Prior work proved that it is possible to find a unique solution to the problem of defining the configuration of electric current underlying observed extracranial magnetic fields, if sufficient priori knowledge of the source configuration is available. This minimum-norm least-squares (MNLS) inverse solution for a magnetic source image (MSI) is extended here to include temporal as well as spatial parameters of the underlying current pattern. This capitalizes on the temporal resolution of magnetoencephalography (MEG), which is on the order of milliseconds. Other forms of functional brain imaging are far less sensitive to the rate of change of states of the brain. Influences on the quality of the resulting MSI by measurement noise and errors in determining the image surface are characterized. A new technique for reducing noise in the inverse problem is developed by taking into consideration the spatial and time-dependence of the noise detected by the sensors. This new approach to regularization reduces the contribution from noisy measurements to the inverse calculation, and therefore improves the stability of the inverse.

Focal cortical dysplasia (FCD) is a common cause of pharmacoresistant epilepsy that is amenable to surgical resective treatment. The identification of structural FCD by magnetic resonance imaging (MRI) can contribute to the detection of the epileptogenic zone and improve the outcome of epilepsy surgery. MR epilepsy protocols that include specific T1 and T2 weighted, and fluid-attenuated inversion recovery (FLAIR) sequences give complementary information about the characteristic imaging features of FCD; focal cortical thickening, blurring of the gray-white junction, high FLAIR signal, and gyral anatomical abnormalities. Novel imaging techniques such as magnetic resonance spectroscopy (MRS), magnetization transfer imaging (MTI), and diffusion tensor imaging (DTI) can improve the sensitivity of MR to localize the anatomical lesion. Functional/metabolic techniques such as positron emission tomography (PET), ictal subtraction single photon emission computed tomography (SPECT), functional MRI (fMRI), and magnetic source imaging (MSI) have the potential to visualize the metabolic, vascular, and epileptogenic properties of the FCD lesion, respectively. Identification of eloquent areas of cortex, to assist in the surgical resection plan, can be obtained non-invasively through the use of fMRI and MSI. Although a significant number of FCD lesions remain unidentified using current neuroimaging techniques, future advances should result in the identification of an increasing number of these cortical malformations.