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Brain resection is curative for a subset of patients with drug resistant epilepsy but up to half will fail to achieve sustained seizure freedom in the long term. There is a critical need for accurate prediction tools to identify patients likely to have recurrent postoperative seizures. Results from preclinical models and intracranial EEG in humans suggest that the window of time immediately before and after a seizure ("peri-ictal") represents a unique brain state with implications for clinical outcome prediction. Using a dataset of 294 patients who underwent temporal lobe resection for seizures, we show that machine learning classifiers can make accurate predictions of postoperative seizure outcome using 5 min of peri-ictal scalp EEG data that is part of universal presurgical evaluation (AUC 0.98, out-of-group testing accuracy > 90%). This is the first approach to seizure outcome prediction that employs a routine non-invasive preoperative study (scalp EEG) with accuracy range likely to translate into a clinical tool. Decision curve analysis (DCA) shows that compared to the prevalent clinical-variable based nomogram, use of the EEG-augmented approach could decrease the rate of unsuccessful brain resections by 20%., (© 2024. The Author(s).)

Introduction: Business practices have influenced human health for centuries, yet an overarching concept to study these activities across nations, time periods, and industries (called 'the commercial determinants of health' (CDH)) has emerged only recently. The purpose of this review was to assess the descriptive characteristics of CDH research and to identify remaining research gaps., Methods: We systematically searched four databases (Scopus, OVID Medline, Ovid Embase, and Ovid Global Health) on Sept 13, 2022 for literature using CDH terms that described corporate activities that have the potential to influence population health and/or health equity (n = 116). We evaluated the following characteristics of the literature: methods employed, industries studied, regions investigated, funders, reported conflicts of interest, and publication in open-access formats., Results: The characteristics of the articles included that many were conceptual (50/116 articles; 43%) or used qualitative methods (37; 32%). Only eight articles (7%) used quantitative or mixed methods. The articles most often discussed corporate activities in relation to the food and beverage (51/116; 44%), tobacco (20; 17%), and alcohol industries (19; 16%), with limited research on activities occurring in other industries. Most articles (42/58 articles reporting a regional focus; 72%) focused on corporate activities occurring in high-income regions of the world., Conclusions: Our findings indicate that literature that has used CDH terms and described corporate practices that influence human health has primarily focused on three major industries in higher-income regions of the world. Qualitative methods were the most common empirical method for investigating these activities. CDH-focused investigations of corporate practices conducted by less-studied industries (e.g., social media) and in lower-income regions are recommended. Longitudinal quantitative studies assessing the associations between corporate practices and a range of health outcomes is also a necessary next step for this field., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Burgess et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Epilepsy with eyelid myoclonia (EMA) is characterized by eyelid myoclonia, eyelid closure sensitivity, and photosensitivity. EEG may manifest with frontal-predominant (FPEDs) or occipital-predominant epileptiform discharges (OPEDs). Data on clinical and electrographic features of these two subtypes are lacking. The purpose of our research was to look at baseline electroclinical features of EMA subtypes and to study electrographic findings of patients with EMA during intermittent photic stimulation (IPS)., Methods: We retrospectively identified all patients who had photoparoxysmal responses on EEGs performed at Cleveland clinic between January 01, 2012, and December 31, 2019. Patients who met diagnostic criteria for EMA were studied further., Results: Of the 249 patients with photoparoxysmal responses, 70 (28.1%) had EMA (62 [88.6%] female; the mean age of epilepsy onset: 7.0 ± 7.9 years). Patients with EMA had either FPEDs or OPEDs. Eleven patients with EMA (15.7%) had seizures (4 absence, 5 myoclonic and 2 bilateral tonic-clonic) during IPS. Patients with OPEDs were more likely to have drug-resistant epilepsy; occipital focal IEDs and other focal IEDs (other than frontal/occipital) on baseline EEG; and generalized IEDs with occipital predominance, generalized IEDs with no predominance, or focal IEDs during IPS. Predictors of seizure occurrence during photic stimulation included the presence of focal occipital IEDs on baseline EEG, generalized IEDs with frontal predominance during IPS, and photoparoxysmal response outlasting the stimulus., Conclusions: Our study provides evidence that EMA has two distinct subtypes, which differ in clinical characteristics, baseline EEG, and EEG during photic stimulation. We highlight diagnostic and prognostic implications of these findings. Our study also details EEG characteristics of patients with EMA during IPS., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 by the American Clinical Neurophysiology Society.)

One of the major challenges of modern epileptology is the underutilization of epilepsy surgery for treatment of patients with focal, medication resistant epilepsy (MRE). Aggravating this distressing failure to deliver optimum care to these patients is the underuse of proven localizing tools, such as magnetoencephalography (MEG), a clinically validated, non-invasive, neurophysiological method used to directly measure and localize brain activity. A sizable mass of published evidence indicates that MEG can improve identification of surgical candidates and guide pre-surgical planning, increasing the yield of SEEG and improving operative outcomes. However, despite at least 10 common, evidence supported, clinical scenarios in MRE patients where MEG can offer non-redundant information and improve the pre-surgical evaluation, it is regularly used by only a minority of USA epilepsy centers. The current state of the art in MEG sensors employs SQUIDs, which require cooling with liquid helium to achieve superconductivity. This sensor technology has undergone significant generational improvement since whole head MEG scanners were introduced around in 1990s, but still has limitations. Further advances in sensor technology which may make ME G more easily accessible and affordable have been eagerly awaited, and development of new techniques should be encouraged. Of late, optically pumped magnetometers (OPMs) have received considerable attention, even prompting some potential acquisitions of new MEG systems to be put on hold, based on a hope that OPMs will usher in a new generation of MEG equipment and procedures. The development of any new clinical test used to guide intracranial EEG monitoring and/or surgical planning must address several specific issues. The goal of this commentary is to recognize the current state of OPM technology and to suggest a framework for it to advance in the clinical realm where it can eventually be deemed clinically valuable to physicians and patients. The American Clinical MEG Society (ACMEGS) strongly supports more advanced and less expensive technology and looks forward to continuing work with researchers to develop new sensors and clinical devices which will improve the experience and outcome for patients, and perhaps extend the role of MEG. However, currently, there are no OPM devices ready for practical clinical use. Based on the engineering obstacles and the clinical tradeoffs to be resolved, the assessment of experts suggests that there will most likely be another decade relying solely on "frozen SQUIDs" in the clinical MEG field., (© 2023 International League Against Epilepsy.)

Objective: The significance of ictal magnetoencephalography (MEG) is not well appreciated. We evaluated the relationships between ictal MEG, MRI, intracranial electroencephalography (ICEEG), surgery and postoperative seizure outcome., Methods: A total of 45 patients (46 cases) with ictal MEG who underwent epilepsy surgery was included. We examined the localization of each modality, surgical resection area and seizure freedom after surgery., Results: Twenty-one (45.7%) out of 46 cases were seizure-free at more than 6 months follow-up. Median duration of postoperative follow-up was 16.5 months. The patients in whom ictal, interictal single equivalent current dipole (SECD) and MRI lesion localization were completely included in the resection had a higher chance of being seizure-free significantly (p < 0.05). Concordance between ictal and interictal SECD localizations was significantly associated with seizure-freedom. Concordance between MRI lesion and ictal SECD, concordance between ictal ICEEG and ictal and interictal SECD, as well as concordance between ictal ICEEG and MRI lesion were significantly associated with seizure freedom., Conclusions: Ictal MEG can contribute useful information for delineating the resection area in epilepsy surgery., Significance: Resection should include ictal, interictal SECDs and MRI lesion localization, when feasible. Concordant ictal and interictal SECDs on MEG can be a favorable predictor of seizure freedom., Competing Interests: Conflicts of interest The authors report no competing interests., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Summary: Neuroimaging and neurophysiology techniques can add a significant contribution to the comprehension of infantile spasms (IS) and hypsarrhythmia. Functional MRI and magnetoencephalography (MEG) are two noninvasive tools that can be used in young children with IS. In the past two decades, interesting data about IS have emerged from functional MRI and MEG studies. Regarding their clinical utility, MEG has supported the concept that epileptic spasms can have a focal origin. Moreover, MEG might contribute to the localization of the epileptogenic zone in children with IS under investigation for epilepsy surgery. Functional MRI data have contributed to improve the knowledge about the physiopathology of IS and hypsarrhythmia. It has demonstrated abnormal brainstem involvement during the high-amplitude slow waves of hypsarrhythmia and cortical involvement during the epileptiform discharges. Since the feasibility of these techniques has been demonstrated in infants, it is possible that, in the future, larger functional MRI and MEG studies might contribute to the treatment and the definition of the long-term prognosis of children with IS., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 by the American Clinical Neurophysiology Society.)

The Genomics Education Partnership (GEP) engages students in a course-based undergraduate research experience (CURE). To better understand the student attributes that support success in this CURE, we asked students about their attitudes using previously published scales that measure epistemic beliefs about work and science, interest in science, and grit. We found, in general, that the attitudes students bring with them into the classroom contribute to two outcome measures, namely, learning as assessed by a pre- and postquiz and perceived self-reported benefits. While the GEP CURE produces positive outcomes overall, the students with more positive attitudes toward science, particularly with respect to epistemic beliefs, showed greater gains. The findings indicate the importance of a student's epistemic beliefs to achieving positive learning outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Lopatto et al.)

Multimodal image integration (MMII) is a promising tool to help delineate the epileptogenic zone (EZ) in patients with medically intractable focal epilepsies undergoing presurgical evaluation. We report here the detailed methodology of MMII and an overview of the utility of MMII at the Cleveland Clinic Epilepsy Center from 2014 to 2018, exemplified by illustrative cases. The image integration was performed using the Curry platform (Compumedics Neuroscan ™ , Charlotte, NC, USA), including all available diagnostic modalities such as Magnetic resonance imaging (MRI), Positron Emission Tomography (PET), single-photon emission computed tomography (SPECT) and Magnetoencephalography (MEG), with additional capability of trajectory planning for intracranial EEG (ICEEG), particularly stereo-EEG (SEEG), as well as surgical resection planning. In the 5-year time span, 467 patients underwent MMII; of them, 98 patients (21%) had a history of prior neurosurgery and recurring seizures. Of the 467 patients, 425 patients underwent ICEEG implantation with further CT co-registration to identify the electrode locations. A total of 351 patients eventually underwent surgery after MMII, including 197 patients (56%) with non-lesional MRI and 223 patients (64%) with extra-temporal lobe epilepsy. Among 269 patients with 1-year post-operative follow up, 134 patients (50%) had remained completely seizure-free. The most common histopathological finding is focal cortical dysplasia. Our study illustrates the usefulness of MMII to enhance SEEG electrode trajectory planning, assist non-invasive/invasive data interpretation, plan resection strategy, and re-evaluate surgical failures. Information presented by MMII is essential to the understanding of the anatomo-functional-electro-clinical correlations in individual cases, which leads to the ultimate success of presurgical evaluation of patients with medically intractable focal epilepsies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jin, Choi, Bulacio, Alexopoulos, Burgess, Murakami, Bingaman, Najm and Wang.)

Concise history of fascinating magnetoencephalography (MEG) technology and catalog of very selected milestone preclinical and clinical MEG studies are provided as the background. The focus is the societal context defining a journey of MEG to and through clinical practice and formation of the American Clinical MEG Society (ACMEGS). We aspired to provide an objective historic perspective and document contributions of many professionals while focusing on the role of ACMEGS in the growth and maturation of clinical MEG field. The ACMEGS was born (2006) out of inevitability to address two vital issues-fair reimbursement and proper clinical acceptance. A beacon of accountable MEG practice and utilization is now an expanding professional organization with the highest level of competence in practice of clinical MEG and clinical credibility. The ACMEGS facilitated a favorable disposition of insurances toward MEG in the United States by combining the national replication of the grassroots efforts and teaming up with the strategic partners-particularly the American Academy of Neurology (AAN), published two Position Statements (2009 and 2017), the world's only set of MEG Clinical Practice Guidelines (CPGs; 2011) and surveys of clinical MEG practice (2011 and 2020) and use (2020). In addition to the annual ACMEGS Course (2012), we directly engaged MEG practitioners through an Invitational Summit (2019). The Society remains focused on the improvements and expansion of clinical practice, education, clinical training, and constructive engagement of vendors in these issues and pivotal studies toward additional MEG indications. The ACMEGS not only had the critical role in the progress of Clinical MEG in the United States and beyond since 2006 but positioned itself as the field leader in the future.

Purpose: The purported underutilization of magnetoencephalography (MEG) among the USA epilepsy centers has never been studied, and any evidence-based understanding of its magnitude is lacking., Methods: Two hundred twenty-five National Association of Epilepsy Centers centers (2016) were invited to participate anonymously in a 13-question web-based survey of clinical practice focused on MEG use., Results: On average, centers (N = 70; 61 of which were level 4) reported <6 epileptologists, >7 dedicated epilepsy monitoring unit beds, 206 phase 1 studies, 15 phase 2 studies, 10 direct resections, and 9 indirect resections; 27% owned MEG. On average, 11.2 MEGs per year were ordered for epilepsy localization and 7.6 for any presurgical mapping modalities. Wada test aka the intracarotid sodium amobarbital procedure (ISAP) (43%) and functional MRI (29%) were preferred over MEG (4%) for language mapping. The number of epileptologists and the number of epilepsy monitoring unit beds correlated positively with the most clinical volumes. The centers who own a MEG had surgical volumes significantly higher than those without. The number and complexity of patients as well as the proximity of a MEG were perceived as significant contributors/obstacles to increased MEG use., Conclusions: Only the centers with larger surgical volumes incorporate MEG regularly in presurgical evaluation of patients with drug-resistant epilepsy. A reversal of the pervasive underutilization of epilepsy surgery can benefit from MEG, but this requires a sustained concerted promotion by the epilepsy and MEG communities.

The report generated by the magnetoencephalographer's interpretation of the patient's magnetoencephalography examination is the magnetoencephalography laboratory's most important product and is a representation of the quality of the laboratory and the clinical acumen of the personnel. A magnetoencephalography report is not meant to enumerate all the technical details that went into the test nor to fulfill some imagined requirements of the electronic health record. It is meant to clearly and concisely answer the clinical question posed by the referring doctor and to convey the key findings that may inform the next step in the patient's care. The graphical component of a magnetoencephalography report is ordinarily the most welcomed by the referring doctor. Much of the text of the report may be glossed over, so the illustrations must be sufficiently annotated to provide clear and unambiguous findings. The particular images chosen for the report will be a function of the analysis software but should be selected and edited for maximum clarity. There should be a composite pictorial summary slide at the beginning or at the end of the report, which accurately conveys the gist of the report. Along with representative source localizations, reports should contain examples of the simultaneously recorded EEG that enable the referring physician to determine whether epileptic discharges occurred and whether they are consistent with the patient's previously recorded spikes. Information and images (e.g., statistics, magnetic field patterns) that provide convincing evidence of the validity of the source location should also be included.

Unfamiliarity with the indications for and benefits of magnetoencephalography (MEG) persists, even in the epilepsy community, and hinders its acceptance to clinical practice, despite the evidence. The wide treatment gap for patients with drug-resistant epilepsy and immense underutilization of epilepsy surgery had similar effects. Thus, educating referring physicians (epileptologists, neurologists, and neurosurgeons) both about the value of epilepsy surgery and about the potential benefits of MEG can achieve synergy and greatly improve the process of selecting surgical candidates. As a practical step toward a comprehensive educational process to benefit potential MEG users, current MEG referrers, and newcomers to MEG, the authors have elected to provide an illustrated guide to 10 everyday situations where MEG can help in the evaluation of people with drug-resistant epilepsy. They are as follows: (1) lacking or imprecise hypothesis regarding a seizure onset; (2) negative MRI with a mesial temporal onset suspected; (3) multiple lesions on MRI; (4) large lesion on MRI; (5) diagnostic or therapeutic reoperation; (6) ambiguous EEG findings suggestive of "bilateral" or "generalized" pattern; (7) intrasylvian onset suspected; (8) interhemispheric onset suspected; (9) insular onset suspected; and (10) negative (i.e., spikeless) EEG. Only their practical implementation and furtherance of personal and collective education will lead to the potentially impactful synergy of the two-MEG and epilepsy surgery. Thus, while fulfilling our mission as physicians, we must not forget that ignoring the wealth of evidence about the vast underutilization of epilepsy surgery - and about the usefulness and value of MEG in selecting surgical candidates - is far from benign neglect.

Noise sources in magnetoencephalography (MEG) include: (1) interference from outside the shielded room, (2) other people and devices inside the shielded room, (3) physiologic or nonphysiologic sources inside the patient, (4) activity from inside the head that is unrelated to the signal of interest, (5) intrinsic sensor and recording electronics noise, and (6) artifacts from other apparatus used during recording such as evoked response stimulators. There are other factors which corrupt MEG recording and interpretation and should also be considered "artifacts": (7) inadequate positioning of the patient, (8) changes in the head position during the recording, (9) incorrect co-registration, (10) spurious signals introduced during postprocessing, and (11) errors in fitting. The major means whereby magnetic interference can be reduced or eliminated are by recording inside a magnetically shielded room, using gradiometers that measure differential magnetic fields, real-time active compensation using reference sensors, and postprocessing with advanced spatio-temporal filters. Many of the artifacts that plague MEG are also seen in EEG, so an experienced electroencephalographer will have the advantage of being able to transfer his knowledge about artifacts to MEG. However, many of the procedures and software used during acquisition and analysis may themselves contribute artifact or distortion that must be recognized or prevented. In summary, MEG artifacts are not worse than EEG artifacts, but many are different, and-as with EEG-must be attended to.

Purpose: Broader utilization of magnetoencephalography (MEG) and optimization of clinical practice remain strategic goals of the American Clinical Magnetoencephalography Society. Despite the implementation of the first MEG Clinical Practice Guidelines, clinical adoption has been less than expected, prompting a reassessment., Methods: Twenty-five clinical MEG centers were invited to participate anonymously in a survey of clinical practice., Results: Centers (N = 18) mostly operated within an academic medical center (10/18), were owned by the "hospital" (10/18), associated with a level 4 National Association of Epilepsy center (15/18), and directed by neurologists (10/18). A total of 873 (median 59) epilepsy studies, 1,179 evoked fields (of all types), and 1,607 (median 30) research MEG studies were reported. Fourteen of 17 centers serve children (median 35%), but only 5 of 14 sedate children for MEG. All (N = 14) centers record EEG simultaneous with MEG, and 57% used dipole source localization. The median reporting time for epilepsy studies was 12 and 10 days for presurgical mapping studies. Most (12/14) were favorable toward the Clinical Practice Guidelines and "formalized certification" but were against mandating the latter., Conclusions: A plateau in MEG volumes suggests that MEG has not become a part of the standard of care, and correspondingly, the Clinical Practice Guidelines appeared to have had little impact on clinical practice. The American Clinical Magnetoencephalography Society must continue to engage magnetoencephalographers, potential referrers, and vendors.

Normal variants, although not occurring frequently, may appear similar to epileptic activity. Misinterpretation may lead to false diagnoses. In the context of presurgical evaluation, normal variants may lead to mislocalizations with severe impact on the viability and success of surgical therapy. While the different variants are well known in EEG, little has been published in regard to their appearance in magnetoencephalography. Furthermore, there are some magnetoencephalography normal variants that have no counterparts in EEG. This article reviews benign epileptiform variants and provides examples in EEG and magnetoencephalography. In addition, the potential of oscillatory configurations in different frequency bands to appear as epileptic activity is discussed.

Magnetoencephalography is the noninvasive measurement of miniscule magnetic fields produced by brain electrical currents, and is used most fruitfully to evaluate epilepsy patients. While other modalities infer brain function indirectly by measuring changes in blood flow, metabolism, and oxygenation, magnetoencephalography measures neuronal and synaptic function directly with submillisecond temporal resolution. The brain's magnetic field is recorded by neuromagnetometers surrounding the head in a helmet-shaped sensor array. Because magnetic signals are not distorted by anatomy, magnetoencephalography allows for a more accurate measurement and localization of brain activities than electroencephalography. Magnetoencephalography has become an indispensable part of the armamentarium at epilepsy centers., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A hallmark of the research experience is encountering difficulty and working through those challenges to achieve success. This ability is essential to being a successful scientist, but replicating such challenges in a teaching setting can be difficult. The Genomics Education Partnership (GEP) is a consortium of faculty who engage their students in a genomics Course-Based Undergraduate Research Experience (CURE). Students participate in genome annotation, generating gene models using multiple lines of experimental evidence. Our observations suggested that the students' learning experience is continuous and recursive, frequently beginning with frustration but eventually leading to success as they come up with defendable gene models. In order to explore our "formative frustration" hypothesis, we gathered data from faculty via a survey, and from students via both a general survey and a set of student focus groups. Upon analyzing these data, we found that all three datasets mentioned frustration and struggle, as well as learning and better understanding of the scientific process. Bioinformatics projects are particularly well suited to the process of iteration and refinement because iterations can be performed quickly and are inexpensive in both time and money. Based on these findings, we suggest that a dynamic of "formative frustration" is an important aspect for a successful CURE., (©2020 Author(s). Published by the American Society for Microbiology.)

Objective: Presurgical evaluation of patients with operculoinsular epilepsy and negative MRI presents major challenges. Here the authors examined the yield of noninvasive modalities such as voxel-based morphometric MRI postprocessing, FDG-PET, subtraction ictal SPECT coregistered to MRI (SISCOM), and magnetoencephalography (MEG) in a cohort of patients with operculoinsular epilepsy and negative MRI., Methods: Twenty-two MRI-negative patients were included who had focal ictal onset from the operculoinsular cortex on intracranial EEG, and underwent focal resection limited to the operculoinsular cortex. MRI postprocessing was applied to presurgical T1-weighted volumetric MRI using a morphometric analysis program (MAP). Individual and combined localization yields of MAP, FDG-PET, MEG, and SISCOM were compared with the ictal onset location on intracranial EEG. Seizure outcomes were reported at 1 year and 2 years (when available) using the Engel classification., Results: Ten patients (45.5%, 10/22) had operculoinsular abnormalities on MAP; 5 (23.8%, 5/21) had operculoinsular hypometabolism on FDG-PET; 4 (26.7%, 4/15) had operculoinsular hyperperfusion on SISCOM; and 6 (30.0%, 6/20) had an MEG cluster (3 tight, 3 loose) within the operculoinsular cortex. The highest yield of a 2-test combination was 59.1%, seen with MAP and SISCOM, followed by 54.5% with MAP and FDG-PET, and also 54.5% with MAP and MEG. The highest yield of a 3-test combination was 68.2%, seen with MAP, MEG, and SISCOM. The yield of the 4-test combination remained at 68.2%. When all other tests were negative or nonlocalizing, unique information was provided by MAP in 5, MEG in 1, SISCOM in 2, and FDG-PET in none of the patients. One-year follow-up was available in all patients, and showed 11 Engel class IA, 4 class IB, 4 class II, and 3 class III/IV. Two-year follow-up was available in 19 patients, and showed 9 class IA, 3 class IB, 1 class ID, 3 class II, and 3 class III/IV., Conclusions: This study highlights the individual and combined values of multiple noninvasive modalities for the evaluation of nonlesional operculoinsular epilepsy. The 3-test combination of MAP, MEG, and SISCOM represented structural, interictal, and ictal localization information, and constituted the highest yield. MAP showed the highest yield of unique information when other tests were negative or nonlocalizing.

Clinical neurophysiologic signals cover a broad range of frequencies. Filters help to emphasize waveforms that are of clinical or research interest and to mold their frequency characteristics to suit the purpose of the investigation. Some frequency content is obvious and well known, such as the alpha rhythm (8-11Hz) or spindles (12-14Hz) in the EEG. Other frequencies are not initially discriminable from background activity and require filtering in order to examine them, such as high-frequency oscillations (80-500Hz) in EEG and brainstem auditory evoked potentials (100-3000Hz). Often used to mitigate the effects of background noise or artifact, filters can be used specifically to attenuate unwanted frequencies, such as mains interference (50 or 60Hz) and electrode offset potential (<0.1Hz). For digital instrumentation, an antialiasing filter (below Nyquist) is always needed prior to sampling by the analog-to-digital converter. Once the signals are in the digital realm, sophisticated filtering operations can be carried out post hoc; but in order not to be misled, the neurophysiologist must always bear in mind the effect of filtering on the physiological waveform., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Since the purpose of clinical neurophysiology testing is to record the electrical activity of the nervous system, and often to electrically stimulate the peripheral or central nervous system (for evoked potentials, nerve conduction studies, etc.), these tests by their very nature demand an excellent electrical connection to the patient. This direct electrical connection by definition puts the patient at increased risk of electrical shock. When patients suffer from other nonneurological disorders that also require equipment to be attached to or inserted into their body, the additional and more direct electrical pathways to the heart make them even more vulnerable, especially when undergoing monitoring in the operating room or intensive care unit. Although we depend on the hospital's construction and utilities to follow appropriate regulations (the National Electrical Code in the United States) and on the vendors to sell only safe equipment (approved by the Food and Drug Administration in the United States), there may exist combinations of equipment and connections that put the patient at risk of injurious or fatal electrical shock. Regular testing and safe practices, informed by a scientific understanding of the risks, are the responsibilities of the healthcare providers in order to protect the patient from harm from electricity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Magnetoencephalography (MEG) is the noninvasive measurement of the miniscule magnetic fields produced by electrical currents flowing in the brain-the same neuroelectric activity that produces the EEG. MEG is one of several diagnostic tests employed in the evaluation of patients with epilepsy, but without the need to expose the patient to any potentially harmful agents. MEG is especially important in those being considered for epilepsy surgery, in whom accurate localization of the epileptic focus is paramount. While other modalities infer brain function indirectly by measuring changes in blood flow, metabolism, oxygenation, etc., MEG, as well as EEG, measures neuronal and synaptic function directly and, like EEG, MEG enjoys submillisecond temporal resolution. The measurement of magnetic fields provides information not only about the amplitude of the current but also its orientation. MEG picks up the magnetic field from neuromagnetometers surrounding the head in a helmet-shaped array of sensors. Clinical whole-head systems currently have 200-300 magnetic sensors, thereby offering very high resolution. The magnetic signals are not distorted by anatomy, because magnetic susceptibility is the same for all tissues, including the skull. Hence, MEG allows for a more accurate measurement and localization of brain activities than does EEG. Because one of its primary strengths is the ability to precisely localize electromagnetic activity within brain areas, MEG results are always coregistered to the patient's MRI. When combined in this way with structural imaging, it has been called magnetic source imaging (MSI), but MEG is properly understood as a clinical neurophysiologic diagnostic test. Signal processing and clinical interpretation in magnetoencephalography require sophisticated noise reduction and computerized mathematical modeling. Technological advances in these areas have brought MEG to the point where it is now part of routine clinical practice. MEG has become an indispensable part of the armamentarium at epilepsy centers where MEG laboratories are located, especially when patients are MRI-negative or where results of other structural and functional tests are not entirely concordant., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Importance: Literature on ictal magnetoencephalography (MEG) in clinical practice and the relationship to other modalities is limited because of the brevity of routine studies., Objective: To investigate the utility and reliability of ictal MEG in the localization of the epileptogenic zone., Design, Setting, and Participants: A retrospective medical record review and prospective analysis of a novel ictal rhythm analysis method was conducted at a tertiary epilepsy center with a wide base of referrals for epilepsy surgery evaluation and included consecutive cases of patients who experienced epileptic seizures during routine MEG studies from March 2008 to February 2012. A total of 377 studies screened. Data were analyzed from November 2011 to October 2015., Main Outcomes and Measures: Presurgical workup and interictal and ictal MEG data were reviewed. The localizing value of using extended-source localization of a narrow band identified visually at onset was analyzed., Results: Of the 44 included patients, the mean (SD) age at the time of recording was 19.3 (14.9) years, and 25 (57%) were male. The mean duration of recording was 51.2 minutes. Seizures were provoked by known triggers in 3 patients and were spontaneous otherwise. Twenty-five patients (57%) had 1 seizure, 6 (14%) had 2, and 13 (30%) had 3 or more. Magnetoencephalography single equivalent current dipole analysis was possible in 29 patients (66%), of whom 8 (28%) had no clear interictal discharges. Sublobar concordance between ictal and interictal dipoles was seen in 18 of 21 patients (86%). Three patients (7%) showed clear ictal MEG patterns without electroencephalography changes. Ictal MEG dipoles correlated with the lobe of onset in 7 of 8 patients (88%) who underwent intracranial electroencephalography evaluations. Reasons for failure to identify ictal dipoles included diffuse or poor dipolar ictal patterns, no MEG changes, and movement artifact. Resection of areas containing a minimum-norm estimate of a narrow band at onset, not single equivalent current dipole, was associated with sustained seizure freedom., Conclusions and Significance: Ictal MEG data can provide reliable localization, including in cases that are difficult to localize by other modalities. These findings support the use of extended-source localization for seizures recorded during MEG.

Objective: Selected patients with intractable focal epilepsy who have failed a previous epilepsy surgery can become seizure-free with reoperation. Preoperative evaluation is exceedingly challenging in this cohort. We aim to investigate the diagnostic value of two noninvasive approaches, magnetoencephalography (MEG) and ictal single-photon emission computed tomography (SPECT), in patients with failed epilepsy surgery., Methods: We retrospectively included a consecutive cohort of patients who failed prior resective epilepsy surgery, underwent re-evaluation including MEG and ictal SPECT, and had another surgery after the re-evaluation. The relationship between resection and localization from each test was determined, and their association with seizure outcomes was analyzed., Results: A total of 46 patients were included; 21 (46%) were seizure-free at 1-year followup after reoperation. Twenty-seven (58%) had a positive MEG and 31 (67%) had a positive ictal SPECT. The resection of MEG foci was significantly associated with seizure-free outcome (p = 0.002). Overlap of ictal SPECT hyperperfusion zones with resection was significantly associated with seizure-free outcome in the subgroup of patients with injection time ≤20 seconds(p = 0.03), but did not show significant association in the overall cohort (p = 0.46) although all injections were ictal. Patients whose MEG and ictal SPECT were concordant on a sublobar level had a significantly higher chance of seizure freedom (p = 0.05)., Conclusions: MEG alone achieved successful localization in patients with failed epilepsy surgery with a statistical significance. Only ictal SPECT with early injection (≤20 seconds) had good localization value. Sublobar concordance between both tests was significantly associated with seizure freedom. SPECT can provide essential information in MEG-negative cases and vice versa., Significance: Our results emphasize the importance of considering a multimodal presurgical evaluation including MEG and SPECT in all patients with a previous failed epilepsy surgery., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Poststroke pain syndrome (PSPS) is an often intractable disorder characterized by hemiparesis associated with unrelenting chronic pain. Although traditional analgesics have largely failed, integrative approaches targeting affective-cognitive spheres have started to show promise. Recently, we demonstrated that deep brain stimulation (DBS) of the ventral striatal area significantly improved the affective sphere of pain in patients with PSPS. In the present study, we examined whether electrophysiological correlates of pain anticipation were modulated by DBS that could serve as signatures of treatment effects. We recorded event-related fields (ERFs) of pain anticipation using magnetoencephalography (MEG) in 10 patients with PSPS preoperatively and postoperatively in DBS OFF and ON states. Simple visual cues evoked anticipation as patients awaited a painful (PS) or nonpainful stimulus (NPS) to the nonaffected or affected extremity. Preoperatively, ERFs showed no difference between PS and NPS anticipation to the affected extremity, possibly due to loss of salience in a network saturated by pain experience. DBS significantly modulated the early N1, consistent with improvements in affective networks involving restoration of salience and discrimination capacity. Additionally, DBS suppressed the posterior P2 (aberrant anticipatory anxiety) while enhancing the anterior N1 (cognitive and emotional regulation) in responders. DBS-induced changes in ERFs could potentially serve as signatures for clinical outcomes. NEW & NOTEWORTHY We examined the electrophysiological correlates of pain affect in poststroke pain patients who underwent deep brain stimulation (DBS) targeting the ventral striatal area under a randomized, controlled trial. DBS significantly modulated early event-related components, particularly N1 and P2, measured with magnetoencephalography during a pain anticipatory task, compared with baseline and the DBS-OFF condition, pointing to possible mechanisms of action. DBS-induced changes in event-related fields could potentially serve as biomarkers for clinical outcomes.

Background and Rationale: Magnetoencephalography has emerged as a tool for preoperative evaluation in children. We studied magnetoencephalography characteristics in subtypes of focal cortical dysplasia and correlated the findings with postoperative seizure outcome., Methods: Inclusion criteria were children ≤18 years who underwent magnetoencephalography during the preoperative evaluation followed by epilepsy surgery and a histopathologic diagnosis of focal cortical dysplasia between February 2008 and February 2013. Patient demographics, MRI, video electroencephalography, and magnetoencephalography data were reviewed. Postoperative seizure outcome data were categorized per International League against Epilepsy definitions., Results: Of 178 magnetoencephalography studies performed in children during the study period, 33 patients met inclusion criteria. Focal cortical dysplasia type I, II, and III were found on histopathology in 52%, 39%, and 9% of patients, respectively. Thirty patients had positive magnetoencephalography dipoles, including all patients with focal cortical dysplasia type II and III and 82% of patients with focal cortical dysplasia type I. Three patients had magnetoencephalography unique spikes. Brain MRI lesions were noted preoperatively in 21 patients (64%). Twenty-three patients (77%) had surgical resection of magnetoencephalography dipoles and 11 (48%) of them achieved favorable outcome., Conclusions: Magnetoencephalography supplemented scalp electroencephalography data in spike source localization and showed unique spikes in 10% of the focal cortical dysplasia patients. Magnetoencephalography spikes and tight magnetoencephalography clusters were found more frequently in patients with focal cortical dysplasia type II and III as compared with focal cortical dysplasia type I. Presence of an MRI lesion and complete versus incomplete resection of magnetoencephalography cluster did not result in significant difference in postoperative seizure outcome, likely reflecting selection bias of doing magnetoencephalography in only difficult-to-localize epilepsies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Porencephalic cyst/encephalomalacia is often associated with intractable epilepsy. A limited number of studies reported magnetoencephalography's (MEG's) potential to help construct treatment strategy for epilepsies associated with porencephalic cyst/encephalomalacia. The authors present here simultaneous electroencephalography (EEG) and MEG findings in three adult patients with pediatric-onset epilepsy due to porencephalic cyst/encephalomalacia. There were two types of spikes: one type was detected by MEG only (EEG-/MEG+), and the other detected by both EEG and MEG (EEG+/MEG+). Both types were seen in all three cases. The EEG-/MEG+ spikes all formed tight clusters; in contrast, the majority of EEG+/MEG+ spikes formed loose clusters. These data suggest that MEG may be helpful to better identify spike populations in epilepsy patients with porencephalic cyst/encephalomalacia. If hidden spike populations were to be found by MEG, this information would affect the interpretation of patient's pathophysiology and planning of intracranial electrode placement.

Purpose: Children with generalized seizures are often excluded as epilepsy surgery candidates. This prospective study was conducted to evaluate the utility of magnetoencephalography (MEG) to refine the location of the "irritative zone" in children with single lesions on magnetic resonance imaging (MRI) but with generalized ictal electroencephalographic (EEG) findings., Methods: Patients admitted with refractory epilepsy with imaging studies showing focal or hemispheric abnormalities but scalp video EEG showing generalized or multiregional epileptiform abnormalities were included. Patients were encouraged into natural sleep, and simultaneous whole-head MEG/EEG was recorded. Source localization of epileptic spikes on MEG was carried out while blinded to other results. Acceptable dipoles were classified into 3 groups: focal, hemispheric clusters, and single focal cluster with additional widespread dipoles., Results: Nine patients (4 female, 5 males; ages 10 months to 15 years) were included. Two had focal features on clinical semiology, whereas all had generalized or multiregional interictal and ictal EEG. Etiologies included tuberous sclerosis complex (2), postencephalitic sequelae (1), focal cortical dysplasia (1), and unknown (2). Five patients had clear focal lesions on brain MRI whereas the other 2 had focal positron emission tomography (PET) abnormalities. An average of 38 spikes were accepted (average goodness of fit = 85.3%). A single tight cluster of dipoles was identified in 5 patients, 1 had dipoles with propagation from left occipital to right temporal. One patient had 2 distinct dipole clusters. MEG demonstrated focal findings 9 times more often than the simultaneously recorded scalp EEG, and 3 times more often than the associated multiday video EEG recordings., Conclusion: This study shows that neurophysiologic evidence of focal epileptiform abnormalities in patients with focal brain lesions and generalized EEG findings can be strengthened using MEG. Further feasibility of surgical candidacy should be evaluated in these patients.

Purpose: Although a few magnetoencephalography (MEG) systems have been built specifically for infants (<2 years), most children are routinely examined using MEG systems designed primarily to accommodate adult subjects. The practicality of the adult MEG device has not been systematically reviewed in infants with epilepsy. The aim of this study is to investigate whether infant epilepsy patients, whose heads are small relative to the sensor helmet, can have clinically successful MEG recordings using the conventional adult-size MEG device., Methods: We reviewed our database of 964 patients who were referred for routine MEG epilepsy examination between January 2008 and May 2015. We reanalyzed the original data of the infant patients to investigate whether epileptiform discharges of the usual amplitudes could be detected., Results: Nine patients (about 1%) were infants. All the infant MEG records were processed with temporally extended signal space separation to remove environmental artifacts. Seven of the nine were processed with movement compensation processing using continuous head position monitoring. Magnetoencephalography captured epileptic abnormalities in all the infants: interictal in nine and ictal in five. The source amplitudes of 10 representative interictal dipoles from each of the infants ranged from 46.0 to 437.2 (mean: 180.1, SD: ±92.5) nA-m., Conclusions: Despite increased brain to sensor distance, the conventional MEG device can detect epileptic abnormalities in infants, facilitated by monitoring head position and postprocessing with temporally extended signal space separation, with or without movement compensation. Magnetoencephalography is useful for managing infants with epilepsy using the conventional adult machine, without special adaptations for small heads.

Background and Purpose: Rasmussen syndrome, also known as Rasmussen encephalitis, is typically associated with volume loss of the affected hemisphere of the brain. Our aim was to apply automated quantitative volumetric MR imaging analyses to patients diagnosed with Rasmussen encephalitis, to determine the predictive value of lobar volumetric measures and to assess regional atrophy differences as well as monitor disease progression by using these measures., Materials and Methods: Nineteen patients (42 scans) with diagnosed Rasmussen encephalitis were studied. We used 2 control groups: one with 42 age- and sex-matched healthy subjects and the other with 42 epileptic patients without Rasmussen encephalitis with the same disease duration as patients with Rasmussen encephalitis. Volumetric analysis was performed on T1-weighted images by using BrainSuite. Ratios of volumes from the affected hemisphere divided by those from the unaffected hemisphere were used as input to a logistic regression classifier, which was trained to discriminate patients from controls. Using the classifier, we compared the predictive accuracy of all the volumetric measures. These ratios were used to further assess regional atrophy differences and correlate with epilepsy duration., Results: Interhemispheric and frontal lobe ratios had the best prediction accuracy for separating patients with Rasmussen encephalitis from healthy controls and patient controls without Rasmussen encephalitis. The insula showed significantly more atrophy compared with all the other cortical regions. Patients with longitudinal scans showed progressive volume loss in the affected hemisphere. Atrophy of the frontal lobe and insula correlated significantly with epilepsy duration., Conclusions: Automated quantitative volumetric analysis provides accurate separation of patients with Rasmussen encephalitis from healthy controls and epileptic patients without Rasmussen encephalitis, and thus may assist the diagnosis of Rasmussen encephalitis. Volumetric analysis could also be included as part of follow-up for patients with Rasmussen encephalitis to assess disease progression., (© 2016 by American Journal of Neuroradiology.)

Management of MRI-negative patients with intractable focal epilepsy after failed surgery is particularly challenging. In this study, we aim to investigate whether MRI post-processing could identify relevant targets for the re-evaluation of MRI-negative patients who failed the initial resective surgery. We examined a consecutive series of 56 MRI-negative patients who underwent resective surgery and had recurring seizures at 1-year follow-up. T1-weighted volumetric sequence from the pre-surgical MRI was used for voxel-based MRI post-processing which was implemented in a morphometric analysis program (MAP). MAP was positive in 15 of the 56 patients included in this study. In 5 patients, the MAP+ regions were fully resected. In 10 patients, the MAP+ regions were not or partially resected: two out of the 10 patients had a second surgery including the unresected MAP+ region, and both became seizure-free; the remaining 8 patients did not undergo further surgery, but the unresected MAP+ regions were concordant with more than one noninvasive modality in 7. In the 8 patients who had unresected MAP+ regions and intracranial-EEG before the previous surgery, the unresected MAP+ regions were concordant with ictal onset in 6. Our data suggest that scrutiny of the presurgical MRI guided by MRI post-processing may reveal relevant targets for reoperation in nonlesional epilepsies. MAP findings, when concordant with the patient's other noninvasive data, should be considered when planning invasive evaluation/reoperation for this most challenging group of patients.

Central poststroke pain (CPSP) is characterized by hemianesthesia associated with unrelenting chronic pain. The final pain experience stems from interactions between sensory, affective, and cognitive components of chronic pain. Hence, managing CPSP will require integrated approaches aimed not only at the sensory but also the affective-cognitive spheres. A better understanding of the brain's processing of pain anticipation is critical for the development of novel therapeutic approaches that target affective-cognitive networks and alleviate pain-related disability. We used magnetoencephalography (MEG) to characterize the neural substrates of pain anticipation in patients suffering from intractable CPSP. Simple visual cues evoked anticipation while patients awaited impending painful (PS), nonpainful (NPS), or no stimulus (NOS) to their nonaffected and affected extremities. MEG responses were studied at gradiometer level using event-related fields analysis and time-frequency oscillatory analysis upon source localization. On the nonaffected side, significantly greater responses were recorded during PS. PS (vs. NPS and NOS) exhibited significant parietal and frontal cortical activations in the beta and gamma bands, respectively, whereas NPS (vs. NOS) displayed greater activation in the orbitofrontal cortex. On the affected extremity, PS (vs. NPS) did not show significantly greater responses. These data suggest that anticipatory phenomena can modulate neural activity when painful stimuli are applied to the nonaffected extremity but not the affected extremity in CPSP patients. This dichotomy may stem from the chronic effects of pain on neural networks leading to habituation or saturation. Future clinically effective therapies will likely be associated with partial normalization of the neurophysiological correlates of pain anticipation., (Copyright © 2016 the American Physiological Society.)

OBJECT The frontal and insular fiber network in humans remains largely unknown. This study investigated the connectivity of the frontal and anterior insular network in humans using cortico-cortical evoked potential (CCEP). METHODS This retrospective analysis included 18 patients with medically intractable focal epilepsy who underwent stereoelectroencephalography and CCEP. Alternating 1-Hz electrical stimuli were delivered to parts of the frontal lobe and anterior insula (prefrontal cortex [PFC], ventrolateral and dorsolateral premotor area [vPM and dPM, respectively], presupplementary motor area [pre-SMA], SMA, frontal operculum, and anterior insula). A total of 40-60 stimuli were averaged in each trial to obtain CCEP responses. The distribution of CCEP was evaluated by calculating the root mean square of CCEP responses. RESULTS Stimulation of the PFC elicited prominent CCEP responses in the medial PFC and PMs over the ipsilateral hemisphere. Stimulation of the vPM and dPM induced CCEP responses in the ipsilateral frontoparietal areas. Stimulation of the pre-SMA induced CCEP responses in the ipsilateral medial and lateral frontal areas and contralateral pre-SMA, whereas stimulation of the SMA induced CCEP responses in the bilateral frontoparietal areas. Stimulation of the frontal operculum induced CCEP responses in the ipsilateral insula and temporal operculum. CCEPs were observed in the ipsilateral medial, lateral frontal, and frontotemporal operculum in the anterior insular stimulation. Stimulation of the vPM and SMA led to the network in the dominant hemisphere being more developed. CONCLUSIONS Various regions within the frontal lobe and anterior insula were linked to specific ipsilateral and contralateral regions, which may reflect distinct functional roles.

Purpose: Infraslow activity (ISA) occurring during the interictal state in focal epilepsy is largely unstudied. In this exploratory analysis, the authors aimed to characterize features of interictal ISA in a cohort of patients studied by stereoelectroencephography., Methods: The interictal stereoelectroencephography records for 15 consecutive adult patients were retrospectively analyzed, after application of both conventional (1.6-70 Hz) and infraslow (0.01-0.1 Hz) bandpass filters. Visual analysis was complemented by time-frequency analysis to quantify the change in ISA power over hours. Linear correlation coefficient (R) calculations were used to map interictal connectivity in the infraslow band., Results: Interictal ISA background fluctuations were present throughout the interictal state in all patients, manifesting as recurrent and stereotyped oscillations. These oscillations had an apparent modulatory effect on conventional-band activities and spikes ("spike-crested oscillations"). In the infraslow band, the correlations between electrode contacts were shown to have a stable structure over time., Conclusions: Infraslow activity exists as a fundamental component of wideband cortical dynamics in focal epilepsy, with features suggestive of scale-free (1/f) dynamics: evidence of phase-amplitude coupling and functional connectivity in the infraslow band. Rather than viewed as a focal paroxysmal activity, interictal ISA may be better understood as a network process, although this requires further study.