A Novel, Robust, and Portable Platform for Magnetoencephalography using Optically Pumped Magnetometers.

Magnetoencephalography (MEG) measures brain function via assessment of magnetic fields generated by neural currents. Conventional MEG uses superconducting sensors, which place significant limitations on performance, practicality, and deployment; however, the field has been revolutionised in recent years by the introduction of optically-pumped-magnetometers (OPMs). OPMs enable measurement of the MEG signal without cryogenics, and consequently the conception of 'OPM-MEG' systems which ostensibly allow increased sensitivity and resolution, lifespan compliance, free subject movement, and lower cost. However, OPM-MEG remains in its infancy with limitations on both sensor and system design. Here, we report a new OPM-MEG design with miniaturised and integrated electronic control, a high level of portability, and improved sensor dynamic range (arguably the biggest limitation of existing instrumentation). We show that this system produces equivalent measures when compared to an established instrument; specifically, when measuring task-induced beta-band, gamma-band and evoked neuro-electrical responses, source localisations from the two systems were highly comparable and temporal correlation was >0.7 at the individual level and >0.9 for groups. Using an electromagnetic phantom, we demonstrate improved dynamic range by running the system in background fields up to 8 nT. We show that the system is effective in gathering data during free movement (including a sitting-to-standing paradigm) and that it is compatible with simultaneous electroencephalography (EEG - the clinical standard). Finally, we demonstrate portability by moving the system between two laboratories. Overall, our new system is shown to be a significant step forward for OPM-MEG technology and offers an attractive platform for next generation functional medical imaging.

Subclinical epileptiform activity in the Alzheimer continuum: association with disease, cognition and detection method.

BACKGROUND: Epileptic seizures are an established comorbidity of Alzheimer's disease (AD). Subclinical epileptiform activity (SEA) as detected by 24-h electroencephalography (EEG) or magneto-encephalography (MEG) has been reported in temporal regions of clinically diagnosed AD patients. Although epileptic activity in AD probably arises in the mesial temporal lobe, electrical activity within this region might not propagate to EEG scalp electrodes and could remain undetected by standard EEG. However, SEA might lead to faster cognitive decline in AD. AIMS: 1. To estimate the prevalence of SEA and interictal epileptic discharges (IEDs) in a well-defined cohort of participants belonging to the AD continuum, including preclinical AD subjects, as compared with cognitively healthy controls. 2. To evaluate whether long-term-EEG (LTM-EEG), high-density-EEG (hd-EEG) or MEG is superior to detect SEA in AD. 3. To characterise AD patients with SEA based on clinical, neuropsychological and neuroimaging parameters. METHODS: Subjects (n = 49) belonging to the AD continuum were diagnosed according to the 2011 NIA-AA research criteria, with a high likelihood of underlying AD pathophysiology. Healthy volunteers (n = 24) scored normal on neuropsychological testing and were amyloid negative. None of the participants experienced a seizure before. Subjects underwent LTM-EEG and/or 50-min MEG and/or 50-min hd-EEG to detect IEDs. RESULTS: We found an increased prevalence of SEA in AD subjects (31%) as compared to controls (8%) (p = 0.041; Fisher's exact test), with increasing prevalence over the disease course (50% in dementia, 27% in MCI and 25% in preclinical AD). Although MEG (25%) did not withhold a higher prevalence of SEA in AD as compared to LTM-EEG (19%) and hd-EEG (19%), MEG was significantly superior to detect spikes per 50 min (p = 0.002; Kruskall-Wallis test). AD patients with SEA scored worse on the RBANS visuospatial and attention subset (p = 0.009 and p = 0.05, respectively; Mann-Whitney U test) and had higher left frontal, (left) temporal and (left and right) entorhinal cortex volumes than those without. CONCLUSION: We confirmed that SEA is increased in the AD continuum as compared to controls, with increasing prevalence with AD disease stage. In AD patients, SEA is associated with more severe visuospatial and attention deficits and with increased left frontal, (left) temporal and entorhinal cortex volumes. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04131491. 12/02/2020.

Delayed effective connectivity characterizes the epileptogenic zone during stereo-EEG.

OBJECTIVE: Single-pulse electrical stimulations (SPES) can elicit normal and abnormal responses that might characterize the epileptogenic zone, including spikes, high-frequency oscillations and cortico-cortical evoked potentials (CCEPs). In this study, we investigate their association with the epileptogenic zone during stereoelectroencephalography (SEEG) in 28 patients with refractory focal epilepsy. METHODS: Characteristics of CCEPs (distance-corrected or -uncorrected latency, amplitude and the connectivity index) and the occurrence of spikes and ripples were assessed. Responses within the epileptogenic zone and within the non-involved zone were compared using receiver operating characteristics curves and analysis of variance (ANOVA) either in all patients, patients with well-delineated epileptogenic zone, and patients older than 15 years old. RESULTS: We found an increase in distance-corrected CCEPs latency after stimulation within the epileptogenic zone (area under the curve = 0.71, 0.72, 0.70, ANOVA significant after false discovery rate correction). CONCLUSIONS: The increased distance-corrected CCEPs latency suggests that neuronal propagation velocity is altered within the epileptogenic network. This association might reflect effective connectivity changes at cortico-cortical or cortico-subcortico-cortical levels. Other responses were not associated with the epileptogenic zone, including the CCEPs amplitude, the connectivity index, the occurrences of induced ripples and spikes. The discrepancy with previous descriptions may be explained by different spatial brain sampling between subdural and depth electrodes. SIGNIFICANCE: Increased distance-corrected CCEPs latency, indicating delayed effective connectivity, characterizes the epileptogenic zone. This marker could be used to help tailor surgical resection limits after SEEG.

From cryogenic to on-scalp magnetoencephalography for the evaluation of paediatric epilepsy.

Magnetoencephalography (MEG) is a neurophysiological technique based on the detection of brain magnetic fields. Whole-head MEG systems typically house a few hundred sensors requiring cryogenic cooling in a rigid one-size-fits-all (commonly adult-sized) helmet to keep a thermal insulation space. This leads to an increased brain-to-sensor distance in children, because of their smaller head circumference, and decreased signal-to-noise ratio. MEG allows detection and localization of interictal and ictal epileptiform discharges, and pathological high frequency oscillations, as a part of the presurgical assessment of children with refractory focal epilepsy, where electroencephalography is not contributive. MEG can also map the eloquent cortex before surgical resection. MEG also provides insights into the physiopathology of both generalized and focal epilepsy. On-scalp recordings based on cryogenic-free sensors have demonstrated their use in the field of childhood focal epilepsy and should become a reference technique for diagnosing epilepsy in the paediatric population. WHAT THIS PAPER ADDS: Magnetoencephalography (MEG) contributes to the diagnosis and understanding of paediatric epilepsy. On-scalp MEG recordings demonstrate some advantages over cryogenic MEG.

Towards the automated detection of interictal epileptiform discharges with magnetoencephalography.

BACKGROUND: The analysis of clinical magnetoencephalography (MEG) in patients with epilepsy traditionally relies on visual identification of interictal epileptiform discharges (IEDs), which is time consuming and dependent on subjective criteria. NEW METHOD: Here, we explore the ability of Independent Components Analysis (ICA) and Hidden Markov Modeling (HMM) to automatically detect and localize IEDs. We tested our pipelines on resting-state MEG recordings from 10 school-aged children with (multi)focal epilepsy. RESULTS: In focal epilepsy patients, both pipelines successfully detected visually identified IEDs, but also revealed unidentified low-amplitude IEDs. Success was more mitigated in patients with multifocal epilepsy, as our automated pipeline missed IED activity associated with some foci-an issue that could be alleviated by post-hoc manual selection of epileptiform ICs or HMM states. COMPARISON WITH EXISTING METHODS: We compared our results with visual IED detection by an experienced clinical magnetoencephalographer, getting heightened sensitivity and requiring minimal input from clinical practitioners. CONCLUSIONS: IED detection based on ICA or HMM represents an efficient way to identify IED localization and timing. The development of these automatic IED detection algorithms provide a step forward in clinical MEG practice by decreasing the duration of MEG analysis and enhancing its sensitivity.

Tri-axial rubidium and helium optically pumped magnetometers for on-scalp magnetoencephalography recording of interictal epileptiform discharges: a case study.

Cryogenic magnetoencephalography (MEG) enhances the presurgical assessment of refractory focal epilepsy (RFE). Optically pumped magnetometers (OPMs) are cryogen-free sensors that enable on-scalp MEG recordings. Here, we investigate the application of tri-axial OPMs [87Rb (Rb-OPM) and 4He gas (He-OPM)] for the detection of interictal epileptiform discharges (IEDs). IEDs were recorded simultaneously with 4 tri-axial Rb- and 4 tri-axial He-OPMs in a child with RFE. IEDs were identified visually, isolated from magnetic background noise using independent component analysis (ICA) and were studied following their optimal magnetic field orientation thanks to virtual sensors. Most IEDs (>1,000) were detectable by both He- and Rb-OPM recordings. IEDs were isolated by ICA and the resulting magnetic field oriented mostly tangential to the scalp in Rb-OPMs and radial in He-OPMs. Likely due to differences in sensor locations, the IED amplitude was higher with Rb-OPMs. This case study shows comparable ability of Rb-OPMs and He-OPMs to detect IEDs and the substantial benefits of triaxial OPMs to detect IEDs from different sensor locations. Tri-axial OPMs allow to maximize spatial brain sampling for IEDs detection with a limited number of sensors.

Diagnostic and therapeutic approaches in refractory insular epilepsy.

Due to heterogenous seizure semiology and poor contribution of scalp electroencephalography (EEG) signals, insular epilepsy requires use of the appropriate diagnostic tools for its diagnosis and characterization. The deep location of the insula also presents surgical challenges. The aim of this article is to review the current diagnostic and therapeutic tools and their contribution to the management of insular epilepsy. Magnetic resonance imaging (MRI), isotopic imaging, neurophysiological imaging, and genetic testing should be used and interpretated with caution. Isotopic imaging and scalp EEG have demonstrated a lower value in epilepsy from insular compared to temporal origin, which increases the interest of functional MRI and magnetoencephalography. Intracranial recording with stereo-electroencephalography (SEEG) is often required. The insular cortex, being highly connected and deeply located under highly functional areas, is difficult to reach, and its ablative surgery raises functional issues. Tailored resection based on SEEG or alternative curative treatments, such as radiofrequency thermocoagulation, laser interstitial thermal therapy, or stereotactic radiosurgery, have produced encouraging results. The management of insular epilepsy has benefited from major advances in the last years. Perspectives for diagnostic and therapeutic procedures will contribute to better management of this complex form of epilepsy.

On-Scalp Optically Pumped Magnetometers versus Cryogenic Magnetoencephalography for Diagnostic Evaluation of Epilepsy in School-aged Children.

Background Magnetoencephalography (MEG) is an established method used to detect and localize focal interictal epileptiform discharges (IEDs). Current MEG systems house hundreds of cryogenic sensors in a rigid, one-size-fits-all helmet, which results in several limitations, particularly in children. Purpose To determine if on-scalp MEG based on optically pumped magnetometers (OPMs) alleviates the main limitations of cryogenic MEG. Materials and Methods In this prospective single-center study conducted in a tertiary university teaching hospital, participants underwent cryogenic (102 magnetometers, 204 planar gradiometers) and on-scalp (32 OPMs) MEG. The two modalities for the detection and localization of IEDs were compared. The t test was used to compare IED amplitude and signal-to-noise ratio (SNR). Distributed source modeling was performed on OPM-based and cryogenic MEG data. Results Five children (median age, 9.4 years [range, 5-11 years]; four girls) with self-limited idiopathic (n = 3) or refractory (n = 2) focal epilepsy were included. IEDs were identified in all five children with comparable sensor topographies for both MEG devices. IED amplitudes were 2.3 (7.2 of 3.1) to 4.6 (3.2 of 0.7) times higher (P < .001) with on-scalp MEG, and the SNR was 27% (16.7 of 13.2) to 60% (12.8 of 8.0) higher (P value range: .001-.009) with on-scalp MEG in all but one participant (P = .93), whose head movements created pronounced motion artifacts. The neural source of averaged IEDs was located at approximately 5 mm (n = 3) or higher (8.3 mm, n = 1; 15.6 mm, n = 1) between on-scalp and cryogenic MEG. Conclusion Despite the limited number of sensors and scalp coverage, on-scalp magnetoencephalography (MEG) based on optically pumped magnetometers helped detect interictal epileptiform discharges in school-aged children with epilepsy with a higher amplitude, higher signal-to-noise ratio, and similar localization value compared with conventional cryogenic MEG. Online supplemental material is available for this article. © RSNA, 2022 See also the editorial by Widjaja in this issue.

Ictal EEG source imaging and connectivity to localize the seizure onset zone in extratemporal lobe epilepsy.

PURPOSE: To evaluate the yield of Functional Connectivity (FC) in addition to low-density ictal Electrical Source Imaging (ESI) in extratemporal lobe epilepsy (ETLE), using an automated algorithm for analysis. METHOD: Long-term EEG monitoring of consecutive ETLE patients who underwent surgery was reviewed by epileptologists, and seizure onsets characterized by rhythmical activity were identified. A spectrogram-based algorithm was developed to select objectively the parameters of ESI analysis. Two methods for SOZ localization were compared: i) ESI power, based on LORETA exclusively; ii) ESI + FC, including a Granger causality-based connectivity analysis. Results were determined at a sublobar level. The resection zone, in relation to 1-year follow-up surgical outcome, was considered as reference standard for diagnostic accuracy analyses. RESULTS: Ninety-four seizures from 24 patients were analyzed. At seizure-level, ESI power showed 36 % sensitivity and 72 % specificity (accuracy: 45 %). ESI + FC significantly improved the accuracy, with 52 % sensitivity and 84 % specificity (accuracy: 61 %, p = 0.04). Results of ESI + FC were equally valuable in patients with lateralized or bilateral/generalized visual interpretation of ictal EEG. In a patient level sub-analysis, upon blinded clinical interpretation, ESI + FC showed a correct localization in 67 % of patients and substantial inter-rater agreement (kappa = 0.64), against 27 % achieved by ESI power, with fair inter-rater agreement (kappa = 0.37). CONCLUSION: FC significantly improves SOZ localization compared to ESI solely in ETLE. Ictal ESI + FC could represent a novel option in the armamentarium of presurgical evaluation, aiding also in patients with visually non-localizable scalp ictal EEG. Prospective studies evaluating the clinical added value of automated low-density ictal ESI may be justified.