Interference suppression techniques for OPM-based MEG: Opportunities and challenges.

One of the primary technical challenges facing magnetoencephalography (MEG) is that the magnitude of neuromagnetic fields is several orders of magnitude lower than interfering signals. Recently, a new type of sensor has been developed - the optically pumped magnetometer (OPM). These sensors can be placed directly on the scalp and move with the head during participant movement, making them wearable. This opens up a range of exciting experimental and clinical opportunities for OPM-based MEG experiments, including paediatric studies, and the incorporation of naturalistic movements into neuroimaging paradigms. However, OPMs face some unique challenges in terms of interference suppression, especially in situations involving mobile participants, and when OPMs are integrated with electrical equipment required for naturalistic paradigms, such as motion capture systems. Here we briefly review various hardware solutions for OPM interference suppression. We then outline several signal processing strategies aimed at increasing the signal from neuromagnetic sources. These include regression-based strategies, temporal filtering and spatial filtering approaches. The focus is on the practical application of these signal processing algorithms to OPM data. In a similar vein, we include two worked-through experiments using OPM data collected from a whole-head sensor array. These tutorial-style examples illustrate how the steps for suppressing external interference can be implemented, including the associated data and code so that researchers can try the pipelines for themselves. With the popularity of OPM-based MEG rising, there will be an increasing need to deal with interference suppression. We hope this practical paper provides a resource for OPM-based MEG researchers to build upon.

On-scalp MEG system utilizing an actively shielded array of optically-pumped magnetometers.

The spatial resolution of magnetoencephalography (MEG) can be increased from that of conventional SQUID-based systems by employing on-scalp sensor arrays of e.g. optically-pumped magnetometers (OPMs). However, OPMs reach sufficient sensitivity for neuromagnetic measurements only when operated in a very low absolute magnetic field of few nanoteslas or less, usually not reached in a typical magnetically shielded room constructed for SQUID-based MEG. Moreover, field drifts affect the calibration of OPMs. Static and dynamic suppression of interfering fields is thus necessary for good-quality neuromagnetic measurements with OPMs. Here, we describe an on-scalp MEG system that utilizes OPMs and external compensation coils that provide static and dynamic shielding against ambient fields. In a conventional two-layer magnetically shielded room, our coil system reduced the maximum remanent DC-field component within an 8-channel OPM array from 70 to less than 1 nT, enabling the sensors to operate in the sensitive spin exchange relaxation-free regime. When compensating field drifts below 4 Hz, a low-frequency shielding factor of 22 dB was achieved, which reduced the peak-to-peak drift from 1.3 to 0.4 nT and thereby the standard deviation of the sensor calibration from 1.7% to 0.5%. Without band-limiting the field that was compensated, a low-frequency shielding factor of 43 dB was achieved. We validated the system by measuring brain responses to electric stimulation of the median nerve. With dynamic shielding and digital interference suppression methods, single-trial somatosensory evoked responses could be detected. Our results advance the deployment of OPM-based on-scalp MEG in lighter magnetic shields.

Real-Time Tracking of Magnetoencephalographic Neuromarkers during a Dynamic Attention-Switching Task.

In the last few years, a large number of experiments have been focused on exploring the possibility of using non-invasive techniques, such as electroencephalography (EEG) and magnetoencephalography (MEG), to identify auditory-related neuromarkers which are modulated by attention. Results from several studies where participants listen to a story narrated by one speaker, while trying to ignore a different story narrated by a competing speaker, suggest the feasibility of extracting neuromarkers that demonstrate enhanced phase locking to the attended speech stream. These promising findings have the potential to be used in clinical applications, such as EEG-driven hearing aids. One major challenge in achieving this goal is the need to devise an algorithm capable of tracking these neuromarkers in real-time when individuals are given the freedom to repeatedly switch attention among speakers at will. Here we present an algorithm pipeline that is designed to efficiently recognize changes of neural speech tracking during a dynamic-attention switching task and to use them as an input for a near real-time state-space model that translates these neuromarkers into attentional state estimates with a minimal delay. This algorithm pipeline was tested with MEG data collected from participants who had the freedom to change the focus of their attention between two speakers at will. Results suggest the feasibility of using our algorithm pipeline to track changes of attention in near-real time in a dynamic auditory scene.

A 20-channel magnetoencephalography system based on optically pumped magnetometers.

We describe a multichannel magnetoencephalography (MEG) system that uses optically pumped magnetometers (OPMs) to sense the magnetic fields of the human brain. The system consists of an array of 20 OPM channels conforming to the human subject's head, a person-sized magnetic shield containing the array and the human subject, a laser system to drive the OPM array, and various control and data acquisition systems. We conducted two MEG experiments: auditory evoked magnetic field and somatosensory evoked magnetic field, on three healthy male subjects, using both our OPM array and a 306-channel Elekta-Neuromag superconducting quantum interference device (SQUID) MEG system. The described OPM array measures the tangential components of the magnetic field as opposed to the radial component measured by most SQUID-based MEG systems. Herein, we compare the results of the OPM- and SQUID-based MEG systems on the auditory and somatosensory data recorded in the same individuals on both systems.

Similarities and differences between on-scalp and conventional in-helmet magnetoencephalography recordings.

The development of new magnetic sensor technologies that promise sensitivities approaching that of conventional MEG technology while operating at far lower operating temperatures has catalysed the growing field of on-scalp MEG. The feasibility of on-scalp MEG has been demonstrated via benchmarking of new sensor technologies performing neuromagnetic recordings in close proximity to the head surface against state-of-the-art in-helmet MEG sensor technology. However, earlier work has provided little information about how these two approaches compare, or about the reliability of observed differences. Herein, we present such a comparison, based on recordings of the N20m component of the somatosensory evoked field as elicited by electric median nerve stimulation. As expected from the proximity differences between the on-scalp and in-helmet sensors, the magnitude of the N20m activation as recorded with the on-scalp sensor was higher than that of the in-helmet sensors. The dipole pattern of the on-scalp recordings was also more spatially confined than that of the conventional recordings. Our results furthermore revealed unexpected temporal differences in the peak of the N20m component. An analysis protocol was therefore developed for assessing the reliability of this observed difference. We used this protocol to examine our findings in terms of differences in sensor sensitivity between the two types of MEG recordings. The measurements and subsequent analysis raised attention to the fact that great care has to be taken in measuring the field close to the zero-line crossing of the dipolar field, since it is heavily dependent on the orientation of sensors. Taken together, our findings provide reliable evidence that on-scalp and in-helmet sensors measure neural sources in mostly similar ways.

Benchmarking for On-Scalp MEG Sensors.

OBJECTIVE: We present a benchmarking protocol for quantitatively comparing emerging on-scalp magnetoencephalography (MEG) sensor technologies to their counterparts in state-of-the-art MEG systems. METHODS: As a means of validation, we compare a high-critical-temperature superconducting quantum interference device (high Tc SQUID) with the low- Tc SQUIDs of an Elekta Neuromag TRIUX system in MEG recordings of auditory and somatosensory evoked fields (SEFs) on one human subject. RESULTS: We measure the expected signal gain for the auditory-evoked fields (deeper sources) and notice some unfamiliar features in the on-scalp sensor-based recordings of SEFs (shallower sources). CONCLUSION: The experimental results serve as a proof of principle for the benchmarking protocol. This approach is straightforward, general to various on-scalp MEG sensors, and convenient to use on human subjects. The unexpected features in the SEFs suggest on-scalp MEG sensors may reveal information about neuromagnetic sources that is otherwise difficult to extract from state-of-the-art MEG recordings. SIGNIFICANCE: As the first systematically established on-scalp MEG benchmarking protocol, magnetic sensor developers can employ this method to prove the utility of their technology in MEG recordings. Further exploration of the SEFs with on-scalp MEG sensors may reveal unique information about their sources.

A Non-Magnetic Rotating Disk Stimulator for the Study of Neuromagnetic Correlates of Sensorimotor Interaction.

Fine motor skills in humans require close interaction between the motor and the sensory systems. It is still not fully understood, how sensory feedback modulates motor commands. This is due to the fact, that there is no approach for investigating the sensorimotor cortical-interaction in sufficient detail. The fast and precise communication between the sensory and motor-systems requires measurements of cortical activity with high temporal and spatial resolution. Magnetoencephalography (MEG) is capable of both. Previously, we showed that sensory responses, can be observed by repetitive tactile stimulation. Further, motor cortex responses can be generated by periodical increase and decrease of muscle tone. Utilizing both observations we have designed an MEG and magnetic resonance imaging (MRI) compatible stimulator allowing for the study of brain activity related to sensorimotor integration. The stimulator consists of a rotating disk with an elevation such that subject senses with his finger the speed of the disk. With the force applied by the finger onto the disk, the subject can control its speed. During the experiment the subject is asked to keep the speed of the disk constant while the driving torque is systematically manipulated. This closed-loop design is especially useful to analyze the fast and continuous information flow between the two systems. In a single case pilot study using MEG, we could show that a detailed analysis of the sensorimotor-network is possible. In contrast to existing paradigms this setup allows separate time-locked analysis of the sensory- and motor-component independently and therefore the calculation of latency parameters for both systems. In the future this method will help to understand the interaction between the two systems in much greater detail.

Magnetoencephalography in the presurgical evaluation of epilepsy.

Magnetoencephalography (MEG) is an important tool in the presurgical evaluation of patients with medically refractory epilepsy. The appropriate utilization and interpretation of MEG studies can increase the proportion of patients who may be able to further pursue surgical evaluation, refine surgical planning, and potentially increase the probability of seizure freedom after surgery. The aim of this paper is to provide the reader with a comprehensive but accessible guide to MEG, with particular emphasis on acquiring a working knowledge of MEG analysis, identifying patient groups that are most likely to benefit, and clarifying the limitations of this technology.

Ocular and cardiac artifact rejection for real-time analysis in MEG.

BACKGROUND: Recently, magnetoencephalography (MEG) based real-time brain computing interfaces (BCI) have been developed to enable novel and promising methods for neuroscience research. It is well known that artifact rejection prior to source localization largely enhances the localization accuracy. However, many BCI approaches neglect real-time artifact removal due to its time consuming process. NEW METHOD: The method (referred to as ocular and cardiac artifact rejection for real-time analysis, OCARTA) is based on constrained independent component analysis (cICA), where a priori information of the underlying source signals is used to optimize and accelerate signal decomposition. Thereby, prior information is incorporated by using the subject's individual cardiac and ocular activity. The algorithm automatically uses different separation strategies depending on the underlying source activity. RESULTS: OCARTA was tested and applied to data from three different but most commonly used MEG systems (4D-Neuroimaging, VSM MedTech Inc. and Elekta Neuromag). Ocular and cardiac artifacts were effectively reduced within one iteration at a time delay of 1ms performed on a standard PC (Intel Core i5-2410M). COMPARISON WITH EXISTING METHODS: The artifact rejection results achieved with OCARTA are in line with the results reported for offline ICA-based artifact rejection methods. CONCLUSION: Due to the fast and subject-specific signal decomposition the new approach introduced here is capable of real-time ocular and cardiac artifact rejection.

Improving MEG performance with additional tangential sensors.

Recently, the signal space separation (SSS) method, based on the multipole expansion of the magnetic field, has become increasingly important in magnetoencephalography (MEG). Theoretical arguments and simulations suggest that increasing the asymmetry of the MEG sensor array from the traditional, rather symmetric geometry can significantly improve the performance of the method. To test this concept, we first simulated addition of tangentially oriented standard sensor elements to the existing 306-channel Elekta Neuromag sensor array, and evaluated and optimized the performance of the new sensor configuration. Based on the simulation results, we then constructed a prototype device with 18 additional tangential triple-sensor elements and a total of 360 channels. The experimental results from the prototype are largely in agreement with the simulations. In application of the spatial SSS method, the 360-channel device shows an approximately 100% increase in software shielding capability, while residual reconstruction noise of evoked responses is decreased by 20%. Further, the new device eliminates the need for regularization while applying the SSS method. In conclusion, we have demonstrated in practice the benefit of reducing the symmetry of the MEG array, without the need for a complete redesign.

Quantifying the contribution of video in combined video-magnetoencephalographic ictal recordings of epilepsy patients.

INTRODUCTION: Magnetoencephalography (MEG) measures magnetic fields generated by neuronal currents. MEG is complementary to EEG. Considerable body of evidence indicates that ictal MEG recordings can provide useful information for pre-surgical evaluation of epilepsy patients alongside the more established long-term ictal video-EEG. Ictal MEG is recorded in some epilepsy surgery centers. However, a wider adoption of ictal MEG is hampered by lack of tools for synchronized video-MEG recording similar to those of video-EEG. METHODS: We have augmented MEG with a synchronized behavioral video-recording system. To estimate its additional value in ictal recordings, we retrospectively analyzed recordings of 10 epilepsy patients with and without the video. RESULTS: In six patients out of ten, adding the video substantially changed the resulting interpretations. In all six cases the effect was considerable: the number of detected seizures changed by more than 50%. CONCLUSIONS: Synchronized video and audio recording capabilities are important for effective ictal MEG recordings of epilepsy patients.

Hybrid ultra-low-field MRI and magnetoencephalography system based on a commercial whole-head neuromagnetometer.

Ultra-low-field MRI uses microtesla fields for signal encoding and sensitive superconducting quantum interference devices for signal detection. Similarly, modern magnetoencephalography (MEG) systems use arrays comprising hundreds of superconducting quantum interference device channels to measure the magnetic field generated by neuronal activity. In this article, hybrid MEG-MRI instrumentation based on a commercial whole-head MEG device is described. The combination of ultra-low-field MRI and MEG in a single device is expected to significantly reduce coregistration errors between the two modalities, to simplify MEG analysis, and to improve MEG localization accuracy. The sensor solutions, MRI coils (including a superconducting polarizing coil), an optimized pulse sequence, and a reconstruction method suitable for hybrid MEG-MRI measurements are described. The performance of the device is demonstrated by presenting ultra-low-field-MR images and MEG recordings that are compared with data obtained with a 3T scanner and a commercial MEG device.

Slow brain activity (ISA/DC) detected by MEG.

Infraslow activity (ISA), direct coupled (DC), and direct current (DC) are the terms used to describe brain activity that occurs in frequencies below 0.1 Hz. Infraslow activity amplitude increase is also associated with epilepsy, traumatic brain injuries, strokes, tumors, and migraines and has been studied since the early 90s at the Henry Ford Hospital MEG Laboratory. We have used a DC-based magnetoencephalography (MEG) system to validate and characterize the ISA from animal models of cortical spreading depression thought to be the underlying mechanism of migraine and other cortical spreading depression-like events seen during ischemia, anoxia, and epilepsy. Magnetoencephalography characterizes these slow shifts easier than electroencephalography because there is no attenuation of these signals by the skull. In the current study, we report on ISA MEG signals of 12 patients with epilepsy in the preictal and postictal states. In the minutes just before the onset of a seizure, large-amplitude ISA MEG waveforms were detected, signaling the onset of the seizure. It is suggested that MEG assessment of ISA, in addition to activity in the conventional frequency band, can at times be useful in the lateralization of epileptic seizures.

Calibration of a multichannel MEG system based on the signal space separation method.

For an efficient use of multichannel MEG systems, an accurate sensor calibration is extremely important. This includes the knowledge of both channel sensitivities and channel arrangement, which can deviate from original system plans, e.g., because of thermal stresses. In this paper, we propose a new solution to the calibration of a multichannel MEG sensor array based on the signal space separation (SSS) method. It has been shown that an inaccurate knowledge of sensor calibration limits the performances of the SSS method, resulting in a mismatch between the measured neuromagnetic field and its SSS reconstruction. Given a set of known magnetic sources, we show that an objective function, which strongly depends on sensor geometry, can be derived from the principal angle between the measured vector signal and the SSS basis. Hence, the MEG sensor array calibration is carried out by minimizing the objective function through a standard large-scale optimization technique. Details on the magnetic sources and calibration process are presented here. Finally, an application to the calibration of the 153-channel whole-head MEG system installed at the University of Chieti is discussed.

Recording temporal lobe epileptic activity with MEG in a light-weight magnetic shield.

OBJECTIVE: To assess the interictal epileptic discharges (IEDs) detection rate of magnetoencephalography (MEG) recordings performed in a new light-weight magnetic shielding (LMSR) concept in a large group of consecutive patients with presumed mesiotemporal lobe epilepsy (MTLE). METHODS: Thirty-eight patients (23 women; age range: 6-63 years) with presumed MTLE were prospectively studied. MEG investigations were performed with the 306-channel Elekta Neuromag® MEG-system installed in a normal hospital environment into a LMSR (MaxShield, Elekta Oy). Equivalent current dipoles (ECD, g/% > 80%) corresponding to epileptic events were fitted to each patient's spherical head model at IEDs onset and peak and then superimposed on the patient's co-registered MRI. RESULTS: IEDs were observed in 26 out of 38 patients (68.4%). Temporal ECDs were mesial in 14 patients, anterior in 23 patients and posterior in 8 patients. Interestingly, in 6 patients, ECDs fitted at spike-onset were localized in the hippocampus while at the peak of the spike, they had an anterior temporal location. CONCLUSIONS: MEG using LMSR provides adequate signal to noise ratio (SNR) to allow reliable detection and localization of single epileptic abnormalities on continuous MEG data in 68% of patients with presumed MTLE. Moreover, mesial temporal epileptic sources were detected in 54% of patients with abnormal MEG. The SNR of MEG data acquired using the LMSR is therefore suitable for the non-invasive localization of epileptic foci in patients with MTLE. The use of LMSR, which are cheaper and smaller than conventional MSR, should facilitate the development of MEG in clinical environments.

Clinical magnetoencephalography for neurosurgery.

Noninvasive neuroimaging aids in surgical planning and in counseling patients about possible risks of surgery. Magnetoencephalography (MEG) performs the most common types of surgical planning that the neurosurgeon faces, including localization of epileptic discharges, determination of the hemispheric dominance of verbal processing, and the ability to locate eloquent cortex. MEG is most useful when it is combined with structural imaging, most commonly with structural magnetic resonance (MR) imaging and MR diffusion imaging. This article reviews the history of clinical MEG, introduces the basic concepts about the biophysics of MEG, and outlines the basic neurosurgical applications of MEG.

Functional Mapping with Simultaneous MEG and EEG.

We use magnetoencephalography (MEG) and electroencephalography (EEG) to locate and determine the temporal evolution in brain areas involved in the processing of simple sensory stimuli. We will use somatosensory stimuli to locate the hand somatosensory areas, auditory stimuli to locate the auditory cortices, visual stimuli in four quadrants of the visual field to locate the early visual areas. These type of experiments are used for functional mapping in epileptic and brain tumor patients to locate eloquent cortices. In basic neuroscience similar experimental protocols are used to study the orchestration of cortical activity. The acquisition protocol includes quality assurance procedures, subject preparation for the combined MEG/EEG study, and acquisition of evoked-response data with somatosensory, auditory, and visual stimuli. We also demonstrate analysis of the data using the equivalent current dipole model and cortically-constrained minimum-norm estimates. Anatomical MRI data are employed in the analysis for visualization and for deriving boundaries of tissue boundaries for forward modeling and cortical location and orientation constraints for the minimum-norm estimates.

The brain in time: insights from neuromagnetic recordings.

The millisecond time resolution of magnetoencephalography (MEG) is instrumental for investigating the brain basis of sensory processing, motor planning, cognition, and social interaction. We review the basic principles, recent progress, and future potential of MEG in noninvasive tracking of human brain activity. Cortical activation sequences from tens to hundreds of milliseconds can be followed during, e.g., perception, motor action, imitation, and language processing by recording both spontaneous and evoked brain signals. Moreover, tagging of sensory input can be used to reveal neuronal mechanisms of binaural interaction and perception of ambiguous images. The results support the emerging ideas of multiple, hierarchically organized temporal scales in human brain function. Instrumentation and data analysis methods are rapidly progressing, enabling attempts to decode the four-dimensional spatiotemporal signal patterns to reveal correlates of behavior and mental contents.

Measurement of neuromagnetic brain function in pre-school children with custom sized MEG.

Magnetoencephalography is a technique that detects magnetic fields associated with cortical activity [1]. The electrophysiological activity of the brain generates electric fields - that can be recorded using electroencephalography (EEG)- and their concomitant magnetic fields - detected by MEG. MEG signals are detected by specialized sensors known as superconducting quantum interference devices (SQUIDs). Superconducting sensors require cooling with liquid helium at -270 degrees C. They are contained inside a vacumm-insulated helmet called a dewar, which is filled with liquid. SQUIDS are placed in fixed positions inside the helmet dewar in the helium coolant, and a subject's head is placed inside the helmet dewar for MEG measurements. The helmet dewar must be sized to satisfy opposing constraints. Clearly, it must be large enough to fit most or all of the heads in the population that will be studied. However, the helmet must also be small enough to keep most of the SQUID sensors within range of the tiny cerebral fields that they are to measure. Conventional whole-head MEG systems are designed to accommodate more than 90% of adult heads. However adult systems are not well suited for measuring brain function in pre-school chidren whose heads have a radius several cm smaller than adults. The KIT-Macquarie Brain Research Laboratory at Macquarie University uses a MEG system custom sized to fit the heads of pre-school children. This child system has 64 first-order axial gradiometers with a 50 mm baseline[2] and is contained inside a magnetically-shielded room (MSR) together with a conventional adult-sized MEG system [3,4]. There are three main advantages of the customized helmet dewar for studying children. First, the smaller radius of the sensor configuration brings the SQUID sensors into range of the neuromagnetic signals of children's heads. Second, the smaller helmet allows full insertion of a child's head into the dewar. Full insertion is prevented in adult dewar helmets because of the smaller crown to shoulder distance in children. These two factors are fundamental in recording brain activity using MEG because neuromagnetic signals attenuate rapidly with distance. Third, the customized child helmet aids in the symmetric positioning of the head and limits the freedom of movement of the child's head within the dewar. When used with a protocol that aligns the requirements of data collection with the motivational and behavioral capacities of children, these features significantly facilitate setup, positioning, and measurement of MEG signals.

Measurement of brain function in pre-school children using a custom sized whole-head MEG sensor array.

OBJECTIVE: Conventional whole-head MEG systems have fixed sensor arrays designed to accommodate most adult heads. However arrays optimised for adult brain measurements are suboptimal for research with the significantly smaller heads of young children. We wished to measure brain activity in children using a novel whole-head MEG system custom sized to fit the heads of pre-school-aged children. METHODS: Auditory evoked fields were measured from seven 4-year-old children in a 64-channel KIT whole-head gradiometer MEG system. RESULTS: The fit of heads in the MEG helmet dewars, defined as the mean of sensor-to-head centre distances, were substantially better for children in the child helmet dewar than in the adult helmet dewar, and were similar to head fits obtained for adults in a conventional adult MEG system. Auditory evoked fields were successfully measured from all seven children and dipole source locations were computed. CONCLUSIONS: These results demonstrate the feasibility of routinely measuring neuromagnetic brain function in healthy, awake pre-school-aged children. SIGNIFICANCE: The advent of child-sized whole-head MEG systems opens new opportunities for the study of cognitive brain development in young children.