Concurrent spinal and brain imaging with optically pumped magnetometers.

BACKGROUND: The spinal cord and its interactions with the brain are fundamental for movement control and somatosensation. However, brain and spinal electrophysiology in humans have largely been treated as distinct enterprises, in part due to the relative inaccessibility of the spinal cord. Consequently, there is a dearth of knowledge on human spinal electrophysiology, including the multiple pathologies that affect the spinal cord as well as the brain. NEW METHOD: Here we exploit recent advances in the development of wearable optically pumped magnetometers (OPMs) which can be flexibly arranged to provide coverage of both the spinal cord and the brain in relatively unconstrained environments. This system for magnetospinoencephalography (MSEG) measures both spinal and cortical signals simultaneously by employing custom-made scanning casts. RESULTS: We evidence the utility of such a system by recording spinal and cortical evoked responses to median nerve stimulation at the wrist. MSEG revealed early (10 - 15 ms) and late (>20 ms) responses at the spinal cord, in addition to typical cortical evoked responses (i.e., N20). COMPARISON WITH EXISTING METHODS: Early spinal evoked responses detected were in line with conventional somatosensory evoked potential recordings. CONCLUSION: This MSEG system demonstrates the novel ability for concurrent non-invasive millisecond imaging of brain and spinal cord.

Adaptive multipole models of optically pumped magnetometer data.

Multipole expansions have been used extensively in the Magnetoencephalography (MEG) literature for mitigating environmental interference and modelling brain signal. However, their application to Optically Pumped Magnetometer (OPM) data is challenging due to the wide variety of existing OPM sensor and array designs. We therefore explore how such multipole models can be adapted to provide stable models of brain signal and interference across OPM systems. Firstly, we demonstrate how prolate spheroidal (rather than spherical) harmonics can provide a compact representation of brain signal when sampling on the scalp surface with as few as 100 channels. We then introduce a type of orthogonal projection incorporating this basis set. The Adaptive Multipole Models (AMM), which provides robust interference rejection across systems, even in the presence of spatially structured nonlinearity errors (shielding factor is the reciprocal of the maximum fractional nonlinearity error). Furthermore, this projection is always stable, as it is an orthogonal projection, and will only ever decrease the white noise in the data. However, for array designs that are suboptimal for spatially separating brain signal and interference, this method can remove brain signal components. We contrast these properties with the more typically used multipole expansion, Signal Space Separation (SSS), which never reduces brain signal amplitude but is less robust to the effect of sensor nonlinearity errors on interference rejection and can increase noise in the data if the system is sub-optimally designed (as it is an oblique projection). We conclude with an empirical example utilizing AMM to maximize signal to noise ratio (SNR) for the stimulus locked neuronal response to a flickering visual checkerboard in a 128-channel OPM system and demonstrate up to 40 dB software shielding in real data.

Combining OPM and lesion mapping data for epilepsy surgery planning: a simulation study.

When planning for epilepsy surgery, multiple potential sites for resection may be identified through anatomical imaging. Magnetoencephalography (MEG) using optically pumped sensors (OP-MEG) is a non-invasive functional neuroimaging technique which could be used to help identify the epileptogenic zone from these candidate regions. Here we test the utility of a-priori information from anatomical imaging for differentiating potential lesion sites with OP-MEG. We investigate a number of scenarios: whether to use rigid or flexible sensor arrays, with or without a-priori source information and with or without source modelling errors. We simulated OP-MEG recordings for 1309 potential lesion sites identified from anatomical images in the Multi-centre Epilepsy Lesion Detection (MELD) project. To localise the simulated data, we used three source inversion schemes: unconstrained, prior source locations at centre of the candidate sites, and prior source locations within a volume around the lesion location. We found that prior knowledge of the candidate lesion zones made the inversion robust to errors in sensor gain, orientation and even location. When the reconstruction was too highly restricted and the source assumptions were inaccurate, the utility of this a-priori information was undermined. Overall, we found that constraining the reconstruction to the region including and around the participant's potential lesion sites provided the best compromise of robustness against modelling or measurement error.

Real-time, model-based magnetic field correction for moving, wearable MEG.

Most neuroimaging techniques require the participant to remain still for reliable recordings to be made. Optically pumped magnetometer (OPM) based magnetoencephalography (OP-MEG) however, is a neuroimaging technique which can be used to measure neural signals during large participant movement (approximately 1 m) within a magnetically shielded room (MSR) (Boto et al., 2018; Seymour et al., 2021). Nevertheless, environmental magnetic fields vary both spatially and temporally and OPMs can only operate within a limited magnetic field range, which constrains participant movement. Here we implement real-time updates to electromagnetic coils mounted on-board of the OPMs, to cancel out the changing background magnetic fields. The coil currents were chosen based on a continually updating harmonic model of the background magnetic field, effectively implementing homogeneous field correction (HFC) in real-time (Tierney et al., 2021). During a stationary, empty room recording, we show an improvement in very low frequency noise of 24 dB. In an auditory paradigm, during participant movement of up to 2 m within a magnetically shielded room, introduction of the real-time correction more than doubled the proportion of trials in which no sensor saturated recorded outside of a 50 cm radius from the optimally-shielded centre of the room. The main advantage of such model-based (rather than direct) feedback is that it could allow one to correct field components along unmeasured OPM axes, potentially mitigating sensor gain and calibration issues (Borna et al., 2022).

Enabling ambulatory movement in wearable magnetoencephalography with matrix coil active magnetic shielding.

The ability to collect high-quality neuroimaging data during ambulatory participant movement would enable a wealth of neuroscientific paradigms. Wearable magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs) has the potential to allow participant movement during a scan. However, the strict zero magnetic field requirement of OPMs means that systems must be operated inside a magnetically shielded room (MSR) and also require active shielding using electromagnetic coils to cancel residual fields and field changes (due to external sources and sensor movements) that would otherwise prevent accurate neuronal source reconstructions. Existing active shielding systems only compensate fields over small, fixed regions and do not allow ambulatory movement. Here we describe the matrix coil, a new type of active shielding system for OPM-MEG which is formed from 48 square unit coils arranged on two planes which can compensate magnetic fields in regions that can be flexibly placed between the planes. Through the integration of optical tracking with OPM data acquisition, field changes induced by participant movement are cancelled with low latency (25 ms). High-quality MEG source data were collected despite the presence of large (65 cm translations and 270° rotations) ambulatory participant movements.

Non-invasive measurements of ictal and interictal epileptiform activity using optically pumped magnetometers.

Magneto- and electroencephalography (MEG/EEG) are important techniques for the diagnosis and pre-surgical evaluation of epilepsy. Yet, in current cryogen-based MEG systems the sensors are offset from the scalp, which limits the signal-to-noise ratio (SNR) and thereby the sensitivity to activity from deep structures such as the hippocampus. This effect is amplified in children, for whom adult-sized fixed-helmet systems are typically too big. Moreover, ictal recordings with fixed-helmet systems are problematic because of limited movement tolerance and/or logistical considerations. Optically Pumped Magnetometers (OPMs) can be placed directly on the scalp, thereby improving SNR and enabling recordings during seizures. We aimed to demonstrate the performance of OPMs in a clinical population. Seven patients with challenging cases of epilepsy underwent MEG recordings using a 12-channel OPM-system and a 306-channel cryogen-based whole-head system: three adults with known deep or weak (low SNR) sources of interictal epileptiform discharges (IEDs), along with three children with focal epilepsy and one adult with frequent seizures. The consistency of the recorded IEDs across the two systems was assessed. In one patient the OPMs detected IEDs that were not found with the SQUID-system, and in two patients no IEDs were found with either system. For the other patients the OPM data were remarkably consistent with the data from the cryogenic system, noting that these were recorded in different sessions, with comparable SNRs and IED-yields overall. Importantly, the wearability of OPMs enabled the recording of seizure activity in a patient with hyperkinetic movements during the seizure. The observed ictal onset and semiology were in agreement with previous video- and stereo-EEG recordings. The relatively affordable technology, in combination with reduced running and maintenance costs, means that OPM-based MEG could be used more widely than current MEG systems, and may become an affordable alternative to scalp EEG, with the potential benefits of increased spatial accuracy, reduced sensitivity to volume conduction/field spread, and increased sensitivity to deep sources. Wearable MEG thus provides an unprecedented opportunity for epilepsy, and given its patient-friendliness, we envisage that it will not only be used for presurgical evaluation of epilepsy patients, but also for diagnosis after a first seizure.

A lightweight magnetically shielded room with active shielding.

Magnetically shielded rooms (MSRs) use multiple layers of materials such as MuMetal to screen external magnetic fields that would otherwise interfere with high precision magnetic field measurements such as magnetoencephalography (MEG). Optically pumped magnetometers (OPMs) have enabled the development of wearable MEG systems which have the potential to provide a motion tolerant functional brain imaging system with high spatiotemporal resolution. Despite significant promise, OPMs impose stringent magnetic shielding requirements, operating around a zero magnetic field resonance within a dynamic range of ± 5 nT. MSRs developed for OPM-MEG must therefore effectively shield external sources and provide a low remnant magnetic field inside the enclosure. Existing MSRs optimised for OPM-MEG are expensive, heavy, and difficult to site. Electromagnetic coils are used to further cancel the remnant field inside the MSR enabling participant movements during OPM-MEG, but present coil systems are challenging to engineer and occupy space in the MSR limiting participant movements and negatively impacting patient experience. Here we present a lightweight MSR design (30% reduction in weight and 40-60% reduction in external dimensions compared to a standard OPM-optimised MSR) which takes significant steps towards addressing these barriers. We also designed a 'window coil' active shielding system, featuring a series of simple rectangular coils placed directly onto the walls of the MSR. By mapping the remnant magnetic field inside the MSR, and the magnetic field produced by the coils, we can identify optimal coil currents and cancel the remnant magnetic field over the central cubic metre to just |B|= 670 ± 160 pT. These advances reduce the cost, installation time and siting restrictions of MSRs which will be essential for the widespread deployment of OPM-MEG.

Spherical harmonic based noise rejection and neuronal sampling with multi-axis OPMs.

In this study we explore the interference rejection and spatial sampling properties of multi-axis Optically Pumped Magnetometer (OPM) data. We use both vector spherical harmonics and eigenspectra to quantify how well an array can separate neuronal signal from environmental interference while adequately sampling the entire cortex. We found that triaxial OPMs have superb noise rejection properties allowing for very high orders of interference (L=6) to be accounted for while minimally affecting the neural space (2dB attenuation for a 60-sensor triaxial system). We show that at least 11th order (143 spatial degrees of freedom) irregular solid harmonics or 95 eigenvectors of the lead field are needed to model the neural space for OPM data (regardless of number of axes measured). This can be adequately sampled with 75-100 equidistant triaxial sensors (225-300 channels) or 200 equidistant radial channels. In other words, ordering the same number of channels in triaxial (rather than purely radial) configuration may give significant advantages not only in terms of external noise rejection but also by minimizing cost, weight and cross-talk.

Magnetic Field Mapping and Correction for Moving OP-MEG.

BACKGROUND: Optically pumped magnetometers (OPMs) have made moving, wearable magnetoencephalography (MEG) possible. The OPMs typically used for MEG require a low background magnetic field to operate, which is achieved using both passive and active magnetic shielding. However, the background magnetic field is never truly zero Tesla, and so the field at each of the OPMs changes as the participant moves. This leads to position and orientation dependent changes in the measurements, which manifest as low frequency artefacts in MEG data. OBJECTIVE: We model the spatial variation in the magnetic field and use the model to predict the movement artefact found in a dataset. METHODS: We demonstrate a method for modelling this field with a triaxial magnetometer, then show that we can use the same technique to predict the movement artefact in a real OPM-based MEG (OP-MEG) dataset. RESULTS: Using an 86-channel OP-MEG system, we found that this modelling method maximally reduced the power spectral density of the data by 27.8 ± 0.6 dB at 0 Hz, when applied over 5 s non-overlapping windows. CONCLUSION: The magnetic field inside our state-of-the art magnetically shielded room can be well described by low-order spherical harmonic functions. We achieved a large reduction in movement noise when we applied this model to OP-MEG data. SIGNIFICANCE: Real-time implementation of this method could reduce passive shielding requirements for OP-MEG recording and allow the measurement of low-frequency brain activity during natural participant movement.

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.

Using OPMs to measure neural activity in standing, mobile participants.

Optically pumped magnetometer-based magnetoencephalography (OP-MEG) can be used to measure neuromagnetic fields while participants move in a magnetically shielded room. Head movements in previous OP-MEG studies have been up to 20 cm translation and ∼30° rotation in a sitting position. While this represents a step-change over stationary MEG systems, naturalistic head movement is likely to exceed these limits, particularly when participants are standing up. In this proof-of-concept study, we sought to push the movement limits of OP-MEG even further. Using a 90 channel (45-sensor) whole-head OP-MEG system and concurrent motion capture, we recorded auditory evoked fields while participants were: (i) sitting still, (ii) standing up and still, and (iii) standing up and making large natural head movements continuously throughout the recording - maximum translation 120 cm, maximum rotation 198°. Following pre-processing, movement artefacts were substantially reduced but not eliminated. However, upon utilisation of a beamformer, the M100 event-related field localised to primary auditory regions. Furthermore, the event-related fields from auditory cortex were remarkably consistent across the three conditions. These results suggest that a wide range of movement is possible with current OP-MEG systems. This in turn underscores the exciting potential of OP-MEG for recording neural activity during naturalistic paradigms that involve movement (e.g. navigation), and for scanning populations who are difficult to study with stationary MEG (e.g. young children).

Testing covariance models for MEG source reconstruction of hippocampal activity.

Beamforming is one of the most commonly used source reconstruction methods for magneto- and electroencephalography (M/EEG). One underlying assumption, however, is that distant sources are uncorrelated and here we tested whether this is an appropriate model for the human hippocampal data. We revised the Empirical Bayesian Beamfomer (EBB) to accommodate specific a-priori correlated source models. We showed in simulation that we could use model evidence (as approximated by Free Energy) to distinguish between different correlated and uncorrelated source scenarios. Using group MEG data in which the participants performed a hippocampal-dependent task, we explored the possibility that the hippocampus or the cortex or both were correlated in their activity across hemispheres. We found that incorporating a correlated hippocampal source model significantly improved model evidence. Our findings help to explain why, up until now, the majority of MEG-reported hippocampal activity (typically making use of beamformers) has been estimated as unilateral.

Modelling optically pumped magnetometer interference in MEG as a spatially homogeneous magnetic field.

Here we propose that much of the magnetic interference observed when using optically pumped magnetometers for MEG experiments can be modeled as a spatially homogeneous magnetic field. We show that this approximation reduces sensor level variance and substantially improves statistical power. This model does not require knowledge of the underlying neuroanatomy nor the sensor positions. It only needs information about the sensor orientation. Due to the model's low rank there is little risk of removing substantial neural signal. However, we provide a framework to assess this risk for any sensor number, design or subject neuroanatomy. We find that the risk of unintentionally removing neural signal is reduced when multi-axis recordings are performed. We validated the method using a binaural auditory evoked response paradigm and demonstrated that removing the homogeneous magnetic field increases sensor level SNR by a factor of 3. Considering the model's simplicity and efficacy, we suggest that this homogeneous field correction can be a powerful preprocessing step for arrays of optically pumped magnetometers.

Mouth magnetoencephalography: A unique perspective on the human hippocampus.

Traditional magnetoencephalographic (MEG) brain imaging scanners consist of a rigid sensor array surrounding the head; this means that they are maximally sensitive to superficial brain structures. New technology based on optical pumping means that we can now consider more flexible and creative sensor placement. Here we explored the magnetic fields generated by a model of the human hippocampus not only across scalp but also at the roof of the mouth. We found that simulated hippocampal sources gave rise to dipolar field patterns with one scalp surface field extremum at the temporal lobe and a corresponding maximum or minimum at the roof of the mouth. We then constructed a fitted dental mould to accommodate an Optically Pumped Magnetometer (OPM). We collected data using a previously validated hippocampal-dependant task to test the empirical utility of a mouth-based sensor, with an accompanying array of left and right temporal lobe OPMs. We found that the mouth sensor showed the greatest task-related theta power change. We found that this sensor had a mild effect on the reconstructed power in the hippocampus (~10% change) but that coherence images between the mouth sensor and reconstructed source images showed a global maximum in the right hippocampus. We conclude that augmenting a scalp-based MEG array with sensors in the mouth shows unique promise for both basic scientists and clinicians interested in interrogating the hippocampus.

Pragmatic spatial sampling for wearable MEG arrays.

Several new technologies have emerged promising new Magnetoencephalography (MEG) systems in which the sensors can be placed close to the scalp. One such technology, Optically Pumped MEG (OP-MEG) allows for a scalp mounted system that provides measurements within millimetres of the scalp surface. A question that arises in developing on-scalp systems is: how many sensors are necessary to achieve adequate performance/spatial discrimination? There are many factors to consider in answering this question such as the signal to noise ratio (SNR), the locations and depths of the sources, density of spatial sampling, sensor gain errors (due to interference, subject movement, cross-talk, etc.) and, of course, the desired spatial discrimination. In this paper, we provide simulations which show the impact these factors have on designing sensor arrays for wearable MEG. While OP-MEG has the potential to provide high information content at dense spatial samplings, we find that adequate spatial discrimination of sources (< 1 cm) can be achieved with relatively few sensors (< 100) at coarse spatial samplings (~ 30 mm) at high SNR. After this point approximately 50 more sensors are required for every 1 mm improvement in spatial discrimination. Comparable discrimination for traditional cryogenic systems require more channels by these same metrics. We also show that sensor gain errors have the greatest impact on discrimination between deep sources at high SNR. Finally, we also examine the limitation that aliasing due to undersampling has on the effective SNR of on-scalp sensors.

Optically pumped magnetoencephalography in epilepsy.

We demonstrate the first use of Optically Pumped Magnetoencephalography (OP-MEG) in an epilepsy patient with unrestricted head movement. Current clinical MEG uses a traditional SQUID system, where sensors are cryogenically cooled and housed in a helmet in which the patient's head is fixed. Here, we use a different type of sensor (OPM), which operates at room temperature and can be placed directly on the patient's scalp, permitting free head movement. We performed OP-MEG recording in a patient with refractory focal epilepsy. OP-MEG-identified analogous interictal activity to scalp EEG, and source localized this activity to an appropriate brain region.

Author Correction: A tool for functional brain imaging with lifespan compliance.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A tool for functional brain imaging with lifespan compliance.

The human brain undergoes significant functional and structural changes in the first decades of life, as the foundations for human cognition are laid down. However, non-invasive imaging techniques to investigate brain function throughout neurodevelopment are limited due to growth in head-size with age and substantial head movement in young participants. Experimental designs to probe brain function are also limited by the unnatural environment typical brain imaging systems impose. However, developments in quantum technology allowed fabrication of a new generation of wearable magnetoencephalography (MEG) technology with the potential to revolutionise electrophysiological measures of brain activity. Here we demonstrate a lifespan-compliant MEG system, showing recordings of high fidelity data in toddlers, young children, teenagers and adults. We show how this system can support new types of experimental paradigm involving naturalistic learning. This work reveals a new approach to functional imaging, providing a robust platform for investigation of neurodevelopment in health and disease.

Balanced, bi-planar magnetic field and field gradient coils for field compensation in wearable magnetoencephalography.

To allow wearable magnetoencephalography (MEG) recordings to be made on unconstrained subjects the spatially inhomogeneous remnant magnetic field inside the magnetically shielded room (MSR) must be nulled. Previously, a large bi-planar coil system which produces uniform fields and field gradients was used for this purpose. Its construction presented a significant challenge, six distinct coils were wound on two 1.6 × 1.6 m2 planes. Here, we exploit shared coil symmetries to produce coils simultaneously optimised to generate homogenous fields and gradients. We show nulling performance comparable to that of a six-coil system is achieved with this three-coil system, decreasing the strongest field component Bx by a factor of 53, and the strongest gradient dBx/dz by a factor of 7. To allow the coils to be used in environments with temporally-varying magnetic interference a dynamic nulling system was developed with a shielding factor of 40 dB at 0.01 Hz. Reducing the number of coils required and incorporating dynamic nulling should allow for greater take-up of this technology. Interactions of the coils with the high-permeability walls of the MSR were investigated using a method of images approach. Simulations show a degrading of field uniformity which was broadly consistent with measured values. These effects should be incorporated into future designs.

Imaging the human hippocampus with optically-pumped magnetoencephalography.

Optically-pumped (OP) magnetometers allow magnetoencephalography (MEG) to be performed while a participant's head is unconstrained. To fully leverage this new technology, and in particular its capacity for mobility, the activity of deep brain structures which facilitate explorative behaviours such as navigation, must be detectable using OP-MEG. One such crucial brain region is the hippocampus. Here we had three healthy adult participants perform a hippocampal-dependent task - the imagination of novel scene imagery - while being scanned using OP-MEG. A conjunction analysis across these three participants revealed a significant change in theta power in the medial temporal lobe. The peak of this activated cluster was located in the anterior hippocampus. We repeated the experiment with the same participants in a conventional SQUID-MEG scanner and found similar engagement of the medial temporal lobe, also with a peak in the anterior hippocampus. These OP-MEG findings indicate exciting new opportunities for investigating the neural correlates of a range of crucial cognitive functions in naturalistic contexts including spatial navigation, episodic memory and social interactions.