Wearable magnetoencephalography

Functional neuroimaging offers a means to understand brain function and dysfunction. Over decades, different technologies have been developed to provide a non-invasive measure of brain activity that could help us to better understand the mechanisms underlying human cognition. Magnetoencephalography (MEG) is one of these techniques which, over the past 30 years, has been increasingly contributing to neuroscientific studies giving insights into human brain electrophysiology, with excellent temporal resolution and surprisingly high spatial resolution. However, MEG hardware has limitations and it has only been in the past few years that alternative technologies have seen a rapid progress with an intent to overcome the drawbacks of conventional MEG devices. The main limitation of MEG systems is that they rely on superconducting quantum interference devices (SQUIDs) to measure magnetic fields outside the head. This means that they require cryogenic cooling and as a consequence, sensors are fixed in position in a one-size-fits-all helmet. A vacuum is maintained between the subject’s head and the detectors which limits the sensitivity of the measurement, and subjects must remain still in large cumbersome scanners. Advances in the field of quantum technologies mean that magnetic field sensors, such as optically-pumped magnetometers (OPMs), operating at room temperature, are now able to achieve sensitivities similar to that of SQUIDs. This means that room temperature magnetoencephalography (MEG), with a greatly increased flexibility of sensor placement, can now be considered. Furthermore, these new sensors can be placed directly on the scalp surface giving, theoretically, a large increase in the magnitude of the measured signal. In this thesis, we explore the advantages of multi-channel OPM systems using both simulations, and experimental measurements made using commercially available OPMs in combination with a 3D-printed helmet. With the incorporation of field-nulling technologies, we demonstrate a non-restrictive MEG system that could benefit many different participant cohorts, for example children. The results presented highlight the opportunity afforded by OPMs to generate uncooled, potentially low-cost, high sensitivity MEG systems which offer a step change compared to the current generation of cryogenic instrumentation

An introduction to nuclear space

This is a small book (48 pages) that contains a revised and extended version of the notes of seminar lectures given by Bessaga. The authors present a nice introduction to nuclear spaces (with all necessary preliminaries) based on Kolmogorov diameters. They consider only some of the most important topics of the theory of nuclear spaces, namely Kolmogorov diameters, nuclear operators, Mityagin's characterization of nuclear spaces, the theorem on absoluteness of bases in nuclear spaces, the uniqueness problem for bases (together with the theorem on quasiequivalence of regular bases), examples of nuclear Fréchet spaces without basis. Of course, many of the important topics in the theory of nuclear spaces are not even touched. Nevertheless, this book may be recommended to anyone who wants to study nuclear spaces, since it is practically independent of other sources and covers an essential part of the theory. Moreover, the authors do their best to help the reader: the proofs of all theorems are complete and the organization of the material is perfect

On the potential of a new generation of magnetometers for MEG: a beamformer simulation study

Magnetoencephalography (MEG) is a sophisticated tool which yields rich information on the spatial, spectral and temporal signatures of human brain function. Despite unique potential, MEG is limited by a low signal-to-noise ratio (SNR) which is caused by both the inherently small magnetic fields generated by the brain, and the scalp-to-sensor distance. The latter is limited in current systems due to a requirement for pickup coils to be cryogenically cooled. Recent work suggests that optically-pumped magnetometers (OPMs) might be a viable alternative to superconducting detectors for MEG measurement. They have the advantage that sensors can be brought to within ~4 mm of the scalp, thus offering increased sensitivity. Here, using simulations, we quantify the advantages of hypothetical OPM systems in terms of sensitivity, reconstruction accuracy and spatial resolution. Our results show that a multi-channel whole-head OPM system offers (on average) a fivefold improvement in sensitivity for an adult brain, as well as clear improvements in reconstruction accuracy and spatial resolution. However, we also show that such improvements depend critically on accurate forward models; indeed, the reconstruction accuracy of our simulated OPM system only outperformed that of a simulated superconducting system in cases where forward field error was less than 5%. Overall, our results imply that the realisation of a viable whole-head multi-channel OPM system could generate a step change in the utility of MEG as a means to assess brain electrophysiological activity in health and disease. However in practice, this will require both improved hardware and modelling algorithms

A Pilot Study of a Panel of Ocular Inflammation Biomarkers in Patients with Primary Sjögren’s Syndrome

Ocular diseases have a strong impact on individuals, the effects of which extend from milder visual impairment to blindness. Due to this and to their prevalence, these conditions constitute important health, social and economic challenges. Thus, improvements in their early detection and diagnosis will help dampen the impact of these conditions, both on patients and on healthcare systems alike. In this sense, identifying tear biomarkers could establish better non-invasive approaches to diagnose these diseases and to monitor responses to therapy. With this in mind, we developed a solid phase capture assay, based on antibody microarrays, to quantify S100A6, MMP-9 and CST4 in human tear samples, and we used these arrays to study tear samples from healthy controls and patients with Sjögren’s Syndrome, at times concomitant with rheumatoid arthritis. Our results point out that the detection of S100A6 in tear samples seems to be positively correlated to rheumatoid arthritis, consistent with the systemic nature of this autoinflammatory pathology. Thus, we provide evidence that antibody microarrays may potentially help diagnose certain pathologies, possibly paving the way for significant improvements in the future care of these patients.This research was funded by the Basque Government (BIKAINTEK, grant number 48-AF-W2-2019-00006), by the University of the Basque Country (PIFIND19/02, grant number 201900016247), and by ELKARTEK (KK-2019/00086) and MINECO-Retos (PID2019-111139RB-I00) grants to E.V., as well as by FISS-21-RD21/0002/0041 to A.A

Using optically-pumped magnetometers to measure magnetoencephalographic signals in the human cerebellum

KEY POINTS: The application of conventional cryogenic magnetoencephalography (MEG) to the study of cerebellar functions is highly limited because typical cryogenic sensor arrays are far away from the cerebellum and naturalistic movement is not allowed in the recording. A new generation of MEG using optically pumped magnetometers (OPMs) that can be worn on the head during movement has opened up an opportunity to image the cerebellar electrophysiological activity non-invasively. We use OPMs to record human cerebellar MEG signals elicited by air-puff stimulation to the eye. We demonstrate robust responses in the cerebellum. OPMs pave the way for studying the neurophysiology of the human cerebellum. ABSTRACT: We test the feasibility of an optically pumped magnetometer-based magnetoencephalographic (OP-MEG) system for the measurement of human cerebellar activity. This is to our knowledge the first study investigating the human cerebellar electrophysiology using optically pumped magnetometers. As a proof of principle, we use an air-puff stimulus to the eyeball in order to elicit cerebellar activity that is well characterized in non-human models. In three subjects, we observe an evoked component at approx. 50 ms post-stimulus, followed by a second component at approx. 85-115 ms post-stimulus. Source inversion localizes both components in the cerebellum, while control experiments exclude potential sources elsewhere. We also assess the induced oscillations, with time-frequency decompositions, and identify additional sources in the occipital lobe, a region expected to be active in our paradigm, and in the neck muscles. Neither of these contributes to the stimulus-evoked responses at 50-115 ms. We conclude that OP-MEG technology offers a promising way to advance the understanding of the information processing mechanisms in the human cerebellum

Data?driven model optimization for optically pumped magnetometer sensor arrays

© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc. Optically pumped magnetometers (OPMs) have reached sensitivity levels that make them viable portable alternatives to traditional superconducting technology for magnetoencephalography (MEG). OPMs do not require cryogenic cooling and can therefore be placed directly on the scalp surface. Unlike cryogenic systems, based on a well-characterised fixed arrays essentially linear in applied flux, OPM devices, based on different physical principles, present new modelling challenges. Here, we outline an empirical Bayesian framework that can be used to compare between and optimise sensor arrays. We perturb the sensor geometry (via simulation) and with analytic model comparison methods estimate the true sensor geometry. The width of these perturbation curves allows us to compare different MEG systems. We test this technique using simulated and real data from SQUID and OPM recordings using head-casts and scanner-casts. Finally, we show that given knowledge of underlying brain anatomy, it is possible to estimate the true sensor geometry from the OPM data themselves using a model comparison framework. This implies that the requirement for accurate knowledge of the sensor positions and orientations a priori may be relaxed. As this procedure uses the cortical manifold as spatial support there is no co-registration procedure or reliance on scalp landmarks

Optically pumped magnetometers: From quantum origins to multi-channel magnetoencephalography

Optically Pumped Magnetometers (OPMs) have emerged as a viable and wearable alternative to cryogenic, superconducting MEG systems. This new generation of sensors has the advantage of not requiring cryogenic cooling and as a result can be flexibly placed on any part of the body. The purpose of this review is to provide a neuroscience audience with the theoretical background needed to understand the physical basis for the signal observed by OPMs. Those already familiar with the physics of MRI and NMR should note that OPMs share much of the same theory as the operation of OPMs rely on magnetic resonance. This review establishes the physical basis for the signal equation for OPMs. We re-derive the equations defining the bounds on OPM performance and highlight the important trade-offs between quantities such as bandwidth, sensor size and sensitivity. These equations lead to a direct upper bound on the gain change due to cross-talk for a multi-channel OPM system

A new generation of magnetoencephalography: room temperature measurements using optically-pumped magnetometers

Advances in the field of quantum sensing mean that magnetic field sensors, operating at room temperature, are now able to achieve sensitivity similar to that of cryogenically cooled devices (SQUIDs). This means that room temperature magnetoencephalography (MEG), with a greatly increased flexibility of sensor placement can now be considered. Further, these new sensors can be placed directly on the scalp surface giving, theoretically, a large increase in the magnitude of the measured signal. Here, we present recordings made using a single optically-pumped magnetometer (OPM) in combination with a 3D-printed head-cast designed to accurately locate and orient the sensor relative to brain anatomy. Since our OPM is configured as a magnetometer it is highly sensitive to environmental interference. However, we show that this problem can be ameliorated via the use of simultaneous reference sensor recordings. Using median nerve stimulation, we show that the OPM can detect both evoked (phase-locked) and induced (non-phase-locked oscillatory) changes when placed over sensory cortex, with signals ~4 times larger than equivalent SQUID measurements. Using source modelling, we show that our system allows localisation of the evoked response to somatosensory cortex. Further, source-space modelling shows that, with 13 sequential OPM measurements, source-space signal-to-noise ratio (SNR) is comparable to that from a 271-channel SQUID system. Our results highlight the opportunity presented by OPMs to generate uncooled, potentially low-cost, high SNR MEG systems

Multi-channel whole-head OPM-MEG: Helmet design and a comparison with a conventional system

© 2020 The Authors Magnetoencephalography (MEG) is a powerful technique for functional neuroimaging, offering a non-invasive window on brain electrophysiology. MEG systems have traditionally been based on cryogenic sensors which detect the small extracranial magnetic fields generated by synchronised current in neuronal assemblies, however, such systems have fundamental limitations. In recent years, non-cryogenic quantum-enabled sensors, called optically-pumped magnetometers (OPMs), in combination with novel techniques for accurate background magnetic field control, have promised to lift those restrictions offering an adaptable, motion-robust MEG system, with improved data quality, at reduced cost. However, OPM-MEG remains a nascent technology, and whilst viable systems exist, most employ small numbers of sensors sited above targeted brain regions. Here, building on previous work, we construct a wearable OPM-MEG system with ‘whole-head’ coverage based upon commercially available OPMs, and test its capabilities to measure alpha, beta and gamma oscillations. We design two methods for OPM mounting; a flexible (EEG-like) cap and rigid (additively-manufactured) helmet. Whilst both designs allow for high quality data to be collected, we argue that the rigid helmet offers a more robust option with significant advantages for reconstruction of field data into 3D images of changes in neuronal current. Using repeat measurements in two participants, we show signal detection for our device to be highly robust. Moreover, via application of source-space modelling, we show that, despite having 5 times fewer sensors, our system exhibits comparable performance to an established cryogenic MEG device. While significant challenges still remain, these developments provide further evidence that OPM-MEG is likely to facilitate a step change for functional neuroimaging

Wearable neuroimaging: Combining and contrasting magnetoencephalography and electroencephalography

One of the most severe limitations of functional neuroimaging techniques, such as magnetoencephalography (MEG), is that participants must maintain a fixed head position during data acquisition. This imposes restrictions on the characteristics of the experimental cohorts that can be scanned and the experimental questions that can be addressed. For these reasons, the use of ‘wearable’ neuroimaging, in which participants can move freely during scanning, is attractive. The most successful example of wearable neuroimaging is electroencephalography (EEG), which employs lightweight and flexible instrumentation that makes it useable in almost any experimental setting. However, EEG has major technical limitations compared to MEG, and therefore the development of wearable MEG, or hybrid MEG/EEG systems, is a compelling prospect. In this paper, we combine and compare EEG and MEG measurements, the latter made using a new generation of optically-pumped magnetometers (OPMs). We show that these new second generation commercial OPMs, can be mounted on the scalp in an ‘EEG-like’ cap, enabling the acquisition of high fidelity electrophysiological measurements. We show that these sensors can be used in conjunction with conventional EEG electrodes, offering the potential for the development of hybrid MEG/EEG systems. We compare concurrently measured signals, showing that, whilst both modalities offer high quality data in stationary subjects, OPM-MEG measurements are less sensitive to artefacts produced when subjects move. Finally, we show using simulations that OPM-MEG offers a fundamentally better spatial specificity than EEG. The demonstrated technology holds the potential to revolutionise the utility of functional brain imaging, exploiting the flexibility of wearable systems to facilitate hitherto impractical experimental paradigms