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.

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.

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.

Recent work has demonstrated that Optically Pumped Magnetometers (OPMs) can be utilised to create a wearable Magnetoencephalography (MEG) system that is motion robust. In this study, we use this system to map eloquent cortex using a clinically validated language lateralisation paradigm (covert verb generation: 120 trials, ∼10 min total duration) in healthy adults (n = 3). We show that it is possible to lateralise and localise language function on a case by case basis using this system. Specifically, we show that at a sensor and source level we can reliably detect a lateralising beta band (15-30 Hz) desynchronization in all subjects. This is the first study of human cognition using OPMs and not only highlights this technology's utility as tool for (developmental) cognitive neuroscience but also its potential to contribute to surgical planning via mapping of eloquent cortex, especially in young children.

Recently, we introduced a new 'GLM-beamformer' technique for MEG analysis that enables accurate localisation of both phase-locked and non-phase-locked neuromagnetic effects, and their representation as statistical parametric maps (SPMs). This provides a useful framework for comparison of the full range of MEG responses with fMRI BOLD results. This paper reports a 'proof of principle' study using a simple visual paradigm (static checkerboard). The five subjects each underwent both MEG and fMRI paradigms. We demonstrate, for the first time, the presence of a sustained (DC) field in the visual cortex, and its co-localisation with the visual BOLD response. The GLM-beamformer analysis method is also used to investigate the main non-phase-locked oscillatory effects: an event-related desynchronisation (ERD) in the alpha band (8-13 Hz) and an event-related synchronisation (ERS) in the gamma band (55-70 Hz). We show, using SPMs and virtual electrode traces, the spatio-temporal covariance of these effects with the visual BOLD response. Comparisons between MEG and fMRI data sets generally focus on the relationship between the BOLD response and the transient evoked response. Here, we show that the stationary field and changes in oscillatory power are also important contributors to the BOLD response, and should be included in future studies on the relationship between neuronal activation and the haemodynamic response.

This study shows that the spatial specificity of MEG beamformer estimates of electrical activity can be affected significantly by the way in which covariance estimates are calculated. We define spatial specificity as the ability to extract independent timecourse estimates of electrical brain activity from two separate brain locations in close proximity. Previous analytical and simulated results have shown that beamformer estimates are affected by narrowing the time frequency window in which covariance estimates are made. Here we build on this by both experimental validation of previous results, and investigating the effect of data averaging prior to covariance estimation. In appropriate circumstances, we show that averaging has a marked effect on spatial specificity. However the averaging process results in ill-conditioned covariance matrices, thus necessitating a suitable matrix regularisation strategy, an example of which is described. We apply our findings to an MEG retinotopic mapping paradigm. A moving visual stimulus is used to elicit brain activation at different retinotopic locations in the visual cortex. This gives the impression of a moving electrical dipolar source in the brain. We show that if appropriate beamformer optimisation is applied, the moving source can be tracked in the cortex. In addition to spatial reconstruction of the moving source, we show that timecourse estimates can be extracted from neighbouring locations of interest in the visual cortex. If appropriate methodology is employed, the sequential activation of separate retinotopic locations can be observed. The retinotopic paradigm represents an ideal platform to test the spatial specificity of source localisation strategies. We suggest that future comparisons of MEG source localisation techniques (e.g. beamformer, minimum norm, Bayesian) could be made using this retinotopic mapping paradigm.

Functional connectivity (FC) between brain regions is thought to be central to the way in which the brain processes information. Abnormal connectivity is thought to be implicated in a number of diseases. The ability to study FC is therefore a key goal for neuroimaging. Functional connectivity (fc) MRI has become a popular tool to make connectivity measurements but the technique is limited by its indirect nature. A multimodal approach is therefore an attractive means to investigate the electrodynamic mechanisms underlying hemodynamic connectivity. In this paper, we investigate resting state FC using fcMRI and magnetoencephalography (MEG). In fcMRI, we exploit the advantages afforded by ultra high magnetic field. In MEG we apply envelope correlation and coherence techniques to source space projected MEG signals. We show that beamforming provides an excellent means to measure FC in source space using MEG data. However, care must be taken when interpreting these measurements since cross talk between voxels in source space can potentially lead to spurious connectivity and this must be taken into account in all studies of this type. We show good spatial agreement between FC measured independently using MEG and fcMRI; FC between sensorimotor cortices was observed using both modalities, with the best spatial agreement when MEG data are filtered into the β band. This finding helps to reduce the potential confounds associated with each modality alone: while it helps reduce the uncertainties in spatial patterns generated by MEG (brought about by the ill posed inverse problem), addition of electrodynamic metric confirms the neural basis of fcMRI measurements. Finally, we show that multiple MEG based FC metrics allow the potential to move beyond what is possible using fcMRI, and investigate the nature of electrodynamic connectivity. Our results extend those from previous studies and add weight to the argument that neural oscillations are intimately related to functional connectivity and the BOLD response.

Magnetoencephalography (MEG) enables non-invasive real time characterization of brain activity. However, convincing demonstrations of signal contributions from deeper sources such as the hippocampus remain controversial and are made difficult by its depth, structural complexity and proximity to neocortex. Here, we demonstrate a method for quantifying hippocampal engagement probabilistically using simulated hippocampal activity and realistic anatomical and electromagnetic source modelling. We construct two generative models, one which supports neuronal current flow on the cortical surface, and one which supports neuronal current flow on both the cortical and hippocampal surface. Using Bayesian model comparison, we then infer which of the two models provides a more likely explanation of the dataset at hand. We also carry out a set of control experiments to rule out bias, including simulating medial temporal lobe sources to assess the risk of falsely positive results, and adding different types of displacements to the hippocampal portion of the mesh to test for anatomical specificity of the results. In addition, we test the robustness of this inference by adding co-registration error and sensor level noise. We find that the model comparison framework is sensitive to hippocampal activity when co-registration error is <3 mm and the sensor-level signal-to-noise ratio (SNR) is >-20 dB. These levels of co-registration error and SNR can now be achieved empirically using recently developed subject-specific head-casts.