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.

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This study suggests that ultra high field imaging is advantageous in demonstrating detailed structural anatomy of MS lesions. 7T T2* imaging can be used in the future to investigate the pathogenesis of MS lesions. The potential for ultra high field imaging to discriminate between MS white matter lesions and microangiopathic lesions warrants further investigation as this would represent a clinically useful application.

Frequency-specific oscillations and phase-coupling of neuronal populations have been proposed as an essential mechanism for the coordination of activity between brain areas during cognitive tasks. To provide an effective substrate for cognitive function, we reasoned that ongoing functional brain networks should also be able to reorganise and coordinate in a similar manner. To test this hypothesis, we use a novel method for identifying repeating patterns of large-scale phase-coupling network dynamics, and show that resting networks in magnetoencephalography are well characterised by visits to shortlived transient brain states, with spatially distinct power and phase-coupling in specific frequency bands. Brain states were identified for sensory, motor networks and higher-order cognitive networks; the latter include a posterior higher-order cognitive network in the alpha range (8-12Hz) and an anterior higher-order cognitive network in the delta/theta range (1-7Hz). Both higher-order cognitive networks exhibit especially high power and coherence, and contain brain areas corresponding to posterior and anterior subdivisions of the default mode network. Our results show that large-scale cortical phase-coupling networks operate in very specific frequency bands, possibly reflecting functional specialisation at different intrinsic timescales. 2015). However, the evidence for frequency specific phase-coupling in spontaneous activity at timescales associated with fast cognition is limited.Here, we propose that cortical activity at rest can be described by transient, intermittently reoccurring events in which large-scale networks activate with distinct spectral and phasecoupling features. To identify the possible presence of these events, we use a new analysis approach based on the Hidden Markov Model (HMM; Rabiner, 1989). For the first time, this allows for the identification of brain-wide networks (or brain states) characterised by specific patterns of power and phase-coupling connectivity, which, crucially, are spectrallyresolved (i.e. power and phase-coupling are defined as a function of frequency). These patterns are also temporally-resolved, meaning that the method provides a probabilistic estimation of when the different networks are active (see Fig. 1a). Notably, applying this approach to resting MEG recordings of healthy human subjects revealed the distinct temporal and spectral properties of anterior versus posterior regions of the default mode network. The joint description of the spectral, temporal and spatial properties of ongoing neuronal activity provides new insight into the large-scale circuit organization of the brain (Woolrich and Stephan, 2013).

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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.

Cortical lesions are prevalent in multiple sclerosis but are poorly detected using MRI. The double inversion recovery (DIR) sequence is increasingly used to explore the clinical relevance of cortical demyelination. Here we evaluate the agreement between imaging sequences at 3 Tesla (T) and 7T for the presence and appearance of individual multiple sclerosis cortical lesions. Eleven patients with demyelinating disease and eight healthy volunteers underwent MR imaging at 3T (fluid attenuated inversion recovery [FLAIR], DIR, and T 1 -weighted magnetization prepared rapid acquisition gradient echo [MP-RAGE] sequences) and 7T (T 1 -weighted MP-RAGE). There was good agreement between images for the presence of mixed cortical lesions (involving both gray and white matter). However, agreement between imaging sequences was less good for purely intracortical lesions. Even after retrospective analysis, 25% of cortical lesions could only be visualized on a single MRI sequence. Several DIR hyperintensities thought to represent cortical lesions were found to correspond to signal arising from extracortical blood vessels. High-resolution 7T imaging appeared useful for confidently classifying the location of lesions in relation to the cortical/subcortical boundary. We conclude that DIR, FLAIR, and MP-RAGE imaging sequences appear to provide complementary information during the detection of multiple sclerosis cortical lesions. High resolution 7T imaging may facilitate anatomical localization of lesions in relation to the cortical boundary. GRAY MATTER BRAIN pathology was recognized in early neuropathological descriptions of multiple sclerosis (MS) but until recently it has received scant attention. Histology reveals cortical demyelinating lesions, a third of which simultaneously involve subcortical white matter. The finding of neuroaxonal injury within cortical lesions (1-3), along with the high frequency of cortical demyelination in the brains of patients with advanced disability (4), suggests that cortical demyelination could account for some chronic features of MS. The ability to address this hypothesis in vivo has been hindered so far by the low sensitivity of MRI to cortical demyelination.Postmortem MR imaging in MS patients has shown a 1.5 Tesla (T) fluid attenuated inversion recovery (FLAIR) sequence to detect 41% of mixed cortical/subcortical (C/SC) lesions and only 5% of intracortical (IC) lesions (5). The double inversion recovery (DIR) sequence uses two inversion pulses which null signal from both the normal-appearing white matter and the cerebrospinal fluid (CSF). DIR has been shown to increase the detection rate of intra-cortical lesions by 150% when compared with FLAIR in vivo (6-8), still predicting a sensitivity of only $12.5%. In vivo studies comparing FLAIR and DIR in patients with MS have analyzed total lesion number rather than investigating the agreement between sequences for individual cortical lesions (6,8).Factors precluding MRI visualization of cortical demyelination are likely to include the small volum...

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.