Magnetoencephalography (MEG) allows the non-invasive measurement of brain activity at millisecond precision combined with localization of the underlying generators. So far, MEG-systems consisted of superconducting quantum interference devices (SQUIDS), which suffer from several limitations. Recent technological advances, however, have enabled the development of novel MEG-systems based on optically pumped magnetometers (OPMs), offering several advantages over conventional SQUID-MEG systems. Considering potential improvements in the measurement of neuronal signals as well as reduced operating costs, the application of OPM-MEG systems for clinical neuroscience and diagnostic settings is highly promising. Here we provide an overview of the current state-of-the art of OPM-MEG and its unique potential for translational neuroscience. First, we discuss the technological features of OPMs and benchmark OPM-MEG against SQUID-MEG and electroencephalography (EEG), followed by a summary of pioneering studies of OPMs in healthy populations. Key applications of OPM-MEG for the investigation of psychiatric and neurological conditions are then reviewed. Specifically, we suggest novel applications of OPM-MEG for the identification of biomarkers and circuit deficits in schizophrenia, dementias, movement disorders, epilepsy, and neurodevelopmental syndromes (autism spectrum disorder and attention deficit hyperactivity disorder). Finally, we give an outlook of OPM-MEG for translational neuroscience with a focus on remaining methodological and technical challenges.

The electrophysiological activities in the human body generate electric and magnetic fields that can be measured noninvasively by electrodes on the skin, or even, not requiring any contact, by magnetometers. This includes the measurement of electrical activity of brain, heart, muscles and nerves that can be measured in vivo and allows to analyze functional processes with high temporal resolution. To measure these extremely small magnetic biosignals, traditionally highly sensitive superconducting quantum-interference devices have been used, together with advanced magnetic shields. Recently, they have been complemented in usability by a new class of sensors, optically pumped magnetometers (OPMs). These quantum sensors offer a high sensitivity without requiring cryogenic temperatures, allowing the design of small and flexible sensors for clinical applications. In this letter, we describe the advantages of these upcoming OPMs in two exemplary applications that were recently carried out at Physikalisch-Technische Bundesanstalt (PTB): (1) magnetocardiography (MCG) recorded during exercise and (2) auditory-evoked fields registered by magnetoencephalography.

When participants are asked to reproduce an earlier presented duration, EEG recordings typically show a slow potential that develops over the fronto-central regions of the brain and is assumed to be generated in the supplementary motor area (SMA). This contingent negative variation (CNV) has been linked to anticipation, preparation and formation of temporal judgment (Macar, Vidal, and Casini, 1999, Experimental Brain Research, 125(3), 271-80). Although the interpretation of the CNV amplitude is problematic (Kononowicz and Van Rijn, (2011), Frontiers in Integrative Neuroscience, 5(48); Ng, Tobin, and Penney, 2011, Frontiers in Integrative Neuroscience, 5(77)), the observation of this slow potential is extremely robust, and thus one could assume that magnetic recordings of brain activity should show similar activity patterns. However, interval timing studies using durations shorter than one second did not provide unequivocal evidence as to whether CNV has a magnetic counterpart (CMV). As interval timing has been typically associated with durations longer than one second, participants in this study were presented intervals of 2, 3 or 4s that had to be reproduced in setup similar to the seminal work of Elbert et al. (1991, Psychophysiology, 28(6), 648-55) while co-recording EEG and MEG. The EEG data showed a clear CNV during the standard and the reproduction interval. In the reproduction interval the CNV steadily builds up from the onset of interval for both stimulus and response locked data. The MEG data did not show a CNV-resembling ramping of activity, but only showed a pre-movement magnetic field (preMMF) that originated from the SMA, occurring approximately 0.6s before the termination of the timed interval. These findings support the notion that signatures of timing are more straightforwardly measured using EEG, and show that the measured MEG signal from the SMA is constrained to the end of reproduction interval, before the voluntary movement. Moreover, we investigated a link between timing behavior and the early iCNV and late CNV amplitudes to evaluate the hypothesis that these amplitudes reflect the accumulation of temporal pulses. Larger iCNV amplitudes predicted shorter reproduced durations. This effect was more pronounced for the 2s interval reproduction, suggesting that preparatory strategies depend on the length of reproduced interval. Similarly to Elbert et al. (1991, Psychophysiology, 28(6), 648-55), longer reproductions were associated with smaller CNV amplitudes, both between conditions and across participants within the same condition. As the temporal accumulation hypothesis predicts the inverse, these results support the proposal by Van Rijn et al. (2011, Frontiers in Integrative Neuroscience, 5) that the CNV reflects other temporally driven processes such as temporal expectation and preparation rather than temporal accumulation itself.

Magnetoencephalography (MEG) is a neuroimaging technique that measures the magnetic fields of the brain outside of the head. In the past, the most suitable magnetometer for MEG was the superconducting quantum interference device (SQUID), but in recent years, a new type has also been used, the optically pumped magnetometer (OPM). OPMs can be configured to measure multiple directions of magnetic field simultaneously. This work explored whether combining multiple directions of the magnetic field lowers the source localization error of brain sources under various conditions of noise. We simulated dipolar-like sources for multiple configurations of both SQUID- and OPM-MEG systems. To test the performance of a given layout, we calculated the average signal-to-noise ratio and the root mean square of the simulated magnetic field; furthermore, we evaluated the performance of the dipole fit. The results showed that the field direction normal to the scalp yields a higher signal-to-noise ratio and that ambient noise has a much lower impact on its localization error; therefore, this is the optimal choice for source localization when only one direction of magnetic field can be measured. For a low number of OPMs, combining multiple field directions greatly improves the source localization results. Lastly, we showed that MEG sensors that can be placed closer to the brain are more suitable for localizing deeper sources.

The temporal relation between vascular and neuronal responses of the brain to external stimuli is not precisely known. For a better understanding of the neuro-vascular coupling changes in cerebral blood volume and oxygenation have to be measured simultaneously with neuronal currents. With this motivation modulation dc-magnetoencephalography was combined with multi-channel time-resolved near-infrared spectroscopy to simultaneously monitor neuronal and vascular parameters on a scale of seconds. Here, the technique is described, how magnetic and optical signals can be measured simultaneously. In a simple motor activation paradigm (alternating 30 s of finger movement with 30 s of rest for 40 min) both signals were recorded non-invasively over the motor cortex of eight subjects. The off-line averaged signals from both modalities showed distinct stimulation related changes. By plotting changes in oxy- or deoxyhaemoglobin as a function of magnetic field a characteristic trajectory was created, which was similar to a hysteresis loop. A parametric analysis allowed quantitative results regarding the timing of coupling: the vascular signal increased significantly slower than the neuronal signal.

Summary: Objectives : The study of neurovascular coupling greatly benefits from combined measurements of neuronal and vascular signals. Two-step signal processing is developed to extract parameters describing the coupling. Methods : Using a magnetometer in an extremely well shielded room a broadband magnetoencephalogram was simultaneously measured with time-resolved nearinfrared spectroscopy during a motor activity paradigm. The raw MEG and NIRS data were denoised separately using independent component analysis. Results : After averaging the resulting signals showed motor activity-related changes. The temporal correspondence between MEG and NIRS was assessed plotting a combined trajectory and calculating a crosscorrelation. Compared to the MEG signal, at movement onset the NIRS signal showed an onsetdelay in the range of seconds. Conclusions : Multi-variate signal pre-processing followed by temporal delay estimates demonstrated the extraction of neurovascular coupling parameters.