Trust and stakeholder perspectives on the implementation of AI tools in clinical radiology.

OBJECTIVES: To define requirements that condition trust in artificial intelligence (AI) as clinical decision support in radiology from the perspective of various stakeholders and to explore ways to fulfil these requirements. METHODS: Semi-structured interviews were conducted with twenty-five respondents-nineteen directly involved in the development, implementation, or use of AI applications in radiology and six working with AI in other areas of healthcare. We designed the questions to explore three themes: development and use of AI, professional decision-making, and management and organizational procedures connected to AI. The transcribed interviews were analysed in an iterative coding process from open coding to theoretically informed thematic coding. RESULTS: We identified four aspects of trust that relate to reliability, transparency, quality verification, and inter-organizational compatibility. These aspects fall under the categories of substantial and procedural requirements. CONCLUSIONS: Development of appropriate levels of trust in AI in healthcare is complex and encompasses multiple dimensions of requirements. Various stakeholders will have to be involved in developing AI solutions for healthcare and radiology to fulfil these requirements. CLINICAL RELEVANCE STATEMENT: For AI to achieve advances in radiology, it must be given the opportunity to support, rather than replace, human expertise. Support requires trust. Identification of aspects and conditions for trust allows developing AI implementation strategies that facilitate advancing the field. KEY POINTS: • Dimensions of procedural and substantial demands that need to be fulfilled to foster appropriate levels of trust in AI in healthcare are conditioned on aspects related to reliability, transparency, quality verification, and inter-organizational compatibility. •Creating the conditions for trust to emerge requires the involvement of various stakeholders, who will have to compensate the problem's inherent complexity by finding and promoting well-defined solutions.

On-scalp MEG SQUIDs are sensitive to early somatosensory activity unseen by conventional MEG.

Magnetoencephalography (MEG) has a unique capacity to resolve the spatio-temporal development of brain activity from non-invasive measurements. Conventional MEG, however, relies on sensors that sample from a distance (20-40 â€‹mm) to the head due to thermal insulation requirements (the MEG sensors function at 4 â€‹K in a helmet). A gain in signal strength and spatial resolution may be achieved if sensors are moved closer to the head. Here, we report a study comparing measurements from a seven-channel on-scalp SQUID MEG system to those from a conventional (in-helmet) SQUID MEG system. We compared the spatio-temporal resolution between on-scalp and conventional MEG by comparing the discrimination accuracy for neural activity patterns resulting from stimulating five different phalanges of the right hand. Because of proximity and sensor density differences between on-scalp and conventional MEG, we hypothesized that on-scalp MEG would allow for a more high-resolved assessment of these activity patterns, and therefore also a better classification performance in discriminating between neural activations from the different phalanges. We observed that on-scalp MEG provided better classification performance during an early post-stimulus period (10-20 â€‹ms). This corresponded to the electroencephalographic (EEG) component P16/N16 and was an unexpected observation as this component is usually not observed in conventional MEG. This finding shows that on-scalp MEG enables a richer registration of the cortical signal, indicating a sensitivity to what are potentially sources in the thalamo-cortical radiation. We had originally expected that on-scalp MEG would provide better classification accuracy based on activity in proximity to the P60m component compared to conventional MEG. This component indeed allowed for the best classification performance for both MEG systems (60-75%, chance 50%). However, we did not find that on-scalp MEG allowed for better classification than conventional MEG at this latency. We suggest that this absence of differences is due to the limited sensor coverage in the recording, in combination with our strategy for positioning the on-scalp MEG sensors. We show how the current sensor coverage may have limited our chances to register the necessary between-phalange source field dissimilarities for fair hypothesis testing, an approach we otherwise believe to be useful for future benchmarking measurements.

On-scalp MEG sensor localization using magnetic dipole-like coils: A method for highly accurate co-registration.

Source modelling in magnetoencephalography (MEG) requires precise co-registration of the sensor array and the anatomical structure of the measured individual's head. In conventional MEG, the positions and orientations of the sensors relative to each other are fixed and known beforehand, requiring only localization of the head relative to the sensor array. Since the sensors in on-scalp MEG are positioned on the scalp, locations of the individual sensors depend on the subject's head shape and size. The positions and orientations of on-scalp sensors must therefore be measured at every recording. This can be achieved by inverting conventional head localization, localizing the sensors relative to the head - rather than the other way around. In this study we present a practical method for localizing sensors using magnetic dipole-like coils attached to the subject's head. We implement and evaluate the method in a set of on-scalp MEG recordings using a 7-channel on-scalp MEG system based on high critical temperature superconducting quantum interference devices (high-Tc SQUIDs). The method allows individually localizing the sensor positions, orientations, and responsivities with high accuracy using only a short averaging time (≤ 2 â€‹mm, < 3° and < 3%, respectively, with 1-s averaging), enabling continuous sensor localization. Calibrating and jointly localizing the sensor array can further improve the accuracy of position and orientation (< 1 â€‹mm and < 1°, respectively, with 1-s coil recordings). We demonstrate source localization of on-scalp recorded somatosensory evoked activity based on co-registration with our method. Equivalent current dipole fits of the evoked responses corresponded well (within 4.2 â€‹mm) with those based on a commercial, whole-head MEG system.

Spatial suppression in visual motion perception is driven by inhibition: Evidence from MEG gamma oscillations.

Spatial suppression (SS) is a visual perceptual phenomenon that is manifest in a reduction of directional sensitivity for drifting high-contrast gratings whose size exceeds the center of the visual field. Gratings moving at faster velocities induce stronger SS. The neural processes that give rise to such size- and velocity-dependent reductions in directional sensitivity are currently unknown, and the role of surround inhibition is unclear. In magnetoencephalogram (MEG), large high-contrast drifting gratings induce a strong gamma response (GR), which also attenuates with an increase in the gratings' velocity. It has been suggested that the slope of this GR attenuation is mediated by inhibitory interactions in the primary visual cortex. Herein, we investigate whether SS is related to this inhibitory-based MEG measure. We evaluated SS and GR in two independent samples of participants: school-age boys and adult women. The slope of GR attenuation predicted inter-individual differences in SS in both samples. Test-retest reliability of the neuro-behavioral correlation was assessed in the adults, and was high between two sessions separated by several days or weeks. Neither frequencies nor absolute amplitudes of the GRs correlated with SS, which highlights the functional relevance of velocity-related changes in GR magnitude caused by augmentation of incoming input. Our findings provide evidence that links the psychophysical phenomenon of SS to inhibitory-based neural responses in the human primary visual cortex. This supports the role of inhibitory interactions as an important underlying mechanism for spatial suppression.

Characterizing hippocampal dynamics with MEG: A systematic review and evidence-based guidelines.

The hippocampus, a hub of activity for a variety of important cognitive processes, is a target of increasing interest for researchers and clinicians. Magnetoencephalography (MEG) is an attractive technique for imaging spectro-temporal aspects of function, for example, neural oscillations and network timing, especially in shallow cortical structures. However, the decrease in MEG signal-to-noise ratio as a function of source depth implies that the utility of MEG for investigations of deeper brain structures, including the hippocampus, is less clear. To determine whether MEG can be used to detect and localize activity from the hippocampus, we executed a systematic review of the existing literature and found successful detection of oscillatory neural activity originating in the hippocampus with MEG. Prerequisites are the use of established experimental paradigms, adequate coregistration, forward modeling, analysis methods, optimization of signal-to-noise ratios, and protocol trial designs that maximize contrast for hippocampal activity while minimizing those from other brain regions. While localizing activity to specific sub-structures within the hippocampus has not been achieved, we provide recommendations for improving the reliability of such endeavors.

Neural gain control measured through cortical gamma oscillations is associated with sensory sensitivity.

Gamma oscillations facilitate information processing by shaping the excitatory input/output of neuronal populations. Recent studies in humans and nonhuman primates have shown that strong excitatory drive to the visual cortex leads to suppression of induced gamma oscillations, which may reflect inhibitory-based gain control of network excitation. The efficiency of the gain control measured through gamma oscillations may in turn affect sensory sensitivity in everyday life. To test this prediction, we assessed the link between self-reported sensitivity and changes in magneto-encephalographic gamma oscillations as a function of motion velocity of high-contrast visual gratings. The induced gamma oscillations increased in frequency and decreased in power with increasing stimulation intensity. As expected, weaker suppression of the gamma response correlated with sensory hypersensitivity. Robustness of this result was confirmed by its replication in the two samples: neurotypical subjects and people with autism, who had generally elevated sensory sensitivity. We conclude that intensity-related suppression of gamma response is a promising biomarker of homeostatic control of the excitation-inhibition balance in the visual cortex.

From MEG to clinical EEG: evaluating a promising non-invasive estimator of defense-related muscle sympathetic nerve inhibition.

Sudden, unexpected stimuli can induce a transient inhibition of sympathetic vasoconstriction to skeletal muscle, indicating a link to defense reactions. This phenomenon is relatively stable within, but differs between, individuals. It correlates with blood pressure reactivity which is associated with cardiovascular risk. Inhibition of muscle sympathetic nerve activity (MSNA) is currently characterized through invasive microneurography in peripheral nerves. We recently reported that brain neural oscillatory power in the beta spectrum (beta rebound) recorded with magnetoencephalography (MEG) correlated closely with stimulus-induced MSNA inhibition. Aiming for a clinically more available surrogate variable reflecting MSNA inhibition, we investigated whether a similar approach with electroencephalography (EEG) can accurately gauge stimulus-induced beta rebound. We found that beta rebound shows similar tendencies to correlate with MSNA inhibition, but these EEG data lack the robustness of previous MEG results, although a correlation in the low beta band (13-20 Hz) to MSNA inhibition was found (p = 0.021). The predictive power is summarized in a receiver-operating-characteristics curve. The optimum threshold yielded sensitivity and false-positive rate of 0.74 and 0.33 respectively. A plausible confounder is myogenic noise. A more complicated experimental and/or analysis approach is required for differentiating MSNA-inhibitors from non-inhibitors based on EEG, as compared to MEG.

Gamma oscillations point to the role of primary visual cortex in atypical motion processing in autism.

Neurophysiological studies suggest that abnormal neural inhibition may explain a range of sensory processing differences in autism spectrum disorders (ASD). In particular, the impaired ability of people with ASD to visually discriminate the motion direction of small-size objects and their reduced perceptual suppression of background-like visual motion may stem from deficient surround inhibition within the primary visual cortex (V1) and/or its atypical top-down modulation by higher-tier cortical areas. In this study, we estimate the contribution of abnormal surround inhibition to the motion-processing deficit in ASD. For this purpose, we used a putative correlate of surround inhibition-suppression of the magnetoencephalographic (MEG) gamma response (GR) caused by an increase in the drift rate of a large annular high-contrast grating. The motion direction discrimination thresholds for the gratings of different angular sizes (1° and 12°) were assessed in a separate psychophysical paradigm. The MEG data were collected in 42 boys with ASD and 37 typically developing (TD) boys aged 7-15 years. Psychophysical data were available in 33 and 34 of these participants, respectively. The results showed that the GR suppression in V1 was reduced in boys with ASD, while their ability to detect the direction of motion was compromised only in the case of small stimuli. In TD boys, the GR suppression directly correlated with perceptual suppression caused by increasing stimulus size, thus suggesting the role of the top-down modulations of V1 in surround inhibition. In ASD, weaker GR suppression was associated with the poor directional sensitivity to small stimuli, but not with perceptual suppression. These results strongly suggest that a local inhibitory deficit in V1 plays an important role in the reduction of directional sensitivity in ASD and that this perceptual deficit cannot be explained exclusively by atypical top-down modulation of V1 by higher-tier cortical areas.

Globally elevated excitation-inhibition ratio in children with autism spectrum disorder and below-average intelligence.

BACKGROUND: Altered neuronal excitation-inhibition (E-I) balance is strongly implicated in ASD. However, it is not known whether the direction and degree of changes in the E-I ratio in individuals with ASD correlates with intellectual disability often associated with this developmental disorder. The spectral slope of the aperiodic 1/f activity reflects the E-I balance at the scale of large neuronal populations and may uncover its putative alternations in individuals with ASD with and without intellectual disability. METHODS: Herein, we used magnetoencephalography (MEG) to test whether the 1/f slope would differentiate ASD children with average and below-average (< 85) IQ. MEG was recorded at rest with eyes open/closed in 49 boys with ASD aged 6-15 years with IQ ranging from 54 to 128, and in 49 age-matched typically developing (TD) boys. The cortical source activity was estimated using the beamformer approach and individual brain models. We then extracted the 1/f slope by fitting a linear function to the log-log-scale power spectra in the high-frequency range. RESULTS: The global 1/f slope averaged over all cortical sources demonstrated high rank-order stability between the two conditions. Consistent with previous research, it was steeper in the eyes-closed than in the eyes-open condition and flattened with age. Regardless of condition, children with ASD and below-average IQ had flatter slopes than either TD or ASD children with average or above-average IQ. These group differences could not be explained by differences in signal-to-noise ratio or periodic (alpha and beta) activity. LIMITATIONS: Further research is needed to find out whether the observed changes in E-I ratios are characteristic of children with below-average IQ of other diagnostic groups. CONCLUSIONS: The atypically flattened spectral slope of aperiodic activity in children with ASD and below-average IQ suggests a shift of the global E-I balance toward hyper-excitation. The spectral slope can provide an accessible noninvasive biomarker of the E-I ratio for making objective judgments about treatment effectiveness in people with ASD and comorbid intellectual disability.

Brain structural and functional correlates to defense-related inhibition of muscle sympathetic nerve activity in man.

An individual's blood pressure (BP) reactivity to stress is linked to increased risk of hypertension and cardiovascular disease. However, inter- and intra-individual BP variability makes understanding the coupling between stress, BP reactivity, and long-term outcomes challenging. Previous microneurographic studies of sympathetic signaling to muscle vasculature (i.e. muscle sympathetic nerve activity, MSNA) have established a neural predictor for an individual's BP reactivity during short-lasting stress. Unfortunately, this method is invasive, technically demanding, and time-consuming and thus not optimal for widespread use. Potential central nervous system correlates have not been investigated. We used MagnetoEncephaloGraphy and Magnetic Resonance Imaging to search for neural correlates to sympathetic response profiles within the central autonomic network and sensorimotor (Rolandic) regions in 20 healthy young males. The main correlates include (a) Rolandic beta rebound and an anterior cingulate cortex (ACC) response elicited by sudden stimulation and (b) cortical thickness in the ACC. Our findings highlight the involvement of the ACC in reactions to stress entailing peripheral sympathetic responses to environmental stimuli. The Rolandic response furthermore indicates a surprisingly strong link between somatosensory and autonomic processes. Our results thus demonstrate the potential in using non-invasive neuroimaging-based measures of stress-related MSNA reactions, previously assessed only using invasive microneurography.

Visual gamma oscillations predict sensory sensitivity in females as they do in males.

Gamma oscillations are driven by local cortical excitatory (E)-inhibitory (I) loops and may help to characterize neural processing involving excitatory-inhibitory interactions. In the visual cortex reliable gamma oscillations can be recorded with magnetoencephalography (MEG) in the majority of individuals, which makes visual gamma an attractive candidate for biomarkers of brain disorders associated with E/I imbalance. Little is known, however, about if/how these oscillations reflect individual differences in neural excitability and associated sensory/perceptual phenomena. The power of visual gamma response (GR) changes nonlinearly with increasing stimulation intensity: it increases with transition from static to slowly drifting high-contrast grating and then attenuates with further increase in the drift rate. In a recent MEG study we found that the GR attenuation predicted sensitivity to sensory stimuli in everyday life in neurotypical adult men and in men with autism spectrum disorders. Here, we replicated these results in neurotypical female participants. The GR enhancement with transition from static to slowly drifting grating did not correlate significantly with the sensory sensitivity measures. These findings suggest that weak velocity-related attenuation of the GR is a reliable neural concomitant of visual hypersensitivity and that the degree of GR attenuation may provide useful information about E/I balance in the visual cortex.

Additive effect of contrast and velocity suggests the role of strong excitatory drive in suppression of visual gamma response.

It is commonly acknowledged that gamma-band oscillations arise from interplay between neural excitation and inhibition; however, the neural mechanisms controlling the power of stimulus-induced gamma responses (GR) in the human brain remain poorly understood. A moderate increase in velocity of drifting gratings results in GR power enhancement, while increasing the velocity beyond some 'transition point' leads to GR power attenuation. We tested two alternative explanations for this nonlinear input-output dependency in the GR power. First, the GR power can be maximal at the preferable velocity/temporal frequency of motion-sensitive V1 neurons. This 'velocity tuning' hypothesis predicts that lowering contrast either will not affect the transition point or shift it to a lower velocity. Second, the GR power attenuation at high velocities of visual motion can be caused by changes in excitation/inhibition balance with increasing excitatory drive. Since contrast and velocity both add to excitatory drive, this 'excitatory drive' hypothesis predicts that the 'transition point' for low-contrast gratings would be reached at a higher velocity, as compared to high-contrast gratings. To test these alternatives, we recorded magnetoencephalography during presentation of low (50%) and high (100%) contrast gratings drifting at four velocities. We found that lowering contrast led to a highly reliable shift of the GR suppression transition point to higher velocities, thus supporting the excitatory drive hypothesis. No effects of contrast or velocity were found in the alpha-beta range. The results have implications for understanding the mechanisms of gamma oscillations and developing gamma-based biomarkers of disturbed excitation/inhibition balance in brain disorders.

A 7-Channel High-[Formula: see text] SQUID-Based On-Scalp MEG System.

OBJECTIVE: To present the technical design and demonstrate the feasibility of a multi-channel on-scalp magnetoencephalography (MEG) system based on high critical temperature (high-[Formula: see text]) superconducting quantum interference devices (SQUIDs). METHODS: We built a liquid nitrogen-cooled cryostat that houses seven YBCO SQUID magnetometers arranged in a dense, head-aligned array with minimal distance to the room-temperature environment for all sensors. We characterize the performance of this 7-channel system in terms of on-scalp MEG utilization and present recordings of spontaneous and evoked brain activity. RESULTS: The center-to-center spacing between adjacent SQUIDs is 12.0 and 13.4 mm and all SQUIDs are in the range of 1-3 mm of the head surface. The cryostat reaches a base temperature of  âˆ¼ 70 K and stays cold for 16 h with a single 0.9 L filling. The white noise levels of the magnetometers is 50-130 fT/Hz1/2 at 10 Hz and they show low sensor-to-sensor feedback flux crosstalk ( 0.6%). We demonstrate evoked fields from auditory stimuli and single-shot sensitivity to alpha modulation from the visual cortex. CONCLUSION: All seven channels in the system sensitively sample neuromagnetic fields with mm-scale scalp standoff distances. The hold time of the cryostat furthermore is sufficient for a day of recordings. As such, our multi-channel high-[Formula: see text] SQUID-based system meets the demands of on-scalp MEG. SIGNIFICANCE: The system presented here marks the first high-[Formula: see text] SQUID-based on-scalp MEG system with more than two channels. It enables us to further explore the benefits of on-scalp MEG in future recordings.

Characterization of Binding of Magnetic Nanoparticles to Rolling Circle Amplification Products by Turn-On Magnetic Assay.

The specific binding of oligonucleotide-tagged 100 nm magnetic nanoparticles (MNPs) to rolling circle products (RCPs) is investigated using our newly developed differential homogenous magnetic assay (DHMA). The DHMA measures ac magnetic susceptibility from a test and a control samples simultaneously and eliminates magnetic background signal. Therefore, the DHMA can reveal details of binding kinetics of magnetic nanoparticles at very low concentrations of RCPs. From the analysis of the imaginary part of the DHMA signal, we find that smaller MNPs in the particle ensemble bind first to the RCPs. When the RCP concentration increases, we observe the formation of agglomerates, which leads to lower number of MNPs per RCP at higher concentrations of RCPs. The results thus indicate that a full frequency range of ac susceptibility observation is necessary to detect low concentrations of target RCPs and a long amplification time is not required as it does not significantly increase the number of MNPs per RCP. The findings are critical for understanding the underlying microscopic binding process for improving the assay performance. They furthermore suggest DHMA is a powerful technique for dynamically characterizing the binding interactions between MNPs and biomolecules in fluid volumes.

Homogeneous Differential Magnetic Assay.

Assays are widely used for detection of various targets, including pathogens, drugs, and toxins. Homogeneous assays are promising for the realization of point-of-care diagnostics as they do not require separation, immobilization, or washing steps. For low concentrations of target molecules, the speed and sensitivity of homogeneous assays have hitherto been limited by slow binding kinetics, time-consuming amplification steps, and the presence of a high background signal. Here, we present a homogeneous differential magnetic assay that utilizes a differential magnetic readout that eliminates previous limitations of homogeneous assays. The assay uses a gradiometer sensor configuration combined with precise microfluidic sample handling. This enables simultaneous differential measurement of a positive test sample containing a synthesized Vibrio cholerae target and a negative control sample, which reduces the background signal and increases the readout speed. Very low concentrations of targets down to femtomolar levels are thus detectable without any additional amplification of the number of targets. Our homogeneous differential magnetic assay method opens new possibilities for rapid and highly sensitive diagnostics at the point of care.

Localizing on-scalp MEG sensors using an array of magnetic dipole coils.

Accurate estimation of the neural activity underlying magnetoencephalography (MEG) signals requires co-registration i.e., determination of the position and orientation of the sensors with respect to the head. In modern MEG systems, an array of hundreds of low-Tc SQUID sensors is used to localize a set of small, magnetic dipole-like (head-position indicator, HPI) coils that are attached to the subject's head. With accurate prior knowledge of the positions and orientations of the sensors with respect to one another, the HPI coils can be localized with high precision, and thereby the positions of the sensors in relation to the head. With advances in magnetic field sensing technologies, e.g., high-Tc SQUIDs and optically pumped magnetometers (OPM), that require less extreme operating temperatures than low-Tc SQUID sensors, on-scalp MEG is on the horizon. To utilize the full potential of on-scalp MEG, flexible sensor arrays are preferable. Conventional co-registration is impractical for such systems as the relative positions and orientations of the sensors to each other are subject-specific and hence not known a priori. Herein, we present a method for co-registration of on-scalp MEG sensors. We propose to invert the conventional co-registration approach and localize the sensors relative to an array of HPI coils on the subject's head. We show that given accurate prior knowledge of the positions of the HPI coils with respect to one another, the sensors can be localized with high precision. We simulated our method with realistic parameters and layouts for sensor and coil arrays. Results indicate co-registration is possible with sub-millimeter accuracy, but the performance strongly depends upon a number of factors. Accurate calibration of the coils and precise determination of the positions and orientations of the coils with respect to one another are crucial. Finally, we propose methods to tackle practical challenges to further improve the method.

Volume-amplified magnetic bioassay integrated with microfluidic sample handling and high-Tc SQUID magnetic readout.

A bioassay based on a high-Tc superconducting quantum interference device (SQUID) reading out functionalized magnetic nanoparticles (fMNPs) in a prototype microfluidic platform is presented. The target molecule recognition is based on volume amplification using padlock-probe-ligation followed by rolling circle amplification (RCA). The MNPs are functionalized with single-stranded oligonucleotides, which give a specific binding of the MNPs to the large RCA coil product, resulting in a large change in the amplitude of the imaginary part of the ac magnetic susceptibility. The RCA products from amplification of synthetic Vibrio cholera target DNA were investigated using our SQUID ac susceptibility system in microfluidic channel with an equivalent sample volume of 3 µl. From extrapolation of the linear dependence of the SQUID signal versus concentration of the RCA coils, it is found that the projected limit of detection for our system is about 1.0 × 105 RCA coils (0.2 × 10-18 mol), which is equivalent to 66 fM in the 3 µl sample volume. This ultra-high magnetic sensitivity and integration with microfluidic sample handling are critical steps towards magnetic bioassays for rapid detection of DNA and RNA targets at the point of care.

Input-dependent modulation of MEG gamma oscillations reflects gain control in the visual cortex.

Gamma-band oscillations arise from the interplay between neural excitation (E) and inhibition (I) and may provide a non-invasive window into the state of cortical circuitry. A bell-shaped modulation of gamma response power by increasing the intensity of sensory input was observed in animals and is thought to reflect neural gain control. Here we sought to find a similar input-output relationship in humans with MEG via modulating the intensity of a visual stimulation by changing the velocity/temporal-frequency of visual motion. In the first experiment, adult participants observed static and moving gratings. The frequency of the MEG gamma response monotonically increased with motion velocity whereas power followed a bell-shape. In the second experiment, on a large group of children and adults, we found that despite drastic developmental changes in frequency and power of gamma oscillations, the relative suppression at high motion velocities was scaled to the same range of values across the life-span. In light of animal and modeling studies, the modulation of gamma power and frequency at high stimulation intensities characterizes the capacity of inhibitory neurons to counterbalance increasing excitation in visual networks. Gamma suppression may thus provide a non-invasive measure of inhibitory-based gain control in the healthy and diseased brain.

Evaluation of realistic layouts for next generation on-scalp MEG: spatial information density maps.

While commercial magnetoencephalography (MEG) systems are the functional neuroimaging state-of-the-art in terms of spatio-temporal resolution, MEG sensors have not changed significantly since the 1990s. Interest in newer sensors that operate at less extreme temperatures, e.g., high critical temperature (high-T c) SQUIDs, optically-pumped magnetometers, etc., is growing because they enable significant reductions in head-to-sensor standoff (on-scalp MEG). Various metrics quantify the advantages of on-scalp MEG, but a single straightforward one is lacking. Previous works have furthermore been limited to arbitrary and/or unrealistic sensor layouts. We introduce spatial information density (SID) maps for quantitative and qualitative evaluations of sensor arrays. SID-maps present the spatial distribution of information a sensor array extracts from a source space while accounting for relevant source and sensor parameters. We use it in a systematic comparison of three practical on-scalp MEG sensor array layouts (based on high-T c SQUIDs) and the standard Elekta Neuromag TRIUX magnetometer array. Results strengthen the case for on-scalp and specifically high-T c SQUID-based MEG while providing a path for the practical design of future MEG systems. SID-maps are furthermore general to arbitrary magnetic sensor technologies and source spaces and can thus be used for design and evaluation of sensor arrays for magnetocardiography, magnetic particle imaging, etc.

Similarities and differences between on-scalp and conventional in-helmet magnetoencephalography recordings.

The development of new magnetic sensor technologies that promise sensitivities approaching that of conventional MEG technology while operating at far lower operating temperatures has catalysed the growing field of on-scalp MEG. The feasibility of on-scalp MEG has been demonstrated via benchmarking of new sensor technologies performing neuromagnetic recordings in close proximity to the head surface against state-of-the-art in-helmet MEG sensor technology. However, earlier work has provided little information about how these two approaches compare, or about the reliability of observed differences. Herein, we present such a comparison, based on recordings of the N20m component of the somatosensory evoked field as elicited by electric median nerve stimulation. As expected from the proximity differences between the on-scalp and in-helmet sensors, the magnitude of the N20m activation as recorded with the on-scalp sensor was higher than that of the in-helmet sensors. The dipole pattern of the on-scalp recordings was also more spatially confined than that of the conventional recordings. Our results furthermore revealed unexpected temporal differences in the peak of the N20m component. An analysis protocol was therefore developed for assessing the reliability of this observed difference. We used this protocol to examine our findings in terms of differences in sensor sensitivity between the two types of MEG recordings. The measurements and subsequent analysis raised attention to the fact that great care has to be taken in measuring the field close to the zero-line crossing of the dipolar field, since it is heavily dependent on the orientation of sensors. Taken together, our findings provide reliable evidence that on-scalp and in-helmet sensors measure neural sources in mostly similar ways.