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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. [ABSTRACT FROM AUTHOR]

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- ${T}_\text{c}$) 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 $\sim$ 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- ${T}_\text{c}$ SQUID-based system meets the demands of on-scalp MEG. Significance: The system presented here marks the first high- ${T}_\text{c}$ 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: We present a benchmarking protocol for quantitatively comparing emerging on-scalp magnetoencephalography (MEG) sensor technologies to their counterparts in state-of-the-art MEG systems. Methods: As a means of validation, we compare a high-critical-temperature superconducting quantum interference device (high $T_{{c}}$ SQUID) with the low-$T_{{c}}$ SQUIDs of an Elekta Neuromag TRIUX system in MEG recordings of auditory and somatosensory evoked fields (SEFs) on one human subject. Results: We measure the expected signal gain for the auditory-evoked fields (deeper sources) and notice some unfamiliar features in the on-scalp sensor-based recordings of SEFs (shallower sources). Conclusion: The experimental results serve as a proof of principle for the benchmarking protocol. This approach is straightforward, general to various on-scalp MEG sensors, and convenient to use on human subjects. The unexpected features in the SEFs suggest on-scalp MEG sensors may reveal information about neuromagnetic sources that is otherwise difficult to extract from state-of-the-art MEG recordings. Significance: As the first systematically established on-scalp MEG benchmarking protocol, magnetic sensor developers can employ this method to prove the utility of their technology in MEG recordings. Further exploration of the SEFs with on-scalp MEG sensors may reveal unique information about their sources. [ABSTRACT FROM AUTHOR]

Highlights: [•] We model low- and high-T c SQUID arrays in MEG recordings of neural activity in the brain. [•] We compare the total information available to these SQUID arrays. [•] An MEG system based on high-T c technology is capable of producing at least 40% more information than the state-of-the-art in low-T c MEG systems. [•] The gain in information provided by high-T c MEG technology is a result of the closer source-to-sensor standoff distance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We use functionalized iron oxide magnetic multi-core particles of 100 nm in size (hydrodynamic particle diameter) and AC susceptometry (ACS) methods to measure the binding reactions between the magnetic nanoparticles (MNPs) and bio-analyte products produced from DNA segments using the rolling circle amplification (RCA) method. We use sensitive induction detection techniques in order to measure the ACS response. The DNA is amplified via RCA to generate RCA coils with a specific size that is dependent on the amplification time. After about 75 min of amplification we obtain an average RCA coil diameter of about 1 µm. We determine a theoretical limit of detection (LOD) in the range of 11 attomole (corresponding to an analyte concentration of 55 fM for a sample volume of 200 µL) from the ACS dynamic response after the MNPs have bound to the RCA coils and the measured ACS readout noise. We also discuss further possible improvements of the LOD. [ABSTRACT FROM AUTHOR]

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  ∼ 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/Hz 1/2 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.

A bioassay based on a high- T c 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  μ l. 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 × 10 5 RCA coils (0.2 × 10 -18 mol), which is equivalent to 66 fM in the 3  μ l 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.

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.

Background: Magnetoencephalography (MEG) is a method of studying brain activity via recordings of the magnetic field generated by neural activity. Modern MEG systems employ an array of low critical-temperature superconducting quantum interference devices (low-Tc SQUIDs) that surround the head. The geometric distribution of these arrays is optimized by maximizing the information content available to the system in brain activity recordings according to Shannon's theory of noisy channel capacity., New Method: Herein, we present a theoretical comparison of the performance of low- and high-Tc SQUID-based multichannel systems in recordings of brain activity., Results: We find a high-Tc SQUID magnetometer-based multichannel system is capable of extracting at least 40% more information than an equivalent low-Tc SQUID system. The results suggest more information can be extracted from high-Tc SQUID MEG recordings (despite higher sensor noise levels than their low-Tc counterparts) because of the closer proximity to neural sources in the brain., Comparison With Existing Methods: We have duplicated previous results in terms of total information of multichannel low-Tc SQUID arrays for MEG. High-Tc SQUID technology theoretically outperforms its conventional low-Tc counterpart in MEG recordings., Conclusions: A full-head high-Tc SQUID-based MEG system's potential for extraction of more information about neural activity can be used to, e.g., develop better diagnostic and monitoring techniques for brain disease and enhance our understanding of the working human brain., (Copyright © 2013 Elsevier B.V. All rights reserved.)

We demonstrate ElectroWetting-On-Dielectric (EWOD) transport and SQUID gradiometer detection of magnetic nanoparticles (MNPs) suspended in a 2 microl de-ionized water droplet. This proof-of-concept methodology constitutes the first development step towards a highly sensitive magnetic immunoassay platform with SQUID readout and droplet-based sample handling. Magnetic AC-susceptibility measurements were performed on MNPs with a hydrodynamic diameter of 100 nm using a high-Tc dc Superconducting Quantum Interference Device (SQUID) gradiometer as detector. We observed that the signal amplitude per unit volume is 2.5 times higher for a 2 microl sample droplet compared to a 30 microl sample volume.