In this paper, we review the preparation technology, integration in measurement systems and tests of high-T c superconducting quantum interference devices (SQUIDs) intended for biomagnetic applications. A focus is on developments specific to Forschungszentrum Jülich GmbH, Chalmers University of Technology, MedTech West, and the University of Gothenburg, while placing these results in the perspective of those achieved elsewhere. Sensor fabrication, including the deposition and structuring of epitaxial oxide heterostructures, materials for substrates, epitaxial bilayer buffers, bicrystal and step-edge Josephson junctions, and multilayer flux transformers are detailed. The properties of the epitaxial multilayer high-T c direct current SQUID sensors, including their integration in measurement systems with special electronics and liquid nitrogen cryostats, are presented in the context of biomagnetic recording. Applications that include magnetic nanoparticle based molecular diagnostics, magnetocardiography, and magnetoencephalography are presented as showcases of high-T c biomagnetic systems. We conclude by outlining future challenges.

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.

We have performed single- and two-channel high transition temperature (high-Tc) superconducting quantum interference device (SQUID) magnetoencephalography (MEG) recordings of spontaneous brain activity in two healthy human subjects. We demonstrate modulation of two well-known brain rhythms: the occipital alpha rhythm and the mu rhythm found in the motor cortex. We further show that despite higher noise-levels compared to their low-Tc counterparts, high-Tc SQUIDs can be used to detect and record physiologically relevant brain rhythms with comparable signal-to-noise ratios. These results indicate the utility of high-Tc technology in MEG recordings of a broader range of brain activity.

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.