Monitoring magnetic nanoparticle clustering and immobilization with thermal noise magnetometry using optically pumped magnetometers.

Thermal noise magnetometry (TNM) is a recently developed magnetic characterization technique where thermally induced fluctuations in magnetization are measured to gain insight into nanomagnetic structures like magnetic nanoparticles (MNPs). Due to the stochastic nature of the method, its signal amplitude scales with the square of the volume of the individual fluctuators, which makes the method therefore extra attractive to study MNP clustering and aggregation processes. Until now, TNM signals have exclusively been detected by using a superconducting quantum interference device (SQUID) sensor. In contrast, we present here a tabletop setup using optically pumped magnetometers (OPMs) in a compact magnetic shield, as a flexible alternative. The agreement between results obtained with both measurement systems is shown for different commercially available MNP samples. We argue that the OPM setup with low complexity complements the SQUID setup with high sensitivity and bandwidth. Furthermore, the OPM tabletop setup is well suited to monitor aggregation processes because of its excellent sensitivity in lower frequencies. As a proof of concept, we show the changes in the noise spectrum for three different MNP immobilization and clustering processes. From our results, we conclude that the tabletop setup offers a flexible and widely adoptable measurement unit to monitor the immobilization, aggregation, and clustering of MNPs for different applications, including interactions of the particles with biological systems and the long-term stability of magnetic samples.

Biomagnetic signals recorded during transcranial magnetic stimulation (TMS)-evoked peripheral muscular activity.

Transcranial magnetic stimulation (TMS) has widespread clinical applications from diagnosis to treatment. We combined TMS with non-contact magnetic detection of TMS-evoked muscle activity in peripheral limbs to explore a new diagnostic modality that enhances the utility of TMS as a clinical tool by leveraging technological advances in magnetometry. We recorded measurements in a regular hospital room using an array of optically pumped magnetometers (OPMs) inside a portable shield that encloses only the forearm and hand of the subject. We present magnetomyograms (MMG)s of TMS-evoked movement in a human hand, together with a simultaneous surface electromyograph (EMG) data. The biomagnetic signals recorded in the MMG provides detailed spatial and temporal information that is complementary to that of the electric signal channels. Moreover, we identify features in the magnetic recording beyond that of the EMG. This system demonstrates the value of biomagnetic signals in TMS-based clinical approaches and widens its availability and practical potential.

Simulation Study of Different OPM-MEG Measurement Components.

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.

Functional connectivity maps of theta/alpha and beta coherence within the subthalamic nucleus region.

The subthalamic nucleus (STN) is a primary target for deep brain stimulation in Parkinson's disease (PD). Although small in size, the STN is commonly partitioned into sensorimotor, cognitive/associative, and limbic subregions based on its structural connectivity profile to cortical areas. We investigated whether such a regional specialization is also supported by functional connectivity between local field potential recordings and simultaneous magnetoencephalography. Using a novel data set of 21 PD patients, we replicated previously reported cortico-STN coherence networks in the theta/alpha and beta frequency ranges, and looked for the spatial distribution of these networks within the STN region. Although theta/alpha and beta coherence peaks were both observed in on-medication recordings from electrode contacts at several locations within and around the STN, sites with theta/alpha coherence peaks were situated at significantly more inferior MNI coordinates than beta coherence peaks. Sites with only theta/alpha coherence peaks, i.e. without distinct beta coherence, were mostly located near the border of sensorimotor and cognitive/associative subregions as defined by a tractography-based atlas of the STN. Peak coherence values were largely unaltered by the medication state of the subject, however, theta/alpha peaks were more often identified in recordings obtained after administration of dopaminergic medication. Our findings suggest the existence of a frequency-specific topography of cortico-STN coherence within the STN, albeit with considerable spatial overlap between functional networks. Consequently, optimization of deep brain stimulation targeting might remain a trade-off between alleviating motor symptoms and avoiding adverse neuropsychiatric side effects.

Transforming and comparing data between standard SQUID and OPM-MEG systems.

Optically pumped magnetometers (OPMs) have recently become so sensitive that they are suitable for use in magnetoencephalography (MEG). These sensors solve operational problems of the current standard MEG, where superconducting quantum interference device (SQUID) gradiometers and magnetometers are being used. The main advantage of OPMs is that they do not require cryogenics for cooling. Therefore, they can be placed closer to the scalp and are much easier to use. Here, we measured auditory evoked fields (AEFs) with both SQUID- and OPM-based MEG systems for a group of subjects to better understand the usage of a limited sensor count OPM-MEG. We present a theoretical framework that transforms the within subject data and equivalent simulation data from one MEG system to the other. This approach works on the principle of solving the inverse problem with one system, and then using the forward model to calculate the magnetic fields expected for the other system. For the source reconstruction, we used a minimum norm estimate (MNE) of the current distribution. Two different volume conductor models were compared: the homogeneous conducting sphere and the three-shell model of the head. The transformation results are characterized by a relative error and cross-correlation between the measured and the estimated magnetic field maps of the AEFs. The results for both models are encouraging. Since some commercial OPMs measure multiple components of the magnetic field simultaneously, we additionally analyzed the effect of tangential field components. Overall, our dual-axis OPM-MEG with 15 sensors yields similar information to a 62-channel SQUID-MEG with its field of view restricted to the right hemisphere.

Improved spatio-temporal measurements of visually evoked fields using optically-pumped magnetometers.

Recent developments in performance and practicality of optically-pumped magnetometers (OPMs) have enabled new capabilities in non-invasive brain function mapping through magnetoencephalography. In particular, the lack of cryogenic operating conditions allows for more flexible placement of sensor heads closer to the brain, leading to improved spatial resolution and source localisation capabilities. Through recording visually evoked brain fields (VEFs), we demonstrate that the closer sensor proximity can be exploited to improve temporal resolution. We use OPMs, and superconducting quantum interference devices (SQUIDs) for reference, to measure brain responses to flash and pattern reversal stimuli. We find highly reproducible signals with consistency across multiple participants, stimulus paradigms and sensor modalities. The temporal resolution advantage of OPMs is manifest in a twofold improvement, compared to SQUIDs. The capability for improved spatio-temporal signal tracing is illustrated by simultaneous vector recordings of VEFs in the primary and associative visual cortex, where a time lag on the order of 10-20 ms is consistently found. This paves the way for further spatio-temporal studies of neurophysiological signal tracking in visual stimulus processing, and other brain responses, with potentially far-reaching consequences for time-critical mapping of functionality in healthy and pathological brains.

Aesthetics as a common denominator for moral and commercial judgments.

Using fMRI, a core evaluation mechanism was found for aesthetic judgments with add-on neural activities for moral and commercial judgments. We propose that aesthetic evaluations serve as a basic core mechanism implicitly for moral and commercial judgments.

Morality in advertising: An fMRI study on persuasion in communication.

Advertising slogans serve the function of persuasive communication by presenting catchy phrases. To decide whether a slogan is convincing or not, cognitive reasoning is assumed to be complemented by a more implicit and intuitive route of information processing, presumably similar to evaluating normative judgments in moral statements. We employed functional magnetic resonance imaging (fMRI) while Western male subjects judged advertising slogans and moral statements as another decision task with subjective nature. Compared to a neutral control condition that targeted declarative memory and to an aesthetic-related condition, the evaluation processes in both domains engaged the anterior medial prefrontal cortex (mPFC), which is associated with decision-making incorporating personal value. Conjoint activations were also observed in the left temporoparietal junction (TPJ) when compared to the aesthetics condition. Results are discussed with reference to domain-independence, a suspected difference to aesthetic-like appreciations, and functional organization in the mPFC and the TPJ.

Precision Timing with α-ß Oscillatory Coupling: Stopwatch or Motor Control?

Precise timing is crucial for many behaviors ranging from conversational speech to athletic performance. The precision of motor timing has been suggested to result from the strength of phase-amplitude coupling (PAC) between the phase of alpha oscillations (α, 8-12 Hz) and the power of beta activity (ß, 14-30 Hz), herein referred to as α-ß PAC. The amplitude of ß oscillations has been proposed to code for temporally relevant information and the locking of ß power to the phase of α oscillations to maintain timing precision. Motor timing precision has at least two sources of variability: variability of timekeeping mechanism and variability of motor control. It is ambiguous to which of these two factors α-ß PAC should be ascribed: α-ß PAC could index precision of stopwatch-like internal timekeeping mechanisms, or α-ß PAC could index motor control precision. To disentangle these two hypotheses, we tested how oscillatory coupling at different stages of a time reproduction task related to temporal precision. Human participants encoded and subsequently reproduced a time interval while magnetoencephalography was recorded. The data show a robust α-ß PAC during both the encoding and reproduction of a temporal interval, a pattern that cannot be predicted by motor control accounts. Specifically, we found that timing precision resulted from the trade-off between the strength of α-ß PAC during the encoding and during the reproduction of intervals. These results support the hypothesis that α-ß PAC codes for the precision of temporal representations in the human brain.

Aesthetic Experiences Across Cultures: Neural Correlates When Viewing Traditional Eastern or Western Landscape Paintings.

Compared with traditional Western landscape paintings, Chinese traditional landscape paintings usually apply a reversed-geometric perspective and concentrate more on contextual information. Using functional magnetic resonance imaging (fMRI), we discovered an intracultural bias in the aesthetic appreciation of Western and Eastern traditional landscape paintings in European and Chinese participants. When viewing Western and Eastern landscape paintings in an fMRI scanner, participants showed stronger brain activation to artistic expressions from their own culture. Europeans showed greater activation in visual and sensory-motor brain areas, regions in the posterior cingulate cortex (PCC), and hippocampus when viewing Western compared to Eastern landscape paintings. Chinese participants exhibited greater neural activity in the medial and inferior occipital cortex and regions of the superior parietal lobule in response to Eastern compared to Western landscape paintings. On the behavioral level, the aesthetic judgments also differed between Western and Chinese participants when viewing landscape paintings from different cultures; Western participants showed for instance higher valence values when viewing Western landscapes, while Chinese participants did not show this effect when viewing Chinese landscapes. In general, our findings offer differentiated support for a cultural modulation at the behavioral level and in the neural architecture for high-level aesthetic appreciation.

Does airborne ultrasound lead to activation of the auditory cortex?

As airborne ultrasound can be found in many technical applications and everyday situations, the question as to whether sounds at these frequencies can be heard by human beings or whether they present a risk to their hearing system is of great practical relevance. To objectively study these issues, the monaural hearing threshold in the frequency range from 14 to 24 kHz was determined for 26 test subjects between 19 and 33 years of age using pure tone audiometry. The hearing threshold values increased strongly with increasing frequency up to around 21 kHz, followed by a range with a smaller slope toward 24 kHz. The number of subjects who could respond positively to the threshold measurements decreased dramatically above 21 kHz. Brain activation was then measured by means of magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) and with acoustic stimuli at the same frequencies, with sound pressure levels (SPLs) above and below the individual threshold. No auditory cortex activation was found for levels below the threshold. Although test subjects reported audible sounds above the threshold, no brain activity was identified in the above-threshold case under current experimental conditions except at the highest sensation level, which was presented at the lowest test frequency.

Low-beta cortico-pallidal coherence decreases during movement and correlates with overall reaction time.

Beta band oscillations (13-30 Hz) are a hallmark of cortical and subcortical structures that are part of the motor system. In addition to local population activity, oscillations also provide a means for synchronization of activity between regions. Here we examined the role of beta band coherence between the internal globus pallidus (GPi) and (motor) cortex during a simple reaction time task performed by nine patients with idiopathic dystonia. We recorded local field potentials from deep brain stimulation (DBS) electrodes implanted in bilateral GPi in combination with simultaneous whole-head magneto-encephalography (MEG). Patients responded to visually presented go or stop-signal cues by pressing a button with left or right hand. Although coherence between signals from DBS electrodes and MEG sensors was observed throughout the entire beta band, a significant movement-related decrease prevailed in lower beta frequencies (∼13-21 Hz). In addition, patients' absolute coherence values in this frequency range significantly correlated with their median reaction time during the task (r = 0.89, p = 0.003). These findings corroborate the recent idea of two functionally distinct frequency ranges within the beta band, as well as the anti-kinetic character of beta oscillations.

Magnetic field imaging with microfabricated optically-pumped magnetometers.

A multichannel imaging system is presented, consisting of 25 microfabricated optically-pumped magnetometers. The sensor probes have a footprint of less than 1 cm2 and a sensitive volume of 1.5 mm × 1.5 mm × 1.5 mm and connect to a control unit through optical fibers of length 5 m. Operating at very low ambient magnetic fields, the sensor array has an average magnetic sensitivity of 24 fT/Hz1/2, with a standard deviation of 5 fT/Hz1/2 when the noise of each sensor is averaged between 10 and 50 Hz. Operating in Earth's magnetic field, the magnetometers have a field sensitivity around 5 pT/Hz1/2. The vacuum-packaged sensor heads are optically heated and consume on average 76 ± 7 mW of power each. The heating power is provided by an array of eight diode lasers. Magnetic field imaging of small probe coils was obtained with the sensor array and fits to the expected field pattern agree well with the measured data.

M3BA: A Mobile, Modular, Multimodal Biosignal Acquisition Architecture for Miniaturized EEG-NIRS-Based Hybrid BCI and Monitoring.

OBJECTIVE: For the further development of the fields of telemedicine, neurotechnology, and brain-computer interfaces, advances in hybrid multimodal signal acquisition and processing technology are invaluable. Currently, there are no commonly available hybrid devices combining bioelectrical and biooptical neurophysiological measurements [here electroencephalography (EEG) and functional near-infrared spectroscopy (NIRS)]. Our objective was to design such an instrument in a miniaturized, customizable, and wireless form. METHODS: We present here the design and evaluation of a mobile, modular, multimodal biosignal acquisition architecture (M3BA) based on a high-performance analog front-end optimized for biopotential acquisition, a microcontroller, and our openNIRS technology. RESULTS: The designed M3BA modules are very small configurable high-precision and low-noise modules (EEG input referred noise @ 500 SPS 1.39 µVpp, NIRS noise equivalent power NEP750 nm = 5.92 pWpp, and NEP850 nm = 4.77 pWpp) with full input linearity, Bluetooth, 3-D accelerometer, and low power consumption. They support flexible user-specified biopotential reference setups and wireless body area/sensor network scenarios. CONCLUSION: Performance characterization and in-vivo experiments confirmed functionality and quality of the designed architecture. SIGNIFICANCE: Telemedicine and assistive neurotechnology scenarios will increasingly include wearable multimodal sensors in the future. The M3BA architecture can significantly facilitate future designs for research in these and other fields that rely on customized mobile hybrid biosignal modal biosignal acquisition architecture (M3BA), multimodal, near-infrared spectroscopy (NIRS), wireless body area network (WBAN), wireless body sensor network (WBSN).

Linking neuroimaging signals to behavioral responses in single cases: Challenges and opportunities.

Despite rapid progress both in psychology and neuroimaging, there is still a convergence gap between the results of these two scientific disciplines. This is particularly unsatisfactory, as the variability between single subjects needs to be understood both for basic science and for patient diagnostics in, for example, the field of age-related cognitive changes. Active and passive behaviors are the observables in psychology and can be studied alone or in combination with the neuroimaging approach. Various physical signatures of brain activity are the observables in neuroimaging and can be measured concurrent with behaviors. Despite the intrinsic relationship between behaviors and the corresponding neuroimaging patterns and the obvious advantages in integrating behavioral and neuroimaging measurements, the results of combined studies can be difficult to interpret. Experiments are often optimized to yield either a novel behavioral or a novel physiological result, but rarely designed for a better match between the two. Since integrating the results is probably a key to future progress in clinical psychology and basic research, an attempt is made here to identify some difficulties and to provide some ideas for future research.

The 170ms Response to Faces as Measured by MEG (M170) Is Consistently Altered in Congenital Prosopagnosia.

Modularity of face processing is still a controversial issue. Congenital prosopagnosia (cPA), a selective and lifelong impairment in familiar face recognition without evidence of an acquired cerebral lesion, offers a unique opportunity to support this fundamental hypothesis. However, in spite of the pronounced behavioural impairment, identification of a functionally relevant neural alteration in congenital prosopagnosia by electrophysiogical methods has not been achieved so far. Here we show that persons with congenital prosopagnosia can be distinguished as a group from unimpaired persons using magnetoencephalography. Early face-selective MEG-responses in the range of 140 to 200ms (the M170) showed prolonged latency and decreased amplitude whereas responses to another category (houses) were indistinguishable between subjects with congenital prosopagnosia and unimpaired controls. Latency and amplitude of face-selective EEG responses (the N170) which were simultaneously recorded were statistically indistinguishable between subjects with cPA and healthy controls which resolves heterogeneous and partly conflicting results from existing studies. The complementary analysis of categorical differences (evoked activity to faces minus evoked activity to houses) revealed that the early part of the 170ms response to faces is altered in subjects with cPA. This finding can be adequately explained in a common framework of holistic and part-based face processing. Whereas a significant brain-behaviour correlation of face recognition performance and the size of the M170 amplitude is found in controls a corresponding correlation is not seen in subjects with cPA. This indicates functional relevance of the alteration found for the 170ms response to faces in cPA and pinpoints the impairment of face processing to early perceptual stages.

Brief bursts of infrasound may improve cognitive function--an fMRI study.

At present, infrasound (sound frequency < 20 Hz; IS) is being controversially discussed as a potential mediator of several adverse bodily as well as psychological effects. However, it remains unclear, if and in what way IS influences cognition. Here, we conducted an fMRI experiment, in which 13 healthy participants were exposed to IS, while cognitive performance was assessed in an n-back working memory paradigm. During the task, short sinusoidal tone bursts of 12 Hz were administered monaurally with sound pressure levels that had been determined individually in a categorical loudness scaling session prior to the fMRI experiment. We found that task execution was associated with a significant activation of the prefrontal and the parietal cortex, as well as the striatum and the cerebellum, indicating the recruitment of a cognitive control network. Reverse contrast analysis (n-back with tone vs. n-back without tone) revealed a significant activation of the bilateral primary auditory cortex (Brodmann areas 41, 42). Surprisingly, we also found a strong, yet non-significant trend for an improvement of task performance during IS exposure. There was no correlation between performance and brain activity measures in tone and no-tone condition with sum scores of depression-, anxiety-, and personality factor assessment scales (BDI, STAIX1/X2, BFI-S). Although exerting a pronounced effect on cortical brain activity, we obtained no evidence for an impairment of cognition due to brief bursts of IS. On the contrary, potential improvement of working memory function introduces an entirely new aspect to the debate on IS-related effects.

Fetal magnetocardiography measurements with an array of microfabricated optically pumped magnetometers.

Following the rapid progress in the development of optically pumped magnetometer (OPM) technology for the measurement of magnetic fields in the femtotesla range, a successful assembly of individual sensors into an array of nearly identical sensors is within reach. Here, 25 microfabricated OPMs with footprints of 1 cm(3) were assembled into a conformal array. The individual sensors were inserted into three flexible belt-shaped holders and connected to their respective light sources and electronics, which reside outside a magnetically shielded room, through long optical and electrical cables. With this setup the fetal magnetocardiogram of a pregnant woman was measured by placing two sensor belts over her abdomen and one belt over her chest. The fetal magnetocardiogram recorded over the abdomen is usually dominated by contributions from the maternal magnetocardiogram, since the maternal heart generates a much stronger signal than the fetal heart. Therefore, signal processing methods have to be applied to obtain the pure fetal magnetocardiogram: orthogonal projection and independent component analysis. The resulting spatial distributions of fetal cardiac activity are in good agreement with each other. In a further exemplary step, the fetal heart rate was extracted from the fetal magnetocardiogram. Its variability suggests fetal activity. We conclude that microfabricated optically pumped magnetometers operating at room temperature are capable of complementing or in the future even replacing superconducting sensors for fetal magnetocardiography measurements.

Magnetoencephalographic accuracy profiles for the detection of auditory pathway sources.

The detection limits for cortical and brain stem sources associated with the auditory pathway are examined in order to analyse brain responses at the limits of the audible frequency range. The results obtained from this study are also relevant to other issues of auditory brain research. A complementary approach consisting of recordings of magnetoencephalographic (MEG) data and simulations of magnetic field distributions is presented in this work. A biomagnetic phantom consisting of a spherical volume filled with a saline solution and four current dipoles is built. The magnetic fields outside of the phantom generated by the current dipoles are then measured for a range of applied electric dipole moments with a planar multichannel SQUID magnetometer device and a helmet MEG gradiometer device. The inclusion of a magnetometer system is expected to be more sensitive to brain stem sources compared with a gradiometer system. The same electrical and geometrical configuration is simulated in a forward calculation. From both the measured and the simulated data, the dipole positions are estimated using an inverse calculation. Results are obtained for the reconstruction accuracy as a function of applied electric dipole moment and depth of the current dipole. We found that both systems can localize cortical and subcortical sources at physiological dipole strength even for brain stem sources. Further, we found that a planar magnetometer system is more suitable if the position of the brain source can be restricted in a limited region of the brain. If this is not the case, a helmet-shaped sensor system offers more accurate source estimation.