Synthetic Aperture Magnetometry Research Articles

Use of magnetic source imaging to assess recovery after severe traumatic brain injury-an MEG pilot study.

Severe TBI (sTBI) is a devastating neurological injury that comprises a significant global trauma burden. Early comprehensive neurocritical care and rehabilitation improve outcomes for such patients, although better diagnostic and prognostic tools are necessary to guide personalized treatment plans. In this study, we explored the feasibility of conducting resting state magnetoencephalography (MEG) in a case series of sTBI patients acutely after injury (~7 days), and then about 1.5 and 8 months after injury. Synthetic aperture magnetometry (SAM) was utilized to localize source power in the canonical frequency bands of delta, theta, alpha, beta, and gamma, as well as DC-80 Hz. At the first scan, SAM source maps revealed zones of hypofunction, islands of preserved activity, and hemispheric asymmetry across bandwidths, with markedly reduced power on the side of injury for each patient. GCS scores improved at scan 2 and by scan 3 the patients were ambulatory. The SAM maps for scans 2 and 3 varied, with most patients showing increasing power over time, especially in gamma, but a continued reduction in power in damaged areas and hemispheric asymmetry and/or relative diminishment in power at the site of injury. At the group level for scan 1, there was a large excess of neural generators operating within the delta band relative to control participants, while the number of neural generators for beta and gamma were significantly reduced. At scan 2 there was increased beta power relative to controls. At scan 3 there was increased group-wise delta power in comparison to controls. In summary, this pilot study shows that MEG can be safely used to monitor and track the recovery of brain function in patients with severe TBI as well as to identify patient-specific regions of decreased or altered brain function. Such MEG maps of brain function may be used in the future to tailor patient-specific rehabilitation plans to target regions of altered spectral power with neurostimulation and other treatments.

Magnetoencephalography biomarkers of suicide attempt history and antidepressant response to ketamine in treatment-resistant major depression

BackgroundThis study examined magnetoencephalographic (MEG) correlates of suicidal ideation (SI) and suicide attempt history in patients with treatment-resistant major depression (TRD) at baseline and following subanesthetic-dose ketamine infusion. MethodsTwenty-nine drug-free TRD patients (12 suicide attempters/17 non-attempters) participated in a crossover randomized trial of ketamine. MEG data were collected during an attentional dot probe task with emotional face stimuli at baseline and several hours post-ketamine infusion. Synthetic aperture magnetometry was used to project source power in the theta, alpha, beta, and gamma frequencies for angry-neutral, happy-neutral, and neutral-neutral face pairings during a one-second peristimulus period. Mixed models were used to test for clinical, behavioral, and electrophysiological effects of group, emotion, session, and SI score. ResultsKetamine significantly reduced SI and depression across the sample. Post-ketamine, attempters had improved accuracy and non-attempters had reduced accuracy on the task. SI was positively associated with gamma power in regions of the frontal and parietal cortices across groups. In an extended amygdala-hippocampal region, attempters differed significantly in their emotional reactivity to angry versus happy faces as indexed by theta power differences, irrespective of drug. Ketamine significantly reduced the association between alpha power and SI for angry compared with happy faces in a fronto-insular/anterior cingulate region important for regulating sensory attentiveness. LimitationsLimitations include a small sample size of attempters. ConclusionsThe findings highlight key differences in band-limited power between attempters and non-attempters and reinforce previous findings that ketamine has distinct response properties in patients with a suicide history.

Neural Processing Mechanism of Mental Calculation Based on Cerebral Oscillatory Changes: A Comparison Between Abacus Experts and Novices.

Background: Abacus experts could mentally calculate fast some mathematical operations using multi-digit numbers. The temporal dynamics of abacus mental calculation are still unknown although some behavioral and neuroimaging studies have suggested a visuospatial and visuomotor neural process during abacus mental calculation. Therefore, this contribution aims to clarify the significant similarities and the differences between experts and novices by investigating calculation-induced neuromagnetic responses based on cerebral oscillatory changes.Methods: Twelve to 13 healthy abacus experts and 17 non-experts participated in two experimental paradigms using non-invasive neuromagnetic measurements. In experiments 1 and 2, the spatial distribution of oscillatory changes presented mental calculations and temporal frequency profiles during addition while examining multiplication tasks. The MEG data were analyzed using synthetic aperture magnetometry (SAM) with an adaptive beamformer to calculate the group average of the spatial distribution of oscillatory changes and their temporal frequency profiles in source-level analyses.Results: Using a group average of the spatial distribution of oscillatory changes, we observed some common brain activities in both right-handed abacus experts and non-experts. In non-experts, we detected the right dorsolateral prefrontal cortex (DLPFC) and bilateral Intraparietal sulcus (IPS); whereas in experts, detected the bilateral parieto-occipital sulcus (POS), right inferior frontal gyrus (IFG), and left sensorimotor areas mainly. Based on the findings generated, we could propose calculation processing models for both abacus experts and non- experts conveniently.Conclusion: The proposed model of calculation processing in abacus experts and novices revealed that the novices could calculate logically depending on numerical processing in the left IPS. In contrast, abacus experts are utilizing spatial processing using a memorized imaginary abacus, which distributed over the bilateral hemispheres in the IFG and sensorimotor areas.

Synthetic aperture magnetometry and excess kurtosis mapping of Magnetoencephalography (MEG) is predictive of epilepsy surgical outcome in a large pediatric cohort

ObjectiveResective surgery is the most effective treatment option for patients with refractory epilepsy; however identification of patients who will benefit from epilepsy surgery remains challenging. Synthetic aperture magnetometry and excess kurtosis mapping (SAM(g2)) of magnetoencephalography (MEG) is a non-invasive tool that warrants further examination in the pediatric epilepsy population. Here, we examined the utility of MEG with SAM(g2) to determine if MEG epileptiform foci correlates with surgical outcome and to develop a predictive model incorporating MEG information to best assess likelihood of seizure improvement/freedom from resective surgery. Methods564 subjects who had MEG at the Children’s Hospital of Philadelphia between 2010–2015 were screened. Clinical epilepsy history and prior electrographic records were extracted and reviewed and correlated with MEG findings. MEG assessments were made by both a neurologist and neuroradiologist. Predictive models were developed to assess the utility of MEG in determining Engel class at one year and five years after resective epilepsy surgery. ResultsThe number of MEG spike foci was highly associated with Engel class outcome at both one year and five years; however, using MEG data in isolation was not significantly predictive of 5 year surgical outcome. When combined with clinical factors; scalp EEG (single ictal onset zone), MRI (lesional or not), age and sex in a logistic regression model MEG foci was significant for Engel class outcome at both 1 year (p = 0.03) and 5 years (0.02). The percent correctly classified for Engel class at one year was 78.43% and the positive predictive value was 71.43. SignificanceMEG using SAM(g2) analysis in an important non-invasive tool in the identification of those patients who will benefit most from surgery. Integrating MEG data analysis into pre-surgical evaluation can help to predict epilepsy outcome after resective surgery in the pediatric population if utilized with skilled interpretation.

BrainWave: A Matlab Toolbox for Beamformer Source Analysis of MEG Data.

BrainWave is an easy-to-use Matlab toolbox for the analysis of magnetoencephalography data. It provides a graphical user interface for performing minimum-variance beamforming analysis with rapid and interactive visualization of evoked and induced brain activity. This article provides an overview of the main features of BrainWave with a step-by-step demonstration of how to proceed from raw experimental data to group source images and time series analyses. This includes data selection and pre-processing, magnetic resonance image co-registration and normalization procedures, and the generation of volumetric (whole-brain) or cortical surface based source images, and corresponding source time series as virtual sensor waveforms and their time-frequency representations. We illustrate these steps using example data from a recently published study on response inhibition (Isabella et al., 2015) using the sustained attention to response task paradigm in 12 healthy adult participants. In this task participants were required to press a button with their right index finger to a rapidly presented series of numerical digits and withhold their response to an infrequently presented target digit. This paradigm elicited movement-locked brain responses, as well as task-related modulation of brain rhythmic activity in different frequency bands (e.g., theta, beta, and gamma), and is used to illustrate two different types of source reconstruction implemented in the BrainWave toolbox: (1) event-related beamforming of averaged brain responses and (2) beamformer analysis of modulation of rhythmic brain activity using the synthetic aperture magnetometry algorithm. We also demonstrate the ability to generate group contrast images between different response types, using the example of frontal theta activation patterns during error responses (failure to withhold on target trials). BrainWave is free academic software available for download at http://cheynelab.utoronto.ca/brainwave along with supporting software and documentation. The development of the BrainWave toolbox was supported by grants from the Canadian Institutes of Health Research, the National Research and Engineering Research Council of Canada, and the Ontario Brain Institute.

Magnetoencephalography: Clinical and Research Practices.

Magnetoencephalography (MEG) is a neurophysiological technique that detects the magnetic fields associated with brain activity. Synthetic aperture magnetometry (SAM), a MEG magnetic source imaging technique, can be used to construct both detailed maps of global brain activity as well as virtual electrode signals, which provide information that is similar to invasive electrode recordings. This innovative approach has demonstrated utility in both clinical and research settings. For individuals with epilepsy, MEG provides valuable, nonredundant information. MEG accurately localizes the irritative zone associated with interictal spikes, often detecting epileptiform activity other methods cannot, and may give localizing information when other methods fail. These capabilities potentially greatly increase the population eligible for epilepsy surgery and improve planning for those undergoing surgery. MEG methods can be readily adapted to research settings, allowing noninvasive assessment of whole brain neurophysiological activity, with a theoretical spatial range down to submillimeter voxels, and in both humans and nonhuman primates. The combination of clinical and research activities with MEG offers a unique opportunity to advance translational research from bench to bedside and back.

High-gamma activity in the human hippocampus and parahippocampus during inter-trial rest periods of a virtual navigation task

In rodents, hippocampal cell assemblies formed during learning of a navigation task are observed to re-emerge during resting (offline) periods, accompanied by high-frequency oscillations (HFOs). This phenomenon is believed to reflect mechanisms for strengthening newly-formed memory traces. Using magnetoencephalography recordings and a beamforming source location algorithm (synthetic aperture magnetometry), we investigated high-gamma (80–140 Hz) oscillations in the hippocampal region in 18 human participants during inter-trial rest periods in a virtual navigation task. We found right hippocampal gamma oscillations mirrored the pattern of theta power in the same region during navigation, varying as a function of environmental novelty. Gamma power during inter-trial rest periods was positively correlated with theta power during navigation in the first task set when the environment was new and predicted greater performance improvement in the subsequent task set two where the environment became familiar. These findings provide evidence for human hippocampal reactivation accompanied by high-gamma activities immediately after learning and establish a link between hippocampal high-gamma activities and subsequent memory performance.

Source estimation of epileptic activity using eLORETA kurtosis analysis

Exact low-resolution brain electromagnetic tomography (eLORETA) is a technique for three-dimensional representation of the distribution of sources of electrical activity in the brain. Kurtosis analysis allows for identification of spiky...

Frequency-dependent oscillatory neural profiles during imitation

Imitation is a complex process that includes higher-order cognitive and motor function. This process requires an observation-execution matching system that transforms an observed action into an identical movement. Although the low-gamma band is thought to reflect higher cognitive processes, no studies have focused on it. Here, we used magnetoencephalography (MEG) to examine the neural oscillatory changes including the low-gamma band during imitation. Twelve healthy, right-handed participants performed a finger task consisting of four conditions (imitation, execution, observation, and rest). During the imitation and execution conditions, significant event-related desynchronizations (ERDs) were observed at the left frontal, central, and parietal MEG sensors in the alpha, beta, and low-gamma bands. Functional connectivity analysis at the sensor level revealed an imitation-related connectivity between a group of frontal sensors and a group of parietal sensors in the low-gamma band. Furthermore, source reconstruction with synthetic aperture magnetometry showed significant ERDs in the low-gamma band in the left sensorimotor area and the middle frontal gyrus (MFG) during the imitation condition when compared with the other three conditions. Our results suggest that the oscillatory neural activities of the low-gamma band at the sensorimotor area and MFG play an important role in the observation-execution matching system related to imitation.

Deriving frequency-dependent spatial patterns in MEG-derived resting state sensorimotor network: A novel multiband ICA technique.

Recently, independent components analysis (ICA) of resting state magnetoencephalography (MEG) recordings has revealed resting state networks (RSNs) that exhibit fluctuations of band-limited power envelopes. Most of the work in this area has concentrated on networks derived from the power envelope of beta bandpass-filtered data. Although research has demonstrated that most networks show maximal correlation in the beta band, little is known about how spatial patterns of correlations may differ across frequencies. This study analyzed MEG data from 18 healthy subjects to determine if the spatial patterns of RSNs differed between delta, theta, alpha, beta, gamma, and high gamma frequency bands. To validate our method, we focused on the sensorimotor network, which is well-characterized and robust in both MEG and functional magnetic resonance imaging (fMRI) resting state data. Synthetic aperture magnetometry (SAM) was used to project signals into anatomical source space separately in each band before a group temporal ICA was performed over all subjects and bands. This method preserved the inherent correlation structure of the data and reflected connectivity derived from single-band ICA, but also allowed identification of spatial spectral modes that are consistent across subjects. The implications of these results on our understanding of sensorimotor function are discussed, as are the potential applications of this technique. Hum Brain Mapp 38:779-791, 2017. © 2016 Wiley Periodicals, Inc.

Localization of Interictal Epileptic Spikes With MEG: Optimization of an Automated Beamformer Screening Method (SAMepi) in a Diverse Epilepsy Population.

To describe and optimize an automated beamforming technique followed by identification of locations with excess kurtosis (g2) for efficient detection and localization of interictal spikes in patients with medically refractory epilepsy. Synthetic aperture magnetometry with g2 averaged over a sliding time window (SAMepi) was performed in seven patients with focal epilepsy and five healthy volunteers. The effect of varied window lengths on detection of spiking activity was evaluated. Sliding window lengths of 0.5 to 10 seconds performed similarly, with 0.5- and 1-second windows detecting spiking activity in 1 of the 3 virtual sensor locations with highest kurtosis. These locations were concordant with the region of eventual surgical resection in these seven patients who remained seizure-free at 1 year. Average g2 values increased with increasing sliding window length in all subjects. In healthy volunteers, kurtosis values stabilized in data sets longer than 2 minutes. SAMepi using g2 averaged over 1-second sliding time windows in data sets of at least 2 minutes of duration reliably identified interictal spiking and the presumed seizure focus in these seven patients. Screening the five locations with highest kurtosis values for spiking activity is an efficient and accurate technique for localizing interictal activity using magnetoencephalography. SAMepi should be applied using the parameter values and procedure described for optimal detection and localization of interictal spikes. Use of this screening procedure could significantly improve the efficiency of magnetoencephalography analysis if clinically validated.

Temporal accuracy of human cortico-cortical interactions.

The precision in space and time of interactions among multiple cortical sites was evaluated by examining repeating precise spatiotemporal patterns of instances in which cortical currents showed brief amplitude undulations. The amplitudes of the cortical current dipoles were estimated by applying a variant of synthetic aperture magnetometry to magnetoencephalographic (MEG) recordings of subjects tapping to metric auditory rhythms of drum beats. Brief amplitude undulations were detected in the currents by template matching at a rate of 2–3 per second. Their timing was treated as point processes, and precise spatiotemporal patterns were searched for. By randomly teetering these point processes within a time window W, we estimated the accuracy of the timing of these brief amplitude undulations and compared the results with those obtained by applying the same analysis to traces composed of random numbers. The results demonstrated that the timing accuracy of patterns was better than 3 ms. Successful classification of two different cognitive processes based on these patterns suggests that at least some of the repeating patterns are specific to a cognitive process.

Transcranial modulation of brain oscillatory responses: A concurrent tDCS–MEG investigation

Despite the increasing use of transcranial direct current stimulation (tDCS), the physiological mechanisms underlying its effects are still largely unknown. One approach to directly investigate the effects of the neuromodulation technique on the brain is to integrate tDCS with non-invasive neuroimaging in humans. To provide new insight into the neurobiology of the method, DC stimulation (1mA, 600s) was applied concurrently with Magnetoencephalography (MEG), while participants engaged in a visuomotor task before, during and after a period of tDCS. Responses in the motor beta band (15–30Hz) and visual gamma band (30–80Hz) were localised using Synthetic Aperture Magnetometry (SAM). The resulting induced and evoked oscillatory responses were subsequently analysed. A statistically significant reduction of average power in the visual gamma band was observed for anodal compared to sham stimulation. The magnitude of motor evoked responses was also found to be significantly modulated by anodal stimulation. These results demonstrate that MEG can be used to derive inferences on the cortical mechanisms of tDCS.

Simultaneous transcranial direct current stimulation (tDCS) and whole-head magnetoencephalography (MEG): assessing the impact of tDCS on slow cortical magnetic fields

Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0–4Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior.

Frequency-spatial beamformer for MEG source localization

This article introduces a unique and powerful new method for spatial localization of neuronal sources that exploit the high temporal resolution of magnetoencephalography (MEG) data to locate the originating sources within the brain. A traditional frequency beamforming algorithm was adapted from its conventional application to yield information on the spatial location of simulated neuronal signals. The concept is similar to that used in signal source localization in magnetic resonance imaging (MRI) in which spatial location is determined by the frequency of oscillation of the MR signal. Whereas a traditional frequency beamformer uses the time course values of all sensors in the dataset to assign a power value for each possible frequency in the signal, it provides no information on the spatial location of those frequencies. Our approach assigns a power value to each location in the three-dimensional head volume. To compute this power value, the time courses of a subset of sensors closest to that location in space are used rather than all the time courses in the dataset. Our novel technique incorporates actual MEG sensor locations of the closest sensors at each location in space. The approach is relatively simple to implement, yields good spatial resolution, and accurately spatially locates a simulated source in low signal-to-noise environments. In this work, its performance is compared to that of the synthetic aperture magnetometry (SAM) beamformer and shown to exhibit improved spatial resolution.

Cerebral oscillatory activity during simulated driving using MEG.

We aimed to examine cerebral oscillatory differences associated with psychological processes during simulated car driving. We recorded neuromagnetic signals in 14 healthy volunteers using magnetoencephalography (MEG) during simulated driving. MEG data were analyzed using synthetic aperture magnetometry to detect the spatial distribution of cerebral oscillations. Group effects between subjects were analyzed statistically using a non-parametric permutation test. Oscillatory differences were calculated by comparison between “passive viewing” and “active driving.” “Passive viewing” was the baseline, and oscillatory differences during “active driving” showed an increase or decrease in comparison with a baseline. Power increase in the theta band was detected in the superior frontal gyrus (SFG) during active driving. Power decreases in the alpha, beta, and low gamma bands were detected in the right inferior parietal lobe (IPL), left postcentral gyrus (PoCG), middle temporal gyrus (MTG), and posterior cingulate gyrus (PCiG) during active driving. Power increase in the theta band in the SFG may play a role in attention. Power decrease in the right IPL may reflect selectively divided attention and visuospatial processing, whereas that in the left PoCG reflects sensorimotor activation related to driving manipulation. Power decreases in the MTG and PCiG may be associated with object recognition.

Localization of interictal epileptiform activity using magnetoencephalography with synthetic aperture magnetometry in patients with a vagus nerve stimulator.

Magnetoencephalography (MEG) provides useful and non-redundant information in the evaluation of patients with epilepsy, and in particular, during the pre-surgical evaluation of pharmaco-resistant epilepsy. Vagus nerve stimulation (VNS) is a common treatment for pharmaco-resistant epilepsy. However, interpretation of MEG recordings from patients with a VNS is challenging due to the severe magnetic artifacts produced by the VNS. We used synthetic aperture magnetometry (g2) [SAM(g2)], an adaptive beamformer that maps the excessive kurtosis, to map interictal spikes to the coregistered MRI image, despite the presence of contaminating VNS artifact. We present a series of eight patients with a VNS who underwent MEG recording. Localization of interictal epileptiform activity by SAM(g2) is compared to invasive electrophysiologic monitoring and other localizing approaches. While the raw MEG recordings were uninterpretable, analysis of the recordings with SAM(g2) identified foci of peak kurtosis and source signal activity that was unaffected by the VNS artifact. SAM(g2) analysis of MEG recordings in patients with a VNS produces interpretable results and expands the use of MEG for the pre-surgical evaluation of epilepsy.

Delayed and disorganised brain activation detected with magnetoencephalography after mild traumatic brain injury

BackgroundAwareness to neurocognitive issues after mild traumatic brain injury (mTBI) is increasing, but currently no imaging markers are available for mTBI. Advanced structural imaging recently showed microstructural tissue changes and...

Localizing evoked and induced responses to faces using magnetoencephalography

A rich pattern of responses in frequency, time and space are known to be generated in the visual cortex in response to faces. Recently, a number of studies have used magnetoencephalography (MEG) to try to record these responses non-invasively – in many cases using source analysis techniques based on the beamforming method. Here we sought both to characterize best practice for measuring face-specific responses using MEG beamforming, and to determine whether the results produced by the beamformer match evidence from other modalities. We measured activity to visual presentation of face stimuli and phase-scrambled control stimuli, and performed source analyses of both induced and evoked responses using Synthetic Aperture Magnetometry. We localized the gamma-band response to bilateral lateral occipital cortex, and both the gamma-band response and the M170-evoked response to the right fusiform gyrus. Differences in the gamma-band response between faces and scrambled stimuli were confined to the frequency range 50–90 Hz; gamma-band activity at higher frequencies did not differ between the two stimulus categories. We additionally identified a component of the M220-evoked response – localized to the parieto-occipital sulcus – which was enhanced for scrambled vs. unscrambled faces. These findings help to establish that MEG beamforming can localize face-specific responses in time, frequency and space with good accuracy (when validated against established findings from functional magnetic resonance imaging and intracranial recordings), as well as contributing to the establishment of best methodological practice for the use of the beamformer method to measure face-specific responses.

Altered Cortical Swallowing Processing in Patients with Functional Dysphagia: A Preliminary Study

ObjectiveCurrent neuroimaging research on functional disturbances provides growing evidence for objective neuronal correlates of allegedly psychogenic symptoms, thereby shifting the disease concept from a psychological towards a neurobiological model. Functional dysphagia is such a rare condition, whose pathogenetic mechanism is largely unknown. In the absence of any organic reason for a patient's persistent swallowing complaints, sensorimotor processing abnormalities involving central neural pathways constitute a potential etiology.MethodsIn this pilot study we measured cortical swallow-related activation in 5 patients diagnosed with functional dysphagia and a matched group of healthy subjects applying magnetoencephalography. Source localization of cortical activation was done with synthetic aperture magnetometry. To test for significant differences in cortical swallowing processing between groups, a non-parametric permutation test was afterwards performed on individual source localization maps.ResultsSwallowing task performance was comparable between groups. In relation to control subjects, in whom activation was symmetrically distributed in rostro-medial parts of the sensorimotor cortices of both hemispheres, patients showed prominent activation of the right insula, dorsolateral prefrontal cortex and lateral premotor, motor as well as inferolateral parietal cortex. Furthermore, activation was markedly reduced in the left medial primary sensory cortex as well as right medial sensorimotor cortex and adjacent supplementary motor area (p<0.01).ConclusionsFunctional dysphagia - a condition with assumed normal brain function - seems to be associated with distinctive changes of the swallow-related cortical activation pattern. Alterations may reflect exaggerated activation of a widely distributed vigilance, self-monitoring and salience rating network that interferes with down-stream deglutition sensorimotor control.