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Objective: In presurgical evaluation of temporal lobe epilepsy (TLE), selection of the resection side is challenging when bilateral temporal epileptiform discharges or structural abnormalities are present. We aim to evaluate the lateralization value of beamformer analysis of magnetoencephalography (MEG) in TLE.Methods: MEG data from 14 TLE patients were analyzed through beamformer analysis. We measured the hemispherical power distribution of beamformer sources and calculated the lateralization index (LI). We calculated the LI at multiple frequencies to explore the frequency dependency and at the delta frequency to define laterality. LI values ranging from −1 to −0.05 indicated right hemispheric dominance. LI values ranging from 0.05 to 1 indicated left hemispheric dominance. LI values ranging from −0.05 to 0.05 defined bilaterality. We measured the power of beamformer sources with a 9-s duration to explore time dependency.Results: The beamformer analysis showed that 10/14 patients had power dominance ipsilateral to resection. The delta frequency band had a higher lateralization value than other frequency bands. A time-dependent power fluctuation was found in the delta frequency band.Conclusions: MEG beamformer analysis, especially in the delta band, might efficiently provide additional information regarding lateralization in TLE.

Magnetoencephalography (MEG) captures the magnetic fields generated by neuronal current sources with sensors outside the head. In MEG analysis these current sources are estimated from the measured data to identify the locations and time courses of neural activity. Since there is no unique solution to this so-called inverse problem, multiple source estimation techniques have been developed. The nulling beamformer (NB), a modified form of the linearly constrained minimum variance (LCMV) beamformer, is specifically used in the process of inferring interregional interactions and is designed to eliminate shared signal contributions, or cross-talk, between regions of interest (ROIs) that would otherwise interfere with the connectivity analyses. The nulling beamformer applies the truncated singular value decomposition (TSVD) to remove small signal contributions from a ROI to the sensor signals. However, ROIs with strong crosstalk will have high separating power in the weaker components, which may be removed by the TSVD operation. To address this issue we propose a new method, the nulling beamformer with subspace suppression (NBSS). This method, controlled by a tuning parameter, reweights the singular values of the gain matrix mapping from source to sensor space such that components with high overlap are reduced. By doing so, we are able to measure signals between nearby source locations with limited cross-talk interference, allowing for reliable cortical connectivity analysis between them. In two simulations, we demonstrated that NBSS reduces cross-talk while retaining ROIs' signal power, and has higher separating power than both the minimum norm estimate (MNE) and the nulling beamformer without subspace suppression. We also showed that NBSS successfully localized the auditory M100 event-related field in primary auditory cortex, measured from a subject undergoing an auditory localizer task, and suppressed cross-talk in a nearby region in the superior temporal sulcus.

An important aim of an analysis pipeline for magnetoencephalographic (MEG) data is that it allows for the researcher spending maximal effort on making the statistical comparisons that will answer his or her questions. The example question being answered here is whether the so-called beta rebound differs between novel and repeated stimulations. Two analyses are presented: going from individual sensor space representations to, respectively, an across-group sensor space representation and an across-group source space representation. The data analyzed are neural responses to tactile stimulations of the right index finger in a group of 20 healthy participants acquired from an Elekta Neuromag System. The processing steps covered for the first analysis are MaxFiltering the raw data, defining, preprocessing and epoching the data, cleaning the data, finding and removing independent components related to eye blinks, eye movements and heart beats, calculating participants' individual evoked responses by averaging over epoched data and subsequently removing the average response from single epochs, calculating a time-frequency representation and baselining it with non-stimulation trials and finally calculating a grand average, an across-group sensor space representation. The second analysis starts from the grand average sensor space representation and after identification of the beta rebound the neural origin is imaged using beamformer source reconstruction. This analysis covers reading in co-registered magnetic resonance images, segmenting the data, creating a volume conductor, creating a forward model, cutting out MEG data of interest in the time and frequency domains, getting Fourier transforms and estimating source activity with a beamformer model where power is expressed relative to MEG data measured during periods of non-stimulation. Finally, morphing the source estimates onto a common template and performing group-level statistics on the data are covered. Functions for saving relevant figures in an automated and structured manner are also included. The protocol presented here can be applied to any research protocol where the emphasis is on source reconstruction of induced responses where the underlying sources are not coherent.

Magnetoencephalography (MEG) captures the magnetic fields generated by neuronal current sources with sensors outside the head. In MEG analysis these current sources are estimated from the measured data to identify the locations and time courses of neural activity. Since there is no unique solution to this so-called inverse problem, multiple source estimation techniques have been developed. The nulling beamformer (NB), a modified form of the linearly constrained minimum variance (LCMV) beamformer, is specifically used in the process of inferring interregional interactions and is designed to eliminate shared signal contributions, or cross-talk, between regions of interest (ROIs) that would otherwise interfere with the connectivity analyses. The nulling beamformer applies the truncated singular value decomposition (TSVD) to remove small signal contributions from a ROI to the sensor signals. However, ROIs with strong crosstalk will have high separating power in the weaker components, which may be removed by the TSVD operation. To address this issue we propose a new method, the nulling beamformer with subspace suppression (NBSS). Thismethod, controlled by a tuning parameter, reweights the singular values of the gain matrix mapping from source to sensor space such that components with high overlap are reduced. By doing so, we are able to measure signals between nearby source locations with limited cross-talk interference, allowing for reliable cortical connectivity analysis between them. In two simulations, we demonstrated that NBSS reduces cross-talk while retaining ROIs' signal power, and has higher separating power than both the minimum norm estimate (MNE) and the nulling beamformer without subspace suppression. We also showed that NBSS successfully localized the auditory M100 event-related field in primary auditory cortex, measured from a subject undergoing an auditory localizer task, and suppressed cross-talk in a nearby region in the superior temporal sulcus. [ABSTRACT FROM AUTHOR]

An important aim of an analysis pipeline for magnetoencephalographic (MEG) data is that it allows for the researcher spendingmaximal effort onmaking the statistical comparisons that will answer his or her questions. The example question being answered here is whether the so-called beta rebound differs between novel and repeated stimulations. Two analyses are presented: going from individual sensor space representations to, respectively, an across-group sensor space representation and an across-group source space representation. The data analyzed are neural responses to tactile stimulations of the right index finger in a group of 20 healthy participants acquired from an Elekta Neuromag System. The processing steps covered for the first analysis are MaxFiltering the raw data, defining, preprocessing and epoching the data, cleaning the data, finding and removing independent components related to eye blinks, eye movements and heart beats, calculating participants' individual evoked responses by averaging over epoched data and subsequently removing the average response from single epochs, calculating a time-frequency representation and baselining it with non-stimulation trials and finally calculating a grand average, an across-group sensor space representation. The second analysis starts from the grand average sensor space representation and after identification of the beta rebound the neural origin is imaged using beamformer source reconstruction. This analysis covers reading in co-registered magnetic resonance images, segmenting the data, creating a volume conductor, creating a forward model, cutting out MEG data of interest in the time and frequency domains, getting Fourier transforms and estimating source activity with a beamformer model where power is expressed relative to MEG data measured during periods of non-stimulation. Finally, morphing the source estimates onto a common template and performing group-level statistics on the data are covered. Functions for saving relevant figures in an automated and structured manner are also included. The protocol presented here can be applied to any research protocol where the emphasis is on source reconstruction of induced responses where the underlying sources are not coherent. [ABSTRACT FROM AUTHOR]

Beamformers are a widely-used tool in brain analysis with magnetoencephalography (MEG) and electroencephalography (EEG). For the construction of the beamformer filters realistic head volume conductor modeling is necessary for accurately computing the EEG and MEG leadfields, i.e., for solving the EEG and MEG forward problem. In this work, we investigate the influence of including realistic head tissue compartments into a finite element method (FEM) model on the beamformer's localization ability. Specifically, we investigate the effect of including cerebrospinal fluid, gray matter, and white matter distinction, as well as segmenting the skull bone into compacta and spongiosa, and modeling white matter anisotropy. We simulate an interictal epileptic measurement with white sensor noise. Beamformer filters are constructed with unit gain, unit array gain, and unit noise gain constraint. Beamformer source positions are determined by evaluating power and excess sample kurtosis (g2) of the source-waveforms at all source space nodes. For both modalities, we see a strong effect of modeling the cerebrospinal fluid and white and gray matter. Depending on the source position, both effects can each be in the magnitude of centimeters, rendering their modeling necessary for successful localization. Precise skull modeling mainly effected the EEG up to a few millimeters, while both modalities could profit from modeling white matter anisotropy to a smaller extent of 5–10 mm. The unit noise gain or neural activity index beamformer behaves similarly to the array gain beamformer when noise strength is sufficiently high. Variance localization seems more robust against modeling errors than kurtosis.

Beamformers are a widely-used tool in brain analysis with magnetoencephalography (MEG) and electroencephalography (EEG). For the construction of the beamformer filters realistic head volume conductor modeling is necessary for accurately computing the EEG and MEG leadfields, i.e., for solving the EEG and MEG forward problem. In this work, we investigate the influence of including realistic head tissue compartments into a finite element method (FEM) model on the beamformer's localization ability. Specifically, we investigate the effect of including cerebrospinal fluid, gray matter, and white matter distinction, as well as segmenting the skull bone into compacta and spongiosa, and modeling white matter anisotropy. We simulate an interictal epileptic measurement with white sensor noise. Beamformer filters are constructed with unit gain, unit array gain, and unit noise gain constraint. Beamformer source positions are determined by evaluating power and excess sample kurtosis (g2) of the source-waveforms at all source space nodes. For both modalities, we see a strong effect of modeling the cerebrospinal fluid and white and gray matter. Depending on the source position, both effects can each be in the magnitude of centimeters, rendering their modeling necessary for successful localization. Precise skull modeling mainly effected the EEG up to a few millimeters, while both modalities could profit from modeling white matter anisotropy to a smaller extent of 5-10 mm. The unit noise gain or neural activity index beamformer behaves similarly to the array gain beamformer when noise strength is sufficiently high. Variance localization seems more robust against modeling errors than kurtosis. [ABSTRACT FROM AUTHOR]

Pathology in Alzheimer’s disease (AD) starts in the entorhinal cortex and hippocampus. Because of their deep location, activity from these areas is difficult to record with conventional electro- or magnetoencephalography (EEG/MEG). The purpose of this study was to explore hippocampal activity in AD patients and healthy controls using virtual MEG electrodes.We used resting-state MEG recordings from 27 early-onset AD patients (age 60.6 ± 5.4, 12 females, Mini Mental State examination (MMSE) range: 19-28) and 26 cognitively healthy age- and gender-matched controls (age 61.8 ± 5.5, 14 females). Activity was reconstructed using beamformer-based virtual electrodes for 78 cortical regions and 6 hippocampal regions. Group differences in peak frequency and relative power in six frequency bands were identified using permutation testing. For the patients, spearman correlations between the MMSE scores and peak frequency or relative power were calculated. Moreover, receiver operator characteristic curves were plotted to estimate the diagnostic accuracy.We found a lower hippocampal peak frequency in AD compared to controls, which, in the patients, correlated positively with MMSE (r(25) = .61; p < .01) whereas hippocampal relative theta power correlated negatively with MMSE (r(25) = -.54; p < .01). Cortical peak frequency was also lower in AD in association areas. Furthermore, cortical peak frequency correlated positively with MMSE (r(25) = .43; p < 0.05). In line with this finding, relative theta power was higher in AD across the cortex, and relative alpha and beta power was lower in more circumscribed areas. The average cortical relative theta power was the best discriminator between AD and controls (sensitivity 82%; specificity 81%). Using beamformer-based virtual electrodes, we were able to detect hippocampal activity in AD. In AD, this hippocampal activity is slowed, and correlates better with cognition than the (slowed) activity in cortical areas. On the other hand, the average cortical relative power in the theta band was shown to be the best diagnostic discriminator. We postulate that this novel approach using virtual electrodes can be used in future research to quantify functional interactions between the hippocampi and cortical areas.

Pathology in Alzheimer's disease (AD) starts in the entorhinal cortex and hippocampus. Because of their deep location, activity from these areas is difficult to record with conventional electro- or magnetoencephalography (EEG/MEG). The purpose of this study was to explore hippocampal activity in AD patients and healthy controls using "virtual MEG electrodes". We used resting-state MEG recordings from 27 early onset AD patients [age 60.6 ± 5.4, 12 females, mini-mental state examination (MMSE) range: 19-28] and 26 cognitively healthy age- and gender-matched controls (age 61.8 ± 5.5, 14 females). Activity was reconstructed using beamformer-based virtual electrodes for 78 cortical regions and 6 hippocampal regions. Group differences in peak frequency and relative power in six frequency bands were identified using permutation testing. For the patients, spearman correlations between the MMSE scores and peak frequency or relative power were calculated. Moreover, receiver operator characteristic curves were plotted to estimate the diagnostic accuracy. We found a lower hippocampal peak frequency in AD compared to controls, which, in the patients, correlated positively with MMSE [r(25) = 0.61; p < 0.01] whereas hippocampal relative theta power correlated negatively with MMSE [r(25)=-0.54; p < 0.01]. Cortical peak frequency was also lower in AD in association areas. Furthermore, cortical peak frequency correlated positively with MMSE [r(25) = 0.43; p < 0.05]. In line with this finding, relative theta power was higher in AD across the cortex, and relative alpha and beta power was lower in more circumscribed areas. The average cortical relative theta power was the best discriminator between AD and controls (sensitivity 82%; specificity 81%). Using beamformer-based virtual electrodes, we were able to detect hippocampal activity in AD. In AD, this hippocampal activity is slowed, and correlates better with cognition than the (slowed) activity in cortical areas. On the other hand, the average cortical relative power in the theta band was shown to be the best diagnostic discriminator. We postulate that this novel approach using virtual electrodes can be used in future research to quantify functional interactions between the hippocampi and cortical areas. [ABSTRACT FROM AUTHOR]

Increasing evidence from invasive intracranial recordings suggests that the matured brain generates both physiological and pathological high-frequency signals. The present study was designed to detect high-frequency brain signals in the developing brain using newly developed magnetoencephalography (MEG) methods. Twenty healthy children were studied with a high sampling rate MEG system. Functional high-frequency brain signals were evoked by electrical stimulation applied to the index fingers. To determine if the high-frequency neuromagnetic signals are true brain responses in high-frequency range, we analyzed the MEG data using the conventional averaging as well as newly developed time-frequency analysis along with beamforming. The data of healthy children showed that very high-frequency brain signals (> 1000 Hz) in the somatosensory cortex in the developing brain could be detected and localized using MEG. The amplitude of very high-frequency brain signals was significantly weaker than that of the low-frequency brain signals. Very high-frequency brain signals showed a much earlier latency than those of a low-frequency. Magnetic source imaging (MSI) revealed that a portion of the high-frequency signals was from the somatosensory cortex, another portion of the high-frequency signals was probably from the thalamus. Our results provide evidence that the developing brain generates high-frequency signals that can be detected with the noninvasive technique of MEG. MEG detection of high-frequency brain signals may open a new window for the study of developing brain function.

Frontal midline theta rhythm (Fmθ) appears widely distributed over medial prefrontal areas in EEG recordings, indicating focused attention. Although mental calculation is often used as an attention-demanding task, little has been reported on calculation-related activation in Fmθ experiments. In this study we used spatially filtered MEG and permutation analysis to precisely localize cortical generators of the magnetic counterpart of Fmθ, as well as other sources of oscillatory activity associated with mental calculation processing (i.e., arithmetic subtraction). Our results confirmed and extended earlier EEG/MEG studies indicating that Fmθ during mental calculation is generated in the dorsal anterior cingulate and adjacent medial prefrontal cortex. Mental subtraction was also associated with gamma event-related synchronization, as an index of activation, in right parietal regions subserving basic numerical processing and number-based spatial attention. Gamma event-related desynchronization appeared in the right lateral prefrontal cortex, likely representing a mechanism to interrupt neural activity that can interfere with the ongoing cognitive task.

Inaccuracy of EEG electrode coordinates forms an error term in forward model generation and ultimate source reconstruction performance. This error arises from the combination of both intrinsic measurement noise of the digitization apparatus and manual coregistration error when selecting corresponding points on anatomical MRI volumes. A common assumption is that such an error would lead only to displacement of localized sources. Here, we measured electrode positions on a 3D-printed full-scale replica head, using three different techniques: a fringe projection 3D scanner, a novel Flying Triangulation 3D sensor, and a traditional electromagnetic digitizer. Using highly accurate fringe projection data as ground truth, the Flying Triangulation sensor had a mean error of 1.5 mm while the electromagnetic digitizer had a mean error of 6.8 mm. Then, again using the fringe projection as ground truth, individual EEG simulations were generated, with source locations across the brain space and a range of sensor noise levels. The simulated datasets were then processed using a beamformer in conjunction with the electrode coordinates registered with the Flying Triangulation and electromagnetic digitizer methods. The beamformer’s output SNR was severely degraded with the digitizer-based positions but less severely with the Flying Triangulation coordinates. Therefore, the seemingly innocuous error in electrode registration may result in substantial degradation of beamformer performance, with output SNR penalties up to several decibels. In the case of low-SNR signals such as deeper brain structures or gamma band sources, this implies that sensor coregistration accuracy could make the difference between successful detection of such activity or complete failure to resolve the source.

We have explored both the benefits and detriments of providing electrical input through a cochlear implant in one ear to the auditory system of young children. A cochlear implant delivers electrical pulses to stimulate the auditory nerve, providing children who are deaf with access to sound. The goals of implantation are to restrict reorganization of the deprived immature auditory brain and promote development of hearing and spoken language. It is clear that limiting the duration of deprivation is a key factor. Additional considerations are the onset, etiology, and use of residual hearing as each of these can have unique effects on auditory development in the pre-implant period. New findings show that many children receiving unilateral cochlear implants are developing mature-like brainstem and thalamo-cortical responses to sound with long term use despite these sources of variability; however, there remain considerable abnormalities in cortical function. The most apparent, determined by implanting the other ear and measuring responses to acute stimulation, is a loss of normal cortical response from the deprived ear. Recent data reveal that this can be avoided in children by early implantation of both ears simultaneously or with limited delay. We conclude that auditory development requires input early in development and from both ears.

Noninvasive studies to predict regions of seizure onset are important to choose grid locations for subsequent invasive cortical recordings prior to resective surgery for patients with medically intractable epilepsy. The neurosurgeon needs to know both the seizure onset zone (SOZ) and the region of immediate cortical spread to determine the epileptogenic zone (EZ) to be resected. The immediate zone of spread may be immediately adjacent, on a nearby gyrus, in a different lobe, and sometimes even in the contralateral cerebral hemisphere. We reviewed consecutive simultaneous EEG/MEG recordings on 162 children with medically intractable epilepsy. We analyzed the MEG signals in the bandwidth 20-70 Hz with a beamformer algorithm, synthetic aperture magnetometry (SAM), at a 2.5 mm voxel spacing throughout the brain (virtual sensor locations) with the kurtosis statistic (g2) to determine presence of excess kurtosis ( ) consistent with intermittent increased high frequency spikiness of the background. The MEG time series was reconstructed (virtual sensor signals) at each of these virtual sensor locations (VSLs). The VS signals were further examined with a relative peak amplitude spike detection algorithm. The time of VS spike detection was compared to the simultaneous EEG and MEG sensor signals for the presence of conventional epileptiform spike morphology in the latter signals. The time of VS spike detection was compared across VSLs to determine earliest and last VSL to show a VS spike. Seven subjects showed delay in activation across VS locations detectable on visual examination. We compared the VS locations that showed earliest and later VS spikes with the locations on intracranial grid locations by electrocorticography (ECoG) that showed spikes and both onset and spread of seizures. We compared completeness of resection of VS locations to postoperative outcome. The VS locations for spike onset and spread were similar to locations for ictal onset and spread by ECoG.

Increasing evidence from invasive intracranial recordings suggests that the matured brain generates both physiological and pathological high-frequency signals. The present study was designed to detect high-frequency brain signals in the developing brain using newly developed magnetoencephalography (MEG) methods. Twenty healthy children were studied with a high-sampling rate MEG system. Functional high-frequency brain signals were evoked by electrical stimulation applied to the index fingers. To determine if the highfrequency neuromagnetic signals are true brain responses in high-frequency range, we analyzed the MEG data using the conventional averaging as well as newly developed timefrequency analysis along with beamforming.The data of healthy children showed that very high-frequency brain signals (>1000 Hz) in the somatosensory cortex in the developing brain could be detected and localized using MEG. The amplitude of very high-frequency brain signals was significantly weaker than that of the low-frequency brain signals. Very high-frequency brain signals showed a much earlier latency than those of a low-frequency. Magnetic source imaging (MSI) revealed that a portion of the high-frequency signals was from the somatosensory cortex, another portion of the high-frequency signals was probably from the thalamus. Our results provide evidence that the developing brain generates high-frequency signals that can be detected with the non-invasive technique of MEG. MEG detection of high-frequency brain signals may open a new window for the study of developing brain function. [ABSTRACT FROM AUTHOR]

Frontal midline theta rhythm (Fmθ) appears widely distributed over medial prefrontal areas in EEG recordings, indicating focused attention. Although mental calculation is often used as an attention-demanding task, little has been reported on calculation-related activation in Fmθ experiments. In this study we used spatially filtered MEG and permutation analysis to precisely localize cortical generators of the magnetic counterpart of Fmθ, as well as other sources of oscillatory activity associated with mental calculation processing (i.e., arithmetic subtraction). Our results confirmed and extended earlier EEG/MEG studies indicating that Fmθ during mental calculation is generated in the dorsal anterior cingulate and adjacent medial prefrontal cortex. Mental subtraction was also associated with gamma event-related synchronization, as an index of activation, in right parietal regions subserving basic numerical processing and number-based spatial attention. Gamma event-related desynchronization appeared in the right lateral prefrontal cortex, likely representing a mechanism to interrupt neural activity that can interfere with the ongoing cognitive task. [ABSTRACT FROM AUTHOR]

Inaccuracy of EEG electrode coordinates forms an error term in forward model generation and ultimate source reconstruction performance. This error arises from the combination of both intrinsic measurement noise of the digitization apparatus and manual coregistration error when selecting corresponding points on anatomical MRI volumes. A common assumption is that such an error would lead only to displacement of localized sources. Here, we measured electrode positions on a 3D-printed full-scale replica head, using three different techniques: a fringe projection 3D scanner, a novel “Flying Triangulation” 3D sensor, and a traditional electromagnetic digitizer. Using highly accurate fringe projection data as ground truth, the Flying Triangulation sensor had a mean error of 1.5 mm while the electromagnetic digitizer had a mean error of 6.8 mm. Then, again using the fringe projection as ground truth, individual EEG simulations were generated, with source locations across the brain space and a range of sensor noise levels. The simulated datasets were then processed using a beamformer in conjunction with the electrode coordinates registered with the Flying Triangulation and electromagnetic digitizer methods. The beamformer’s output SNR was severely degraded with the digitizer-based positions but less severely with the Flying Triangulation coordinates. Therefore, the seemingly innocuous error in electrode registration may result in substantial degradation of beamformer performance, with output SNR penalties up to several decibels. In the case of low-SNR signals such as deeper brain structures or gamma band sources, this implies that sensor coregistration accuracy could make the difference between successful detection of such activity or complete failure to resolve the source. [ABSTRACT FROM AUTHOR]

What are the functional neuroimaging measurements required for more fully characterizing the events and locations of neocortical activity? A prime assumption has been that modulation of cortical activity will inevitably be reflected in changes in energy utilization (for the most part) changes of glucose and oxygen consumption. Are such a measures complete and sufficient? More direct measures of cortical electrophysiological activity show event or task-related modulation of amplitude or band-limited oscillatory power. Using magnetoencephalography (MEG), these measures have been shown to correlate well with energy utilization sensitive BOLD fMRI. In this paper, we explore the existence of state changes in electrophysiological cortical activity that can occur independently of changes in averaged amplitude, source power or indices of metabolic rates. In addition, we demonstrate that such state changes can be described by applying a new measure of complexity, rank vector entropy (RVE), to source waveform estimates from beamformer-processed MEG. RVE is a non-parametric symbolic dynamic informational entropy measure that accommodates the wide dynamic range of measured brain signals while resolving its temporal variations. By representing the measurements by their rank values, RVE overcomes the problem of defining embedding space partitions without resorting to signal compression. This renders RVE-independent of absolute signal amplitude. In addition, this approach is robust, being relatively free of tunable parameters. We present examples of task-free and task-dependent MEG demonstrating that RVE provides new information by uncovering hidden dynamical structure in the apparent turbulent (or chaotic) dynamics of spontaneous cortical activity. [ABSTRACT FROM AUTHOR]