Magnetoencephalography in Stroke Recovery and Rehabilitation

Magnetoencephalography (MEG) is a non-invasive neurophysiological technique used to study the cerebral cortex. Currently, MEG is mainly used clinically to localize epileptic foci and eloquent brain areas in order to avoid damage during neurosurgery. MEG might, however, also be of help in monitoring stroke recovery and rehabilitation. This review focuses on experimental use of MEG in neurorehabilitation. MEG has been employed to detect early modifications in neuroplasticity and connectivity, but there is insufficient evidence as to whether these methods are sensitive enough to be used as a clinical diagnostic test. MEG has also been exploited to derive the relationship between brain activity and movement kinematics for a motor-based brain-computer interface. In the current body of experimental research, MEG appears to be a powerful tool in neurorehabilitation, but it is necessary to produce new data to confirm its clinical utility

During visual word recognition, phonology is accessed within 100 ms and may be mediated by a speech production code: evidence from magnetoencephalography

Debate surrounds the precise cortical location and timing of access to phonological information during visual word recognition. Therefore, using whole-head magnetoencephalography (MEG), we investigated the spatiotemporal pattern of brain responses induced by a masked pseudohomophone priming task. Twenty healthy adults read target words that were preceded by one of three kinds of nonword prime: pseudohomophones (e.g., brein–BRAIN), where four of five letters are shared between prime and target, and the pronunciation is the same; matched orthographic controls (e.g., broin–BRAIN), where the same four of five letters are shared between prime and target but pronunciation differs; and unrelated controls (e.g., lopus–BRAIN), where neither letters nor pronunciation are shared between prime and target. All three priming conditions induced activation in the pars opercularis of the left inferior frontal gyrus (IFGpo) and the left precentral gyrus (PCG) within 100 ms of target word onset. However, for the critical comparison that reveals a processing difference specific to phonology, we found that the induced pseudohomophone priming response was significantly stronger than the orthographic priming response in left IFG/PCG at ∼100 ms. This spatiotemporal concurrence demonstrates early phonological influences during visual word recognition and is consistent with phonological access being mediated by a speech production code

On Linearly Constrained Minimum Variance Beamforming

Beamforming is a widely used technique for source localization in signal processing and neuroimaging. A number of vector-beamformers have been introduced to localize neuronal activity by using magnetoencephalography (MEG) data in the literature. However, the existing theoretical analyses on these beamformers have been limited to simple cases, where no more than two sources are allowed in the associated model and the theoretical sensor covariance is also assumed known. The information about the effects of the MEG spatial and temporal dimensions on the consistency of vector-beamforming is incomplete. In the present study, we consider a class of vector-beamformers defined by thresholding the sensor covariance matrix, which include the standard vector-beamformer as a special case. A general asymptotic theory is developed for these vector-beamformers, which shows the extent of effects to which the MEG spatial and temporal dimensions on estimating the neuronal activity index. The performances of the proposed beamformers are assessed by simulation studies. Superior performances of the proposed beamformers are obtained when the signal-to-noise ratio is low. We apply the proposed procedure to real MEG datasets derived from five sessions of a human face-perception experiment, finding several highly active areas in the brain. A good agreement between these findings and the known neurophysiology of the MEG response to human face perception is shown

Automated detection of epileptic ripples in MEG using beamformer-based virtual sensors

Objective. In epilepsy, high-frequency oscillations (HFOs) are expressively linked to the seizure onset zone (SOZ). The detection of HFOs in the noninvasive signals from scalp electroencephalography (EEG) and magnetoencephalography (MEG) is still a challenging task. The aim of this study was to automate the detection of ripples in MEG signals by reducing the high-frequency noise using beamformer-based virtual sensors (VSs) and applying an automatic procedure for exploring the time-frequency content of the detected events. Approach. Two-hundred seconds of MEG signal and simultaneous iEEG were selected from nine patients with refractory epilepsy. A two-stage algorithm was implemented. Firstly, beamforming was applied to the whole head to delimitate the region of interest (ROI) within a coarse grid of MEG-VS. Secondly, a beamformer using a finer grid in the ROI was computed. The automatic detection of ripples was performed using the time-frequency response provided by the Stockwell transform. Performance was evaluated through comparisons with simultaneous iEEG signals. Main results. ROIs were located within the seizure-generating lobes in the nine subjects. Precision and sensitivity values were 79.18% and 68.88%, respectively, by considering iEEG-detected events as benchmarks. A higher number of ripples were detected inside the ROI compared to the same region in the contralateral lobe. Significance. The evaluation of interictal ripples using non-invasive techniques can help in the delimitation of the epileptogenic zone and guide placement of intracranial electrodes. This is the first study that automatically detects ripples in MEG in the time domain located within the clinically expected epileptic area taking into account the time-frequency characteristics of the events through the whole signal spectrum. The algorithm was tested against intracranial recordings, the current gold standard. Further studies should explore this approach to enable the localization of noninvasively recorded HFOs to help during pre-surgical planning and to reduce the need for invasive diagnostics.Peer ReviewedPostprint (author's final draft

Interactions between visual and semantic processing during object recognition revealed by modulatory effects of age of acquisition

The age of acquisition (AoA) of objects and their names is a powerful determinant of processing speed in adulthood, with early-acquired objects being recognized and named faster than late-acquired objects. Previous research using fMRI (Ellis et al., 2006. Traces of vocabulary acquisition in the brain: evidence from covert object naming. NeuroImage 33, 958–968) found that AoA modulated the strength of BOLD responses in both occipital and left anterior temporal cortex during object naming. We used magnetoencephalography (MEG) to explore in more detail the nature of the influence of AoA on activity in those two regions. Covert object naming recruited a network within the left hemisphere that is familiar from previous research, including visual, left occipito-temporal, anterior temporal and inferior frontal regions. Region of interest (ROI) analyses found that occipital cortex generated a rapid evoked response (~ 75–200 ms at 0–40 Hz) that peaked at 95 ms but was not modulated by AoA. That response was followed by a complex of later occipital responses that extended from ~ 300 to 850 ms and were stronger to early- than late-acquired items from ~ 325 to 675 ms at 10–20 Hz in the induced rather than the evoked component. Left anterior temporal cortex showed an evoked response that occurred significantly later than the first occipital response (~ 100–400 ms at 0–10 Hz with a peak at 191 ms) and was stronger to early- than late-acquired items from ~ 100 to 300 ms at 2–12 Hz. A later anterior temporal response from ~ 550 to 1050 ms at 5–20 Hz was not modulated by AoA. The results indicate that the initial analysis of object forms in visual cortex is not influenced by AoA. A fastforward sweep of activation from occipital and left anterior temporal cortex then results in stronger activation of semantic representations for early- than late-acquired objects. Top-down re-activation of occipital cortex by semantic representations is then greater for early than late acquired objects resulting in delayed modulation of the visual response

Comparison of beamformer implementations for MEG source localization

Beamformers are applied for estimating spatiotemporal characteristics of neuronal sources underlying measured MEG/EEG signals. Several MEG analysis toolboxes include an implementation of a linearly constrained minimum-variance (LCMV) beamformer. However, differences in implementations and in their results complicate the selection and application of beamformers and may hinder their wider adoption in research and clinical use. Additionally, combinations of different MEG sensor types (such as magnetometers and planar gradiometers) and application of preprocessing methods for interference suppression, such as signal space separation (SSS), can affect the results in different ways for different implementations. So far, a systematic evaluation of the different implementations has not been performed. Here, we compared the localization performance of the LCMV beamformer pipelines in four widely used open-source toolboxes (MNE-Python, FieldTrip, DAiSS (SPM12), and Brainstorm) using datasets both with and without SSS interference suppression. We analyzed MEG data that were i) simulated, ii) recorded from a static and moving phantom, and iii) recorded from a healthy volunteer receiving auditory, visual, and somatosensory stimulation. We also investigated the effects of SSS and the combination of the magnetometer and gradiometer signals. We quantified how localization error and point-spread volume vary with the signal-to-noise ratio (SNR) in all four toolboxes. When applied carefully to MEG data with a typical SNR (3-15 dB), all four toolboxes localized the sources reliably; however, they differed in their sensitivity to preprocessing parameters. As expected, localizations were highly unreliable at very low SNR, but we found high localization error also at very high SNRs for the first three toolboxes while Brainstorm showed greater robustness but with lower spatial resolution. We also found that the SNR improvement offered by SSS led to more accurate localization.Peer reviewe

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

Enhancing the Signal of Corticomuscular Coherence

The availability of multichannel neuroimaging techniques, such as MEG and EEG, provides us with detailed topographical information of the recorded magnetic and electric signals and therefore gives us a good overview on the concomitant signals generated in the brain. To assess the location and the temporal dynamics of neuronal sources with noninvasive recordings, reconstruction tools such as beamformers have been shown to be useful. In the current study, we are in particular interested in cortical motor control involved in the isometric contraction of finger muscles. To this end we are measuring the interaction between the dynamics of brain signals and the electrical activity of hand muscles. We were interested to find out whether in addition to the well-known correlated activity between contralateral primary motor cortex and the hand muscles, additional functional connections can be demonstrated. We adopted coherence as a functional index and propose a so-called nulling beamformer method which is computationally efficient and addresses the localization of multiple correlated sources. In simulations of cortico-motor coherence, the proposed method was able to correctly localize secondary sources. The application of the approach on real electromyographic and magnetoencephalographic data collected during an isometric contraction and rest revealed an additional activity in the hemisphere ipsilateral to the hand involved in the task

The impact of MEG source reconstruction method on source-space connectivity estimation: A comparison between minimum-norm solution and beamforming.

Despite numerous important contributions, the investigation of brain connectivity with magnetoencephalography (MEG) still faces multiple challenges. One critical aspect of source-level connectivity, largely overlooked in the literature, is the putative effect of the choice of the inverse method on the subsequent cortico-cortical coupling analysis. We set out to investigate the impact of three inverse methods on source coherence detection using simulated MEG data. To this end, thousands of randomly located pairs of sources were created. Several parameters were manipulated, including inter- and intra-source correlation strength, source size and spatial configuration. The simulated pairs of sources were then used to generate sensor-level MEG measurements at varying signal-to-noise ratios (SNR). Next, the source level power and coherence maps were calculated using three methods (a) L2-Minimum-Norm Estimate (MNE), (b) Linearly Constrained Minimum Variance (LCMV) beamforming, and (c) Dynamic Imaging of Coherent Sources (DICS) beamforming. The performances of the methods were evaluated using Receiver Operating Characteristic (ROC) curves. The results indicate that beamformers perform better than MNE for coherence reconstructions if the interacting cortical sources consist of point-like sources. On the other hand, MNE provides better connectivity estimation than beamformers, if the interacting sources are simulated as extended cortical patches, where each patch consists of dipoles with identical time series (high intra-patch coherence). However, the performance of the beamformers for interacting patches improves substantially if each patch of active cortex is simulated with only partly coherent time series (partial intra-patch coherence). These results demonstrate that the choice of the inverse method impacts the results of MEG source-space coherence analysis, and that the optimal choice of the inverse solution depends on the spatial and synchronization profile of the interacting cortical sources. The insights revealed here can guide method selection and help improve data interpretation regarding MEG connectivity estimation

A unified view on beamformers for M/EEG source reconstruction

Beamforming is a popular method for functional source reconstruction using magnetoencephalography (MEG) and electroencephalography (EEG) data. Beamformers, which were first proposed for MEG more than two decades ago, have since been applied in hundreds of studies, demonstrating that they are a versatile and robust tool for neuroscience. However, certain characteristics of beamformers remain somewhat elusive and there currently does not exist a unified documentation of the mathematical underpinnings and computational subtleties of beamformers as implemented in the most widely used academic open source software packages for MEG analysis (Brainstorm, FieldTrip, MNE, and SPM). Here, we provide such documentation that aims at providing the mathematical background of beamforming and unifying the terminology. Beamformer implementations are compared across toolboxes and pitfalls of beamforming analyses are discussed. Specifically, we provide details on handling rank deficient covariance matrices, prewhitening, the rank reduction of forward fields, and on the combination of heterogeneous sensor types, such as magnetometers and gradiometers. The overall aim of this paper is to contribute to contemporary efforts towards higher levels of computational transparency in functional neuroimaging