John C. Mosher

Electromagnetic brain mapping

There has been tremendous advances in our ability to produce images of human brain function. Applications of functional brain imaging extend from improving our understanding of the basic mechanisms of cognitive processes to better characterization of pathologies that impair normal function. Magnetoencephalography (MEG) and electroencephalography (EEG) (MEG/EEG) localize neural electrical activity using noninvasive measurements of external electromagnetic signals. Among the available functional imaging techniques, MEG and EEG uniquely have temporal resolutions below 100 ms. This temporal precision allows us to explore the timing of basic neural processes at the level of cell assemblies. MEG/EEG source localization draws on a wide range of signal processing techniques including digital filtering, three-dimensional image analysis, array signal processing, image modeling and reconstruction, and, blind source separation and phase synchrony estimation. We describe the underlying models currently used in MEG/EEG source estimation and describe the various signal processing steps required to compute these sources. In particular we describe methods for computing the forward fields for known source distributions and parametric and imaging-based approaches to the inverse problem.

Multiple dipole modeling and localization from spatio-temporal MEG data

The authors present general descriptive models for spatiotemporal MEG (magnetoencephalogram) data and show the separability of the linear moment parameters and nonlinear location parameters in the MEG problem. A forward model with current dipoles in a spherically symmetric conductor is used as an example: however, other more advanced MEG models, as well as many EEG (electroencephalogram) models, can also be formulated in a similar linear algebra framework. A subspace methodology and computational approach to solving the conventional least-squares problem is presented. A new scanning approach, equivalent to the statistical MUSIC method, is also developed. This subspace method scans three-dimensional space with a one-dipole model, making it computationally feasible to scan the complete head volume.<<ETX>>

Brainstorm: a user-friendly application for MEG/EEG analysis

Brainstorm is a collaborative open-source application dedicated to magnetoencephalography (MEG) and electroencephalography (EEG) data visualization and processing, with an emphasis on cortical source estimation techniques and their integration with anatomical magnetic resonance imaging (MRI) data. The primary objective of the software is to connect MEG/EEG neuroscience investigators with both the best-established and cutting-edge methods through a simple and intuitive graphical user interface (GUI).

A sensor-weighted overlapping-sphere head model and exhaustive head model comparison for MEG.

The spherical head model has been used in magnetoencephalography (MEG) as a simple forward model for calculating the external magnetic fields resulting from neural activity. For more realistic head shapes, the boundary element method (BEM) or similar numerical methods are used, but at greatly increased computational cost. We introduce a sensor-weighted overlapping-sphere (OS) head model for rapid calculation of more realistic head shapes. The volume currents associated with primary neural activity are used to fit spherical head models for each individual MEG sensor such that the head is more realistically modelled as a set of overlapping spheres, rather than a single sphere. To assist in the evaluation of this OS model with BEM and other head models, we also introduce a novel comparison technique that is based on a generalized eigenvalue decomposition and accounts for the presence of noise in the MEG data. With this technique we can examine the worst possible errors for thousands of dipole locations in a realistic brain volume. We test the traditional single-sphere model, three-shell and single-shell BEM, and the new OS model. The results show that the OS model has accuracy similar to the BEM but is orders of magnitude faster to compute.

Recursive MUSIC: A framework for EEG and MEG source localization

The multiple signal classification (MUSIC) algorithm can be used to locate multiple asynchronous dipolar sources from electroencephalography (EEG) and magnetocncephalography (MEG) data. The algorithm scans a single-dipole model through a three-dimensional (3-D) head volume and computes projections onto an estimated signal subspace. To locate the sources, the user must search the head volume for multiple local peaks in the projection metric. This task is time consuming and subjective. Here, the authors describe an extension of this approach which they refer to as recursive MUSIC (R-MUSIC). This new procedure automatically extracts the locations of the sources through a recursive use of subspace projections. The new method is also able to locate synchronous sources through the use of a spatio-temporal independent topographies (IT) model. This model defines a source as one or more nonrotating dipoles with a single time course. Within this framework, the authors are able to locate fixed, rotating, and synchronous dipoles. The recursive subspace projection procedure that they introduce here uses the metric of canonical or subspace correlations as a multidimensional form of correlation analysis between the model subspace and the data subspace, by recursively computing subspace correlations, the authors build up a model for the sources which account for a given set of data. They demonstrate here how R-MUSIC can easily extract multiple asynchronous dipolar sources that are difficult to find using the original MUSIC scan. The authors then demonstrate R-MUSIC applied to the more general IT model and show results for combinations of fixed, rotating, and synchronous dipoles.

Error bounds for EEG and MEG dipole source localization

General formulas are presented for computing a lower bound on localization and moment error for electroencephalographic (EEG) or magnetoencephalographic (MEG) current source dipole models with arbitrary sensor array geometry. Specific EEG and MEG formulas are presented for multiple dipoles in a head model with 4 spherical shells. Localization error bounds are presented for both EEG and MEG for several different sensor configurations. Graphical error contours are presented for 127 sensors covering the upper hemisphere, for both 37 sensors and 127 sensors covering a smaller region, and for the standard 10-20 EEG sensor arrangement. Both 1- and 2-dipole cases were examined for all possible dipole orientations and locations within a head quadrant. The results show a strong dependence on absolute dipole location and orientation. The results also show that fusion of the EEG and MEG measurements into a combined model reduces the lower bound. A Monte Carlo simulation was performed to check the tightness of the bounds for a selected case. The simple head model, the low power noise and the few strong dipoles were all selected in this study as optimistic conditions to establish possibly fundamental resolution limits for any localization effort. Results, under these favorable assumptions, show comparable resolutions between the EEG and the MEG models, but accuracy for a single dipole, in either case, appears limited to several millimeters for a single time slice. The lower bounds increase markedly with just 2 dipoles. Observations are given to support the need for full spatiotemporal modeling to improve these lower bounds. All of the simulation results presented can easily be scaled to other instances of noise power and dipole intensity.

Microtesla MRI of the human brain combined with MEG.

One of the challenges in functional brain imaging is integration of complementary imaging modalities, such as magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). MEG, which uses highly sensitive superconducting quantum interference devices (SQUIDs) to directly measure magnetic fields of neuronal currents, cannot be combined with conventional high-field MRI in a single instrument. Indirect matching of MEG and MRI data leads to significant co-registration errors. A recently proposed imaging method--SQUID-based microtesla MRI--can be naturally combined with MEG in the same system to directly provide structural maps for MEG-localized sources. It enables easy and accurate integration of MEG and MRI/fMRI, because microtesla MR images can be precisely matched to structural images provided by high-field MRI and other techniques. Here we report the first images of the human brain by microtesla MRI, together with auditory MEG (functional) data, recorded using the same seven-channel SQUID system during the same imaging session. The images were acquired at 46 microT measurement field with pre-polarization at 30 mT. We also estimated transverse relaxation times for different tissues at microtesla fields. Our results demonstrate feasibility and potential of human brain imaging by microtesla MRI. They also show that two new types of imaging equipment--low-cost systems for anatomical MRI of the human brain at microtesla fields, and more advanced instruments for combined functional (MEG) and structural (microtesla MRI) brain imaging--are practical.

EEG source localization and imaging using multiple signal classification approaches

Equivalent current dipoles are a powerful tool for modeling focal sources. The dipole is often sufficient to adequately represent sources of measured scalp potentials, even when the area of activation exceeds 1 cm2 of cortex. Traditional least-squares fitting techniques involve minimization of an error function with respect to the location and orientation of the dipoles. The existence of multiple local minima in this error function can result in gross errors in the computed source locations. The problem is further compounded by the requirement that the model order, i.e. the number of dipoles, be determined before error minimization can be performed. An incorrect model order can produce additional errors in the estimated source parameters. Both of these problems can be avoided using alternative search strategies based on the MUSIC (multiple signal classification) algorithm. Here the authors review the MUSIC approach and demonstrate its application to the localization of multiple current dipoles from EEG data. The authors also show that the number of detectable sources can be determined in a recursive manner from the data. Also, in contrast to least-squares, the method can find dipolar sources in the presence of additional non-dipolar sources. Finally, extensions of the MUSIC approach to allow the modeling of distributed sources are discussed.

Ripple classification helps to localize the seizure-onset zone in neocortical epilepsy

Purpose:  Fast ripples are reported to be highly localizing to the epileptogenic or seizure‐onset zone (SOZ) but may not be readily found in neocortical epilepsy, whereas ripples are insufficiently localizing. Herein we classified interictal neocortical ripples by associated characteristics to identify a subtype that may help to localize the SOZ in neocortical epilepsy. We hypothesize that ripples associated with an interictal epileptiform discharge (IED) are more pathologic, since the IED is not a normal physiologic event.

On MEG forward modelling using multipolar expansions

Magnetoencephalography (MEG) is a non-invasive functional imaging modality based on the measurement of the external magnetic field produced by neural current sources within the brain. The reconstruction of the underlying sources is a severely ill-posed inverse problem typically tackled using either low-dimensional parametric source models, such as an equivalent current dipole (ECD), or high-dimensional minimum-norm imaging techniques. The inability of the ECD to properly represent non-focal sources and the over-smoothed solutions obtained by minimum-norm methods underline the need for an alternative approach. Multipole expansion methods have the advantages of the parametric approach while at the same time adequately describing sources with significant spatial extent and arbitrary activation patterns. In this paper we first present a comparative review of spherical harmonic and Cartesian multipole expansion methods that can be used in MEG. The equations are given for the general case of arbitrary conductors and realistic sensor configurations and also for the special cases of spherically symmetric conductors and radially oriented sensors. We then report the results of computer simulations used to investigate the ability of a first-order multipole model (dipole and quadrupole) to represent spatially extended sources, which are simulated by 2D and 3D clusters of elemental dipoles. The overall field of a cluster is analysed using singular value decomposition and compared to the unit fields of a multipole, centred in the middle of the cluster, using subspace correlation metrics. Our results demonstrate the superior utility of the multipolar source model over ECD models in providing source representations of extended regions of activity.