Epilepsia, **(*):1–18, 2007

doi: 10.1111/j.1528-1167.2007.01381.x

CRITICAL REVIEWS AND INVITED COMMENTARY

EEG source localization in focal epilepsy: Where are
we now?

†Chris Plummer, ‡§A. Simon Harvey, and ∗ †Mark Cook

Centre for Clinical Neurosciences and Neurological Research, St Vincent’s Hospital, Fitzroy, Victoria, Australia;
Departments of †Medicine and ‡Paediatrics, University of Melbourne, Parkville, Victoria, Australia;
and §Department of Neurology, Royal Children’s Hospital, Parkville, Victoria, Australia

SUMMARY

ing some of the key studies performed in the field,
with emphasis given to clinical work published in
the last five years. In doing so, we discuss why
ESL techniques have not made an impact on routine epilepsy practice, underlining some of the current problems and controversies in the field. We
conclude by examining where ESL currently sits
alongside magnetoencephalography and combined
EEG-functional magnetic resonance imaging in the
investigation of focal epilepsy.
KEY WORDS: Source modeling, Dipole, Distributed, Electroencephalography, Magnetoencephalography, Functional magnetic resonance
imaging.

Electroencephalographic source localization (ESL)
by noninvasive means is an area of renewed interest in clinical epileptology. This has been driven by
innovations in the computer-assisted modeling of
dipolar and distributed sources for the investigation of focal epilepsy; a process fueled by the everincreasing computational power available to researchers for the analysis of scalp EEG recordings.
However, demonstration of the validity and clinical utility of these mathematically derived source
modeling techniques has struggled to keep pace.
This review evaluates the current clinical “fitness"
of ESL as applied to the focal epilepsies by examin-

C ONCEPTS AND C ONTROVERSIES

to the clinical validity and utility of these mathematically complex, often nonintuitive, modeling techniques. As
such, will ESL ever realize a place in the routine workup of patients with focal epilepsy? If so, what is the current level of evidence and what additional evidence is
required for ESL to achieve this status? Has ESL been
swept aside in recent years by the newer neuroimaging
modalities of magnetoencephalography (MEG) and combined EEG-functional magnetic resonance imaging (EEGfMRI)?

In the last five years, research in the field of electroencephalographic source localization (ESL) produced more
than 150 scientific papers on computer-assisted mathematical techniques for dipolar and distributed source modeling. By comparison, less than half of this number of publications addressed the clinical validation of such techniques for the investigation of focal epilepsy. Most clinical studies featured less than 20 subjects and few were
conducted prospectively. Such an imbalance might be explained away by the relative efficiency with which ESL
simulation studies yield publishable results, particularly in
the view of the advancing computational power and data
storage capacity of the modern PC processor. However,
this explanation falls short of addressing the confusion,
even cynicism, among neurologists and neurosurgeons as

The fundamentals of ESL
As a discipline that aims to localize the sources of electric currents within the brain that give rise to recordable
potential fields at the scalp (Fig. 1), ESL is almost as old
as the science of EEG itself (Jayakar et al., 1991). Since
the days of paper analog recordings, ESL in the generic
sense has been “geared up” in the last few decades by
computer-assisted source modeling techniques on the back
of digital EEG technology. Computer-assisted ESL (we
now limit “ESL” to this context) brings with it a new set of
challenges to the same goal that faced first generation electroencephalographers; that is the noninvasive localization

Accepted October 9, 2007; Online Early publication xxxxxx
Address correspondence to Chris Plummer, Centre for Clinical Neurosciences and Neurological Research, St Vincent’s Hospital, 5th Floor
Daly Wing, 35 Victoria Parade, Fitzroy, Victoria, Australia 3065. E-mail:
chris.plummer@svhm.org.au
Blackwell Publishing, Inc.
!
C 2007 International League Against Epilepsy

1

Note the polarity inversion of the dipolar field that occurs across the course of the discharge. maximal at T5). Forward models range Epilepsia. larger surface negative temporal sharp wave (at offset marker. and the latter are sub-divided into boundary and finite element method (BEM. Note the earlier.2007. Spherical shell and realistic models are the two versions of forward modeling used in ESL today (Fig. FEM) models. (C) Isopotential field plots for 36-msec period following peak of early spike wave component of same BFEC discharge. Plummer et al.2 C. models the brain. C ILAE Epilepsia ! of epileptogenic networks in the patient presenting with epilepsy. or source network. (B) Butterfly plot showing superimposed waveforms for the 19 channels. small surface negative frontal sharp wave (at onset marker. more concentric.01381. It is the set of conditions specified to the forward problem that distinguishes one forward model from another. The MGFP curve for the BFEC sharp wave complex is shown. MGFP (Mean Global Field Power). Figure 1. **(*):1–18. (A) Scalp recorded 19-channel EEG using Common Average Reference from a patient with BFEC. skull.1111/j.” its projected (lead) field passing through modeled compartments and tissue interfaces to reach the recording electrodes. its compartments segmented from the patient’s MRI scan. The left frontal field is initially surface negative (blue) and later surface positive (red).x from simple (a single spherical shell models the brain surface) to complex (a four-layered realistic model. also referred to as the volume conductor or forward model. maximal at F3) and the later. The forward problem is solved by specifying a set of conditions (compartments. the forward model will enable the computation of a specific potential field at its surface (Wilson & .1528-1167. and scalp surfaces). The isopotential lines demonstrate that the later surface negative temporal field has a broader distribution than the earlier. “performs. The forward model by analogy is the “stage” on which the source. Values at the extreme right of channel waveforms correspond to surface potential points (in microVolts) at the −24. We touch on the application of these models in the next section. surfaces. cerebrospinal fluid. 2007 doi: 10.22 msec latency marker (midway between onset and offset interval markers. For a specific electrical source. Abbreviations: BFEC (Benign Focal Epilepsy of Childhood). or four) overlapping shell models. while the left temporal field is initially surface positive (red) and later surface negative (blue). asterisked). Two fundamental problems exist in the practice of ESL—forward and inverse. negative values indicate deflections above the zero potential line. conductivities) for the head model. The former vary in complexity from single shell to multiple (two. three. As is customary. 2). negative frontal field.

1853). **(*):1–18. the forward problem will give a “unique” solution. skull. a property that allows conductivity values to vary within each compartment. note how well the FEM captures the shape of the brain in the modeling of its innermost compartment. the inverse problem is made soluble by the incorporation of mathematical constraints into inverse modeling algorithms. This means that tissue anisotropy can be factored into algorithms that solve the forward problem.01381. CSF. constraint conditions distinguish one inverse model from the next. has no unique solution. CSF. The evolution of forward modeling in ESL.1528-1167. Thus. as illustrated here with a 4-shell model projected over a digitally reconstructed cortex from an averaged MRI scan. The BEM models are composed of overlapping. by contrast. 2 shell.3 EEG Source Localization in Focal Epilepsy Figure 2. The mathematics of inverse modeling can be quite complex and it is not the purpose of this paper to summarize the algebraic pros and cons of the several dipolar and Epilepsia. Different compartments are usually given different conductivity values. This is the problem the electroencephalographer attempts to solve in routine clinical practice. As distinct from the 4-shell model. FEM (Finite Element Method). The inverse problem.brain. Spherical shell models range in complexity from one to four overlapping shell surfaces to model the head as a volume conductor (single shell. MRI (Magnetic Resonance Image).1111/j. inferior surfaces. 1950). Similarly in ESL. skin. the FEM models are composed of multiple. supplemented perhaps by information from anatomical or functional imaging studies. This is particularly the case at the brain’s deeper. each layer having been computer generated from segmented T 1 -weighted MRI surfaces (scalp.brain. two-dimensional. in theory. skin). The two major inverse modeling approaches are the dipolar and distributed modeling methods. solid tetrahedra. 3 shell. three-dimensional. skull. Realistic head models (BEM and FEM) are so called because they better approximate the shape of the human brain than do shell models. but conductivity within each compartment is assumed to be isotropic and homogenous. In contrast. Just as volume compartment and boundary conditions distinguish one forward model from the next. In practice. traditionally with a mind’s eye rendering of candidate sources drawn from the various EEG montage digital displays. CSF (cerebrospinal fluid). C ILAE Epilepsia ! Bayley. That is. skull.brain.brain.2007. an infinite number of source permutations can.x . the experienced electroencephalographer “constrains” the infinite possible solutions to the inverse problem by applying their working knowledge of epileptogenesis in the focal epilepsy syndromes to the patient’s clinical picture. 4 shell. skull. and cortex). triangulated mesh layers (or boundaries). explain a specific potential field recorded at the surface (Helmholtz. 2007 doi: 10. Abbreviations: BEM (Boundary Element Method).

It is worth pointing out that different types of dipole symbols are used in the ESL literature. but frees it to assume an orientation and strength to explain the variance Epilepsia.. orientation. Each dipole is fitted to a single time point at successive 4-msec intervals across that part of the interictal discharge shown in Figures 1A... In contrast. This means there are far more data sampling points (viz.. 2004a). 2004a). or three (rarely more) dipoles to apply to the inverse algorithm in question. This is because. What should be stressed though is that dipolar methods are “overdetermined” (Fuchs et al. but investigators do not routinely spell out surface negative and surface positive aspects of such dipole symbols. Two of the most commonly used inverse algorithms in ESL are the moving and rotating dipole methods.22 msec) approximates the halfway point of the upswing phase of the surface negative discharge. on current evidence. Instead. (B) LORETA distributed inverse model used with a BEM forward model. +z upward). 3A). Relative dipole size is in proportion to dipole strength or amplitude.” fixed in space but free to assume any orientation and strength. each point representing a “minidipole. Note the relatively diffuse distribution of the current density map spanning the left central sulcal region. smaller surface negative frontal sharp wave seen in the BFEC discharge is represented by the smaller. electrodes) than there are dipole parameters in determining the ESL solution.1528-1167. 2007 doi: 10.01381. Brighter signal intensities indicate higher current density values (scaled as microamperes per square millimeter). Orthogonal axes are shown (+x left.x in the measured data across any time interval (Fuchs et al. The predefined solution space (be it the whole brain volume or just the cortical volume) is split into multiple points. Hence. That is.2007. (A) ESL example of a Moving dipole inverse model used with an FEM forward model based on the same BFEC sharp wave complex depicted in Figure 1. Broad.4 C. but frees it in space to assume a location. ESL (EEG source localization). lighter green dipoles represent the upswing phase of the larger.1111/j. 2004. Plummer et al. darker green dipoles. . Figure 3. a point which. FEM (finite element method). 1B. C ILAE Epilepsia ! distributed models available in ESL—for reviews see (Darvas et al. Michel et al. The moving algorithm constrains the dipole to instants in time (successive 4 msec time instants in a 256 Hz recording are usually solved). there are far fewer sampling points than possible ESL solutions. The rotating algorithm constrains the dipole to a location in space. +y posterior. LORETA (Low Resolution Electromagnetic Tomography). while the larger. Appreciate that the single time point chosen for display (−24. distributed methods are “under-determined” (Fuchs et al. blurred ESL solutions are quite typical for the LORETA method. Also note that an example of a confidence ellipsoid is shown attached to one of the larger dipoles (asterisked). Due to the enormous number of permutations that stem from such mini-dipole networks. postprocessing constraints need to be applied to achieve a unique ESL solution. Abbreviations: BEM (boundary element method). Note that each color-coded dipole symbol is made up of a spherical end directed toward the surface negative cortex and a straightened tip directed toward the surface positive cortex. and strength to best explain the measured EEG data at each time instant (Fig. 1999) in the sense that the investigator preselects one. all offering a theoretically plausible explanation for the measured EEG signal. later surface negative temporal sharp wave. BFEC (Benign Focal Epilepsy of Childhood). the earlier. the working premise is that multiple sources may be simultaneously active across multiple locations at a given instant in time. appears to most reliably reflect the state of the corresponding intracranial potential field. no assumption is made on the number of dipoles used to solve the inverse problem. 1999). **(*):1–18.. two. unlike dipole modeling strategies.

It is probably under-emphasized that in terms of presentday clinical utility. LORETA applies a modeling constraint based on the idea that neighboring neuronal populations are more likely (than nonneighboring ones) to undergo synchronous depolarization during a spontaneous discharge or an evoked response (Pascual-Marqui et al. while it has been theorized that the brain–skull interface dampens the voltage of a dipole point to one-eighth of its strength. It is often misunderstood that the inverse and forward problems are interdependent. boundary element methods) assume homogenous. himself warning that “excessive emphasis on volume conduction and total reliance on biophysics are not the answer to EEG signal analysis” (Niedermeyer. 1967). 1997).5 EEG Source Localization in Focal Epilepsy Low-resolution electromagnetic tomography (LORETA) is one of the more familiar distributed modeling algorithms used in ESL (Fig. **(*):1–18. in practice. The second factor is the absence of agreed-upon tissue conductivity values for the various tissue compartments in the human head. inferior aspects of the brain compared to overlapping shell models (Ebersole. Research efforts aimed at further advancing realistic models. 2002). lie in (a) deciding on which of the available forward and inverse models are the most appropriate to apply. such assumptions may not always be in touch with electrophysiological reality..2007. or more commonly indirectly. the mathematical algorithms specified to each problem are independently set (Scherg et al. Thus. 2007). Scant attention has been given to the latter in the ESL literature to date. They are only interdependent in the sense that both are required to generate an ESL solution. LORETA modeling tends to generate broad. 1996. The latter give dipole location errors of up to 30 mm in the rostral direction—spherical shell models commonly mislocalize known mesial tempo- ral lobe source activity to the frontal lobe (Cuffin. 1999). it should be kept in mind that skull conductivity actually improves with increasing skull thickness due to the accompanying increase in the ratio of cancellous to cortical bone—marrow conductivity being higher than that of cortical bone (Nunez & Srinivasan. 1994). and orbitofrontal brain surfaces (Ebersole. it should be appreciated that the effects of signal propagation (primarily via cortico-cortical pathways) on scalp EEG voltage topography are not factored into equations designed to solve the forward problem. The first is the extra computational demand that complicates the integration of tissue anisotropy parameters into the forward modeling algorithm. But on this point. regions that commonly “play host” to the epileptogenic zone in focal epilepsy. Errors in dipole orientation were also noted to increase when spherical models were used in place of realistic models in a more recent simulation study (Crouzeix et al. 2007 doi: 10. using simultaneously acquired intracranial EEG. Niedermeyer reminds us of Jasper’s observation 40 years ago that “propagation along conducting pathways represents the most important mechanism of signal spread (especially as regards epileptiform signals)” (Jasper. such that they are brought “closer to reality. the wide range of values published for the skull-to-brain conductivity ratio in humans is at least partly due to inherent discrepancies between in vitro and in vivo based findings (Nunez & Srinivasan. and (b) translating the theoretical impact governed by the choice of a particular forward–inverse modeling set-up into terms that define the clinical impact of such a choice on the patient’s diagnosis and management. The two major challenges then.. Moreover. This is important to appreciate because any ESL solution can be reached when any inverse model is coupled with any forward model. On the forward problem and its problems The relative disconnect at the technical–clinical interface of ESL research is exemplified by the forward problem.. the latter influencing Epilepsia. is optimized with the use of realistic head models that more accurately delineate the nonspherical. In any case. and scalp that are based on an in vitro study published 40 years ago (Geddes & Baker..1528-1167. a more recent in vivo study suggests that the inter-individual variability of these properties may limit the generalizability of tissue conductivity values for realistic models (Ha et al.” remain hamstrung by three factors. 3B). For example. While finite element methods aim to satisfy the more physiological anisotropic. As discussed later. Spherical models conform to frontal and parietal brain convexities reasonably well but are found wanting when it comes to the modeling of infero-occipital. 2006a). While these observations are important. 2003a). 1997a).1111/j. The digital reconstruction of realistic forward models that predict the impact of volume conduction on the generation of scalp potentials remains a central theme in biophysics EEG research. using estimates of concordance with other functional and anatomical studies. infero.. There is little doubt that the modeling of basal source activity. smoothed ESL solutions as neighborhood sources are model term conditioned to assume similar strengths. isotropic conduction within compartments and limit conductivity variability to surface boundaries alone. However. as in temporal lobe epilepsy. the “individualization” of forward modeling would expectedly depend on regional nuances in individual skull thickness and cranial contouring relative to the brain. the property that differentiates spherical from realistic head models simply relates to model shape. heterogeneous conduction that takes place within tissue compartments and across tissue boundaries (Fuchs et al. 1999). Clinical studies often apply conductivity values for the brain. Most clinical studies preselect a particular forward–inverse modeling combination (shell or realistic-dipolar or distributed) and test its performance in a particular clinical setting either directly. 2006a).. rather than to any more advanced feature (Fuchs et al. most realistic models (viz.01381.x .and mesial temporal. 2003). 2005). 1969).. Roth et al. skull.

rather than the source-to-electrode distance. Our present understanding of EEG signal generation is actually based on the electrophysiological theory that the EEG waveform is the product of a myriad of dipoles. potential field maximum that better delineates the origin .x et al. a phenomenon not easily appreciated from the traditional visual inspection of the EEG waveform alone (Ebersole. As Ebersole has repeatedly emphasized. On the inverse problem and its misconceptions Just as forward models vary in complexity from single shell models to multicompartment realistic models.. Plummer et al. that flux in polarity within the cortical space (Brazier. It is the linear summation of the extracellular components of these pyramidal cell microcircuits. Although speculative. 2000).1111/j. Gloor. 1985). both dipolar and distributed. a dipole is not a discrete anatomical construct but a theoretical concept on which the modeling of relatively large segments of synchronously discharging cortex is based (Ebersole & Hawes-Ebersole. if not more. Likewise. 2002). 1C). (A) Dipole models provide point-like anatomical solutions for spike and seizure localization It is tempting to interpret dipoles as point sources of interictal or ictal activity when they are pitched.” depth-weighted minimum norm. Passive loops of extracellular current are set up to complete the local circuit (Buzsaki et al. it is typically the contralateral surface-positive. dipole and distributed models carry little electrophysiological relevance Electroencephalograph literally means “electrical brain picture”— “electro-encephalo-gramma” being the Greek roots (Knott. the pyramidal cell experiences a progressive wave of depolarization along the length of the axon. inverse dipolar models range from single fixed dipoles fitted to single time points (as with fixed and moving dipoles) to multiple dipoles that overlap in three-dimensional space across time intervals (as with rotating and regional spatiotemporal dipoles). the relative clinical impact of such a parameter on volume conduction (vs brain-skull and scalp-air interface effects) remains unqualified. and not the ipsilateral surface-negative. 1949. 1978). distributed models can be broadly classified into those that use “linear” mathematics (as with the so called “minimum norm. z location in space is the sine qua non of a dipole model’s accuracy. as Gotman points out. 1994). 1999) and whose strength.01381. positive and negative. The third problem that needs to be resolved is the clinical relevance of incorporating brain tissue anisotropy into forward modeling calculations via finite element methods. it can be appreciated that both surface polarity maxima (positive and negative) of the potential field carry useful localizing information (Fig. that determines EEG surface polarity. anisotropic modeling of brain tissue may offer some much needed insight into the biophysical properties of interictal and ictal source propagation occurring across cortical regions. This misconception is understandable given the millimeter margins of error that are often cited for dipole positions in simulation studies. The orientation of the dipole is just as.. (C) As artificial concepts.6 C. largely by virtue of the multidirectional nature of white matter fiber tracts (Nunez & Srinivasan. While diffusion tensor imaging (DTI) techniques are beginning to avail quantification of white matter anisotropy (Mori & van Zijl.2007. However. particularly in the biophysics literature. The immediate relevance of this becomes apparent when one considers that approximately 98% of pyramidal cell input in humans is via cortico-cortical connections (Braitenberg. as a definition it is somewhat vague and. 2003). 2006a). Perhaps the most common error in EEG reading is to see the electrode that registers the peak voltage of an epileptiform discharge as the one that lies closest to the source (Ebersole. over a coregistered image from the patient’s MRI scan. Following its excitation at the postsynaptic membrane. electrode distance and electrode orientation relative to the cortical surface (Binnie et al. and LORETA models) and those that use nonlinear mathematics (as with L1 norm methods). Average white matter resistivity is approximately double that of gray matter. 1985). informative of the behavior of a putative source. It is useful to visualize this extended source activity through the conceptual lens of Gloor’s solid angle theory (Gloor. Unfortunately.1528-1167. With this is mind. The threshold cortical area for a spike to be seen by the scalp electrodes is 10 cm2 (Tao Epilepsia. for a given time point or time interval.. the dipole most reliably models the maximum potential of a source whose intracerebral field is often quite extensive (Merlet & Gotman. (B) The dipole marks the “center of mass” of the source This is an oft-quoted phrase in the ESL literature. 2007 doi: 10. **(*):1–18. 1985. and orientation can change quite rapidly across the time course of an epileptiform discharge. This is especially so when ESL studies not uncommonly infer that a dipole’s x. 2003). or dipolar configurations. 2007). that configures the source and its projection to the scalp as a recordable potential field. Gloor’s theory reminds us that it is the cortical configuration (area and orientation) of the source in relation to the recording electrode. rather than presenting a didactic discussion on the variety of inverse algorithms. The state of a dipole’s orientation within milliseconds of spike or seizure onset can shed light on patterns of corticocortical propagation. simultaneous surface-depth recordings suggest that. as is often done in publications. 2003b). location. Ebersole. For instance. 2005). we will address some of the key concepts in inverse modeling as a series of common misconceptions. available in ESL today (some of which we discuss further in the next section). Rather than visualizing a dipole as the center of a mass of equivalent current. 1982). The electromotive force behind dipolar field generation is the resting membrane potential of the pyramidal neuron. there is actually no proof for it despite its longevity as a concept (Gotman. y.

. that it is the earlier component of the epileptiform discharge at the scalp. averaging carries the inherent risk of mislocalizing single events if the latter are not truly monomorphic (Braga et al. too many difficulties with image coregistration. misleading in terms of the probability that the ESL result actually models the original interictal or ictal source. he stresses the importance of using a forward noise filter for ESL. the greater is the probability that the dipole resides at the fit location for a given time point or time interval. On theoretical estimates. In electrophysiological terms. rather than a zero-phase shift filter. While averaging can improve the “localizability” of the earlier components of focal epileptiform discharges (to the point where it tends to be done routinely in research). 2004b).5–1 Hz cut-off (Scherg et al.. the SNR is commonly optimized by averaging single events. the electrophysiological relevance of dipole modeling theory at the macro-scalar level (lobar and sublobar) will likely remain intact (Nunez & Srinivasan. by definition. relates to its reproducibility and. It is rather the “next tier”—the application of macro-scalar theory. the signal is often well removed from the original source due to the effects of cortico-cortical propagation. 1990). to routine epilepsy patient work-up—that needs more rigorous proof of concept at this point in time. 1987). 2004b) and clinical (Plummer et al. Electrode caps are not an ideal answer to this problem as electrode-scalp contacts can be unreliable and their use for long-term EEG monitoring is impractical. Various methods. 1999). 1993. it is important to keep the spatial limitations of dipole modeling in perspective. 2003). there is the penalty of having to measure and fix hundreds of electrodes to the scalp. too much computer knowledge. small CE volumes tend to occur in the vicinity of the spike’s peak where the SNR is typically higher.2007. By the same token. and thus facilitate the task of distinguishing source origin from source propagation. however. which most closely matches the location and field of the source as suggested by the corresponding intracranial EEG activity (Fig. lies between 100 and 200 (Gevins. It has become increasingly recognized that ESL results based on spike peak activity. pending the suitability of the forward–inverse modeling set-up. the so-called Nyquist criterion. to its capacity to explain the signal variance at the scalp electrodes. an ap- proach that is still seen in clinical studies.x . One dipole models upwards of around 10 cm2 of cortical tissue. Chitoku et al.1111/j. Srinivasan et al. as is usually the case at the spike peak. Assuming technically satisfactory EEG signal acquisition. Along these lines. 2007) studies. (E) ESL is too cumbersome to perform. perhaps not surprisingly. should be interpreted with caution.1528-1167. such as phase coherence and global field power correlation (Lehmann. 2007 doi: 10. The effect is to minimize the contribution of slower frequencies that are less likely to figure in the earliest source activity. 1A. strength). The problem then lies with the accurate modeling of earlier phase interictal or ictal activity when the signal is often buried in noise. This is why it is important not to regard dipole solutions as point-like millimeter (let alone submillimeter) indices of abnormally discharging cortex. the smaller the CE volume. such a logarithmic leap in spatial dimension has led Nunez to propose that. and too many time demands make it impractical for routine use in the clinical setting There remains no fixed agreement on the minimum number of scalp electrodes required for clinically useful ESL in focal epilepsy. This is because simultaneous surfacedepth recordings reveal. One scalp electrode is estimated to record the synchronized and aligned space-averaged potentials of around 108 to 109 neurons (Nunez & Srinivasan. In a similar vein. One cubic millimeter of human neocortex contains around 105 neurons and 109 synapses. 2002.7 EEG Source Localization in Focal Epilepsy and propagation of ictal or interictal source activity in mesial versus lateral temporal lobe epilepsy (Ebersole & Wade.. should there be a major shift in our future understanding of epileptogenesis at the micro-scalar level (cellular and subcellular). 2006a). 2006a). At the scalp recorded spike peak. Thus.01381. few studies have rigorously examined the clinical impact of single versus averaged event selection in dipolar and distributed modeling. The stability of an ESL solution. Scherg has emphasized that source activity onset is best demarcated with a higher low-filter setting. 1996). the parameters that define it (location. In other words. as the latter tends to artificially blur signal onset and offset. However. a recently introduced strategy to help quantify the probability of an ESL solution is the confidence ellipsoid (CE) volume calculation (Fuchs et al. The loading Epilepsia. An inverse relationship between the CE volume and the SNR has been demonstrated in both simulation (Fuchs et al. Dipoles fitted with CE volumes are. the minimal number of scalp electrodes required for optimal EEG spatial resolution.3A). It is technically true because dipole and distributed modeling solutions are most stable when the signal to noise ratio (SNR) is highest.. **(*):1–18. “free to roam” within the confines of the ellipsoid space without its inverse fit parameters impacting on the forward fit solution beyond the level of noise attached to the solution subspace (Fig. The above tenet is. recommending a 2–10 Hz frequency threshold range instead of the more traditional 0. or more specifically. Too many electrodes.. orientation. in the form of ESL. (D) The surface negative peak of the highest amplitude spike from the scalp EEG recording gives the most reliable ESL result This is both partly true and false.. have been used to help pool “identical” discharges for averaging purposes. 1B).. While high-density electrode arrays can improve the spatial resolution of surface EEG signal topography.

for distributed ESL solutions to be sufficiently spatially resolved.g. this is. “EPIFOCUS” (Grave de Peralta Melendez et al. not unlike fMRI signal thresholds.2007. distributed algorithms are computationally more demanding such that. **(*):1–18. Hence. 2001). The computer technology. Coregistration problems are more readily overcome with the recent availability of MRI compatible electrodes and the ability to perform less artifact-laden EEG recordings in the MRI scanner. This means that it is difficult to appreciate the relative timing of overlapping source components contributing to the modeled Epilepsia. In fact. the authors argued that ESL results were contaminated by noise (toward spike onset) and by propagation effects (toward spike peak). with little change from a 63 to a 123 electrode set-up (Lantz et al. spatiotemporal relationships between successive. 2007) but await clinical validation.1528-1167. understandably. Also. as is commonly the case. modeling seizure sources. three different voltage field maps during the rising phase of the scalp-recorded spike per patient (range one to five). Using a novel spatiotemporal cluster analysis technique..01381. particularly in light of the work carried out in the field in the last few years? What recent progress has been made toward the clinical validation of ESL? We explore some fundamental questions that warrant closer scrutiny if ESL is to assume a clinical role in routine epilepsy practice. as with the use of inferior temporal arrays in temporal lobe epilepsy. 2003a).. perhaps surprisingly. A more recent study in a group of 14 patients with refractory focal epilepsy and Engel class 1 surgical outcomes showed that ESL accuracy. because the inverse model used was a single fit applied to a combined dipolar-distributed algorithm. All had an Engel class 1 surgical outcome. such as the cortex.. more studies in the manner of Lantz et al. Some of this modeling error can be limited by preconstraining the ESL solution to anatomically meaningful boundaries.8 C. as all spikes were averaged. can provide clinically valid ESL results based on intracranial EEG localization (Ebersole. 2001. Plummer et al. with the possible exceptions of ambulatory monitoring EEG and OR/ICU EEG” (Krauss & Webber. Until then. They wondered how stable the scalp EEG field was from spike onset to spike peak. for most present applications. 1999). 2001). ESL solutions can only be calculated for time instants.. e. does their implicit observation on the clinical worth of ESL still hold.1111/j. a benefit carried by distributed over dipolar modeling methods (Wagner et al. is not an uncommon misconception. The question of optimum scalp electrode number for ESL may be settled by default with the future development of quicker methods that reliably fix high-density electrode arrays to the scalp.. on average. However. so the application of a “half-way point” rule to ESL when fewer electrodes are employed. show promise (Fuchs et al. which is virtually never the case. This only holds if the distributed model is perfectly correct. Krauss and Webber still have it that “digital EEG has not significantly expanded the clinical role of EEG. Lantz et al. current density thresholds are set which. While source orientation was not considered and single-spike peaks were modeled. on which current-generation ESL relies. C LINICAL S TUDIES IN D IPOLAR AND D ISTRIBUTED ESL Despite the clinically based research efforts in ESL by Ebersole and others over the last two decades. They based their observations on the spike-averaged recordings of 16 patients with symptomatic focal epilepsy.” seems reasonable enough. indexed by the distance from the nearest surgical margin to the location of a single fit inverse model. It should be noted that 125 electrodes were used in the study. the first study to have systematically examined this issue in a well-defined patient group. they saw. are needed. The “distributed-ness” of a distributed algorithm’s solution is generally not the direct representation of the potential field of the actual source. (F) Distributed models display sources as current density field maps that are “closer to reality” than dipole modeled sources This. improved by around 2 cm from a 31 to a 63 electrode set-up. 2005). the generalizability of the results to single-spike . 2003a). the more established anatomical pathways of interictal and ictal discharge propagation are not factored into current density threshold settings. of scalp electrodes over putative cortical foci. When ESL was performed on these different voltage maps. 2001) for each field map.. Newly developed coregistration methods. 2003b). is not entirely clear. While their premise that “an expanded clinical role for digital EEG may depend partially on validating advanced analysis techniques. much of the apparent “field” effect results from the distributed algorithm’s inexactness in modeling the source. independent time-point fits cannot be fully resolved. Either side of this point. the source model location coincided with the MRI lesion location for all patients within a fairly narrow time window across the upswing phase of the spike—around the halfway point. has become more accessible to clinicians in the last five years due to improvements in the user interface of software operating systems.. based on the use of mutual three-dimensional “virtual landmarks” from patient MRI datasets. Finally. by virtue of their under-determined nature. Dipole simulation work has also demonstrated that nonuniform sampling with 10–10 scalp positions in the region of interest and 10–20 positions elsewhere can provide reliable estimates of source characteristics (Benar & Gotman.x cortical activity across the early spike interval (Scherg et al. Which part of the spike should be modeled? Lantz and colleagues have carefully examined this issue (Lantz et al. 2007 doi: 10. are typically arbitrary. Also.

MN solutions therefore typically localize to the superficial cortex and a mathematical depth weighting term is often applied to “counteract” Epilepsia. Interictal EEG recordings were acquired using 19–29 scalp electrodes. 2004b). thus making it difficult to disentangle interlobar or interhemispheric propagation effects from effects potentially attributable to multiple independent sources on ESL outcome. 17 extratemporal). From a subgroup of 24 patients who underwent surgery (17 temporal. there is the concern that the investigators were not blinded to the patients’ para-clinical data during the source fitting procedure. and the type 2 dipole with a lateral temporal lobe source (Ebersole and Wade. Comparative results on normal (mock) MRI data would have further strengthened the case for the robustness of their source localization technique. seven extratemporal). shifts on a scale of tens of milliseconds across the earliest phase of spike interval.1111/j. based on the earlier observations of Ebersole and Wade. “usually by confirming the incongruence between structural abnormality and ictal EEG abnormality” (10 patients) and leading “to the decision not to proceed with invasive EEG recording and further surgical resection. resection boundaries are variably wider than lesion boundaries and so measurement bias may have inflated the accuracy of their ESL results. 18 had an ESL maximum that fell within the border of the nearest resection margin (three temporal. While the results are encouraging.2007.01381. 2006) more recently examined ESL accuracy in a pediatric epilepsy surgical cohort (13 temporal.” Unfortunately. and each ESL analysis was performed in a timely manner. The clinical immediacy of this problem was reemphasized by a recent depth electrode study that showed that postsurgical success in medically refractory TLE relies heavily on the spatial resolution of the ictal onset zone on a sublobar scale (Chabardes et al. a heterogeneous group of 44 epilepsy surgery candidates undertook a supplementary 128 channel surface recording for the purpose of single source dipolar-distributed modeling (EPIFOCUS). The spatiotemporal modeling was actually limited to the use of a single (regional) dipole. Most cases were lesional (83%). with standardized electrode positions prefitted to the outermost shell. 2002) looked at the contribution of spatiotemporal dipole modeling to the clinical decision making process in 100 presurgical patients with refractory focal epilepsy. Scalp ictal EEG recordings from a 27-electrode set-up (10–20 positions plus three inferior temporal electrode pairs) were analyzed. and by extension the ESL result. an experience that contradicts recent findings on the relative clinical utility of dipole modeling in focal epilepsy (Plummer et al. 1994). the authors quoted an 8 h time cost for the analysis from start to finish.9 EEG Source Localization in Focal Epilepsy modeling is uncertain. with the largest subgroup having unilateral hippocampal sclerosis (53%). ESL results were strictly categorized as type 1 (vertical) and type 2 (radial) dipoles.1528-1167. From the 93 patients who recorded ictal EEG phenomena. it was concluded that ESL influenced the clinical interpretation in 14 cases. range: 7–33 months). three extratemporal were nonconcordant). and it performed zero-phase shift filtering on the EEG raw data. 2005). What is especially striking about this study is the degree of accuracy achieved for the localization despite the fact that each patient’s MRI brain was morphed to fit a threeshell sphere for the forward model set-up. Interestingly. Still. Lastly. 2007). and even earlier in the ictus. recognizing the inter-changeability of type 1 and 2 dipolar patterns in both forms of TLE (Ebersole. two of the nonconcordant extratemporal cases were mirror localized to the contralateral hemisphere. The same research group (Sperli et al. MN).. their respective presurgical MRI lesions sitting close to the parieto-occipital midline. all but two patients had concordant ESL findings at a lobar level. In the largest prospective interictal ESL study to date (Michel et al.. it gave no information on postsurgical outcome. 2007 doi: 10. the study contains several methodological deficiencies. 2000).. Of the remaining 31 patients. who equated the type 1 dipole with a mesiobasal temporal lobe source. An Engel class 1 outcome was shared by 16 of the 18 cases (mean follow up 19 months. 1990). **(*):1–18. as the investigators do point out.. How well does ESL corroborate epilepsy surgery findings? The largest prospective study to date on this topic (Boon et al. a breakdown of the distance from nearest resection boundary to nearest lesion boundary in each of the surgical cases may have been more informative. largely by virtue of discharge propagation effects occurring early in the interictus. the study is the first to systematically quantify the increasingly appreciated concept that the surface voltage topography. Of the 32 patients who had an identifiable focus.. Also. the investigators quoted a high level of agreement between the intracranially directed interictal and ictal localization and the high-density surface electrode-directed ESL result (five of seven cases). A distributed inverse model was applied in this case (depth-weighted minimum norm. 62 patients could not undergo ESL analysis due to excessive artifact contamination. ESL results were constrained to the cortical gray matter and based on the midway point of the averaged spike’s upswing phase. Although the intracranial and 128 channel recordings were not performed simultaneously. seven of whom underwent invasive recording in addition to the routine presurgical work up.x . It was not blinded. Also. This classification was subsequently seen as an oversimplification by Ebersole himself. The MN algorithm favors current density solutions that explain surface electromagnetic fields with the least net strength per time point (Hamalainen & Ilmoniemi. Rather than countering this point by stressing the ESL concordance for scalp and intracranial recordings in the few patients who had both performed.

it should be appreciated that distributed models are based on complex sets of mathematical assumptions that are yet to achieve clinical validation. In a follow-up study (Zumsteg et al. While the present results need to be reproduced by other investigators. The decision to exclude 11 patterns from the LORETA analysis due to the suspected nonfocality of the source (based on the local FO field) seems unusual. How well does scalp ESL model interictal and ictal onset as defined by intracranial recordings? Zumsteg and colleagues also performed statistical postprocessing of a distributed algorithm (LORETA) in a retrospective study of 15 patients with symptomatic mesial TLE (MTLE) (Zumsteg et al. no postoperative MRI was available and the “epileptogenic region” was mapped via an interpretation of the surgical notes.. a premise that was supported by their “corrected” modeling of two of these cases when ESL was repeated with a highdensity electrode set-up (128 channels). The authors argued that the three mislocalized cases (all temporal) stemmed from the inadequate sampling of the inferior temporal region.000 FO spikes.2007. with both the raw and SNPM LORETA results derived from the simultaneous scalp EEG recording (23 electrode set-up). 18%). range: 2–24 months). 14 could be localized by scalp ESL based on the rising phase of the spike-averaged waveform. mesially placed activation that correlated well with the local FO field. In a majority of the cases (19/30). **(*):1–18. Several important findings came from their meticulous analysis of over 4. The relationship between the epileptogenic zone and the putative epileptogenic lesion is far from direct—for review see Rosenow & Luders (2001). but there dipole orientation was more haphazard. With solutions that are as visually “seductive as functional MRI” (Ebersole. should be interpreted cautiously. preceded the spike peak. Epilepsia.x From 19 local field “patterns” seen by the FO electrodes (11 patterns excluded). either scalp signal averaging (60%) or FO spike correlation (13%) was needed to confidently identify the corresponding lower voltage scalp spikes (no scalp signal was seen despite such EEG postprocessing in the remainder. ESL accuracy was determined in this study by the degree of overlap (arbitrary 50% minimum) between the resection boundary (defined as the “epileptogenic region”) and a statistically deconstructed depth-weighted MN map (earliest vowel-wise activity p < 0.” The results were encouraging with a 90% concordance between ESL location and nearest resection border and an 87% postoperative seizure freedom rate (mean follow up 13 months. they used nonparametric mapping (SNPM).1528-1167. As with their previous paper. Presumably as a result of the blurred. which the authors defined as the region of “discharge onset. thereby avoiding an assumption that the “raw” ESL results necessarily conformed to a Gaussian statistical distribution. Only 9% of FO spikes were identified “de novo” at the scalp. and use of only two supplementary inferior temporal electrode pairs).01381. occurred in either direction (mesial to lateral. and 11 “lateral”). 1997a). They compared the interictal localization suggested by recordings from foramen ovale (FO) electrodes. 2007 doi: 10. A different group of investigators (Nayak et al. The authors reasoned that the de novo spikes (100+ microV) were the product of summated propagation from the deeper mesial source configuration and that the smaller . there was no blinding in this study. which look directly at the hippocampus. it should be stressed that studies using lesion or resection margins to validate ESL results. Otherwise. and was not associated with Engel class outcome. lateral to mesial). One of the benefits of distributed over dipolar modeling is that the former is generally better equipped to display extended source configurations.. the investigators used the same patients and the same SNPM LORETA technique to explore the nature of spike propagation in MTLE.10 C. Interestingly. 2004) used dipole modeling to help characterize the relationship between the FO recorded field and the corresponding scalp EEG field in a retrospective study of 20 patients with MTLE.. 2004a). they did not indicate which FO pattern belonged to which patient. de novo scalp spikes were associated with a shallower FO field gradient and were seen up to 2 msec later than the small scalp spikes.. background). signal propagation was evident in 16 patterns. they regarded it as the first attempt to examine the accuracy of a distributed inverse model using simultaneously acquired scalp and intracranial EEG recordings. 2006). The latter were associated with a wider scalp field with around 20% of these peaking in amplitude at the contralateral scalp. The use of a statistical discriminator in the present study might be seen as a step in the right direction in this validation process.0001 vs.1111/j. all 30 FO field patterns were included in this study (19 “mesial” from the earlier study. Raw LORETA maps typically showed basolateral temporal activation. This study draws out some of the inherent difficulties associated with ESL based on current-generation distributed modeling methods. diffuse nature of the MN-based solution. Also. Plummer et al. However.. While the authors noted several limitations in the retrospective study design (reliance on FO electrodes to capture large propagating fields. even in Engel class 1 cohorts. Based on the SNPM LORETA activation sequence. the level of accuracy obtained with a 10–20 electrode set-up does support a potential role for ESL in the routine clinical setting. Unlike the study by Sperli and colleagues (Sperli et al. 2005). 2006). this tendency (Michel et al. Finally. Dipole localization placed de novo spikes at the retro-orbital region and smaller spikes at the mesial temporal region. while the authors tabulated Engel class surgical outcomes at one year for each patient (most were class 1). use of a three-shell forward model coregistered with a generic brain MRI. while the corresponding SNPM LORETA images showed more discrete.

In a related publication (Assaf & Ebersole.1528-1167. The authors examined the EEG recordings of 40 TLE patients who required intracranial electrode implantation as part of the surgical work-up. 1997). Relatively few ictal studies addressing the correlation between scalp and intracranial ESL have ever been published and. and surgical outcome). spike peaks were also modeled. as the authors argue.x . this might well result in “partially compensated” mislocalization to the retro-orbital region. particularly in light of the generally held view that deep mesial discharges are only seen at the scalp by virtue of propagation alone (Ebersole. For ease of comparison. then confining ESL to the spike peak may well exaggerate the influence of signal propagation on the final result. 2007 doi: 10. **(*):1–18. Indeed. it was argued that the retro-orbital dipole localization was likely the result of distortion of the scalp EEG field with the preferential propagation of current through the superior orbital fissures. but was Epilepsia.2007. The main ictal studies are limited to dipole modeling and arguably the most influential publication is 10 years old (Assaf & Ebersole. Notwithstanding the Engel class 1 outcome for all patients. most studies have used presurgical TLE patient cohorts. the authors showed how their dipole modeling approach might be used to anticipate surgical success following either standard or modified anteromesial temporal lobectomy (AMTL). pathology. the authors did not show patient clinical data (radiology. the presurgical work-up having been performed between 1990 and 1998. Spatiotemporal dipole modeling was carried out on scalp data that had been acquired with a 25-electrode set-up (standard 10–20 set-up plus three inferior temporal electrode pairs). Multiple source components were modeled in 13 patients in whom an oblique dipole model (“geometric mean” of above three source components) was thought to explain seizure onset at the inferolateral temporal cortex. The results were impressive. Dipole models were then matched with the ictal localization suggested by the intracranial recordings and expressed as positive predictive values. the many discharge patterns captured at the scalp relative to the deeper FO field were the probable manifestation of a continuum of source behavior effects—from discharges seen only by the FO electrodes. to those seen slightly later at the scalp by virtue of signal propagation. 1999). as a retrospective study. scalp and intracranial EEG recordings were not simultaneously acquired and the authors did not indicate that they were fully blinded to the intracranial data when scalp ESL was performed. it is also quite possible that their use of a modified (Maudsley) 10–20 electrode array (Margerison et al. This is perhaps not surprising given the relatively good correlation between interictal and ictal lateralization in TLE (Blume et al. After a minimum follow-up period of two years. this work demonstrates the value of using lower voltage spikes to study interictal source behavior in MTLE and it challenges the view that MTLE scalp spikes are the exclusive byproducts of cortico-cortical propagation from deeper mesial structures. averaged ictal rhythm seen at the scalp. the authors did nonetheless go on to discuss their ESL findings at this level. they found that postsurgical seizure freedom was more likely to occur in patients whose dipole modeling suggested a dominant or leading basal source. Nevertheless. or how well the leading dipole model dominated the second dipole fit when their respective source components overlapped spatiotemporally. The probing of such spatiotemporal effects with a more sophisticated forward–inverse modeling set-up would have been very worthwhile. It should be noted that. was the use of a single fixed dipole and a single shell model. a more rigorous analysis of the consistency of dipole modeling for each seizure in each patient would have been useful. horizontal tangential dipole (temporal tip source) and entorhinal onset (83%).01381. Finally. The investigators selected the dominant and/or leading dipole model that “explained” the earliest recognizable.. When combined with the anticipated opposing effect of spherical forward modeling in MTLE on dipole localization (upward displacement to the frontal lobe). Also. to those seen more globally by virtue of volume conduction. However. For example. 2003a). The implication here perhaps is that dedicated identification of low-amplitude spikes in MTLE can provide very useful ESL information that is potentially more physiologically plausible given the fact that dipole modeling is fundamentally reliant on the principles of volume conduction. Moreover. All patients had an Engel class 1 outcome with a mean follow-up of one year. the investigators chose the dipole fit that best “explained” the early ictal rhythm but did not describe the adequacy of the best fit in more quantitative terms. If de novo spikes were the product of discharge propagation. For instance.. As the authors indicated. it is unclear how well the dipole model explained the signal variance in each case. horizontal radial dipole (lateral source) and neocortical onset (80%). Dipoles with different orientations were preassigned to model different sublobar divisions of the temporal cortical surface. 1970). effected downward displacement of the dipole. the ictal ESL results are largely in agreement with previous interictal ESL results in TLE. While acknowledging that this simplified modeling set-up was not designed to interrogate source behavior at the neurophysiological level. 2001). many seizures were captured (212 in total) but the statistical analysis was only done on a patient-wise basis.11 EEG Source Localization in Focal Epilepsy spikes (20–40 microV) were the product of volume conduction. A criticism of this aspect of the study however. which should have been available. much like the previously described interictal work.1111/j. with high positive predictive values found for the following source and seizure onset match-ups: vertical tangential dipole (basal source) and hippocampal onset (89%). which gives electrodes a better “view” of inferior brain convexities.

have a limited view of the temporal neocortex. Of the few ictal ESL studies that have compared simultaneously acquired scalp and intracranial EEG in focal epilepsy.3 mm to 38. the investigators are the first to have systematically examined the spatial resolution of dipole localization as the seizure pattern evolves at the scalp electrodes. The latter association was explained on the basis that neocortical foci are unlikely to be resected adequately by AMTL.01381. involve a measure of speculation on the part of the investigator. Separating source origin from propagation will. the earliest ictal rhythm seen at the scalp was always associated with intracranial discharges occupying large areas of cortex. scalp-intracranial EEG studies. **(*):1–18. most likely to occur in patients whose dipole modeling did not implicate a lateral source. it is difficult to look past the methodical study by Merlet and Gotman in which the accuracy of spatiotemporal dipole modeling from scalp EEG (28–40 channel setup) was judged in relation to the localization suggested by depth and/or epidural electrode recordings (Merlet & Gotman. that dipole orientation carries far more weight than dipole location in modeling source origin and/or propagation. and the epileptogenic zone will remain untested. While this study represents one of the most carefully conducted analyses of ESL to date. such as those discussed above.8 mm.4 mm. versus discharge onset. the seizure onset zone. on which the measurements were based.1111/j. Of the nine patients (seven lesion-negative) who met this condition. had dominant dipoles that coincided with the locations of intracranially recorded voltage maxima during the earlier ictal pattern. it is the orientation of the dipole—and the extended area of cortex to which that dipole projects—that yields a truer indication of ESL validity in modeling ictal or interictal patterns of onset and propagation. Further. Much emphasis was given to the physical separation of the dominant dipole to “dominant” electrode in trying to validate the scalpderived ESL result. 2001).2007. irritative zone. anterior tip. only half had scalp EEG changes that were concomitant with seizure onset as suggested by the intracranial recording. that dipoles model cortical surfaces in centimeter dimensions. of the six patients who returned a stable ESL result at some point during the seizure. one following the other. as with sampling that sufficiently includes mesial. The authors did point out that their quoted distances should not be regarded as error margins.3 Hz) and applied “start” markers for their ictal modeling at a latency well before any deflection was noted in the scalp trace (based on a figure supplied). the capacity for ESL to help characterize the interplay between the lesion. but ideally for all patients. assessing ESL spatial accuracy by location of the intracranial EEG maxima is problematic. Patients were excluded from ESL if they did not have at least two reproducible seizure patterns recorded at the scalp. are necessarily limited by the extent to which the cortex is sampled at depth.8 mm and 38. 2001). the investigators used a relatively low high-pass filter setting (0. . ideally with the use of electrode arrays that sample larger areas of cortex. It is therefore possible that early ictal signal quality may have been compromised for ESL. and two others (four of six). an intracranial ictal rhythm that was bilateral with maximal amplitude at the mesial temporal region. is highly dependent on the orientation of the actual source as it “faces” the recording electrodes. However. in such circumstances. measures of “spatial inconsistency” for ESL results ranged from 15. As noted by other investigators. To illustrate.x one considers the following factors: that intracranial EEG localization carries an inherent error due to the problem of under-sampling the cortical garland. the authors concluded that mesial onset seizures are prone to mislocalization by scalp ESL based on their concordance measurements from the amygdala (maximal intracranial signal) to the anterior temporal region (dominant dipole location) in two patients (20. These distances are modest when Epilepsia. such distances are not unexpected in light of the recognized patterns of ictal and interictal propagation in MTLE. The dominant source in each case implicated a neocortical temporal focus with distances from the “main” dipole to the nearest (maximal amplitude) intracranial electrode as follows: 5. FO electrodes only sample the entorhinal cortex and orthogonal depth arrays. The above ESL findings await replication. inferior. Two of these patients.1528-1167. without such studies. It should be emphasized here that the use of intracranial EEG recordings as a “gold standard” validation tool for ESL is problematic. the interpretation of the findings was perhaps slightly misdirected. and that the amplitude of the ictal discharge. 8. and lateral temporal lobe cortical surfaces in the case of TLE interictal and ictal ESL. For instance.4 mm). Plummer et al. but rather as measures of concordance. Because scalp-derived ESL localization is more likely to reflect discharge propagation. leading to noisier. as used in the last study (Merlet & Gotman.3 mm. In fact. Lastly. However. the three patients with unstable ESL results had. but this was only the case for two of the six patients when the second (later) ictal pattern was modeled. However meticulously conducted. Once again. 2007 doi: 10. A consecutive series of 15 presurgical patients with various forms of refractory partial epilepsy were enrolled in the study.5 mm. By specifying this condition. More useful would have been a clear description of dipole orientation for the spatiotemporal models applied to each ictal pattern for these two patients. less-stable dipole solutions. six patients (five lesion-negative) had averaged ictal patterns that could produce a sufficiently stable and interpretable ESL result. even in the modified approach when the lateral surgical margin is extended. by the time an ictal rhythm was seen at the scalp. and 20. In a new finding though.12 C.

2003). which promise better spatial resolution than that offered by currentgeneration ESL. as observed by Brodmann nearly 100 years ago.1528-1167. 1998. But the implication here is that anatomy and physiology are measured with the same ruler. A recent paper by Fischer and colleagues has looked to redress this issue with the calculation of ellipsoid volumes based on dipole cluster variability for a population of spikes in a presurgical group (Fischer et al. For ESL then. And for source localization in MEG. Therefore. While the use of such a simple inverse algorithm in MSI might better suit the modeling of the “cleaner” signal topography of magnetic versus electrical fields.2007. one might imagine that if a patch of discharging cortex is likened to a 10-cm2 piece of undulating cheese. Indeed. pyramidal arborization. it should be noted that to date no study has been published which compares source modeling accuracy for simultaneously acquired MEG and EEG recordings against simultaneously acquired intracranial data (as the surrogate “gold” standard) in a prospective. Signal acquisition techniques have improved for both methods. The practice of “pitting” MEG against EEG in the source imaging literature has perhaps been overdone. 1909). the interpretation of MEG source localization accuracy on the millimeter scale. Gyri also account for much of the cortical homunculus in man (Welker. Thus.” This is because MEG is blind to the radial vector component of the electric field. and cortico-cortical connections are richer at gyral crowns than at fissural walls (Wong. both the forward and inverse problems need to be resolved with suitable models to achieve a tenable solution. This fact—that MEG-based source localization is answerable to the same kind of fundamental mathematical problems that underpin ESL—is easily overwhelmed by the glare of the technology on offer. **(*):1–18. As Wong reminds us. However. as if the cheese had been “made Swiss. MEG and EEG-fMRI have attracted greater research interest than that enjoyed by ESL in recent times. For MEG. 2005). Even if MEG becomes more portable and affordable at some future date. rather than in a cumbersome.1111/j. should be eyed with at least a degree of caution. Has ESL been marginalized by MEG? It should be emphasized that the principles of signal detection and source localization for EEG apply just as equally to MEG. MEG only picks up part of the cortical activity generated by the source(s). and there is now an evolving consensus that the combined use of these techniques (in the rare situation when both are accessible) optimizes source localization accuracy (Fuchs et al. and not just part of it. 2002).. “Enthusiasm for MEG (relative to EEG) has been boosted by both genuine scientific considerations and poorly justified commercial pressures” (Nunez & Srinivasan. It is repeatedly emphasized in the MSI literature that. For EEGfMRI. piece-wise manner.. while MEG’s view will be clearer. it is a mistake to think that MEG is immune from the same properties of signal propagation as EEG. It is interesting to note that MEG source imaging (MSI) researchers have almost exclusively applied single fixed dipoles to model spikes in focal epilepsy. but restricted. novel ways of recording EEG in the hostile MRI environment have given researchers the chance to better understand how cortical and subcortical hemodynamic response patterns are coupled to scalp recorded spike and seizure patterns.01381. MEGbased modeling has an inherent bias for superficial sources because the magnetic field decays very rapidly from scalp surface (Hamalainen et al. there are two immediate questions. To coin an analogy. 1998). apart from the obvious practical advantages currently held by EEG over MEG (pediatric and ictal studies. the magnetic field is less “complicated” by variably admixed radial and tangential vectors and it is less distorted by the skull–scalp interface. 1985). “Modeling the magnetic field based on the assumption that the field” can be represented by a single fixed dipole is “fraught with difficulties similar to those inherent in the modeling of electrical fields based on this assumption” (Gloor. While comparisons between the two methods will continue to be made. signal detection in MEG depends on the recruitment of a sufficient population of discharging cortical neurons that are synchronized in time and aligned in space. ESL is likely to maintain an important stake in noninvasive source modeling. the cumulative gyral surface only accounts for a third of the total surface area of the human brain (Brodmann. 2006b). cortical vascularization. Nunez puts it another way. EEG and MEG “see” spike and seizure discharges quite differently. blinded manner for focal epilepsy. This is because. cortical lamination.. Gloor puts it bluntly.13 EEG Source Localization in Focal Epilepsy OTHER N ONINVASIVE S OURCE L OCALIZATION M ETHODS If publication output is anything to go by. 2006b). have allowed recordings to be done in a single step. Epilepsia.x . the area of cortex required for contemporary MEG arrays to detect an interpretable field is still in the order of 3 cm2 at best (Oishi et al. While these latter qualities are true enough. EEG’s field of view will be blurred and distorted by the overlying cellophane wrapper. 1993). although blind to radial source components (from gyral crests). long-term monitoring are largely prohibited by head movement artifacts). 2007 doi: 10. Barkley & Baumgartner.. That is. modern high-density sensor arrays that encompass the whole head. most of the cortex is seen by MEG arrays because. as is the usual case in the MSI literature. MEG technology is seductive but expensive. A common misconception in this regard is that MEG is more accurate than EEG in defining source activity owing to its superior spatial resolution and its relative immunity to field distortion by volume conductor effects (Nunez & Srinivasan.

Demonstration of the relationships between cortical anatomy. gyrus. have found favorable correlations between MSI location and the localization suggested by either intracranial recordings or postsurgical seizure recurrence rates—for keynote studies see (Stefan et al. surface electrical field. position. Figure 4.1111/j. are represented electrically in the modeling of interictal or ictal events. and they assume orientations and positions that attempt to explain the polarity characteristics of this surface field (D). are shown. and surface rendered cortical images. C ILAE Epilepsia ! 1990. The redundancy of the “anatomical two-thirds” argument is made clearer when it is recalled that dipoles are not anatomically based constructs. Despite these caveats. B). It is the net configuration (orientation. comprising multiple sulci and gyri. a phenomenon that is generally ill suited to single fixed dipole modeling strategies as discussed earlier. or even lobe (A. Abbreviations: MRI (Magnetic Resonance Image). Pataraia et al.1528-1167.01381. Note that dipoles (rotating over 40 msec epoch) and the associated confidence ellipsoid volumes do not conform to either the position or orientation of a particular sulcus... most of which are understandably interictal. 2007 doi: 10. Many clinical studies. 4). oblique (C) and from above (D). **(*):1–18. Wong. a practice commonly adhered to in MEG epilepsy studies. Much of the immediate fissural region is dedicated to propagation of interictal/ictal discharges. and dipole model for a right frontotemporal spike in a patient with focal epilepsy. Rather.2007. C). 2004) and . T 1 -weighted MRI coronal (A) and sagittal (B) views. and strength) of “micro” dipolar fields (variably seen by the surface electrodes as they project orthogonally from numerous. support for MSI as a legitimate source localization technique has grown.14 C. Plummer et al. but representations of the Epilepsia. dipoles model the summated electrical field recorded at the scalp electrodes (surface negative over right hemisphere and surface positive over left hemisphere in this case. individual gyral and sulcal surfaces) that is ultimately modeled by the dipole solution.x summated electrical field generated by areas of cortex large enough to include both gyral and fissural surfaces (Fig. 2003. large areas of cortex. This is especially so if modeling is restricted to the spike peak. 1998). Therefore.

1997b. the validity of a one-size-fits-all HRF must be questioned when the pathology presumed to be responsible for the patient’s epilepsy interferes with the regional integrity of the normal blood–brain barrier (viz. 2004). Can EEG-fMRI optimize the spatial resolution of ESL? The ability to correlate the interictal waveform of EEG with the blood oxygen level dependent (BOLD) response of fMRI is a relatively recent development in functional imaging in epilepsy (Seeck et al. To begin with. the so-called hemodynamic response function (HRF). (which.1111/j. 2006). lags EEG by a factor of 1.15 EEG Source Localization in Focal Epilepsy for reviews see (Ebersole. 2004). Aside from the variability in the HRF that can occur between individuals (Aguirre et al. 1998.. The idea is that spike-correlated fMRI data can be used to constrain the ESL solution to one or other “regions of interest. by default.” however loosely via the HRF. the use of ESL with EEG-fMRI to rationalize the temporal dynamics of fMRI. more can be gained by respecting the independence of the two methods for source localization in focal epilepsy. **(*):1–18. Krakow et al.. Krakow et al. Less intuitive then. as pointed out in a more recent review (Makela et al. vascular malformations). 2006) that deactivation might arise from a generalized state of functional de-afferentation (akin to a “state of suspended animation”).x . In this study. Several authors have proposed that simultaneously acquired fMRI should enhance the spatial resolution of ESL (Liu et al. we believe that ESL will Epilepsia. is the significance of a decrease in the BOLD signal. and given the relatively inharmonious relationship between EEG and fMRI signal dynamics. And. despite the promising spatial resolution of fMRI. 1998) and between spike populations (Bagshaw et al..... The disjointed spatiotemporal relationship between EEG and fMRI is underscored by the fact that the fMRI BOLD signal is a physiological response tied to brain structure and one that is not dependent on the synchronized and aligned neuronal activity on which both EEG and MEG are based..01381. later dipole corresponding to BOLD activation at the sylvian fissure. the relative temporal blurring of the BOLD response makes it virtually impossible to tease out discharge onset from discharge propagation in contemporary EEGfMRI recordings. forfeited when it comes to the fMRI BOLD analysis. 1999. Still adding to the complexity of the EEG-fMRI relationship is the observation that both neuronal excitation and inhibition can lead to an increase in the BOLD signal (Gotman et al. The converse approach. the use of fMRI as a default ESL constraint cannot be recommended at this stage.” It has been proposed (Kobayashi et al.. In short then. 2000). However. may be a more fruitful approach.. A recent EEGfMRI study in benign partial epilepsy with centrotemporal spikes suggests that multiple spatiotemporal dipole modeling can help unravel the temporal sequence of BOLD activation associated with interictal discharges (Boor et al. is heavily influenced by operator-dependent thresholding of the signal). the EEG-fMRI marriage has not been so cosy.. 2007 doi: 10. 1998. Most trials have been performed retrospectively on small patient groups when investigators have not been blinded to the patient’s corresponding MRI data. Based on the progress made in clinically directed research in the last 5–10 years. the temporal resolution of fMRI. using ESL to understand the significance of BOLD activity in focal epilepsy. oedema. levels of intra. no large prospective trial incorporating a randomized “control” group (with sham lesion margins) has been carried out. 2006). Barkley. C ONCLUSION This review has examined the current state of EEG source localization (ESL) as it applies to focal epilepsy.000.and interoperator concordance for MSI localization results in these studies have not been clearly assessed. the pattern of BOLD activation was thought to capture the spatial onset and propagation of the corresponding electrical event. This means that the electrical field and the hemodynamic response generated by an epileptiform discharge must be “coupled” by an archetypal time-constant. 2007). and a second. given our incomplete grasp of the fundamental determinants of the BOLD response in EEG-fMRI signal acquisition.2007. However. 1994) are. from a relative increase in inhibition occurring at the level of the soma. 2002). Based on the ESL sequence. centrotemporal spikes were characterized by an initial dipole corresponding to BOLD activation at the central sulcus. Phillips et al. that is. gliosis. seems more logical. a process that is less energy consuming than inhibition occurring at the level of the postsynaptic membrane. it must be remembered. We have outlined the important principles that guide the methodological approach to contemporary ESL and we have highlighted some of the common misconceptions related to dipole and distributed modeling. Because scalp EEG is used to signpost interictal and ic- tal events for interpretation of the BOLD. Accumulating evidence suggests that the spatiotemporal relationship between the two is far from straightforward. Indeed. Much like MSI.” Such a constraint might be expected to hold more physiological credence than traditional dipole or distributed ESL constraints that are founded on relatively pure mathematics. one is left with analyzing only that fraction of the BOLD activity that has been “lassoed. the converse. Goldman et al.. or.1528-1167.. Electrical events unseen at the scalp—and estimates of simultaneously detectable surface: depth spikes have been put as low as 1:2000—(Alarcon et al. to electrical events visible at the scalp. or “deactivation. This is because the BOLD signal is thought to reflect neuronal energy consumption in a broad sense. 2000.. which is dependent on the properties of blood flow and blood deoxygenation. Similarly.

(c) a greater awareness of the importance of source orientation in defining inverse modeling solutions. Michael Wagner and Dr. Raven Press. Clin Neurophysiol 118:901–909. Holloway GM. Chabardes S. such as confidence ellipsoid volumes. (d) the avoidance of restricting source modeling to spike peaks such that earlier spike components are routinely included in the ESL analysis. Neuroimage 8:360–369.” This is perhaps a better way to judge the relative merits of source localization strategies—by understanding the respective limitations of each method from the start. (2001) Non-uniform spatial sampling in EEG source analysis. Kutschke G. Kahane P. Neurol. We confirm that we have read the Journal’s position on issues involved in ethical publication and we affirm that this report is consistent with those guidelines. Caemaert L. The first author would like to personally thank Dr. (2004) EEG-fMRI of focal epileptic spikes: analysis with multiple haemodynamic functions and comparison with gadolinium-enhanced MR angiograms. Barth. (2003) The cellular basis of EEG activity. (2007) Combined spike-related functional MRI and multiple source analysis in the noninvasive spike localization of benign rolandic epilepsy. Mr. and Mr. and (g) when permitted by the SNR. Psychiatry 57:435–449. Van Hoey G. Electroencephalogr Clin Neurophysiol 53:453–458. Boor S. BOLD homodynamic responses. . With this approach. (2004) Controversies in neurophysiology. Achten E.01381. Van Walleghem P. New York. Hawco C. Brain 128:1818–1831. Dekker E. Kobayashi E. Boon P. with elimination of the tendency to use source location as the cardinal determinant of ESL accuracy. Alarcon G. or the one that should be most valued. Tassi L. Polkey CE. (1949) A study of the electrical fields of the surface of the head. Jacobs J. including intracranial EEG localization. Boor R. Proceedings of the 23rd Annual International Conference of the IEEE 1:903–905. the leading source localization approach. Barkley GL. Gotman J. ESL continues to hold promise as a potential clinical tool that offers to teach us much about the recruitment and propagation of interictal and ictal discharges in focal epilepsy. Engineering in Medicine and Biology Society. (1999) Visual and quantitative ictal EEG predictors of outcome after temporal lobectomy. In fact. and one that is founded on the well-established electrophysiological principles of EEG.x couragement and debate on the topic. Aghakhani Y. 1–11. 443–465. noninvasive. Plummer et al. we anticipate that the following conditions need to be met: (a) blinded. Pike GB. Vanrumste B.16 C. Barkley GL. Vonck K. (f) the inclusion of error measures. 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