- Email: [email protected]
MSI dipole variability mean unreliability?
Clinical Neurophysiology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Letter to the Editor Does MEG/MSI unreliability?
dipole
variability
mean
The field of a magnetoencephalography (MEG)/magnetic source imaging (MSI) (Cohen, 1968) has grown considerably over the last 45 years. As clinicians worldwide know, thousands of patients with epilepsy have benefited directly from the insight about their epileptic foci provided by MEG/MSI (Bagic et al., 2009). Taken together, one gets the impression that MSI should be considered a mature clinical field by now (Bagic, 2011). Thus, it remains perplexing why MEG/MSI has, in some minds, not earned the status of a ‘‘routine’’ clinical test. Have there not been a number of clinical studies (Knowlton et al., 2008a,b, 2009; Sutherling et al., 2008; etc.) proving its additive value to non-invasive presurgical evaluations of patients with medically-resistant epilepsy? Or is it simply because epilepsy clinicians are traditionally conservative and leery of new technology? Alternatively, could a negative bias be continuing to play a role? Wennberg and Cheyne (2013a) have attempted to examine the ‘‘reliability’’ of MEG source localization using a single, supposedly ‘‘well-characterized’’, temporal neocortical spike focus. Their hypothesis is that the scatter of dipoles of individual spikes reflects a localization imprecision of MEG methodology. In the process of this investigation, the authors did corroborate the usefulness of several procedures that are known to improve source modeling accuracy, such as bandpass filtering and spike averaging to enhance the signal to noise (S/N) of an MEG or EEG spike. However, their welcomed recommendations for the routine use of these protocols are in contrast to several areas of concern, namely their insistence on the ‘‘identical’’ nature of their recorded spikes, their somewhat misleading use of the term ‘‘reliability’’, and their conclusion that the source of dipole location variability from spike to spike is due to ‘‘the limitation in spatial accuracy of the source localization technique’’. The authors’ stated objective was ‘‘to assess the reliability of magnetic source imaging (MSI) of anterior temporal spikes through detailed analysis of the localization and orientation of source solutions obtained for a large number of spikes that were separately confirmed by intracranial EEG (ICEEG) to be focally generated within a single, well-characterized spike focus’’. Unfortunately, ‘‘reliability’’ can be an emotionally charged word, when used in a clinical setting. It infers that one is attempting to determine whether the results of a test, or indeed the procedure itself, are trustworthy. Perhaps, ‘‘consistency’’ or ‘‘variability’’ would be a more neutral term? Inferences aside, the term, reliability, might have been justified had they really been able to do repeated source localizations on identical spikes, but that is a physiological impossibility (Ebersole, 2003; Spencer et al., 2008; Haider and McCormick, 2009; Sabolek et al., 2012). Even in idealized cases of nearly identical spikes, it is the background MEG or EEG activity, unrelated to the spikes
themselves, that is always variable and represents ‘‘noise’’ in this situation (Bast et al., 2004, 2006; de Jongh et al., 2005; Ramantani et al., 2006). Background noise is a key determinant of dipole scattering. Clearly, that is why spike averaging, just like evoked potential averaging, works to improve the S/N (Scherg et al., 1999; Ebersole, 2003; Ramantani et al., 2006). Furthermore, spike foci that produce scalp-recordable spikes are quite large in area (Cooper et al., 1965; Ebersole, 2003; Tao et al., 2005) and have within them complex neural networks (van Diessen et al., 2013). All these elements are unlikely to be involved to the same extent and with identical synchrony from spike to spike. Thus, there is also some intrinsic variability in the signal, that would also contribute to dipole scattering (Scherg and Ebersole, 1993, 1994; Murro et al., 1995; Braun et al., 1997; Ebersole, 2000, 2003). Accordingly, the authors’ persistent use of the expression, ‘‘identical spikes’’, is clearly inaccurate. It would appear that the authors’ claim of identical spikes was based principally on intracranial EEG recordings. Unfortunately their intracranial spatial sampling, using only a total of 16 contacts (three 4-contact subdural strips and one 4-contact depth electrode), is hardly optimal and cannot justify their claim of ‘‘complete characterization’’ of this anterior temporal focus. The four-contact strip on the lateral surface of the temporal tip, that recorded nearly all the spike activity, provided only an impression of the AP dimension of the focus. There was no coverage of the basal, superior, or mesial aspect of the temporal tip. This is not sufficient to claim that ‘‘all the spikes have an identical source’’. Similarly, only using 19 10–20 electrodes (without subtemporal coverage) to compare and equate scalp EEG spikes recorded with simultaneous ICEEG to those recorded with simultaneous MEG is also inadequate. Note that the EEG field maps in their Fig. 1 do not resolve either the negative or the positive field maxima, let alone any other variability in the subtemporal fields. Accordingly, it is very unlikely that by ‘‘careful visual inspection’’ they could be certain that the spikes recorded with ICEEG were identical to those recorded with MEG. Finally, the authors themselves provide us with a glimpse of the variability in their studied spike population. The tracings of raw EEG in Fig. 1 show a number example spikes that are far from identical. Regardless of what the authors stated, the spike population chosen for study was not ‘‘the classical anterior temporal spike’’ that originates in the infero-lateral and lateral aspect of the anterior temporal lobe (Ebersole and Wade, 1991; Ebersole, 2003), but rather it was a temporal tip spike, the field of which had principally a tangential, not radial, orientation. This was good for a study of MEG, given its sensitivity to tangential field orientations (Ebersole,1991; Fuchs et al., 1998; Murro et al., 1995; Nakasato et al., 1994; Scheler et al., 2007; Haueisen et al., 2012; Agirre-Arrizubieta et al., 2014). However, the EEG dipole solution for this interictal population was also not typical for classic anterior
http://dx.doi.org/10.1016/j.clinph.2014.01.037 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
2
Letter to the Editor / Clinical Neurophysiology xxx (2014) xxx–xxx
temporal spikes. These typically have a more radial orientation, are modeled by EEG dipoles that are usually two to three cm deep to the generating cortex (Ebersole and Wade, 1991; Ebersole, 2003). Accordingly, the authors should temper their claim that the results reflect the classic anterior temporal spike. Furthermore, it is curious that dipole scattering with EEG source imaging (ESI) was not included in the discussion, given that comparisons between MEG and EEG source imaging was one thrust of the paper. A number of studies using simultaneous MEG and EEG have shown that EEG dipole scatter is greater than that of MEG (Nakasato et al., 1994; Mikuni et al., 1997; Oishi et al., 2002; Zijlmans, 2002; Scheler et al., 2004, 2007; Ossenblok et al., 2007). MEG spike dipole clusters are nearly always smaller than EEG clusters of the same spikes and often smaller than that shown in this study. In fact, the authors themselves also show, in an accompanying study of ESI (Wennberg and Cheyne, 2013b), that dipole models of single EEG spikes vary widely in location with up to a third being ‘‘physiologically invalid’’. Given the known physiological variability in any spike focus (Cohen et al., 2002; Sabolek et al., 2012) and given the effect of variable background MEG (or EEG) activity on a resultant spike field (Ramantani et al., 2006), one cannot hypothesize, as did the authors, that ‘‘in this particular well characterized case of a focal spike generator, a reliable source localization technique should return an identical solution for each spike analyzed’’. Although some may believe that the extent of an MEG dipole cluster is related to the actual size of the epileptic focus, this is not the case with most experienced clinical MEG practitioners. However, a small dipole cluster does mean a stable interictal source (Ebersole, 1991, 2003), and this has been shown to be a good predictor of epilepsy surgery success (Otsubo et al., 2001; Chitoku et al., 2003; Assaf et al., 2004; Ebersole, 2003; Fischer et al., 2005; Oishi et al., 2006; Ramachandran-Nair et al., 2007; Agirre-Arrizubieta et al., 2014). Thus, this feature of an MSI result is useful clinically without having to believe that dipole cluster size infers knowledge about focus size. Perhaps what is most unfortunate about the authors’ conclusions is their insistence that MEG dipole scatter is a function of the ‘‘limitations in the spatial accuracy of the source localization technique’’. This might be justified if repeating a dipole localization of the same MEG spike leads to different results, but it does not. This conclusion also might have been given support had they shown that minor variations in spike parameters lead to inconsistent and unusually large variations in dipole location, but this was not shown. Such an investigation is worthy of future consideration. However, given the known relationship that signal and noise have with dipole variability and given the intrinsic physiological variability of individual spikes, we simply cannot accept the authors’ conclusion that the source modeling technique is to blame for dipole scatter. MEG/MSI is a proven, useful clinical tool. It may not be ‘‘the’’ answer; but it is ‘‘an’’ answer, along with other available functional methods for the question of where is the epileptogenic focus (Bagic et al., 2009). MEG/MSI does not replace EEG; rather it is complementary and additive to EEG (Ebersole et al., 1993; Fuchs et al., 1998; Ebersole and Ebersole, 2010). All clinicians want to utilize the best and most complete relevant information available before making important clinical decisions (Burgess et al., 2011a, 2011b). A balanced presentation of the related research findings has the critical role in helping them achieve this goal. It is unfortunate that the authors did not temper their negative position toward MEG source modeling, lest physicians seeking understanding be lead to believe falsely that MEG/MSI is clinically ‘‘unreliable’’.
References Agirre-Arrizubieta Z, Thai NJ, Valentín A, Furlong PL, Seri S, Selway RP, et al. The value of magnetoencephalography to guide electrode implantation in epilepsy. Brain Topogr 2014;27:197–207. Assaf BA, Karkar KM, Laxer KD, Garcia PA, Austin EJ, Barbaro NM, et al. Magnetoencephalography source localization and surgical outcome in temporal lobe epilepsy. Clin Neurophysiol 2004;115:2066–76. Bagic A, Funke ME, Ebersole J, ACMEGS Position Statement Committee. American Clinical MEG Society (ACMEGS) position statement: the value of magnetoencephalography (MEG)/magnetic source imaging (MSI) in noninvasive presurgical evaluation of patients with medically intractable localization-related epilepsy. J Clin Neurophysiol 2009;26:290–3. Bagic AI. Disparities in clinical magnetoencephalography practice in the United States: a survey-based appraisal. J Clin Neurophysiol 2011;28:341–7. Bast T, Boppel T, Rupp A, Harting I, Hoechstetter K, Fauser S, et al. Noninvasive source localization of interictal EEG spikes: effects of signal-to-noise ratio and averaging. J Clin Neurophysiol 2006;23:487–97. Bast T, Oezkan O, Rona S, Stippich C, Seitz A, Rupp A, et al. EEG and MEG source analysis of single and averaged interictal spikes reveals intrinsic epileptogenicity in focal cortical dysplasia. Epilepsia 2004;45:621–31. Braun C, Kaiser S, Kincses WE, Elbert T. Confidence interval of single dipole locations based on EEG data. Brain Topogr 1997;10:31–9. Burgess RC, Barkley GL, Bagic´ AI. Turning a new page in clinical magnetoencephalography: practicing according to the first clinical practice guidelines. J Clin Neurophysiol 2011a;28:336–40. Burgess RC, Funke ME, Bowyer SM, Lewine JD, Kirsch HE, Bagic, A.I. for the ACMEGS Clinical Practice Guideline (CPG) Committee. American Clinical Magnetoencephalography Society Clinical Practice Guideline 2: presurgical functional brain mapping using magnetic evoked fields. J Clin Neurophysiol 2011b;28:355–61. Chitoku S, Otsubo H, Ichimura T, Saigusa T, Ochi A, Shirasawa A, et al. Characteristics of dipoles in clustered individual spikes and averaged spikes. Brain Dev 2003;25:14–21. Cohen D. Magnetoencephalography: evidence of magnetic fields produced by alpha-rhythm currents. Science 1968;161:784–6. Cohen I, Navarro V, Clemenceau S, Baulac M, Miles R. On the origin of interictal activity in human temporal lobe epilepsy in vitro. Science 2002;298:1418–21. Cooper R, Winter AL, Crow HJ, Walter WG. Comparison of subcortical, cortical and scalp activity using chronically indwelling electrodes in man. Electroencephalogr Clin Neurophysiol 1965;18:217–28. de Jongh A, de Munck JC, Gonçalves SI, Ossenblok P. Differences in MEG/EEG epileptic spike yields explained by regional differences in signal-to-noise ratios. J Clin Neurophysiol 2005;22:153–8. Ebersole JS. Equivalent dipole modeling: a new EEG method for epileptogenic focus localization. In: Pedley TA, Meldrum BS, editors. Recent advances in epilepsy. 5th ed. Edinburgh: Churchill Livingstone; 1991. p. 51–72. Ebersole JS. EEG voltage topography and dipole source modeling of epileptiform potentials. In: Eberolse JS, Pedley TA, editors. Current practice of clinical electroencephalography. 3rd ed. Lippincott Williams & Wilkins; 2003. p. 732–52. Ebersole JS, Wade PB. Spike voltage topography identifies two types of frontotemporal epileptic foci. Neurology 1991;41:1425–33. Ebersole JS. Noninvasive localization of epileptogenic foci by EEG source modeling. Epilepsia 2000;41:S24–33. Ebersole JS, Ebersole SM. Combining MEG and EEG source modeling in epilepsy evaluations. J Clin Neurophysiol 2010;27:360–71. Fischer MJ, Scheler G, Stefan H. Utilization of magnetoencephalography results to obtain favourable outcomes in epilepsy surgery. Brain 2005;128:153–7. Fuchs M, Wagner M, Wischmann HA, Köhler T, Theissen A, Drenckhahn R, et al. Improving source reconstructions by combining bioelectric and biomagnetic data. Electroencephalogr Clin Neurophysiol 1998;107:93–111. Haider B, McCormick DA. Rapid neocortical dynamics: cellular and network mechanisms. Neuron 2009;62:171–89. Haueisen J, Funke M, Güllmar D, Eichardt R. Tangential and radial epileptic spike activity: different sensitivity in EEG and MEG. J Clin Neurophysiol 2012;29:327–32. Knowlton RC, Elgavish RA, Limdi N, Bartolucci A, Ojha B, Blount J, et al. Functional imaging: I. Relative predictive value of intracranial electroencephalography. Ann Neurol 2008a;64:25–34. Knowlton RC, Elgavish RA, Bartolucci A, Ojha B, Limdi N, Blount J, et al. Functional imaging: II. Prediction of epilepsy surgery outcome. Ann Neurol 2008b;64:35–41. Knowlton RC, Razdan SN, Limdi N, Elgavish RA, Killen J, Blount J, et al. Effect of epilepsy magnetic source imaging on intracranial electrode placement. Ann Neurol 2009;65:716–23. Mikuni N, Nagamine T, Ikeda A, Terada K, Taki W, Kimura J, et al. Simultaneous recording of epileptiform discharges by MEG and subdural electrodes in temporal lobe epilepsy. Neuroimage 1997;5:298–306. Murro AM, Smith JR, King DW, Park YD. Precision of dipole localization in a spherical volume conductor: a comparison of referential EEG, magnetoencephalography and scalp current density methods. Brain Topogr 1995;8:119–25.
Letter to the Editor / Clinical Neurophysiology xxx (2014) xxx–xxx Nakasato N, Levesque MF, Barth DS, Baumgartner C, Rogers RL, Sutherling WW. Comparisons of MEG, EEG, and ECoG source localization in neocortical partial epilepsy in humans. Electroencephalogr Clin Neurophysiol 1994;91:171–8. Oishi M, Kameyama S, Masuda H, Tohyama J, Kanazawa O, Sasagawa M, et al. Single and multiple clusters of magnetoencephalographic dipoles in neocortical epilepsy: significance in characterizing the epileptogenic zone. Epilepsia 2006;47:355–64. Oishi M, Otsubo H, Kameyama S, Morota N, Masuda H, Kitayama M, et al. Epileptic spikes: magnetoencephalography versus simultaneous electrocorticography. Epilepsia 2002;43:1390–5. Ossenblok P, de Munck JC, Colon A, Drolsbach W, Boon P. Magnetoencephalography is more successful for screening and localizing frontal lobe epilepsy than electroencephalography. Epilepsia 2007;48:2139–49. Otsubo H, Ochi A, Elliott I, Chuang SH, Rutka JT, Jay V, et al. MEG predicts epileptic zone in lesional extrahippocampal epilepsy: 12 pediatric surgery cases. Epilepsia 2001;42:1523–30. Ramachandran-Nair R, Otsubo H, Shroff MM, Ochi A, Weiss SK, Rutka JT, et al. MEG predicts outcome following surgery for intractable epilepsy in children with normal or nonfocal MRI findings. Epilepsia 2007;48:149–57. Ramantani G, Boor R, Paetau R, Ille N, Feneberg R, Rupp A, et al. MEG versus EEG: influence of background activity on interictal spike detection. J Clin Neurophysiol 2006;23:498–508. Sabolek HR, Swiercz WB, Lillis KP, Cash SS, Huberfeld G, Zhao G, et al. A candidate mechanism underlying the variance of interictal spike propagation. J Neurosci 2012;32:3009–21. Scheler G, Fischer MJ, Genow A, Hummel C, Rampp S, Paulini A, et al. Spatial relationship of source localizations in patients with focal epilepsy: Comparison of MEG and EEG with a three spherical shells and a boundary element volume conductor model. Hum Brain Mapp 2007;28:315–22. Scheler G, Fischer M , Hummel C , Genow A, Stefan H. Variation of MEG and EEG localisations due to different volume conductors. In: Halgren E, Ahlfors S, Hämäläinen M, Cohen D, editors. BIOMAG 2004. Boston, USA: Proceedings of the 14th International Conference on Biomagnetism; 2004. p. 751. Scherg M, Bast T, Berg P. Multiple source analysis of interictal spikes: goals, requirements, and clinical value. J Clin Neurophysiol 1999;16:214–24. Scherg M, Ebersole JS. Brain source imaging of focal and multifocal epileptiform EEG activity. Neurophysiol Clin 1994;24:51–60. Scherg M, Ebersole JS. Models of brain sources. Brain Topogr 1993;5:419–23. Spencer SS, Goncharova II, Duckrow RB, Novotny EJ, Zaveri HP. Interictal spikes on intracranial recording: behavior, physiology, and implications. Epilepsia 2008;49:1881–92.
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Sutherling WW, Mamelak AN, Thyerlei D, Maleeva T, Minazad Y, Philpott L, et al. Influence of magnetic source imaging for planning intracranial EEG in epilepsy. Neurology 2008;71:990–6. Tao JX, Ray A, Hawes-Ebersole S, Ebersole JS. Intracranial EEG substrates of scalp EEG interictal spikes. Epilepsia 2005;46:669–76. van Diessen E, Diederen SJ, Braun KP, Jansen FE, Stam CJ. Functional and structural brain networks in epilepsy: What have we learned? Epilepsia 2013;54:1855–65. Wennberg R, Cheyne D. Reliability of MEG source imaging of anterior temporal spikes: analysis of an intracranially characterized spike focus. Clin Neurophysiol 2013. http://dx.doi.org/10.1016/j.clinph.2013.08.032. pii: S13882457(13)01123-1, [Epub ahead of print]PMID: 24210513. Wennberg R, Cheyne D. EEG source imaging of anterior temporal lobe spikes: validity and reliability. Clin Neurophysiol 2013. http://dx.doi.org/10.1016/ j.clinph.2013.09.042. pii: S1388-2457(13)01124-3, [Epub ahead of print] PMID: 24210516. Zijlmans M, Huiskamp GM, Leijten FS, Van Der Meij WM, Wieneke G, Van Huffelen AC. Modality-specific spike identification in simultaneous magnetoencephalography/electroencephalography: a methodological approach. J Clin Neurophysiol 2002;19:183–91.
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Anto Bagic´ University of Pittsburgh Comprehensive Epilepsy Center (UPCEC), UPMC MEG Epilepsy Program, Department of Neurology, University of Pittsburgh Medical School, Suite 811, Kaufmann Medical Building, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA ⇑ Tel.: +1 412 692 4603; fax: +1 412 692 4636. E-mail address: [email protected] John S. Ebersole MEG and Functional Mapping Program, Atlantic Neuroscience Institute Epilepsy Center, 99 Beauvoir Avenue, Summit, NJ 07902, USA E-mail addresses: [email protected] Available online xxxx
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Letter to the Editor Does MEG/MSI unreliability?
dipole
variability
mean
The field of a magnetoencephalography (MEG)/magnetic source imaging (MSI) (Cohen, 1968) has grown considerably over the last 45 years. As clinicians worldwide know, thousands of patients with epilepsy have benefited directly from the insight about their epileptic foci provided by MEG/MSI (Bagic et al., 2009). Taken together, one gets the impression that MSI should be considered a mature clinical field by now (Bagic, 2011). Thus, it remains perplexing why MEG/MSI has, in some minds, not earned the status of a ‘‘routine’’ clinical test. Have there not been a number of clinical studies (Knowlton et al., 2008a,b, 2009; Sutherling et al., 2008; etc.) proving its additive value to non-invasive presurgical evaluations of patients with medically-resistant epilepsy? Or is it simply because epilepsy clinicians are traditionally conservative and leery of new technology? Alternatively, could a negative bias be continuing to play a role? Wennberg and Cheyne (2013a) have attempted to examine the ‘‘reliability’’ of MEG source localization using a single, supposedly ‘‘well-characterized’’, temporal neocortical spike focus. Their hypothesis is that the scatter of dipoles of individual spikes reflects a localization imprecision of MEG methodology. In the process of this investigation, the authors did corroborate the usefulness of several procedures that are known to improve source modeling accuracy, such as bandpass filtering and spike averaging to enhance the signal to noise (S/N) of an MEG or EEG spike. However, their welcomed recommendations for the routine use of these protocols are in contrast to several areas of concern, namely their insistence on the ‘‘identical’’ nature of their recorded spikes, their somewhat misleading use of the term ‘‘reliability’’, and their conclusion that the source of dipole location variability from spike to spike is due to ‘‘the limitation in spatial accuracy of the source localization technique’’. The authors’ stated objective was ‘‘to assess the reliability of magnetic source imaging (MSI) of anterior temporal spikes through detailed analysis of the localization and orientation of source solutions obtained for a large number of spikes that were separately confirmed by intracranial EEG (ICEEG) to be focally generated within a single, well-characterized spike focus’’. Unfortunately, ‘‘reliability’’ can be an emotionally charged word, when used in a clinical setting. It infers that one is attempting to determine whether the results of a test, or indeed the procedure itself, are trustworthy. Perhaps, ‘‘consistency’’ or ‘‘variability’’ would be a more neutral term? Inferences aside, the term, reliability, might have been justified had they really been able to do repeated source localizations on identical spikes, but that is a physiological impossibility (Ebersole, 2003; Spencer et al., 2008; Haider and McCormick, 2009; Sabolek et al., 2012). Even in idealized cases of nearly identical spikes, it is the background MEG or EEG activity, unrelated to the spikes
themselves, that is always variable and represents ‘‘noise’’ in this situation (Bast et al., 2004, 2006; de Jongh et al., 2005; Ramantani et al., 2006). Background noise is a key determinant of dipole scattering. Clearly, that is why spike averaging, just like evoked potential averaging, works to improve the S/N (Scherg et al., 1999; Ebersole, 2003; Ramantani et al., 2006). Furthermore, spike foci that produce scalp-recordable spikes are quite large in area (Cooper et al., 1965; Ebersole, 2003; Tao et al., 2005) and have within them complex neural networks (van Diessen et al., 2013). All these elements are unlikely to be involved to the same extent and with identical synchrony from spike to spike. Thus, there is also some intrinsic variability in the signal, that would also contribute to dipole scattering (Scherg and Ebersole, 1993, 1994; Murro et al., 1995; Braun et al., 1997; Ebersole, 2000, 2003). Accordingly, the authors’ persistent use of the expression, ‘‘identical spikes’’, is clearly inaccurate. It would appear that the authors’ claim of identical spikes was based principally on intracranial EEG recordings. Unfortunately their intracranial spatial sampling, using only a total of 16 contacts (three 4-contact subdural strips and one 4-contact depth electrode), is hardly optimal and cannot justify their claim of ‘‘complete characterization’’ of this anterior temporal focus. The four-contact strip on the lateral surface of the temporal tip, that recorded nearly all the spike activity, provided only an impression of the AP dimension of the focus. There was no coverage of the basal, superior, or mesial aspect of the temporal tip. This is not sufficient to claim that ‘‘all the spikes have an identical source’’. Similarly, only using 19 10–20 electrodes (without subtemporal coverage) to compare and equate scalp EEG spikes recorded with simultaneous ICEEG to those recorded with simultaneous MEG is also inadequate. Note that the EEG field maps in their Fig. 1 do not resolve either the negative or the positive field maxima, let alone any other variability in the subtemporal fields. Accordingly, it is very unlikely that by ‘‘careful visual inspection’’ they could be certain that the spikes recorded with ICEEG were identical to those recorded with MEG. Finally, the authors themselves provide us with a glimpse of the variability in their studied spike population. The tracings of raw EEG in Fig. 1 show a number example spikes that are far from identical. Regardless of what the authors stated, the spike population chosen for study was not ‘‘the classical anterior temporal spike’’ that originates in the infero-lateral and lateral aspect of the anterior temporal lobe (Ebersole and Wade, 1991; Ebersole, 2003), but rather it was a temporal tip spike, the field of which had principally a tangential, not radial, orientation. This was good for a study of MEG, given its sensitivity to tangential field orientations (Ebersole,1991; Fuchs et al., 1998; Murro et al., 1995; Nakasato et al., 1994; Scheler et al., 2007; Haueisen et al., 2012; Agirre-Arrizubieta et al., 2014). However, the EEG dipole solution for this interictal population was also not typical for classic anterior
http://dx.doi.org/10.1016/j.clinph.2014.01.037 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
2
Letter to the Editor / Clinical Neurophysiology xxx (2014) xxx–xxx
temporal spikes. These typically have a more radial orientation, are modeled by EEG dipoles that are usually two to three cm deep to the generating cortex (Ebersole and Wade, 1991; Ebersole, 2003). Accordingly, the authors should temper their claim that the results reflect the classic anterior temporal spike. Furthermore, it is curious that dipole scattering with EEG source imaging (ESI) was not included in the discussion, given that comparisons between MEG and EEG source imaging was one thrust of the paper. A number of studies using simultaneous MEG and EEG have shown that EEG dipole scatter is greater than that of MEG (Nakasato et al., 1994; Mikuni et al., 1997; Oishi et al., 2002; Zijlmans, 2002; Scheler et al., 2004, 2007; Ossenblok et al., 2007). MEG spike dipole clusters are nearly always smaller than EEG clusters of the same spikes and often smaller than that shown in this study. In fact, the authors themselves also show, in an accompanying study of ESI (Wennberg and Cheyne, 2013b), that dipole models of single EEG spikes vary widely in location with up to a third being ‘‘physiologically invalid’’. Given the known physiological variability in any spike focus (Cohen et al., 2002; Sabolek et al., 2012) and given the effect of variable background MEG (or EEG) activity on a resultant spike field (Ramantani et al., 2006), one cannot hypothesize, as did the authors, that ‘‘in this particular well characterized case of a focal spike generator, a reliable source localization technique should return an identical solution for each spike analyzed’’. Although some may believe that the extent of an MEG dipole cluster is related to the actual size of the epileptic focus, this is not the case with most experienced clinical MEG practitioners. However, a small dipole cluster does mean a stable interictal source (Ebersole, 1991, 2003), and this has been shown to be a good predictor of epilepsy surgery success (Otsubo et al., 2001; Chitoku et al., 2003; Assaf et al., 2004; Ebersole, 2003; Fischer et al., 2005; Oishi et al., 2006; Ramachandran-Nair et al., 2007; Agirre-Arrizubieta et al., 2014). Thus, this feature of an MSI result is useful clinically without having to believe that dipole cluster size infers knowledge about focus size. Perhaps what is most unfortunate about the authors’ conclusions is their insistence that MEG dipole scatter is a function of the ‘‘limitations in the spatial accuracy of the source localization technique’’. This might be justified if repeating a dipole localization of the same MEG spike leads to different results, but it does not. This conclusion also might have been given support had they shown that minor variations in spike parameters lead to inconsistent and unusually large variations in dipole location, but this was not shown. Such an investigation is worthy of future consideration. However, given the known relationship that signal and noise have with dipole variability and given the intrinsic physiological variability of individual spikes, we simply cannot accept the authors’ conclusion that the source modeling technique is to blame for dipole scatter. MEG/MSI is a proven, useful clinical tool. It may not be ‘‘the’’ answer; but it is ‘‘an’’ answer, along with other available functional methods for the question of where is the epileptogenic focus (Bagic et al., 2009). MEG/MSI does not replace EEG; rather it is complementary and additive to EEG (Ebersole et al., 1993; Fuchs et al., 1998; Ebersole and Ebersole, 2010). All clinicians want to utilize the best and most complete relevant information available before making important clinical decisions (Burgess et al., 2011a, 2011b). A balanced presentation of the related research findings has the critical role in helping them achieve this goal. It is unfortunate that the authors did not temper their negative position toward MEG source modeling, lest physicians seeking understanding be lead to believe falsely that MEG/MSI is clinically ‘‘unreliable’’.
References Agirre-Arrizubieta Z, Thai NJ, Valentín A, Furlong PL, Seri S, Selway RP, et al. The value of magnetoencephalography to guide electrode implantation in epilepsy. Brain Topogr 2014;27:197–207. Assaf BA, Karkar KM, Laxer KD, Garcia PA, Austin EJ, Barbaro NM, et al. Magnetoencephalography source localization and surgical outcome in temporal lobe epilepsy. Clin Neurophysiol 2004;115:2066–76. Bagic A, Funke ME, Ebersole J, ACMEGS Position Statement Committee. American Clinical MEG Society (ACMEGS) position statement: the value of magnetoencephalography (MEG)/magnetic source imaging (MSI) in noninvasive presurgical evaluation of patients with medically intractable localization-related epilepsy. J Clin Neurophysiol 2009;26:290–3. Bagic AI. Disparities in clinical magnetoencephalography practice in the United States: a survey-based appraisal. J Clin Neurophysiol 2011;28:341–7. Bast T, Boppel T, Rupp A, Harting I, Hoechstetter K, Fauser S, et al. Noninvasive source localization of interictal EEG spikes: effects of signal-to-noise ratio and averaging. J Clin Neurophysiol 2006;23:487–97. Bast T, Oezkan O, Rona S, Stippich C, Seitz A, Rupp A, et al. EEG and MEG source analysis of single and averaged interictal spikes reveals intrinsic epileptogenicity in focal cortical dysplasia. Epilepsia 2004;45:621–31. Braun C, Kaiser S, Kincses WE, Elbert T. Confidence interval of single dipole locations based on EEG data. Brain Topogr 1997;10:31–9. Burgess RC, Barkley GL, Bagic´ AI. Turning a new page in clinical magnetoencephalography: practicing according to the first clinical practice guidelines. J Clin Neurophysiol 2011a;28:336–40. Burgess RC, Funke ME, Bowyer SM, Lewine JD, Kirsch HE, Bagic, A.I. for the ACMEGS Clinical Practice Guideline (CPG) Committee. American Clinical Magnetoencephalography Society Clinical Practice Guideline 2: presurgical functional brain mapping using magnetic evoked fields. J Clin Neurophysiol 2011b;28:355–61. 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Anto Bagic´ University of Pittsburgh Comprehensive Epilepsy Center (UPCEC), UPMC MEG Epilepsy Program, Department of Neurology, University of Pittsburgh Medical School, Suite 811, Kaufmann Medical Building, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA ⇑ Tel.: +1 412 692 4603; fax: +1 412 692 4636. E-mail address: [email protected] John S. Ebersole MEG and Functional Mapping Program, Atlantic Neuroscience Institute Epilepsy Center, 99 Beauvoir Avenue, Summit, NJ 07902, USA E-mail addresses: [email protected] Available online xxxx