Magnetoencephalography in Pediatric Neuroimaging

Developmental Science 5:3 (2002), pp 361–370

MagnetoencephalographyBlackwell Publishers Ltd in pediatric neuroimaging Ritva Paetau

Department of Child Neurology, Hospital for Children and Adolescents, University of Helsinki; Brain Research Unit, Helsinki University of Technology; BioMag Laboratory; Helsinki University Central Hospital, Finland

Abstract

Neural currents give rise to electroencephalogram (EEG) and magnetoencephalogram (MEG). MEG has selective sensitivity to tangential currents (from ﬁssural cortex), and less distorted signals compared with EEG. A major goal of MEG is to determine the location and timing of cortical generators for event-related responses, spontaneous brain oscillations or epileptiform activity. MEG provides a spatial accuracy of a few mm under optimal conditions, combined with an excellent submillisecond temporal resolution, which together enable spatiotemporal tracking of distributed neural activities, e.g. during cognitive tasks or epileptic discharges. While the present focus of pediatric MEG is on tailored epilepsy surgery, the complete noninvasiveness of MEG also provides unlimited possibilities to study the brain functions of healthy and developmentally deviant children.

Introduction 1996; Kamada, Moller, Saguer, Kassubek, Kaltenhauser, Kober, Uberall, Lauffer, Wenzel & Vieth, 1998; Kubota, Magnetoencephalography (MEG) detects weak extra- Takeshita, Sakakihara & Yangisawa, 2000), on the Landau- cranial magnetic fields, and allows determination of Kleffner syndrome and related disorders (Paetau, Kajola, their intracranial sources. Magnetic source imaging Korkman, Hämäläinen, Granström & Hari, 1991; Paetau, (MSI) means procedures which combine the MEG 1994; Lewine, Andrews, Chez, Patil, Devinsky, Smith, Kan- sources with anatomical magnetic resonance imaging ner, Davis, Funke, Jones, Chong, Provencal, Weisend, Lee & (MRI). The term MEG is used in the present paper to Orrison, 1999; Paetau, Granström, Blomstedt, Jousmäki, cover both MEG and MSI. Korkman & Liukkonen, 1999; Sobel, Aung, Otsubo & After the first recordings of human magnetic alpha Smith, 2000), on sensory cortex properties in progressive rhythm (Cohen, 1968), MEG technology and its appli- myoclonus epilepsies (Karhu, Hari, Paetau, Kajola & cations to neuroscience and clinical research have pro- Mervaala, 1994; Lauronen, 2001; Forss, Silen & Kar- gressed at an accelerating rate during the past 20 years. jalainen, 2001), and on dyslexia (Heim, Eulitz, Several excellent reviews are available on various aspects Kaufmann, Fuchter, Pantev, Lamprecht-Dinnesen, Matulat, of the MEG method (e.g. Williamson & Kaufman, 1981; Scheer, Borstel & Elbert, 2000; Simos, Breier, Fletcher, Weinberg, Stroink & Katila, 1985; Hari & Ilmoniemi, Bergman & Papanicolaou, 2000). This article will briefly 1986; Sato, Balish & Muratore, 1991; Hämäläinen, Hari, review the basic principles of MEG and give some exam- Ilmoniemi, Knuutila & Lounasmaa, 1993; Gallen, Hir- ples of the present use of MEG in children. schkoff & Buchanan, 1995; Lewine & Orrison Jr., 1995; Hari, 1998; Forss, Nakasato, Ebersole, Nagamine & Salmelin, 2000; Otsubo & Snead, 2001). At present, over Basic principles of MEG one hundred MEG installations worldwide contribute to our knowledge about the function and development A moving electric charge is always associated with an of the human brain. Most MEG studies have been electric field and a concomitant magnetic field surround- conducted with adult subjects, but some MEG data ing the axis of movement (Figure 1a). Electroencephalo- already exist on children. Pediatric MEG studies have gram (EEG) and MEG signals are believed to reflect mainly focused on epilepsy surgery (Paetau, Hämäläinen, synchronous postsynaptic currents in thousands of par- Hari, Kajola, Karhu, Larsen, Lindahl & Salonen, 1994; allel apical dendrites. Despite being ultimately due to the Chuang, Otsubo, Hwang, Orrison & Lewine, 1995; same primary currents, EEG and MEG signals differ at Minassian, Otsubo, Weiss, Elliott, Rutka & Snead, 1999), some important points. First, only tangential currents, on rolandic epilepsy (Kubota, Oka, Kin & Sakakihara, parallel to the head surface, give rise to an extracranial 1996; Minami, Gondo, Yamamoto, Yanai, Tasaki & Ueda, magnetic field. Because the apical dendrites typically run

Address for correspondence: Hospital for Children and Adolescents, P.O. Box 280, FIN-00029 HUS, Finland; e-mail: ritva.paetau@hus.ﬁ

Therefore, tumors, cysts, calcified lesions and skull defects cause less distortion on MEG than EEG signals (van der Broek, Reinders, Donderwinkel & Peters, 1998). Third, signal attenuation in EEG is caused by poorly conducting tissue, while the magnetic field fades off proportionally to the second power of the distance from the source. Infants and persons with small heads should preferably be studied with systems composed of two part-head devices adjustable according to the head size or with specially designed baby devices. Fourth, different practical problems hamper data acquisition. MEG sensors are in a rigid helmet and the head has to be kept immobile with respect to the helmet. Long-term recordings or recordings of major motor seizures are so far not possible with MEG, but continuous monitoring of the head position may offer relief to some of the movement problems. Finally, MEG and EEG have partly differing artifact profiles: MEG is less sensitive to muscle artifacts than EEG. On the other hand, magnetic materials moving with respiration (traces from craniotomy drills, some shunt materials, tooth braces, cochlear implants, etc.) may cause serious artifacts or even destroy the MEG data.

Instrumentation

The brain’s magnetic fields are extremely weak (on the − Figure 1 Physical basis of MEG signals. (a) The intracellular order of 10 15 Tesla) and need to be heavily amplified, current I in the apical dendrite of a pyramidal cell is associated while much stronger environmental magnetic noise from with a surrounding magnetic field B. (b) In the brain, pyramidal power lines or electronic equipment must be suppressed. cells typically are perpendicular to cortex surface, and may be MEG measurements are carried out in magnetically radial (white arrows), oblique or tangential (dark arrows) to the shielded rooms, using sensitive superconducting quan- scalp. Only the tangential currents and the tangential tum interference devices (SQUIDs) (Zimmermann, Thiene component of oblique currents contribute to the extracranial & Harding, 1970). The MEG sensors consist of a flux magnetic field, which can be detected by sensitive SQUID transformer coupled to a SQUID, which amplifies the magnetometers. (c) Dipolar magnetic field pattern viewed from above. B in indicates the magnetic flux into the head and B weak extracranial magnetic field and transforms it into out the flux out from the head. An equivalent current dipole voltage. The sensors are immersed in liquid helium and (ECD; the thick black arrow) represents the concerted action attached on a concave bottom of a container, where they of all fissural dipoles. Its orientation is parallel to the isofield typically lie at a distance of 3–4 cm from the cortex. lines and it is located underneath the steepest gradient halfway A flux transformer may be planar, and gives the between the in- and out-flowing flux. Its depth determines the largest signal at the sharpest field gradient right above distance between the two extremes, and its strength is a local brain current, or axial giving maximum signals proportional to the number of active pyramidal cells. at both the field extremes. At present, several companies manufacture whole-head devices with 64–306 sensors for perpendicular to the cortex surface, MEG signals mainly clinical and experimental work. The present examples arise in fissure walls (Figure 1b). The EEG signals, on come from experiments with a planar 122-SQUID gradi- the other hand, are dominated by radial currents, while ometer, Neuromag-122™, and a planar-axial 306-SQUID the tangential ones may require signal averaging to be device Vectorview, 4-D Neuroimaging, Helsinki, Finland. detected. This complementary sensitivity to current orientation warrants combined use of EEG and MEG Data acquisition whenever possible. Second, inhomogeneous tissue con- ductivity of the human head tends to spread out the During the experiments, the subject is sitting or lying EEG signal, but does not alter the magnetic fields. with his/her head inside a sensor helmet as close to the

© Blackwell Publishers Ltd. 2002 Magnetoencephalography 363 sensors as possible. Head movements are minimized by Brain–muscle interaction can be studied using MEG- using videotape films, visual stimuli, neck collars or head EMG coherence analysis, an important new method for fixating bite bars. identification of the motor cortex (Salenius, Portin, The exact head position within the helmet is often Kajola, Salmelin & Hari, 1997; Mäkelä, Kirveskari, determined with three or four coils pasted around the Seppä, Hämäläinen, Forss, Avikainen, Salonen, Salenius, head. Prior to data acquisition, the position of these Kovala, Randell, Jääskeläinen & Hari, 2001). It requires coils is sensed with a 3-D digitizer within an individual a few minutes of weak voluntary isometric muscle head coordinate system based on three fiducial points: contraction, and can be successfully recorded from the left and right preauricular points and the nasion. school-age children. Brief magnetic signals from the coils allow determination of the head position within the helmet. For later Data analysis alignment of MEG and MRI data, the fiducial points are identified on the subject’s MRI slices. The MEG data are displayed as traces, similar to tradi- EEG, electromyogram (EMG), electro-oculogram, tional EEG signals allowing epileptiform spikes, evoked electrocardiogram, finger movements, voice phono- response components and other graphoelements to be grams, etc. can be monitored during MEG acquisition, easily recognized (Figures 2a, 2b). The same data are provided that nonmagnetic materials are used inside the concomitantly displayed as time-varying magnetic field shielded room. Evoked responses to auditory, somatosensory or visual stimuli require little cooperation and are routinely recorded in the context of presurgical mapping even in young children. Typically, more than one hundred evoked responses have to be averaged during 4–8 minutes in school-age children until a satisfactory signal-to-noise ratio is achieved. The youngest children often have large- amplitude background activity and require more averages and longer recordings. Auditory experiments take even longer, because the common target signal, the magnetic auditory evoked 100-ms response, N100m – labeled according to event-related potential (ERP) terminology (Taylor & Baldeweg, this issue) – can only be detected at long interstimulus intervals in young children (Paetau, Ahonen, Salonen & Sams, 1995; Rojas, Walker, Sheeder, Teale & Reite, 1998). The same is true for a number of other long-latency responses. Mismatch negativity (MMN) is a long-latency auditory evoked vertex-negative potential to infrequent devi- ants in a sequence of homogeneous standard stimuli peaking at 200–400 ms in adults and children. Its magnetic counterpart, the mismatch field (MMF), is generated by the auditory cortex, and has been widely studied in healthy adults (Hari, Hämäläinen, Ilmoniemi, Kaukoranta, Figure 2 Source analysis of epileptiform spikes. (a) A nose-up Reinikainen, Salminen, Alho, Näätänen & Sams, 1984; top view from a planar 122-SQUID display. The 600-ms epoch Sams, Kaukoranta, Hämäläinen & Näätänen, 1991; Levänen, shows epileptiform spikes with two local amplitude maximae, Hari, McEvoy & Sams, 1993; Näätänen, Lehtokoski, Lennes, enlarged in (b). Traces and concomitant field patterns (c) are Cheour, Huotilainen, Iivonen, Vainio, Alku, Ilmoniemi, screened for dipolar field patterns, occurring here at 304 and Luuk, Allik, Sinkkonen & Alho, 1997; Vihla, Lounasmaa 330 ms. Dipolar fields are modeled with a single equivalent current dipole (ECD; white and black arrows). ECD activity over & Salmelin, 2000). Recording responses to hundreds of time (d) shows a consistent activity pattern, with right- rare deviant stimuli also means long sessions, but the hemisphere activity (R) leading the left-hemisphere activity (L) interesting potential of MMN in early language dis- by 25 ms during repeated spikes (superimposed). The two ECDs crimination (Cheour, Ceponiene, Lehtokoski, Luuk, Allik, together explain 80–40% of the overall field variance Alho & Näätänen, 1998) warrants developmental MEG (Goodness-of-fit %) during spikes. (e) Dipole locations (boxes) studies in babies and young children. and orientations (tails) in the upper bank of sylvian fissure.

© Blackwell Publishers Ltd. 2002 364 Ritva Paetau patterns (Figure 2c). The goal of data analysis is to only partly in time, the single dipole model may be determine which brain currents underlie a particular spike adequate at a particular time point. The effects of or evoked response, i.e. to solve the ‘inverse problem’. that dipole can be removed from the analysis by a signal- Unfortunately, an infinite number of current distributions space projection procedure (Uusitalo & Ilmoniemi, may result in exactly the same field pattern, and there is 1997) and a new single dipole may be fitted to the resid- no unique solution to the inverse problem (Sarvas, 1987). ual field. Finally, all dipoles together are used to explain To rule out false possibilities, the brain and the brain the data. Complex source patterns (e.g. in the visual currents have to be appropriately modeled and further cortex) may be best visualized by using minimum cur- constraints are needed to rule out unphysiological or rent estimate-based maps instead of dipoles (Uutela, anatomically impossible solutions. Hämäläinen & Somersalo, 1999). A single dipole model provides a good first approxi- mation of local brain activity. After screening the magnetic field patterns, dipolar fields (Figures 1c & 2c–e) are Examples of pediatric MEG explained with an equivalent current dipole (ECD) found by a least-squares search. The single dipole fit Presurgical mapping of epileptic and eloquent cortex is repeated at short intervals (e.g. 1 ms) to explore the stability of the solution, and to find the time point Tailored epilepsy surgery is one of the major rationales when the largest dipole moment coincides with the least for MEG recordings. In temporal-lobe epilepsy (for confidence volume and the largest goodness-of-fit value anatomical terms, see Figure 3), MEG identifies correctly or the best correlation coefficient. An ideal ECD should half of the sources, but only 20–50% of mesial temporal explain most of the field variance, and it should main- lobe foci (Brockhaus, Lehnertz, Wienbruch, Kowalik, tain an anatomically stable location over a few ms. Such Burr, Elbert, Hoke & Elger, 1996; Knowlton, Laxer, an ECD represents the mean current location and orien- Aminoff, Roberts, Wong & Rowley, 1997), and 50–70% tation in an active area. The single dipole model is only of the lateral temporal-lobe foci (Smith, Schwartz, Gal- valid if the active area is small. Extended cortical len, Orrison, Lewine, Murro, King & Park, 1995; sources with several parallel ECDs will be misinterpreted Wheless, Willmore, Breier, Kataki, Smith, King, Meador, by the single dipole algorithm as one giant, deeply Park, Loring, Clifton, Baumgartner, Thomas, Constan- situated source. Simultaneous currents of different tinou & Papanicolau, 1999). Deep orbitofrontal epileptic orientations and locations often suit multi-dipole analysis activity, expectedly, is poorly identified by MEG, but (Mosher, Lewis & Leahy, 1992). If the sources overlap extratemporal convexial foci are detected in 44–92% of patients (Paetau et al., 1994; Smith, Gallen & Schwartz, 1994; Smith et al., 1995; Brockhaus et al., 1996; Knowlton et al., 1997; Wheless et al., 1999) and the highest percent- age comes from children with normal MRI (Minassian et al., 1999). For good surgery outcome, all epileptogenic cortex should be removed and lesions of eloquent cortex, i.e. of the primary sensorimotor and language areas should be avoided as far as possible. Somatosensory evoked fields (SEFs) to electric or tactile stimulation are equally reliable as cortical stimulation to identify the somatotopically organized primary sensory cortex in the central sulcus (Sutherling, Crandall, Engel, Darcey, Cahan & Barth, 1988; Smith, Gallen & Schwartz, 1994; Minassian et al., 1999; Mäkelä et al., 2001). Abnormal low-frequency activity may occasionally contaminate the averaged response and increase the localization error. The error is proportional to the signal-to-noise ratio, and increases in young subjects with large-amplitude background Figure 3 Schematic brain viewed from the left. Only the lateral temporal cortex is visible. The mesial temporal cortex lines the activity. In epilepsy patients, the distance between inner surface of the temporal lobe. Perisylvian cortex SEF sources from two successive recordings of the same encompasses the shaded temporal, frontal and parietal banks individual was larger in the age group 4–8 years than of the sylvian fissure. 12–16 years (16 ± 3 mm vs 4 ± 1 mm).

Localization of the primary motor cortex by MEG- which may have large individual variations (Ojemann, EMG coherence has proved successful in patients with Ojemann, Lettich & Berger, 1989). Papanicolaou, Simos, brain tumors (Mäkelä et al., 2001) and with epilepsy Breier, Zouridakis, Willmore, Wheless, Constantinou, (Paetau, unpublished observations). Figure 4 shows Maggio and Gormley (1999) reported a word recogni- presurgery MEG data from a girl with drug-resistant tion task for noninvasive lateralization and localization epilepsy and cortical dysplacia in left frontal lobe. of language cortex using MEG. The subjects listened or Her interictal MEG spikes originated at the anterior and read abstract English nouns, and they had to indicate if posterior borders of the dysplastic sulcus. MEG local- a noun had been presented earlier during the session. ized the primary motor and sensory cortices 1.5 cm Evoked magnetic responses to memorized words were posterior to the dysplastic area. The lesion was removed averaged. A single dipole analysis over a time window of with no resultant paresis and >90% reduction of 150–700 ms poststimulus showed approximately twice seizures. as many good dipoles (correlation coefﬁcient ≥0.9) in Language-related cortex should not be lesioned by the left than in the right hemisphere. This empirical cri- brain surgery. While critical language functions most com- terion for language lateralization was recently reported monly reside in the left hemisphere, right-hemisphere to match the Wada test (Breier, Simos, Zoudriakis, language dominance or bilateral language representation Wheless, Willmore, Constantinou, Maggio & Papanico- occasionally occur in epilepsy surgery patients. For the laou, 1999) and cortical stimulation mapping in patients intracarotid amobarbital procedure or the Wada test with tumors or epilepsy (Simos, Papanicolaou, Breier, (Wada & Rasmussen, 1960), a short-acting barbiturate is Wheless, Constantinou, Gormley & Maggio, 1999). The injected to one hemisphere at a time. The neural functions word recognition paradigm, however, failed to activate of the injected side are paralyzed for a few minutes, the left temporoparietal cortex in dyslexic children during which contralateral hemisphere language functions (Simos, Breier, Fletcher, Bergman & Papanicolaou, 2000), can be selectively tested. Wada test is the golden whose language dominance might remain ambiguous standard for presurgery assessment of language domi- by the number of left- vs right-hemisphere dipoles. nance, while cortical stimulation mapping is the Salmelin, Hari, Lounasmaa and Sams (1994) found standard to identify subhemispheric language areas, that overt picture naming activates several brain areas of

Figure 4 Presurgical mapping of epileptic generators and sensorimotor cortex. Brain sources of magnetic spikes (white squares), of auditory and somatosensory evoked activity (white circles in auditory cortex and primary somatosensory cortex, SI), and of EMG- coherent motor activity (black circles in primary motor cortex, MI). Dotted lines indicate a deep dysgenetic sulcus.

© Blackwell Publishers Ltd. 2002 366 Ritva Paetau healthy adults in a sequential manner, beginning in the have been proposed to be causally related to cognitive occipital visual areas, progressing bilaterally to the tem- disability. Some LK children develop giant auditory N100m poral and frontal lobes. Pediatric epilepsy patients and responses with similar auditory cortex sources and healthy children from five years up show similar naming- reactivity as the normal N100m, but with morphology related activity patterns, but also individual variations. and amplitude identical to the patient’s epileptic spikes Figure 5 compares the results of presurgical MEG and (Paetau, 1994). LK patients’ verbal auditory agnosia of cortical stimulation mapping during a picture naming can, therefore, be understood as local epilepsy of the test. The suprasylvian cortex, the posterior superior auditory cortex, activated by sounds! temporal sulcus, the supramarginal cortex, and the ante- Spontaneous language recovery in LK syndrome is rior tip of the temporal lobe were repeatedly activated in disappointing. More than two-thirds of the LK patients the left hemisphere. According to cortical stimulation, remain permanently and often severely disabled (Deonna, the suprasylvian MEG sources were associated with Peter & Ziegler, 1989). Morrell, Whisler, Smith, Hoeppner, motor responses from the mouth area, while stimulation Pierre-Louis, Kanner, Buelow, Ristanovic, Bergen, Chez of the superior temporal sulcus elicited dysnomia. Other and Hasegawa (1995) have shown that selected LK MEG sources were not covered by the electrode grid and patients greatly benefit from epilepsy surgery or may not tested. This example shows that language-related even be cured, provided that the epileptic activity is MEG sources were correctly localized, but a naming entirely paced by a restricted area in one hemisphere. task cannot separate the sources of specific language MEG alone or combined with EEG has proved useful processes such as motor planning, articulation or semantic in identifying the sources of epileptic activity in LK, as comprehension, and more sophisticated task paradigms well as in childhood epileptic autistic regression dis- must be developed before the noninvasive language orders. Despite widespread spike-and-wave discharges, localization by MEG can substitute the invasive the sources have consistently been in rather restricted methods. areas, usually in the intra- and perisylvian cortex (Paetau et al., 1991; Paetau, 1994; Morrell et al., 1995; Lewine et al., 1999; Paetau, Granström, Blomstedt, Jousmäki, MEG in acquired epileptiform regression syndromes Korkman & Liukkonen, 1999). Occasionally also nonsylvian Acquired epileptic regression syndromes are disabling sources may be found (Sobel et al., 2000). childhood disorders, where a previously healthy child Several brain areas may become active during the deteriorates over a week to months. The children may or course of a single spike-and-wave complex, and accurate may not show overt seizures, but their EEG usually dis- timing between these generators is crucial to finding plays almost continuous epileptiform spike-and-wave the pacemaker. Multi-dipole analysis of spike-and-wave activity, especially during sleep. In acquired epileptic discharges (Figure 6) identified a single intrasylvian aphasia or the Landau-Kleffner syndrome, LK (Landau pacemaker with monosynaptic connections to the same & Kleffner, 1957), the regression affects receptive language hemisphere in one LK patient (A). In another patient and/or auditory perception. Epileptiform spike-and- (B) one right sylvian source paced both ipsilateral and wave discharges appear during the first few weeks, and contralateral activity. Such single-pacemaker patients would benefit from surgical lesions (multiple subpial transsections, MST) applied to the pacemaker area. Patient A underwent MST on her right auditory cortex, and her auditory perception of environmental sounds improved essentially over the next 3 months. Patient C with bilateral, independent, sylvian-paced circuits and independent local spikes was not recommended for surgery. For children with epileptic regression disorders and widespread discharges, coregistered MEG and EEG provides at present the most efficient way to identify possible surgery candidates.

Figure 5 Language-related MEG activity compared to cortical Conclusions stimulation mapping of the left hemisphere. MEG sources are shown in white and stimulation sites in black symbols. Open MEG and EEG are fundamentally different compared and black symbols indicate the subdural grid placement. to functional magnetic resonance imaging (fMRI),

ing of distributed brain activities during a number of cognitive tasks (Salmelin et al., 1994; Helenius, Salmelin, Service & Conolly, 1998) or epileptic discharges (Hari, Ahonen, Forss, Granström, Hämäläinen, Kajola, Knuu- tila, Lounasmaa, Mäkelä, Paetau, Salmelin & Simola, 1993; Paetau et al., 1999). So far, MEG technology has been most widely used within basic neuroscience in an attempt to reveal cortical activation dynamics in a multitude of tasks of the working human brain. The complete noninvasiveness of MEG enables detailed and repeated studies in healthy subjects, children, as well as neurological and psychiatric patients. Technical improvements, such as infant-size helmets, effective movement correction algorithms, and fast new subroutines for data analysis are constantly developed to better meet the clinical demands. In patient work, MEG is routinely used for mapping the central sulcus, but with an increasing number of MEG-compatible experimental setups being standard- ized, the technique ultimately bears potential for tailored assessment of specific neural circuitries and cognitive processes. Finally, combining imaging modalities with Figure 6 Spatiotemporal activity patterns during epileptic complementary weak and strong sides provides the most spikes in three patients with Landau-Kleffner syndrome. Each reliable individual brain model for both scientific patient’s spikes were modeled with the number of ECDs research and medical care. necessary to explain the signal. To explore cortical spread patterns, the set of ECDs was aligned after peak activity of each independent ECD in turn (shaded). Superimposed traces Acknowledgements represent the ECD solution for several unaveraged spikes. Modified from Paetau et al. (1999). Financially supported by Helsinki University Central Hospital subsidy TYH1334 and by grants from Arvo and positron emission tomography (PET) or other anatomical Lea Ylppö Foundation and Finska Läkaresällskapet. imaging methods, where the spatial resolution is based I thank professor Riitta Hari for comments on the on voxel size. The 3-D sources of electromagnetic data manuscript. are based on mathematical models, and adequacy of the model is of critical importance for correct solution. With the precaution, the spatial resolution of MEG is gener- References ally good, ranging from a few mm on the superficial Breier, J., Simos, P., Zoudriakis, G., Wheless, J., Willmore, L., fissures to a few cm in the basal temporal and frontal Constantinou, J., Maggio, W., & Papanicolaou, A. (1999). areas (Tarkiainen, Hämäläinen & Salmelin, 1996; Leahy, Language dominance determined by magnetic source imag- Mosher, Spencer, Huang & Lewine, 1998), which is often ing. A comparison with the Wada procedure. Neurology, 53, sufficient for practical decisions. Even though the exact 938–945. location of MEG sources should be confirmed by elec- Brockhaus, A., Lehnertz, K., Wienbruch, C., Kowalik, A., trocorticography (ECoG) before surgical lesioning, a Burr, W., Elbert, T., Hoke, M., & Elger, C. (1996). Pos- whole-head MEG effectively identifies the brain areas to sibilities and limitations of magnetic source imaging of be sampled by ECoG. This is of particular importance methohexital-induced epileptiform patterns in temporal lobe in patients without structural brain lesions, in whom epilepsy patients. Electroencephalography and Clinical Neuro- physiology, 102, 423–436. localization of the epileptic area is entirely based on its Cheour, M., Ceponiene, R., Lehtokoski, A., Luuk, A., Allik, J., electrophysiological and metabolic properties. Alho, K., & Näätänen, R. (1998). Development of language- The most important advantage of MEG and EEG specific phoneme representations in the infant brain. Nature over any present functional imaging modality is their Neuroscience, 1, 351–353. submillisecond temporal resolution. At present, MEG Chuang, S., Otsubo, H., Hwang, P., Orrison, W.J., & Lewine, J. provides the most efficient single tool for real-time track- (1995). Pediatric magnetic source imaging. In J. Kucharczyk,

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