Journal of Pediatric Epilepsy 2 (2013) 73–85 73

DOI 10.3233/PEP-13040
IOS Press

Review Article

Current and emerging potential for

magnetoencephalography in pediatric epilepsy
Christos Papadelisa,b,*, Chellamani Harinib, Banu Ahtama,c, Chiran Doshia,b, Ellen Granta,c,d,e
and Yoshio Okadaa,b
a
Fetal-Neonatal Neuroimaging & Developmental Science Center, Boston Children’s Hospital, Harvard Medical
School, Boston, MA, USA
b
Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
c
Division of Newborn Medicine, Department of Medicine, Boston Children’s Hospital, Harvard Medical School,
Boston, MA, USA
d
Department of Radiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
e
Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical
Imaging, Charlestown, MA, USA

Received 15 March 2013

Revised 18 May 2013
Accepted 18 May 2013

Abstract. Magnetoencephalography (MEG) is a noninvasive neuroimaging tool that is increasingly becoming useful for presurgical
delineation of epileptogenic zones and eloquent cortex in both lesional and non-lesional pediatric cases. During the past 10 yrs, the
use of MEG in pediatric epilepsy research has increased. This paper starts with a review of the use of MEG in pediatric epilepsy. We
then describe the protocol used for epilepsy patients at the pediatric MEG facility in Boston Children’s Hospital and present two case
studies of intractable epilepsy obtained in our laboratory -cortical dysplasia and tuberous sclerosis complex -to illustrate our metho-
dology in localizing epileptiform generators. In both cases, we are able to localize generators of interictal spikes in the irritative zone
just outside the lesion. We also present results on localization of the somatosensory cortex based on our pediatric MEG system to
illustrate the utility of MEG for identification of the eloquent cortex. We complete this review by considering advantages and limita-
tions of MEG in children with epilepsy, its future developments and research applications. Application of MEG in pediatric epilepsy
will accelerate during the coming years as different types of pediatric whole-head MEG systems and more advanced data analysis
methods become available to the researchers and clinicians. These advances will lead to greater use of MEG as a complement to clin-
ical electroencephalography, with improved noninvasive delineation of the epileptogenic zone.

Keywords: Magnetoencephalography, pediatric epilepsy, tuberous sclerosis complex, cortical dysplasia, pediatric magnetoence-
phalography systems, human brain development

1. Introduction [1]. It can have a major impact on the development of

Childhood epilepsy is a common neurological dis-
order with a prevalence rate of 4–6 per 1,000 children
*Corresponding author: Christos Papadelis, Boston Children’s
Hospital, Harvard Medical School, Department of Neurology, 9 Hope
Avenue, Waltham, MA 02453 USA. Tel.: +1 781 216 1128; Fax: +1
781 216 1172; E-mail: christos.papadelis@childrens.harvard.edu.
children [2] and may significantly affect their later adult
life. Long term follow up studies in childhood-onset epi-
lepsy indicate favorable outcome in about two-thirds of
children [3,4]. The International League Against Epi-
lepsy task force has defined drug resistant epilepsy as
failure of adequate trials of two tolerated, appropriately
chosen and used antiepileptic drug schedules (whether

2146-457X/13/$27.50 © 2013 – IOS Press and the authors. All rights reserved
74 C. Papadelis et al. / Potential for MEG in pediatric epilepsy
as monotherapies or in combination) to achieve sus-
tained seizure freedom [5]. This helps to select pat-
ients who can be evaluated further for possible
epilepsy surgery. It has been estimated that approxi-
mately 30% of epilepsy patients become medically
intractable [6–9] and some may eventually require
resective epileptic surgery. To be successful, epileptic
surgery should achieve a seizure-free state with mini-
mal or no functional deficits. This requires (i) careful
delineation of the epileptogenic zone, and (ii) ana-
tomic localization of the eloquent cortex [10]. The
epileptogenic zone is the ‘area of cortex that is indis-
pensable for the generation of epileptic seizures’ [11].
The epileptogenic zone in practice refers to the mini-
mum amount of tissue that needs to be resected to
ensure seizure freedom [12].
Crucial to the success of surgical treatment is the
availability of a robust pre-surgical marker that identi-
fies the epileptogenic zone and the functionally rele-
vant eloquent cortex. Techniques to estimate the
epileptogenic zone can be traced back to ancient times
[13]. Nowadays, multimodal imaging and neuro-
physiological tests are used in pediatric epilepsy to
presurgically define the epileptogenic zone and the
eloquent cortex. Magnetic resonance imaging (MRI)
[14], MRI with post processing techniques such as
voxel based morphometry, and diffusion tensor imaging
(DTI) [15] have revolutionized the presurgical work-up
by enabling improved detection of the epileptogenic
lesion. Non-invasive functional neuroimaging methods,
such as positron emission tomography [16], single-
photon emission computed tomography [17], and func-
tional MRI [18], have permitted improved localization
of the functional deficit zone and the relevant eloquent
cortex.
Magnetoencephalography (MEG) [19] is consid-
ered as one of the promising tools to localize and
visualize sources of epileptic activity in the pediatric
population. It has been used clinically in adults since
1980s to characterize the irritative zone and, in some
studies, the ictal onset zone. The irritative zone is
the region that produces interictal epileptogenic dis-
charges [10]. The ictal-onset zone is the region where
seizures are generated. MEG is particularly useful in
patients with normal MRI findings [20,21] that repre-
sent up to 40% of epilepsy cases undergoing presur-
gical evaluation [22] and usually have less favorable
surgical outcomes compared to patients with focal
epileptogenic lesions seen on MRI [23]. Patients with
multifocal or diffuse disease may also benefit [24,25]
from MEG.
2. Basic principles of MEG
MEG is a non-invasive electrophysiological ima-
ging technique used to measure extremely weak mag-
netic fields produced by electrical currents in active
neurons of the human brain. The magnetic field of the
earth is ~50 microTesla (0.5 × 10-4 T). MEG signals
are on the order of 10 picoTesla to 10 femtoTesla
(1 × 10-11T − 1 × 10-14 T). Thousands of nearby neu-
rons that are in a similar orientation have to act simul-
taneously for their magnetic field to be measurable at
the scalp [26,27]. Synchronized neuronal activity is
best observed at the cortical pyramidal cells that
are aligned perpendicular to the surface of the cortex
[28–30]. The main sources of the magnetic fields
recorded by MEG are considered to be the postsynap-
tic currents in the apical dendrites of these cortical pyr-
amidal cells [31–35], though recent studies have
challenged this notion by showing that action potentials
may also be recorded [36–42]. MEG is most sensitive
to the currents that are tangential to the surface of the
scalp. Magnetic fields produced by radial sources
do not usually come out to the surface of the head
[29,43–45]. MEG offers an excellent temporal resolu-
tion in the range of sub-milliseconds and a very good
localization accuracy of a few millimeters, especially
for superficial cortical sources [46].
The MEG equipment is located inside magnetically
shielded rooms (MSR) where the recordings are per-
formed. Magnetically shielded rooms are equipped
with adjustable lighting and audio-visual communi-
cation systems that allow communication with the
technicians seated outside. Shielded environments
minimize the interference of MEG recordings from
external electromagnetic sources (i.e. power lines,
radiofrequency signals from portable devices, electri-
cal devices and computers, magnetic fields from mov-
ing magnetized objects such as cars, elevators, and
trains). Brain activity is measured by positioning the
patient head inside a helmet that contains magnetic
field detection coils which are inductively coupled
to very sensitive magnetic field detection devices
called superconducting quantum interference devices
(SQUIDs). The assembly consisting of a detection
coil and a SQUID is made of superconductors, which
lose electrical resistivity below a critical temperature,
near the temperature (–268.95 °C) of liquid helium.
SQUIDs convert the magnetic flux passing through
the detection coils into voltage changes [47,48]. Modern
MEG systems are usually equipped with a high number
of SQUIDs (more than 300) offering simultaneous
 C. Papadelis et al. / Potential for MEG in pediatric epilepsy 75

recording of brain activity from different parts of
the brain.
The goal of this paper is to give a review of the use
of MEG in pediatric epilepsy, to describe the protocol
used for epilepsy patients at the pediatric MEG facility
in Boston Children’s Hospital, to consider advantages
and limitations of MEG in children with epilepsy,
and to discuss future developments and research appli-
cations. Some earlier review papers are available on the
use of MEG in pediatric epilepsy [49–51].
3. Protocol for pediatric epilepsy MEG
3.1. Equipment
Our laboratory is equipped with a pediatric MEG
system, called BabySQUID, which was designed by
one of us (Yoshio Okada) and built by Tristan Inc.
(San Diego, CA, USA) [52]. The system is installed
in an MSR (Fig. 1). BabySQUID is designed to take
advantage of the thin scalp and skull of newborns and
infants, which may be as thin as 2–3 mm on the dorsal
surface at birth [53]. The detection coils are placed
just 7–10 mm below the headrest, where the head of a
patient is placed for testing (Fig. 1a). This gap is
approximately half the gap for conventional adult
MEG systems, making signal strengths at the sensors
stronger by a factor of about four since the signal
strength increases as inverse of square of the gap.
The short gap also provides higher spatial resolution,
since it is approximately linear with the inverse of the
gap. BabySQUID can measure MEG signals with 76
axial gradiometers (Fig. 1b) within an oval region of
interest (ROI) of 12–14 cm in diameter (Fig. 1a).
High-density electroencephalography (ECG), electroo-
culography (EOG), and electrocardiography recordings
are routinely recorded simultaneously with the MEG
signals. The EEG signals are recorded with a 128-
channel EEG system (ANT-Neuro, Netherlands) by
using caps suitable for toddlers and children. MEG and
volumetric MRI coregistration are performed using an
in-house procedure, described in Section 3.2. For the cor-
egistration, we use a 6-degree-of-freedom commercial
motion tracking device (FASTRAK, Polhemus Inc.,
USA) located in our preparation room, and an opti-
cal tracking system (Polaris, Northern Digital Inc.,
Canada) located in the MSR (Fig. 1c).
3.2. Patient preparation
Patient preparation is minimal, and the examination
is generally well tolerated. The entire session lasts
about 2–3 hrs with the actual measurements lasting
around 60 min. We ask parents to bring the child sleep
deprived by either skipping a nap or waking her/him up

Fig. 1. The BabyMEG facility at Boston Children’s Hospital at Waltham. Upper left panel (a): The headrest where the child places her/his head
during the recordings. Lower left panel (b): Schematic diagram of the partial coverage sensor array consists of 76 axial gradiometers. Right panel
(c): Overview of the BabySQUID system inside the shielded room. A stereoscopic Polaris camera is used for coregistration of the anatomical
data with the functional data.
76 C. Papadelis et al. / Potential for MEG in pediatric epilepsy

Fig. 2. Coregistration procedure. (a) Marks made with a non-toxic washable marker on anatomical landmarks of the face of a child. These points are
digitized by both Polhemus and Polaris systems. (b) Magnetic resonance images – extracted head surface of a child (on gray) coregistered with
digitized points extracted by Polaris system and the BabySQUID sensor array (yellowish surface covering the left somatosensory cortex).

earlier in the morning, and let the child go to sleep in our
facility once the preparation procedure is completed. We
do not use sedation for our recordings. Patients change
their clothing to a non-metallic hospital gown. The
child’s head is then digitized with the FASTRAK sys-
tem. If the patient is old enough, s/he will be asked
to sit on a chair where the FASTRAK transmitter is
attached. The FASTRAK receiver is placed securely
on patient’s head with a headband (Fig. 2a). If the
patient is an infant or a toddler, s/he lies down on a
changing bed. With a non-toxic washable marker, basic
anatomical landmarks on the face and the ears are
marked such as the nasion, left and right pre-auricular
points, the forehead, the cheeks, and the chin (Fig. 2a).
The assistant then uses the stylus to digitally mark the
basic anatomical landmarks that were previously identi-
fied on the face and ears. Beyond the basic anatomical
landmarks, additional points are also recorded to com-
pute an accurate transformation matrix between the
FASTRAK and the Polaris systems (Fig. 2b).
The EEG cap, EOG and ECG electrodes are placed
on patient’s head, face and chest, respectively. EEG
electrode locations are digitized with the digital pen,
and the well of each electrode is filled with conduc-
tive gel. Once asleep, we bring the patient on top of
the bed of the BabySQUID cart. Parents can monitor
their child via a liquid crystal display screen located
outside the MSR. The assistant is always in the MSR
during the recording. S/he places the patient’s head on
the headrest and coordinates the recording sessions.
The previously marked anatomical landmarks on the
face are digitized with the stylus of the Polaris system
before each recording. If the patient moves her/his head
after the digitization, the assistant repeats the procedure.
Since the BabySQUID has a partial coverage, it allows
recordings only from a specific ROI each time. Based
on our experience with this system, the coverage is large
enough for us to localize cortical generators of MEG
signals below the array. The placement of the particular
ROI is guided by previous EEG findings from long-term
EEG monitoring recordings.
3.3. Data recordings and analysis
3.3.1. Data recordings and preprocessing
MEG, EEG, and peripheral recordings are performed
at a sampling rate of 1,024 Hz for at least four runs, each
lasting 10 mins, while the patient is asleep. The data are
then preprocessed and visually inspected for interictal
MEG and EEG sharp waves as well as bursts of rhyth-
mic activity by an experienced epileptologist. Abnormal
interictal events are classified based on similar topo-
graphic characteristics, and then averaged in order to
increase the signal to noise ratio (SNR) of the MEG
signal. Source localization is estimated for both aver-
aged (per category) as well as single events. For MEG
and EEG data analysis, two software packages are
used: Brainstorm [54] and MNE-Suite (Minimum Norm
Estimation-Suite) [55]. Coregistration is performed by
in-house software developed by one of us (Chiran Doshi).
Biological artifacts, such as heartbeats, are removed by
the signal-space projection algorithm implemented in
BrainStorm software [56].
3.3.2. Source localization
Source localization requires solving the forward and
inverse problems of bioelectromagnetics. The forward
 C. Papadelis et al. / Potential for MEG in pediatric epilepsy
problem in MEG has a unique solution. It is calculated
using the Maxwell equations, the magnetic field mea-
sured outside the scalp from a known distribution of
neural activity generators. It is important to have an
accurate forward model because MEG source modeling
analyses make a comparison of the measured data with
the predicted signals by the model [47] and the solution
of the forward problem is often a prerequisite for source
localization analyses [47].
The estimation of the most probable intra-cranial
current sources in the brain from the observed extra-
cranial MEG recordings is called the ‘inverse problem’
[47,48]. The inverse problem is an ill-posed problem,
meaning that it does not have a unique solution. This
is due to the fact that a specific set of measured bioe-
lectric signals at the sensor level can be generated by
an infinite number of source generator configurations
[55]. A priori knowledge about the source generators
is thus necessary to constrain the inverse problem solu-
tion. There are two main categories of source localiza-
tion methods: (i) the equivalent current dipole (ECD)
[57], and (ii) the distributed source modeling. The
ECD model assumes that the MEG signal is generated
by one (or more) focal sources. Each source is then
described by an infinitesimally small line current ele-
ment and the task is to find the location, direction and
moment of each ECD. The distributed source modeling
methods assume that the locations of the source dipoles,
and sometimes their orientations, are fixed, while their
amplitudes and/or orientations are estimated from the
measured data. The ECD is extensively used in epilepsy
studies, while distributed source models have started
to be applied more recently in the analysis of MEG
epilepsy data.
In our laboratory, we use three source imaging algo-
rithms in order to localize the interictal activity and the
burst rhythmic activity: the single-dipole ECD, the whi-
tened minimum norm estimates (wMNE) [55], and the
dynamic statistical parametric mapping (dSPM) [58].
The MNE algorithm is one of the earliest algorithms
developed for cortical source imaging and is based on
the L2-norm minimization. Its main limitation is its
low resolution and the bias it introduces towards super-
ficial sources. The wMNE is a modification of MNE,
which rectifies the bias issue to some extent. However,
low resolution of wMNE remains to be a problem.
dSPM has recently been introduced [58] in the study
of epilepsy. It provides spatiotemporal source distri-
bution with millisecond temporal resolution by impos-
ing anatomical information about the cortical surface
derived from MRI and noise normalization of the
77
minimum norm estimate. Clinical studies using
dSPM in patients with partial epilepsy suggest that
it has advantages over a single-dipole model in ana-
lyzing interictal MEG spikes [59,60]. Because the
technical details of each imaging algorithm are
beyond the scope of this article, we provide here
only a brief summary of their basic concepts.
For estimating the forward model, we currently use
the symmetric boundary element method (BEM) that
incorporates information from three realistic layers
(scalp, inner skull, outer skull). The OpenMEEG soft-
ware is used for the estimation of the BEM forward
model [61,62]. BEM is a commonly used forward
model for both MEG and EEG, because of its speed
and modest demands for computer memory. To analyze
the MEG and high-density EEG data from our epilepsy
pediatric patients, we calculate the ECD, MNE, and
dSPM at the peak of both averaged as well as single
interictal spikes for the purpose of estimating the spatio-
temporal cortical source distribution. Source localiza-
tion solutions are mapped onto both a cortical surface
and a volumetric image. The ECDs with goodness of
fit > 70% are considered adequate as possible cortical
sources. Virtual or synthetic depth electrodes, con-
structed by appropriate mathematic weighting of the
MEG sensors, are ‘placed’ at locations of epileptogenic
activity. They are used to identify the time-activity pro-
file at these locations allowing the morphological char-
acterization of the regional electric activity.
3.3.3. MRI and DTI Imaging
Whole-brain MRI is performed on our standard
clinical 3T system. We collect MRI data from those
patients who do not have an MRI scan close (<6 mo)
to the time of the MEG/EEG recording. This is in order
to estimate an accurate forward model. For accurately
localizing sources of neuronal activity from MEG/
EEG recordings, it is necessary to co-register MEG/
EEG data with structural MRI data. Our imaging proto-
col includes a multi-echo T1-weighted magnetization-
prepared rapid-acquisition gradient-echo sequence, using
1 mm3 isotropic voxel size; in addition, echo-planar based
navigators are added in each repetition time (TR) to
correct for potential patient motion. Diffusion imaging
is acquired in the axial plane, using 30 images with
b = 1000 s/mm2 and ten images with b = 0 s/mm2, isotro-
pic voxel size of 2 mm3. If time permits and if the subject
is cooperative, additional diffusion directions and multi-
ple b-values can be obtained for a better quality image.
The overall acquisition time of the MRI and DTI data
78 C. Papadelis et al. / Potential for MEG in pediatric epilepsy

do not exceed 30 mins. DTI data from our patients are
not presented in this paper.
3.3.4. Case studies
3.3.4.1. Temporal lobe dysplasia patient
A 3-year-old girl with uncomplicated birth and peri-
natal history presented with her first seizure when she
was 2.5-years-old. She had complex partial seizure char-
acterized by behavioral arrest, unresponsive with left
sided head and eye deviation and both hands fisting.
MRI revealed abnormal T2 signal involving the subcor-
tical and deep white matter of the left temporal lobe and
overlying cortex without post-contrast enhancement,
consistent with a cortical malformation/migrational
abnormality. Interictal EEG had multifocal spikes over
the left hemisphere in the left temporal parietal region,
occasional right temporal spikes, and rare spikes in the
left frontal region. Ictal EEG captured eight clinical sei-
zures consisting of leftward head deviation. The seizure
onset was broadly in the left hemisphere, not well loca-
lized. Fourteen electrographic seizures were also identi-
fied, all having onset in the left temporo-parietal region
(electrodes P3 or P3/P7), except one with broad left
hemisphere seizure with maximum at left anterior tem-
poral region. Ictal single-photon emission computed
tomography indicated hyper-perfusion surrounding the
persistently hypo-perfused region of cortical dysplasia
in the left temporal lobe.
Twenty minutes of MEG data were recorded during
sleep. The sensor array covered the left temporal and
left anterior parietal lobes. Two groups of interictal
spikes were classified based on the topography of the
measured activity at the sensor array. The first group
of interictal spikes was localized in the proximity of
the lesion in the left temporal lobe. The second group
was localized at the left parietal cortex. Fig. 3 presents
two interictal events from the first group of activity
(Fig. 3a), the topography of activity at the peak of the
first event indicating a dipolar pattern (Fig. 3b), and
their localization by using the wMNE (Figs. 3c, 3d,
and 3e). The localization of these events was consis-
tently in the proximity of the lesion as it was indicated
by both wMNE and ECD methods (Fig. 4).
3.3.4.2. Tuberous sclerosis complex (TSC) patient
A 4-years-old girl with refractory epilepsy, as a result
of TSC, with uncomplicated perinatal history presen-
ted with her first seizure when she was 4-month-old.
Cardiac rhabdomyoma, revealed by echocardiography,
resulted in the diagnosis of TSC1 mutation. MRI
showed multifocal cortical tubers in the bilateral fron-
tal, parietal and occipital lobes. Mineralization of the
cortical tuber in the right parieto-occipital lobe was

Fig. 3. Magnetoencephalography (MEG) data from a child with temporal lobe dysplasia. (a) MEG sensor time traces for 3 secs of recordings.
Two interictal spikes are identified (green arrow indicates one). (b) MEG activity topography at the peak of the first spike indicated with a green
arrow in (a). (c and d) whitened minimum norm estimates (wMNE) source localization of the single spike localized at the proximity of the tem-
poral lobe lesion (marked with yellow dashed line). (e) wMNE source localization results projected at the cortical surface of the patient.
 C. Papadelis et al. / Potential for MEG in pediatric epilepsy 79

SNR was achieved. MEG data from single as well as

averaged data indicated a focal source in the proximity
of a large tuber in the upper right quadrant (Fig. 5).
ECDs of single events were also localized at the same
location (>20 spikes in a 1-cm area) (not shown).

3.3.5. Localization of eloquent cortex

Fig. 4. Magnetoencephalography source localization data of interic-
tal activity with the use of equivalent current dipoles and whitened
minimum norm estimates for multiple single events and averaged
data respectively. Both techniques localized the interictal activity
sources at the proximity of the temporal lobe lesion.
also observed. Routine and ambulatory EEG indicated
very frequent right posterior temporal/occipital sharp
waves (electrodes P8/O2). Left frontal spikes were also
observed along with intermittent left frontal slowing
(electrode F3). One-hour MEG and high-density EEG
data were recorded during sleep. The sensor array was
covering the parieto-occipital lobe for 40 min and the
left fronto-temporal lobe for 20 min. A high number of
interictal spikes (>50) were detected with a consistent
spatiotemporal pattern indicating a focal right parieto-
occipital source. The spikes were averaged and a high
3.3.5.1. Somatosensory projection areas
We have consistently found that MEG is useful for
identifying the eloquent cortex. Here we illustrate the
results for somatosensory projection areas in the pri-
mary somatosensory (SI) cortex. The tip of the fingers
(Digits 1, 3 and 5) of the right hand and of the right
big toe were stimulated with a tactile stimulator by
applying a brief air puff (10 ms) to a plastic membrane
which expanded physically to stimulate the skin. The
activations in the contralateral somatosensory cortex
were recorded with BabySQUID. Fig. 6 shows the
results for one subject. The projection sites are all
located along the posterior bank of the central sulcus
with the well-known somatotopic arrangement. These
results can be easily obtained from each subject by aver-
aging 50–100 responses, requiring 100–200 sec per site
of stimulation. The capability of MEG for source locali-
zation has been well demonstrated during the past 20 yrs
and presurgical localization of eloquent cortices is a
clinically approved procedure.

Fig. 5. Magnetoencephalography data from a child with tuberous sclerosis complex. Upper panel: averaged interictal spikes (left) with the same
spatiotemporal profile, and its corresponding whitened minimum norm estimates source localization (center and right). The interictal activity was
localized at the proximity of the tubor. Lower panel: one of the interictal spikes (left) used to estimate the averaged signal at the upper panel, and
its corresponding whitened minimum norm estimates source localization (center and right). There is a consistency between the localization of
averaged and single event.
80 C. Papadelis et al. / Potential for MEG in pediatric epilepsy
Fig. 6. Source localization results (whitened minimum norm esti-
mates) for tactile responses from stimulation of digits 1, 3, 5, and
big toe. Black line: central sulcus.
4. Current clinical applications in pediatric
epilepsy
MEG is predominantly used for the localization of
interictal activity in the investigation of children with
both lesional [63] and non-lesional cases [20,64–66].
The MEG source localization of interictal activity
(clusters and scatters) predicts the irritative zone
observed on the intracranial video-EEG recordings
[51]. MEG spike sources that form a single cluster
(≥20 spikes in 1-cm area) indicate that the distribution
of sources correlates with the seizure-onset zone (SoZ),
part of the symptomatogenic zone and irritative zone
observed on intracranial video EEG recordings [67,68].
Thus, the addition of MEG to the clinical evaluation of
medically refractory epilepsy patients can help to gener-
ate a hypothesis regarding epileptogenic foci in epilepsy
patients and may improve the postsurgical outcomes of
the patients [69–72].
Although MEG is predominantly used for the loca-
lization of interictal activity, an increasing number of
recent studies report the localization of ictal activity
by using multichannel MEG systems, which was con-
firmed by intraoperative Electrocorticography (ECoG)
[69,73–76]. Ictal MEG in pediatric population demon-
strates good concordance with the SoZ as defined by
the current gold standards: intracranial EEG and surgi-
cal outcome [77]. To capture a seizure during a clinical
MEG recording is however methodologically chall-
enging because (i) the time of MEG recordings in clini-
cal setup is limited (1–2 h) decreasing significantly the
possibility of capturing a seizure; (ii) the movement arti-
facts that occur frequently with seizures can be detri-
mental to the quality of MEG recording [78]; (iii) both
ictal MEG and EEG signals often have a low SNR,
which may not allow for accurate source localization
analysis, and (iv) the magnetic field attenuates rapidly
as the distance from focus to MEG sensors increases,
and distant sources in the mesial temporal cortex
[79,80] as well as those in the basal temporal, in the
basal frontal, and in the deep interhemispheric areas
might go undetected. Recent studies have proposed
new signal processing tools considering also the fre-
quency content of the ictal MEG activity for detecting
and localizing these events [81]. The investigation of
the magnetic field manifestations at the seizure onset
can provide valuable information about the SoZ, though
several studies have reported that ictal MEG occasion-
ally failed to localize the SoZ [69,74,75].
5. Advantages and limitations of MEG in
children with epilepsy
Compared to other neuroimaging methods, MEG
presents a unique set of significant advantages but
also limitations compared to EEG. Preparation for an
MEG recording is faster and easier. With MEG, the
brain activity can be measured immediately after pla-
cing the children’s head inside the special helmet,
since there is no need to attach any sensors over the
head. Unlike EEG signals [84], MEG signals are not
distorted by skull conductivity [82,83]. MEG is also
less distorted than EEG by unfused regions of the cra-
nial bone such as fontanel or suture [30]. Moreover,
MEG signals are reference free providing absolute
measurements of the magnetic field produced by the
brain, in contrast to EEG, which provides potential
differences between two locations. MEG signals can
be measured with a high density of magnetic field
sensors [52]. In contrast, high-density EEG always
faces the problem of salt bridge between the electro-
des when the head is small like in children, thus limit-
ing significantly the number of EEG sensors that can
be used in children.
Although MEG does have the aforementioned advan-
tages, the issue of relative localization capabilities of
MEG and EEG is still a matter of debate. The locali-
zation accuracy of scalp EEG and MEG have been
compared in studies with computer simulations,
phantom constructions resembling the human brain,
artificial dipoles implanted in epilepsy patients during
 C. Papadelis et al. / Potential for MEG in pediatric epilepsy
presurgical evaluation, and invasive EEG recordings
[85]. Phantom studies have reported that MEG offers
higher (almost x2) localization accuracy than EEG
[86,87]. When artificial dipoles were implanted in epi-
lepsy patients, MEG localization was slightly better
than the localization of EEG (8 and 10 mm for MEG
and EEG respectively). However, computer simulation
studies have surprisingly reported that EEG is more
accurate than MEG for the same number of sensors
averaged over many source locations and orientations
[88]. MEG preferentially records activity from tangen-
tial sources, thus recording activity predominantly from
sulci. MEG provides an excellent localization accuracy
of a few mm for superficial tangential generators [46]
up to the level where it is possible to determine the
cytoarchitectonic identity of a brain region [46,89].
There is no evidence that scalp EEG can reach such a
high level of localization accuracy for superficial corti-
cal sources, even if an equal number of sensors are used.
In clinical setup, the localization of the epileptogenic
zone is most commonly defined noninvasively with
video-EEG using scalp electrodes. Video-EEG usually
records data from a relatively low number of electrodes
(~20) compared to most modern MEG systems that
record electromagnetic signals from a high number of
sensors (usually >300). Thus, the MEG localization
accuracy cannot be reached by the standard video-
EEG recordings in typical clinical settings, even if we
assume that the forward problem is successfully solved.
However, EEG is more sensitive than MEG for radial
sources [30].
There are some distinct limitations of MEG. Video-
EEG provides long recordings increasing the possibi-
lity of detecting and recording ictal events. Capturing
ictal events with MEG, though feasible [75,76,90,91],
can be difficult due to cooperation of the child, cost,
and access to the facility. In addition, unlike EEG,
MEG sensors can not conform to the shape of head
of each individual since the helmet and sensor array
within the helmet are all fixed in shape. This is a ser-
ious limitation of MEG for pediatric research since
head size increases with age, especially during the
first 2 yrs after full-term birth.
Compared to the ECoG, which is the gold standard
in the localization of epileptogenic region, MEG
potentially has an advantage in pediatric patients in
whom long-term invasive monitoring is not possible
or challenging. ECoG recording has some risks for
producing infection and bleeding. MEG can simulta-
neously and non-invasively detect and record cortical
activity from the entire cerebral cortex with a large
81
number of sensors, while the investigation of the
ROI is limited in ECoG to the area of craniotomy.
At a practical level, MEG is more expensive than EEG
to set up and operate in a clinical environment. The con-
struction of an MEG facility is about 20 to 50 times more
expensive than the cost of setting up an EEG laboratory.
The operation cost is also quite high for MEG since
all the commercial systems use liquid helium.
6. Future of MEG in pediatric epilepsy research
We predict that the use of MEG in basic and clinical
studies of pediatric epilepsy will accelerate during the
next several years as new MEG instruments are intro-
duced. First of all, over the next 2–3 yrs whole-head
pediatric MEG systems will become available. Most
of the pediatric epilepsy work based on MEG has been
carried out using adult MEG systems that are subopti-
mal for the pediatric population. Recently, a whole-head
MEG system was completed based on the BabySQUID
we have been using and installed at Children’s Hospital
of Philadelphia [92]. This is similar to the BabySQUID
in design, but it provides a whole-head instead of a
regional coverage. One of us (Yoshio Okada) has been
developing a second-generation pediatric whole-head
MEG system based on the BabySQUID in collaboration
with Tristan Inc. This system – babyMEG – is scheduled
for installation at our hospital during the fall of 2013. As
results start to appear in the literature based on these sys-
tems, we expect other sites will install a similar system.
There are currently more than 10 sites in the world
active in MEG-based pediatric epilepsy research – all
of them except our group have been using adult MEG
systems.
The operating cost of MEG facilities will also
decrease. The biomagnetic industry has recognized the
need to reduce the operating cost of MEG systems.
Therefore, some companies are now developing portable
helium recyclers that can reliquefy evaporating helium
gas (e.g. GWR Instruments, San Diego, CA). Others
have been developing 100% helium recycling systems
(e.g. [93]; Elekta-Neuromag, Oy, Helsinki, Finland).
In addition to the improvements on the pediatric
whole-head MEG systems based on low-temperature
(L-Tc) SQUIDs, we anticipate seeing other types of
MEG instruments that can provide comparable quality
of data from children. These new instruments eliminate
some of the basic limitations of the conventional MEG.
One possibility is the development of a pediatric MEG
system based on high-temperature (H-Tc) SQUIDs.
82 C. Papadelis et al. / Potential for MEG in pediatric epilepsy
Recently, it has been shown that it should be possible
to build an MEG system with a system noise compar-
able to that of L-Tc SQUID MEG systems, but using
H-Tc SQUIDs (operating at liquid nitrogen tempera-
ture of –196.15 °C) [94]. This type of system reduces
the operating costs because it uses liquid nitrogen.
Such a system can be attached to a liquid nitrogen recy-
cler, which recycles 100% of liquid nitrogen. Another
possibility is the introduction of a whole-head MEG
system based on atomic magnetometers that are small
enough to be used like an array of EEG electrodes [95].
The array based on miniature atomic magnetometers
can be used like EEG with the shape of the array made
to conform to the head shape of individual children.
The atomic magnetometers operate at room tempera-
ture without requiring liquid nitrogen or helium. The
sensitivity of these miniature atomic magnetometers
operating at room temperature is approaching the level
of MEG systems based on L-Tc SQUIDs.
We also see advances in the software clinicians will
have access to for analyzing electrophysiological data
in pediatric epilepsy. Today when MEG data are col-
lected, results are displayed in the form similar to spon-
taneous EEG data, namely as a continuous stream of
data showing spontaneous brain activity. The results
may be averaged over similar responses to increase data
quality for event-related cortical activity and are then
shown at the sensor level that is in terms of waveforms
measured by each sensor. The data become more useful
when they are seen as activities projected onto the
brain or in some regions within the brain. This techni-
que is generally called magnetic source imaging (MSI).
Although this concept was introduced many years ago,
MSI has remained as an off-line process requiring a long
period of data analysis. We predict that the field will see
strong advances in the area of real-time MSI that will
allow the clinicians to see source images in the brain
immediately after MEG measurements – this feature
should help expedite clinical decision making (e.g.
[96]). We see that all of these advances will lead to
greater use of MEG in pediatric epilepsy in the near
future.
References
[1] Cowan LD, Bodensteiner JB, Leviton A, Doherty L. Prevalence
of the epilepsies in children and adolescents. Epilepsia 1989;
30(1):94–106.
[2] Stores G. School-children with epilepsy at risk for learning and
behaviour problems. Dev Med Child Neurol 1978;20(4): 502–8.
[3] Sillanpää M, Schmidt D. Natural history of treated childhood-
onset epilepsy: prospective, long-term population-based study.
Brain 2006;129(Pt 3):617–24.
[4] Geerts A, Arts WF, Stroink H, Peeters E, Brouwer O, Peters B,
et al. Course and outcome of childhood epilepsy: a 15-year
follow-up of the Dutch Study of Epilepsy in Childhood.
Epilepsia 2010;51(7):1189–97.
[5] Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen
Hauser W, Mathern G, et al. Definition of drug resistant
epilepsy: consensus proposal by the ad hoc Task Force of the
ILAE Commission on Therapeutic Strategies. Epilepsia 2010;
51(6):1069–77.
[6] Engel J Jr. Etiology as a risk factor for medically refractory
epilepsy: a case for early surgical intervention. Neurology
1998;51(5):1243–4.
[7] Kwan P, Brodie MJ. Early identification of refractory epi-
lepsy. N Engl J Med 2000;342(5):314–9.
[8] Berg AT, Shinnar S, Levy SR, Testa FM, Smith-Rapaport S,
Beckerman B. Early development of intractable epilepsy in
children: a prospective study. Neurology 2001;56(11):1445–52.
[9] Farrell K, Wirrell E, Whiting S. The definition and prediction
of intractable epilepsy in children. Adv Neurol 2006;97:
435–42.
[10] Datta A, Loddenkemper T. The epileptogenic zone. In: Wyllie E,
Cascino G, Gidal B, Goodkin H, editors. Wyllie’s treatment
of epilepsy. Principles & practice. 5th ed. Philadelphia:
Lippincott, Williams & Wilkins, 2011; p 818–27.
[11] Rosenow F, Lüders H. Presurgical evaluation of epilepsy.
Brain 2001;124(Pt 9):1683–700.
[12] Jayakar P. Invasive EEG monitoring in children: when,
where, and what? J Clin Neurophysiol 1999;16(5):408–18.
[13] Temkin O. The falling sickness: A history of epilepsy from
the Greeks to the beginnings of modern neurology. 2nd ed.
Baltimore: Johns Hopkins University Press, 1994.
[14] Durá-Travé T, Yoldi-Petri ME, Esparza-Estaún J, Gallinas-
Victoriano F, Aguilera-Albesa S, Sagastibelza-Zabaleta A.
Magnetic resonance imaging abnormalities in children with
epilepsy. Eur J Neurol 2012;19(8):1053–9.
[15] Widjaja E, Geibprasert S, Otsubo H, Snead OC 3rd, Mah-
moodabadi SZ. Diffusion tensor imaging assessment of the
epileptogenic zone in children with localization-related epi-
lepsy. AJNR Am J Neuroradiol 2011;32(10):1789–94.
[16] Sood S, Chugani HT. Functional neuroimaging in the pre-
operative evaluation of children with drug-resistant epilepsy.
Child’s Nerv Syst 2006;22(8):810–20.
[17] Kaminska A, Chiron C, Ville D, Dellatolas G, Hollo A,
Cieuta C, et al. Ictal SPECT in children with epilepsy: com-
parison with intracranial EEG and relation to postsurgical
outcome. Brain 2003;126(Pt 1):248–60.
[18] Wilke M, Pieper T, Lindner K, Dushe T, Staudt M, Grodd W,
et al. Clinical functional MRI of the language domain
in children with epilepsy. Hum Brain Mapp 2011;32(11):
1882–93.
[19] Cohen D. Magnetoencephalography: evidence of magnetic fields
produced by alpha-rhythm currents. Science 1968;161(3843):
784–6.
[20] RamachandranNair 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(1):149–57.
[21] Wennberg R. Magnetic source imaging versus intracranial
electroencephalogram: Neocortical versus temporolimbic epi-
lepsy surgery. Ann Neurol 2006;60(2):271.
 C. Papadelis et al. / Potential for MEG in pediatric epilepsy
[22] Carne RP, O’Brien TJ, Kilpatrick CJ, MacGregor LR, Hicks
RJ, Murphy MA, et al. MRI-negative PET-positive temporal
lobe epilepsy: a distinct surgically remediable syndrome.
Brain 2004;127(Pt 10):2276–85.
[23] Blume WT, Ganapathy GR, Munoz D, Lee DH. Indices of
resective surgery effectiveness for intractable nonlesional
focal epilepsy. Epilepsia 2004;45(1):46–53.
[24] Shibasaki H, Ikeda A, Nagamine T. Use of magnetoencepha-
lography in the presurgical evaluation of epilepsy patients.
Clin Neurophysiol 2007;118(7):1438–48.
[25] Kamimura T, Tohyama J, Oishi M, Akasaka N, Kanazawa O,
Sasagawa M, et al. Magnetoencephalography in patients with
tuberous sclerosis and localization-related epilepsy. Epilepsia
2006;47(6):991–7.
[26] Okada YC, Nicholson C, Llinas R. Magnetoencephalography
(MEG) as a new tool for non-invasive realtime analysis of nor-
mal and abnormal brain activity in humans. In: Ottoson D,
Rostene W, editors. Visualization of brain functions. New York:
Stockton Press, 1989; p. 245–66.
[27] Okada YC, Wu J, Kyuhou S. Genesis of MEG signals in a
mammalian CNS structure. Electroencephalogr Clin Neuro-
physiol 1997;103(4):474–85.
[28] Okada YC. Neurogenesis of evoked magnetic fields, somato-
sensory evoked magnetic field, motor field, auditory evoked
field, visual evoked field and endogenous magnetic field. In:
Williamson SJ, Romani GL, Kaufman L, Modena I, editors.
An interdisciplinary approach. Biomagnetism. New York:
Plenum Press, 1983; p. 399–468.
[29] Okada YC, Nicholson C. Magnetic evoked field associated
with transcortical currents in turtle cerebellum. Biophys J
1988;53(5):723–31.
[30] Lew S, Sliva D, Choe M-S, Grant PE, Okada Y, Wolters CH,
et al. Effect of sutures and fontanels on MEG and EEG
source analysis with an infant FEM head model. Neuroimage
(in press).
[31] Wu J, Okada YC. Physiological bases of the synchronized
population spikes and slow wave of the magnetic field gener-
ated by a guinea-pig longitudinal CA3 slice preparation.
Electroencephalogr Clin Neurophysiol 1998;107(5):361–73.
[32] Wu J, Okada YC. Roles of a potassium afterhyperpolariza-
tion current in generating neuromagnetic fields and field
potentials in longitudinal CA3 slices of the guinea-pig. Clin
Neurophysiol 1999;110(11):1858–67.
[33] Wu J, Okada YC. Roles of calcium- and voltage-sensitive
potassium currents in the generation of neuromagnetic signals
and field potentials in a CA3 longitudinal slice of the guinea-
pig. Clin Neurophysiol 2000;111(1):150–60.
[34] Murakami S, Zhang T, Hirose A, Okada YC. Physiological
origins of evoked magnetic fields and extracellular field
potentials produced by guinea-pig CA3 hippocampal slices.
J Physiol 2002;544(Pt 1):237–51.
[35] Murakami S, Hirose A, Okada YC. Contribution of ionic cur-
rents to magnetoencephalography (MEG) and electroence-
phalography (EEG) signals generated by guinea-pig CA3
slices. J Physiol 2003;553(Pt 3):975–85.
[36] Curio G, Mackert BM, Burghoff M, Koetitz R, Abraham-
Fuchs K, Härer W. Localization of evoked neuromagnetic
600 Hz activity in the cerebral somatosensory system. Elec-
troencephalogr Clin Neurophysiol 1994;91(6):483–7.
[37] Hashimoto I, Mashiko T, Imada T. Somatic evoked high-
frequency magnetic oscillations reflect activity of inhibitory
interneurons in the human somatosensory cortex. Electroen-
cephalogr Clin Neurophysiol 1996;100(3):189–203.
83
[38] Ikeda H, Leyba L, Bartolo A, Wang Y, Okada YC. Synchronized
spikes of thalamocortical axonal terminals and cortical neurons
are detectable outside the pig brain with MEG. J Neurophysiol
2002;87(1):626–30.
[39] Ikeda H, Wang Y, Okada YC. Origins of the somatic N20
and high-frequency oscillations evoked by trigeminal stimu-
lation in the piglets. Clin Neurophysiol 2005;116(4):827–41.
[40] Murakami S, Okada Y. Contributions of principal neocortical
neurons to magnetoencephalography and electroencephalo-
graphy signals. J Physiol 2006;575(Pt 3):925–36.
[41] Kimura T, Ozaki I, Hashimoto I. Impulse propagation along
thalamocortical fibers can be detected magnetically outside
the human brain. J Neurosci 2008;28(47):12535–8.
[42] Papadelis C, Leonardelli E, Staudt M, Braun C. Can magneto-
encephalography track the afferent information flow along
white matter thalamo-cortical fibers? Neuroimage 2012;60(2):
1092–105.
[43] Geselowitz, DB. On the magnetic field generated outside an
inhomogeneous volume conductor by internal current sources.
IEEE Trans Magn 1970;6:346–7.
[44] Grynszpan F, Geselowitz DB. Model studies of the magneto-
cardiogram. Biophys J 1973;13(9):911–25.
[45] Cohen D, Hosaka H. Part II: magnetic field produced by a
current dipole. J Electrocardiol 1976;9(4):409–17.
[46] Papadelis C, Poghosyan V, Fenwick PB, Ioannides AA.
MEG’s ability to localise accurately weak transient neural
sources. Clin Neurophysiol 2009;120(11):1958–70.
[47] Hamalainen M. Hari R. Magnetoencephalographic characteriza-
tion of dynamic brain activation: Basic principles and methods
of data collection and source analysis. In: Toga AW, Mazziotta
JC, editors. Brain mapping: The methods. San Diego: Academic
Press; 2002; p. 227–53.
[48] Paetau R. Magnetoencephalography in pediatric neuroima-
ging. Dev Sci 2002;5(3):361–70.
[49] Grondin R, Chuang S, Otsubo H, Holowka S, Snead OC 3rd,
Raybaud C, et al. The role of magnetoencephalography in pedia-
tric epilepsy surgery. Child’s Nerv Syst 2006;22(8):779–85.
[50] Schwartz ES, Dlugos DJ, Storm PB, Dell J, Magee R, Flynn
TP, et al. Magnetoencephalography for pediatric epilepsy:
how we do it. AJNR Am J Neuroradiol 2008;29(5):832–7.
[51] Ochi A, Otsubo H. Magnetoencephalography-guided epilepsy
surgery for children with intractable focal epilepsy: SickKids
experience. Int J Psychophysiol 2008;68(2):104–10.
[52] Okada Y, Pratt K, Atwood C, Mascarena A., Reineman R,
Nurminen J, et al. BabySQUID: a mobile, high-resolution
multichannel MEG system for neonatal brain assessment.
Rev Sci Instrum 2006;77:24301–9.
[53] Hansman CF. Growth of interorbital distance and skull thick-
ness as observed in roentgenographic measurements. Radiology
1966;86(1):87–96.
[54] Tadel F, Baillet S, Mosher JC, Pantazis D, Leahy RM.
Brainstorm: a user-friendly application for MEG/EEG analy-
sis. Comput Intell Neurosci 2011;2011:879716.
[55] Hämäläinen MS, Ilmoniemi RJ. Interpreting magnetic fields
of the brain: minimum norm estimates. Med Biol Eng Com-
put 1994;32(1):35–42.
[56] Nolte G, Curio G. The effect of artifact rejection by signal-
space projection on source localization accuracy in MEG
measurements. IEEE Trans Biomed Eng 1999;46(4):400–8.
[57] Hämäläinen M, Hari R, Ilmoniemi R, Knuutila J, Lounasmaa O.
Magnetoencephalography-theory, instrumentation, and appli-
cations to noninvasive studies of the working human brain.
Rev Mod Phys 1993;65:1–93.
84 C. Papadelis et al. / Potential for MEG in pediatric epilepsy
[58] Dale AM, Liu AK, Fischl BR, Buckner RL, Belliveau JW,
Lewine JD, et al. Dynamic statistical parametric mapping:
combining fMRI and MEG for high-resolution imaging of
cortical activity. Neuron 2000;26(1):55–67.
[59] Shiraishi H, Ahlfors SP, Stufflebeam SM, Takano K, Okajima M,
Knake S, et al. Application of magnetoencephalography in
epilepsy patients with widespread spike or slow-wave
activity. Epilepsia 2005;46(8):1264–72.
[60] Shiraishi H, Stufflebeam SM, Knake S, Ahlfors SP, Sudo A,
Asahina N, et al. Dynamic statistical parametric mapping for
analyzing the magnetoencephalographic epileptiform activity
in patients with epilepsy. J Child Neurol 2005;20(4):363–9.
[61] Gramfort A, Papadopoulo T, Olivi E, Clerc M. OpenMEEG:
opensource software for quasistatic bioelectromagnetics.
Biomed Eng Online 2010;9:45.
[62] Kybic J, Clerc M, Abboud T, Faugeras O, Keriven R,
Papadopoulo T. A common formalism for the integral for-
mulations of the forward EEG problem. IEEE Trans Med
Imaging 2005;24(1):12–28.
[63] Kim H, Lim BC, Jeong W, Kim JS, Chae JH, Kim KJ, et al.
Magnetoencephalography in pediatric lesional epilepsy surgery.
J Korean Med Sci 2012;27(6):668–73.
[64] Otsubo H, Ochi A, Elliott I, Chuang SH, Rutka JT, Jay V, et al.
Snead OC. MEG predicts epileptic zone in lesional extrahippo-
campal epilepsy: 12 pediatric surgery cases. Epilepsia 2001;
42(12):1523–30.
[65] 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 cor-
tical dysplasia. Epilepsia 2004;45(6):621–31.
[66] Seo JH, Holland K, Rose D, Rozhkov L, Fujiwara H, Byars A,
et al. Multimodality imaging in the surgical treatment of
children with nonlesional epilepsy. Neurology 2011;76(1):
41–8.
[67] Iida K, Otsubo H, Mohamed IS, Okuda C, Ochi A, Weiss SK,
et al. Characterizing magnetoencephalographic spike sources
in children with tuberous sclerosis complex. Epilepsia 2005;
46(9):1510–7.
[68] Oishi M, Kameyama S, Masuda H, Tohyama J, Kanazawa O,
Sasagawa M, et al. Single and multiple clusters of magne-
toencephalographic dipoles in neocortical epilepsy: signifi-
cance in characterizing the epileptogenic zone. Epilepsia
2006;47(2):355–64.
[69] Shiraishi H, Watanabe Y, Watanabe M, Inoue Y, Fujiwara T,
Yagi K. Interictal and ictal magnetoencephalographic study
in patients with medial frontal lobe epilepsy. Epilepsia
2001;42(7):875–82.
[70] Tang L, Mantle M, Ferrari P, Schiffbauer H, Rowley HA,
Barbaro NM, et al. Consistency of interictal and ictal onset
localization using magnetoencephalography in patients with
partial epilepsy. J Neurosurg 2003;98(4):837–45.
[71] Stufflebeam SM, Tanaka N, Ahlfors SP. Clinical applications
of magnetoencephalography. Hum Brain Mapp 2009;30(6):
1813–23.
[72] Knowlton RC. Can magnetoencephalography aid epilepsy
surgery? Epilepsy Curr 2008;8(1):1–5.
[73] Stefan H, Schneider S, Feistel H, Pawlik G, Schüler P,
Abraham-Fuchs K, et al. Ictal and interictal activity in
partial epilepsy recorded with multichannel magnetoelec-
troencephalography: correlation of electroencephalography/
electrocorticography, magnetic resonance imaging, single
photon emission computed tomography, and positron emis-
sion tomography findings. Epilepsia 1992;33(5):874–87.
[74] Tilz C, Hummel C, Kettenmann B, Stefan H. Ictal onset loca-
lization of epileptic seizures by magnetoencephalography.
Acta Neurol Scand 2002;106(4):190–5.
[75] Eliashiv DS, Elsas SM, Squires K, Fried I, Engel J Jr. Ictal
magnetic source imaging as a localizing tool in partial epi-
lepsy. Neurology 2002;59(10):1600–10.
[76] Assaf BA, Karkar KM, Laxer KD, Garcia PA, Austin EJ,
Barbaro NM, et al. Ictal magnetoencephalography in temporal
and extratemporal lobe epilepsy. Epilepsia 2003;44(10):1320–7.
[77] Fujiwara H, Greiner HM, Hemasilpin N, Lee KH, Holland-
Bouley K, Arthur T, et al. Ictal MEG onset source localiza-
tion compared to intracranial EEG and outcome: improved
epilepsy presurgical evaluation in pediatrics. Epilepsy Res
2012;99(3):214–24.
[78] Medvedovsky M, Taulu S, Gaily E, Metsähonkala EL,
Mäkelä JP, Ekstein D, et al. Sensitivity and specificity of sei-
zure-onset zone estimation by ictal magnetoencephalography.
Epilepsia 2012;53(9):1649–57.
[79] Baumgartner C, Pataraia E, Lindinger G, Deecke L. Neuro-
magnetic recordings in temporal lobe epilepsy. J Clin Neuro-
physiol 2000;17(2):177–89.
[80] Enatsu R, Mikuni N, Usui K, Matsubayashi J, Taki J, Begum T,
et al. Usefulness of MEG magnetometer for spike detection in
patients with mesial temporal epileptic focus. Neuroimage
2008 Jul 15;41(4):1206–19.
[81] Yagyu K, Takeuchi F, Shiraishi H, Nakane S, Sueda K,
Asahina N, et al. The applications of time-frequency analyses
to ictal magnetoencephalography in neocortical epilepsy.
Epilepsy Res 2010;90(3):199–206.
[82] Barth DS, Sutherling W, Broffman J, Beatty J. Magnetic
localization of a dipolar current source implanted in a sphere
and a human cranium. Electroencephalogr Clin Neurophysiol
1986;63(3):260–73.
[83] Okada YC, Lahteenmäki A, Xu C. Experimental analysis of
distortion of magnetoencephalography signals by the skull.
Clin Neurophysiol 1999;110(2):230–8.
[84] Flemming L, Wang Y, Caprihan A, Eiselt M, Haueisen J,
Okada Y. Evaluation of the distortion of EEG signals caused
by a hole in the skull mimicking the fontanel in the skull of
human neonates. Clin Neurophysiol 2005;116(5):1141–52.
[85] Baumgartner C. Controversies in clinical neurophysiology.
MEG is superior to EEG in the localization of interictal
epileptiform activity: Con. Clin Neurophysiol 2004;115(5):
1010–20.
[86] Gharib S, Sutherling WW, Nakasato N, Barth DS, Baumgartner C,
Alexopoulos N, et al. MEG and ECoG localization accuracy test.
Electroencephalogr Clin Neurophysiol 1995;94(2):109–14.
[87] Leahy RM, Mosher JC, Spencer ME, Huang MX, Lewine
JD. A study of dipole localization accuracy for MEG and
EEG using a human skull phantom. Electroencephalogr Clin
Neurophysiol 1998;107(2):159–73.
[88] Liu AK, Dale AM, Belliveau JW. Monte Carlo simulation
studies of EEG and MEG localization accuracy. Hum Brain
Mapp 2002;16(1):47–62.
[89] Papadelis C, Eickhoff SB, Zilles K, Ioannides AA. BA3b and
BA1 activate in a serial fashion after median nerve stimulation:
direct evidence from combining source analysis of evoked fields
and cytoarchitectonic probabilistic maps. Neuroimage 2011;
54(1):60–73.
[90] Oishi M, Otsubo H, Kameyama S, Wachi M, Tanaka K,
Masuda H, et al. Ictal magnetoencephalographic discharges
from elementary visual hallucinations of status epilepticus.
J Neurol Neurosurg Psychiatry 2003;74(4):525–7.
 C. Papadelis et al. / Potential for MEG in pediatric epilepsy
[91] Yoshinaga H, Ohtsuka Y, Watanabe Y, Inutsuka M, Kita-
mura Y, Kinugasa K, et al. Ictal MEG in two children with
partial seizures. Brain Dev 2004;26(6):403–8.
[92] Edgar JC, Paulson P, Eugene H, Kevin P, Anthony M, Paul M,
et al. Artemis 123: Development of a whole-head infant
MEG system. 18th International Conference on Biomagnetism,
August 26th–30th, 2012, Paris, France.
[93] Takeda T, Okamoto M, Atsuda K, Kobayashi A, Owaki T,
Katagiri K. An efficient helium circulation system with small
GM cryocoolers. Cryogenics 2008;48(1–2):6–11.
85
[94] Poppe U, Dunin-Borkowski RE, Schiek M, Boers F,
Chocholacs H, Dammers J, et al. High-Tc DC SQUIDs for
magnetoencephalography. IEEE Trans Appl Superconduct
2013;23(3):1600705.
[95] Sander TH, Preusser J, Mhaskar R, Kitching J, Trahms L,
Knappe S. Magnetoencephalography with a chip-scale atomic
magnetometer. Biomed Opt Express 2012;3(5):981–90.
[96] Sudre G, Parkkonen L, Bock E, Baillet S, Wang W, Weber DJ.
rtMEG: a real-time software interface for magnetoencepha-
lography. Comput Intell Neurosci 2011;2011:327953.