Pediatric Language and Memory Mapping in Refractory Epilepsy Using Magnetoencephalography
Conditions: Epilepsy
Sponsor: University of Arkansas

  
Office of Research Regulatory Affairs 
 
4301 W. Markham, #813 
Little Rock, AR 72205-7199 
 
https://researchservices.uams.edu/ 
  
 
 
 
 
 
 
Study Title:  
Pediatric Language and Memory Mapping in Refractory Epilepsy 
using Magnetoencephalography  
Version: 
4.0 
Date:   
 
 
1/13/2021 
NCT#: 
 
 
04888637 
 
 
 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
PI: 
Diana Escalona-Vargas, PhD 
Site: Arkansas Children’s Hospital 
Version 43 
IRB 261511 
Date: 12/1309/20210 
Page 1 of 22 
 
Study Title: 
Pediatric Language and Memory Mapping in Refractory Epilepsy 
using Magnetoencephalography 
 
Principal Investigator: 
Diana Escalona-Vargas, PhD 
University of Arkansas for Medical Sciences 
4301 W. Markham Street, Slot #518 
Little Rock, AR 72205 
Telephone: 501-364-3703 
Email: DIEscalonavargas@uams.edu 
 
Sub-Investigator: 
Debopam Samanta, MD 
University of Arkansas for Medical Sciences 
1 Children's Way, Slot #512-15 
Little Rock AR 72202 
Telephone: 501-364-5281 
Email: DSamanta@uams.edu 
 
Linda J. Larson-Prior, PhD 
University of Arkansas for Medical Sciences 
4301 W. Markham St., Slot #568 
Little Rock, AR 72205 
Telephone: 501-526-4889 
Email: LJLarsonPrior@uams.edu 
 
Hari Eswaran, PhD 
University of Arkansas for Medical Sciences 
4301 W. Markham Street, Slot #518 
Little Rock, AR 72205 
Telephone: 501-526-4334 
Email: EswaranHari@uams.edu 
 
Medical Monitor: 
Tara Johnson, MD 
Telephone: 501-364-1850 
Email: TJohnson9@uams.edu   
 
Study location: 
Arkansas Children’s Hospital 
MEG Laboratory 
Arkansas Children's Hospital 
1 Children's Way 
Little Rock, AR, 72202 
 
Sponsor: 
University of Arkansas for Medical Sciences 
 
 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
PI: 
Diana Escalona-Vargas, PhD 
Site: Arkansas Children’s Hospital 
Version 43 
IRB 261511 
Date: 12/1309/20210 
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Table of Contents 
 
Table of Contents ................................................................................................................. 2 
Abbreviations ........................................................................................................................ 3 
Background and Rationale ................................................................................................... 4 
Specific Aims ........................................................................................................................ 7 
Aim 1 .................................................................................................................................... 7 
Aim 2 .................................................................................................................................... 7 
Study Design and Procedures .............................................................................................. 7 
Study Population .................................................................................................................. 8 
Inclusion Criteria .................................................................................................................. 8 
Exclusion Criteria ................................................................................................................. 8 
MEG Acquisition ................................................................................................................... 9 
MEG System Equipment ...................................................................................................... 9 
MEG Preparation Phase ...................................................................................................... 9 
Resting State Measure ........................................................................................................10 
Tasks .................................................................................................................................. 10 
Receptive Language Task ...................................................................................................10 
Memory Task ......................................................................................................................10 
MRI ..................................................................................................................................... 11 
Subject Withdrawal ............................................................................................................. 11 
Risks and Benefits .............................................................................................................. 11 
Adverse Events .................................................................................................................. 12 
Definitions ...........................................................................................................................12 
Monitoring, Recording and Reporting of AEs .......................................................................13 
Expedited Reporting of AEs ................................................................................................14 
Clinical Site Monitoring ....................................................................................................... 15 
Deviations and Violations ................................................................................................... 15 
Data Handling and Recordkeeping ..................................................................................... 15 
Data Analysis ...................................................................................................................... 16 
Preprocessing .....................................................................................................................16 
Source Imaging ...................................................................................................................16 
Statistical Analysis ..............................................................................................................16 
Ethical Considerations ........................................................................................................ 17 
Dissemination of Data ......................................................................................................... 17 
References ......................................................................................................................... 18 
Study Flow Diagram ........................................................................................................... 22 
 
 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
PI: 
Diana Escalona-Vargas, PhD 
Site: Arkansas Children’s Hospital 
Version 43 
IRB 261511 
Date: 12/1309/20210 
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Abbreviations 
ACH 
Arkansas Children’s Hospital 
ACMEGS 
American Clinical Magnetoencephalography Society 
AE 
Adverse Event 
AEF 
Auditory Evoked Field 
APR 
Annual Progress Report 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CT 
Computerized Tomography 
dB 
Decibel 
DOB 
Date of Birth 
ECD 
Equivalent Current Dipole 
ECG 
Electrocardiogram 
EEG 
Electroencephalography 
EOG 
Electrooculogram 
ERF 
Evoked Response Field 
FDA 
US Food and Drug Administration 
fMRI 
Functional Magnetic Resonance Imaging 
HIPAA 
Health Insurance Portability and Accountability Act 
HPI 
Head Position Indicator 
kHz 
Kilo Hertz 
IAT 
Intracarotid Amobarbital Test 
ICF 
Informed Consent Form 
ICH GCP 
International Council for Harmonisation Good Clinical Practice 
IIR 
Infinite Impulse Response 
IRB 
Institutional Review Board 
ISI 
Inter-Stimulus Interval 
LCD 
Liquid Crystal Display 
MEG 
Magnetoencephalography 
MRI 
Magnetic Resonance Imaging 
MRN 
Medical Record Number 
MSR 
Magnetically Shielded Room 
nAm 
NanoAmpere-Meter 
msec 
Millisecond 
ORRA 
Office of Research Regulatory Affairs 
PET 
Positron Emission Tomography 
PI 
Principal Investigator 
s 
second 
SAE 
Serious Adverse Event 
SD 
Standard Deviation 
sLORETA 
Standardized Low Resolution Brain Electromagnetic Tomography 
SPL 
Sound Pressure Level 
SQUIDs 
Superconducting Quantum Interference Devices 
SSP 
Signal-Space Projection 
UADE 
Unanticipated Adverse Device Effect 
UAMS 
University of Arkansas for Medical Sciences 
UPIRTSO 
Unanticipated Problem Involving Risks to Subjects or Others 
VSWM 
Visuospatial Working Memory 
WM 
Working Memory 
 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
PI: 
Diana Escalona-Vargas, PhD 
Site: Arkansas Children’s Hospital 
Version 43 
IRB 261511 
Date: 12/1309/20210 
Page 4 of 22 
Background and Rationale 
Pediatric epilepsy is the most common serious neurological disorder of childhood, affecting 
between 0.5-1% of children and young people under the age of 16 years [1]. Epilepsy is known 
to impair behavior, and adversely affect cognition and learning [2-4]. Antiepileptic drugs are 
effective medications available for epilepsy. However, many patients do not respond to this 
treatment and become resistant. Treatments such as the ketogenic diet, vagal nerve stimulators 
and resective and functional surgery have become available for these drug-resistant patients [5]. 
Surgery for removal of epileptogenic zone is the most effective treatment. The purpose of 
presurgical brain mapping is to facilitate surgical planning, prevent or reduce morbidity, and 
optimize the therapeutic effects of surgery. As part of the presurgical planning, assessment of 
hemispheric language and memory function is performed. The medical standard for determining 
the language dominant hemisphere and memory function prior to surgical resection is the 
intracarotid amobarbital test (IAT), also known as the Wada test [6]. It consists of an injection of 
sodium amobarbital into the left or right internal carotid arteries. This causes a temporary arrest 
of function in each hemisphere for approximately six to ten minutes, during which the 
unanaesthetised hemisphere is functionally assessed. A major drawback of this test is that it 
determines lateralization only, and does not allow intrahemispheric localization of language and 
memory functions. Moreover, because it is relatively invasive, this technique cannot be used with 
normal volunteers and is difficult to use with children. Additionally, the Wada test is associated 
with risks of stroke, infection, and hemorrhage [7]. Over the past decade, there is a significant 
discussion of the clinical utility of non-invasive brain imaging techniques (e.g. functional magnetic 
resonance imaging (fMRI)/ magnetoencephalography (MEG)) relative to the invasive Wada test 
for determination of hemispheric language and memory function. At present, while research has 
pointed to the better spatiotemporal resolution of both behavior and functional brain network 
organization available in brain imaging methods, the lack of language and memory tasks that map 
these functions in single individuals has reduced their clinical utility. The impact of epilepsy on 
language and memory are relevant not only from a clinical perspective but also because it sheds 
light on the underlying neurobiology of both processes. Identifying the patterns of language and 
memory organization prior to surgical intervention could therefore guide tailored resection and 
limit potential loss of function after surgery. 
 
Advances in technology over the past decade have enabled researchers to study the functional 
development of the human brain with MEG, a novel and non-invasive technique with fine temporal 
and spatial resolution. While other modalities infer brain function indirectly (i.e. positron emission 
tomography (PET), computerized tomography (CT), MRI) by measuring changes in blood flow, 
cerebral metabolism and blood oxygenation, MEG records neuronal and synaptic function 
directly. MEG records the tiny biomagnetic fields generated by ionic currents generated by 
populations of synchronously activated neurons in the brain [8]. Evoked responses fields (ERF) 
measured with MEG, much like event-related potentials in electroencephalogram (EEG), are 
waveforms representing variations of brain activity across time following the onset of an external 
stimulus (auditory, visual, etc.). Early components of the ERF waveform (150-200 msec after 
stimulus onset) reflect neurophysiological activity in primary sensory cortices. On the other hand, 
neurophysiological activity represented by later components of the ERF waveform occurs 
primarily in association cortices. By estimating the regions that contribute to systematic variations 
in the late components of the ERF, we can study the brain circuits responsible for cognitive and 
linguistic functions. MEG signal arises from brain sources also seen using electrical signals 
recorded as the EEG. However, MEG is unaffected by scalp, skin and, to a large degree, brain 
tissue in homogeneities and is, therefore, an ideal technology to study brain development. MEG 
is one of several diagnostic techniques employed for the evaluation of patients with epilepsy and 
it is especially important for those patients being considered for epilepsy surgery [9, 10]. Resective 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
PI: 
Diana Escalona-Vargas, PhD 
Site: Arkansas Children’s Hospital 
Version 43 
IRB 261511 
Date: 12/1309/20210 
Page 5 of 22 
epilepsy surgery is performed mainly in the temporal and frontal lobes (selective 
amygdalohippocampectomies, anterior temporal lobectomies, or tailored temporal or frontal 
cortsicectomies). However, it must be previously determined that the resection will not have any 
substantial consequences on cognitive functions, such as language or memory. 
 
fMRI is the most widely used of the minimally/non-invasive techniques for presurgical language 
mapping in children [11]. However, MEG is gaining increasing acceptance as a non-invasive 
method as an adjunctive part of the pre-surgical functional mapping procedure [12]. Especially for 
language identification in pediatric cases, the quiet environment of the MEG room and the head-
motion-tracking methods available in recent MEG systems, increase the likelihood of success 
with language lateralization in young populations. Further, MEG allows examining both 
hemispheres simultaneously, which is especially useful in epileptic populations, in which language 
lateralization is more variable. MEG language localization studies have shown encouraging 
results with a wide variety of paradigms, especially in localization of receptive language areas 
that are well documented [13, 14] and validated [15, 16]. The suitability of MEG language 
lateralization protocols in adults as an alternative to the Wada procedure have been addressed 
with validation studies conducted using various methodologies and exhibit overall high 
concordance rates (about 86-92%) [17-20]. Language lateralization is calculated in both 
hemispheres by localizing dipole sources (equivalent current dipole, ECD model) accounting for 
late auditory evoked field (AEF) components (150-700 ms after stimulus onset). These late 
components localize to language-related areas (mainly within posterior temporal areas) of the 
brain regardless of the modality of stimulus presentation [21]. Depending on the activation task, 
the dipole sources can be used to identify the location of receptive (Wernicke’s area) or expressive 
language-specific (Broca’s area) cortex. The degree of hemispheric asymmetry in the duration or 
strength of activation can also be calculated as an index of hemispheric dominance for language 
functions. Estimations of language lateralization with MEG [22] have mainly been based on 
recognition memory tasks for spoken words [23] or by listening to synthesized vowel sounds [24]. 
Thus, most of the MEG language studies have focused on receptive language areas. However, 
other reports exist on frontal circuits in expressive language [25-27] and basal temporal areas 
during semantic language tasks (verb generation) [28, 29]. Recent MEG language studies have 
reported the feasibility of passive paradigms in children and adolescents under sedation [30] and 
during sleep [31]. A recent MEG study [32] uses a verbal memory and verbal fluency tasks 
showing activation of the left hippocampus and in Wernicke’s area in favor of the left hemisphere. 
Authors found higher concordance rates between a verbal memory paradigm and language 
dominance in controls (using handedness as criterion) and in subjects with epilepsy (using fMRI 
or Wada as criterion), compared with a verbal fluency task. Only the concordance for verbal 
memory reached statistical significance, with 93% agreement. Previous studies in pediatric 
epilepsy have shown atypical language lateralization [33] and that the word recognition task is 
the only language comprehension task used in both children and adults that yields high 
concordance between MEG and the Wada test for language lateralization [22]. Despite all 
contributions of MEG in the assessment of language localization in typically developing 
individuals, studies in pediatric populations with epilepsy is still relatively small especially in single 
subjects, which is necessary for clinical utility. 
 
Memory involves a network of interconnected anatomical brain structures - hippocampus, 
parahippocampal structures, temporal lobe neocortex, amygdala, and the frontal lobe [34, 35]. 
Medically intractable epilepsy may negatively affect cognition by disrupting cognitive processes 
through chronic and persistent seizures. Verbal memory declines in about 30-85% of epileptic 
patients undergoing left temporal lobe resection while non-verbal memory declines in about 30-
50% of the patients when right temporal lobe resection is performed [36, 37]. The standard 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
PI: 
Diana Escalona-Vargas, PhD 
Site: Arkansas Children’s Hospital 
Version 43 
IRB 261511 
Date: 12/1309/20210 
Page 6 of 22 
procedure used to assess the risk of resection-induced loss in memory function prior to epilepsy 
surgery is with the invasive Wada Test together with language assessment. fMRI has been used 
to assess the risk of memory loss in epilepsy [38]. Usually, fMRI studies perform language 
protocols to predict memory outcome. However, this approach assumes collateralization of these 
functions, which has previously been studied, but dissociating these domains of function can be 
difficult, partly due to reorganization, and to overlapping and/or interconnectivity of regions 
involved during cognitive processing. Very few MEG studies exist for memory assessment, and 
most of them have been performed in adult epileptic subjects [39, 40] and less in children. 
Currently, there are insufficient available data to promote the use of MEG for assessment of 
pediatric memory function, as memory function is housed deep in the temporal lobes and is more 
difficult to accurately localize. However, previous studies have shown that it is possible to detect 
hippocampal activity with MEG [41] that will allow the study of deep sources involved in memory.  
 
Working memory (WM) and executive functions are skills developed to deal with complexities in 
life and are necessary for effective and adaptive behaviors. WM is the cognitive system that 
entails maintaining information in mind over a short time to complete an activity. WM is one of the 
most important components of information processing. A dysfunction of the WM system may lead 
to problems in developing cognitive functions, including mental arithmetic, reading, decision 
making and reasoning. WM is constituted by three main components: the central executive, the 
phonological loop, and the visuospatial sketch pad. Each component works to store and 
manipulate information in a temporary short-term memory system that is essential to human 
memory [42]. Executive functions include the control and organization of complex cognitive 
operations that allow a person to plan strategies, solve problems, and modify behaviors as a result 
of new information. The frontal lobes play a crucial role in WM and epilepsy has an impact on 
working memory functioning [43]. Visuospatial working memory (VSWM) involves encoding, 
maintenance, and retrieval of object identity, particularly spatial position [44-47]. VSWM is 
especially important in children during letter/number recognition, reading, writing, and math by 
facilitating recall of shapes and colors as well as their positions and movements. Determination 
of hemispheric memory lateralization plays an important role in the presurgical epilepsy 
evaluation, and very few studies have been conducted in children. The comparisons between 
adults and children reveled a greater activation in large regions of the frontal, parietal and 
temporal lobes, basal ganglia, and cerebellum in adults, while children showed greater activity in 
several occipital regions [48].  In adults, verbal memory has been predominantly lateralized over 
the left temporal lobe and visual-spatial memory over the right hemisphere [49-51]. But in children 
with epilepsy, a clear pattern of hemispheric lateralization of visuospatial memory has not been 
thoroughly investigated and established, and more investigations are needed to further assess 
WM in epilepsy. 
 
How epilepsy affects working memory performance is unclear but evidence suggest disruptions 
in the WM network [52]. MEG studies to examine the hemispheric lateralization of visuospatial 
memory circuitry prior to epilepsy surgery are severely lacking especially in children [53]. 
Importantly, visuospatial memory reorganization with seizure foci from the left and right 
hemispheres has not been investigated in detail. Although a significant role for the mesial 
temporal structure is suspected in visual-spatial memory, technological advances in MEG 
sufficient to detect hippocampal dynamics has become possible only recently [41]. Importantly, 
cortical stimulation and the Wada procedure cannot identify memory-specific circuitry or language 
circuit interactions whose activity patterns are developing in a non-typical brain environment due 
to on-going epileptic activity. Moreover, both cortical stimulation and the Wada are intimately 
related to the narrow time window and not suitable for delineation of neural pathways during 
complex tasks, and the repetition of these procedures to detect reliability cannot be performed. 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
PI: 
Diana Escalona-Vargas, PhD 
Site: Arkansas Children’s Hospital 
Version 43 
IRB 261511 
Date: 12/1309/20210 
Page 7 of 22 
Several tasks exist to assess memory such as n-back task, the Sternberg Item Recognition task 
and others [54]. Some of these tasks require extended periods of time to complete the test or 
require verbal knowledge, which may impede the subject’s ability to complete the test due to age 
or education. Our project proposes the use of an established working memory task that is an n-
back paradigm that has been widely used to investigate working memory processes in 
neuroimaging research in children [55] and it is a simple task that kids can performed [56-59]. An 
n-back task consist of the presentation to participants with a sequence of stimuli and asked to 
answer when a stimulus matches another stimulus “n” trials back. Previous studies in memory 
assessment has shown extensively that n-back tasks are able to find memory disruptions in 
children [60-63] and some studies have noted particular aspects of memory to be more at risk. 
For example, Hershey et al. [61] shows that children with epilepsy scored lower than normative 
scores on measures of spatial tasks with high memory load or long delays, but not on short delay 
memory tasks which were within the normal range. Lindgren et al [62] showed that the percentage 
of children with epilepsy scored lower on visuospatial memory and learning (4%). Children with 
epilepsy appear to be at significant risk for memory impairment. It is not clear what particular 
aspects of memory are more likely to be affected or whether particular syndromes are more likely 
to be associated with particular impairments. Further research is needed to identify the extent and 
nature of the difficulties in children with epilepsy. 
 
 
To address these knowledge gaps, our study will evaluate the utility of ana well-established and 
validated existing clinical MEG protocol that is used to localize study language function in children 
[23, 30, 64]. s and In addition, we will use a widely deployed a new memory protocol [55-59] that 
we have designed to localize assess memory functions in children and young adults with epilepsy. 
The research study itself will be conducted immediately following the standard-of-care MEG 
evaluation, which currently includes the language task. For all consenting subjects, this standard 
language clinical protocol will be supplemented by the addition of the experimental memory task 
and a resting-state MEG acquisition, which will only add an estimated 20-30 minutes to the 
standard protocol time. No treatment/intervention will be performed or evaluated in this pilot 
research study. As accurate localization requires co-registration with an MRI, this additional 
procedure will be required for any study subjects who do not already have an existing MRI scan 
of sufficient quality to be used in the current research study. Our project will improve our 
understanding of the dynamic brain network mechanisms underlying memory and language. 
Specific Aims 
Aim 1 
Feasibility of measuring language and memory functions in pediatric epilepsy with MEG brain 
signals. 
Aim 2 
Characterize language and memory circuitry in pediatric epilepsy subjects with seizure focus from 
the right or left hemispheres. 
Study Design and Procedures 
This is a pilot research study where we will design, develop and implementuse language and 
working memory tasks to study brain activities from children with epilepsy. Specifically Ffor 
language assessment, a well known MEG language protocol will be used and novel signal 
processing techniques will be applied. We will use a design and implement a newwidely utilized  
paradigm to study memory function and adapt signal-processing techniques from previous 
literature for the processing and analysis of MEG signals collected during memory task. We will 
perform a MEG scan and collect data from ten pediatric subjects with drug-resistant focal epilepsy 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
PI: 
Diana Escalona-Vargas, PhD 
Site: Arkansas Children’s Hospital 
Version 43 
IRB 261511 
Date: 12/1309/20210 
Page 8 of 22 
under evaluation for resective surgery. If a MRI scan is available from medical records and images 
have the appropriate characteristics for MEG (see more specifications at MRI section) analysis, 
we will use MRI for MEG source reconstruction. If MRI is not available, we will perform one scan. 
MRI is necessary to obtain brain anatomy for high quality MEG source reconstruction. 
Quantitative parameters will be extracted from MEG data for evaluating language and memory 
functions. This is a pilot research study where we will test the feasibility of the recording of both 
standard language and experimental well-known memory task in patients with epilepsy. This 
research is important to investigate, by a non-invasive means, possible patterns of language and 
memory organization that may in future guide surgery and limit potential loss of these functions. 
 
Study Population 
A total of fifteen (15) pediatric patients with drug-resistant focal epilepsy under evaluation for 
resective surgery will be recruited from the comprehensive epilepsy program of the Arkansas 
Children's Neuroscience Center. If the patient is eligible, they will be informed about this study 
during their routine clinic visits by their clinician, and asked if they are interested in participating. 
Those who express an interest will be provided with the informed consent form (ICF) approved 
by the UAMS Institutional Review Board (IRB). If they agree to participate, they will be scheduled 
for the research visit. Subjects will be compensated with a gift card of $40 which will be given to 
the parent or guardian (for subjects under 18) or to the subject (if over 18) after completion of 
study procedures. 
 
Inclusion Criteria 
• 
8 to 21 years old 
• 
Drug-resistant focal epilepsy 
• 
Enrolled in the Arkansas Children's Neuroscience Center Comprehensive Epilepsy Program 
• 
Under evaluation for resective surgery 
• 
English speakers. This is not a treatment/intervention study. 
 
Exclusion Criteria 
• 
Previous resective surgery for epilepsy 
• 
Presence of progressive neurodegenerative disorders 
• 
Presence of significant magnetic artifacts; electronic, magnetic or metallic implants (e.g. pins, 
screws, shrapnel remains, surgical clips, artificial heart valves, cochlear implants, vascular 
stents pacemakers); or permanent make-up or tattoos made with metallic dyes 
• 
Presence of seizures within 24 hours of the MEG 
• 
Use of sedation during the MEG acquisition 
• 
Inability to be in a seated or supine position during the tasks 
• 
Major medical disorders (e.g. HIV, cancer) 
• 
Significant visual or auditory disabilities 
• 
Physical disabilities that interfere with accomplishment of study tasks (when applicable) 
• 
Claustrophobia, or fear of cramped or confined spaces 
• 
Pregnancy or suspected pregnancy 
• 
Any condition that the investigator feels might put the patient at risk 
 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
PI: 
Diana Escalona-Vargas, PhD 
Site: Arkansas Children’s Hospital 
Version 43 
IRB 261511 
Date: 12/1309/20210 
Page 9 of 22 
MEG Acquisition 
Each subject will have one MEG session with the recordings of baseline resting state, language 
and memory protocols. Subjects will have a break period between the language and memory 
tasks. MEG recordings will be acquired for approximately 35 minutes. The subject will be allowed 
to practice the language and memory tasks before the MEG recording to feel familiar with them. 
This practice phase will be a short version of the task administered by a computer and will take 
approximately 6 minutes. 
 
MEG System Equipment 
Arkansas Children’s Hospital (ACH) hosts the only one 
of its kind in the state and latest-generation whole-head 
MEG system (TRIUX™ neo, see Fig. 1A) with helium 
recycling technology for zero helium boil-off. MEG 
system is a clinical device with Food and Drug 
Administration (FDA) approval. The MEG system 
consists of 306 (see Fig. 1C) Superconducting 
Quantum Interference Devices (SQUIDs). The MEG 
scan is located inside of a magnetically shielded room 
(MSR, see Fig. 1D) to reduce environmental noise to a 
level compatible with the brain signals. The MEG 
system is equipped with a specially designed bed (Fig. 
1A) and chair (Fig. 1B) for supine and seated 
measurements (reclined and upright). MEG laboratory 
is equipped with an audio-video surveillance and 
communication system, and additional electronics to 
design specific protocols to record MEG in response to 
external stimuli. Because exact information about the 
relative position of the head with respect to the sensor 
array is necessary for post-analysis, MEG laboratory is equipped with “head position indicator” 
coils and digitization system to determinate this relative position. The 3-dimensional (3D) 
digitization system is used in the preparation phase before MEG measurements to digitize the 
positions of the coils as well as the landmarks on the head. The locations of the landmarks are 
used to establishing a coordinate transformation between MEG and the anatomical information. 
 
MEG Preparation Phase 
The subject will be first seated in a chair outside of the MSR. One pair of electrooculogram (EOG) 
electrodes will be attached to the lower corner of the left eye and upper corner of the right eye to 
measure eye blinks. Electrocardiogram (ECG) electrodes will be attached to the chest. Five head 
position indicator coils will be attached to the head. Three landmarks (left and right preauricular 
points, and nasion) and the five HPI coils will digitize along with ~200 additional points of the head 
surface with an electromagnetic 3D digitizer (Polhemus Fastrak®). We will take pictures with an 
ACH camera (e.g. standalone camera, tablet or phone device) of the three landmarks and MEG 
coils. Pictures will be used to guide the coregistration between MRI and MEG for source analysis 
and to know precisely where each of the MEG coils and points are located in relation to the head. 
Next, the subject will be placed under the MEG helmet. 
 
 
 
Figure 1: (A-B) Whole-head MEG system with 
a specially designed bed and chair for 
measurements. (C) SQUID sensors. (D) 
Magnetically shielded room (MSR) to reduce 
environmental noise. 
MEG TRIUX™neo system
Superconducting
sensors
A
B
Magnetically
shielded room
C
D

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
PI: 
Diana Escalona-Vargas, PhD 
Site: Arkansas Children’s Hospital 
Version 43 
IRB 261511 
Date: 12/1309/20210 
Page 10 of 22 
Resting State Measure 
Baseline brain activities will be measure for 5 minutes. The subject will be asked to remain still 
with eyes closed and rest. 
 
Tasks 
Receptive Language Task 
We 
will 
follow 
the 
standard 
protocols 
according 
to 
the 
American 
Clinical 
Magnetoencephalography Society (ACMEGS) [64]. The language task corresponds to an 
adapted version [30] of the continuous auditory word recognition protocol previously described by 
Papanicolaou [23] for determining hemispheric dominance of language function. The subject will 
perform a practice session where they will be instructed to “try to remember” a set of ﬁve audibly 
spoken English words, deemed targets. Target words are as follows: jump, little, please, drink, 
and good. Depending on the subject’s overall verbal memory capacity, the target words will be 
presented once or twice during the practice phase. Subsequently, during the MEG recording, the 
ﬁve target words will repeat in a different random order, mixed with a different set of 40 distractors 
(non-repeating words) in each of three blocks of stimuli. Words will be presented for 1 s, one at a 
time, and randomly varied with an interstimulus interval between 2 s and 3 s. The auditory stimuli 
will be delivered binaurally through two long plastic tubes terminating in ear inserts at an intensity 
of 60 dB sound pressure level (SPL) at the ’subject’s outer ear. Target words correspond to four 
monosyllabic and one disyllabic word with a mean frequency in the G6-7 corpus of 158 
occurrences per million (range: 32-194 occurrences ) [65]. For distractors, 40% of words will be 
disyllabic  and the remaining will be monosyllabic with a mean frequency of occurrence of 150 
words per million in the same corpus (range: 18-820). The subject’s task will be to listen to the 
words and lift their index finger of the dominant hand whenever they hear a repeated target word 
(one of the five). After the language task, the subject will be given a break. 
 
Memory Task 
In this project, we will develop use a 
widely deployednew procedure to study 
memory function using a visuospatial 
working memory (VSWM) task that will 
manipulate working memory (WM) load 
by using visual-stimulus complexity [55-
59]. The task will be composed of a two-
dimensional visual grid plane (see Fig. 
2) segmented into nine regular squares, 
each of which might contain a symbol 
“” or “”, otherwise empty. Only two 
symbols will be displayed in the grid. We 
will manipulate the WM load and 
congruency as follows: a) low WM load 
will only have one type of symbol with 
two apparitions in the grid (i.e., circles); 
b) high WM load will have two types of symbols with six apparitions in the grid (i.e., circles and 
crosses). Congruency will be manipulated by matched or unmatched encoding and retrieval 
stimuli. A total of 96 stimuli will be designed: 24 low-WM load-congruent; 24 low-WM load-
incongruent; 24 high-WM load-congruent; and 24 high-WM load-incongruent. 
 
Figure 2: Memory task; examples of experimental conditions. A: 
encoding stimulus; B: retrieval stimulus 
 
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+ 
 
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High WM load 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
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Site: Arkansas Children’s Hospital 
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The symbols and grid plane will be white on a black background. The type font will be Arial with 
80pp size. Each trial will begin with a central fixation cross-displayed for 300 ms, followed by 
encoding, maintenance, and retrieval phases. The symbols and grid will appear for 1 s (encoding 
phase), then a blank inter-stimulus interval (ISI) will display for 1.5 s (maintenance phase). Next, 
the symbols and grid will appear for 1 s (retrieval phase). The subject will be tasked with indicating 
whether the encoding stimulus matched the retrieval stimulus using two buttons; one for 
“congruent” and the other for “incongruent” response. Button type will be counterbalanced among 
subjects. The task will take around 16 minutes. The visual stimuli will be projected through an 
LCD projector onto a white screen located about 0.5 m in front of the subject and subtending 1.0-
4.0 and 0.5 degrees of horizontal and vertical visual angle, respectively. A MEG compatible 
keyboard will be used to measure the subject’s responses for “congruent” and “incongruent”. The 
subject will practice the memory task before going to the MEG system using a computer from 
MEG laboratory. This practice phase will consist of a short version of the memory task with 
duration of approximately 4 minutes. 
 
MRI 
MRI will be used to obtain individual anatomical brain information for MEG source reconstruction. 
MRI characteristics for MEG is a fast T1 scan containing tip of nose, both ears, and top of the 
head. If a previous MRI is available from medical records, we may use if it has the appropriate 
characteristics for MEG and if subject did not have any neurosurgery after this specific MRI. 
Otherwise, if no MRI is available, the subject will have an MRI scan of the brain. 
 
Subject Withdrawal 
Participants may withdraw at any time for any reason, without penalty. No data will be collected 
about the subject following withdrawal from the study. Any subject withdrawing their consent to 
participate in the study or their authorization to use their protected health information will be 
withdrawn from the study. Additionally, the investigator may choose to remove subjects from the 
study for any reason. 
 
Risks and Benefits 
The measurement principles of MEG have no harmful effects on subjects. It does not expose the 
subject to any medication, radiation, or magnetic fields. It non-invasively measures the magnetic 
fields produced by the human brain. 
 
There is no loud noise generated during acquisition, hence the MEG environment is generally 
considered as relatively comfortable to subjects, including young children. A possible risk from 
MEG is the spontaneous boil-off (evaporation) of the liquid helium used for refrigeration of the 
superconducting sensing system. Although very unlikely, boil-off can occur with minimal risk to 
subjects. The MEG instrument has safety valves to prevent pressure from building inside the 
helium reservoir, and if helium is released, the air ventilation inside the MSR has been designed 
to rapidly exhaust the extremely volatile helium gas out of the MSR. Although helium is inert, there 
is a risk of oxygen depletion inside the MSR, in case of massive helium boil-off. It would take only 
seconds for the attending personnel to open the MSR door, which would immediately resolve the 
situation. Overall, the risk and potential harm from spontaneous helium boil-off in the MEG is 
minimal and much lower than that from MRI quenching, for instance. This study will include a 
MEG scan of language and memory testing. There are no known risks of language and memory 
testing, although some subjects may become frustrated by the tasks or uncomfortable. If this 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
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Diana Escalona-Vargas, PhD 
Site: Arkansas Children’s Hospital 
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occurs, breaks will be offered in which subjects may move or change their position until 
comfortable. The measures of MEG, uses standard clinical tape to stick the coils and EOG/ECG 
electrodes to the subject’s head and chest that may produce mild skin irritation. 
 
Besides the MEG measurements, a structural MRI may be obtained if the subject does not have 
one with appropriate characteristics for MEG in the medical record. There are also no adverse 
side effects known for MRI, although some subjects may experience temporary claustrophobia, 
anxiety, or dizziness. Ferromagnetic artifacts may heat, twist or pull in the MRI. The effect of the 
strong magnetic fields on fetuses is not well known. Therefore, as is typical with MRI research, 
subjects with ferromagnetic implants and pregnant women will be excluded from the study. 
Subjects will be carefully screened and required to complete the ACH's MRI safety questionnaire. 
If they qualify for scanning, they will change in a gown, and all magnetic parts have to be removed. 
 
Another potential risk to subjects is the potential for loss of confidentiality. Measures to protect 
the confidentiality of subjects will be implemented as described in the Data Handling and 
Recordkeeping section below. 
 
The standard-of-care clinical MEG protocol includes the language task, but the experimental 
memory task has not been approved by the FDA or ACMEGS [43]. As such, this data will not be 
utilized in presurgical planning and will be used only for research purposes. Accordingly, there 
are no guarantees that participation will yield direct benefits to the subjects; however, the 
knowledge gained from the study could potentially benefit patients in the future. There will be no 
financial charges to the subject as a result of participation in this study. 
 
Adverse Events 
Definitions 
Adverse Event: An adverse event (AE) is any symptom, sign, illness or experience that develops 
or worsens in severity during the course of the study. For the purposes of this study, AEs will be 
collected from the time of consent through the end of the MEG tasks, or following the MRI scan if 
one is required. Intercurrent illnesses or injuries should be regarded as AEs. 
 
Serious Adverse Event: A serious adverse event (SAE) means any untoward medical occurrence 
with the device: An event is “serious” if it involves considerable detriment or harm to one or more 
persons (who may or may not be subjects), or required intervention to prevent one or more 
persons from experiencing considerable detriment or harm. SAEs include: 
• 
Death 
• 
Life-threatening experience - Disease or condition where the likelihood of death is high unless 
the course of the disease/condition is interrupted or diseases/conditions with potentially fatal 
outcomes where the end point of the clinical trial analysis is survival 
• 
Inpatient hospitalization or prolongation of hospitalization 
• 
Persistent or significant disability/incapacity 
• 
Congenital anomaly/birth defect in subject’s offspring 
• 
Any other important medical event that, based upon appropriate medical judgment, may 
jeopardize the subject and may require medical or surgical intervention to prevent one of the 
outcomes listed above. Examples include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, the development of drug dependency or drug abuse, suicidal ideation 
or attempts, or the unintentional revealing of some genetic information to insurers. 
 

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Site: Arkansas Children’s Hospital 
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Although an event may be considered “serious” based on previous criteria and should be reported 
to ORRA immediately, not all SAEs meet IRB or FDA Expedited Reporting criteria. 
 
To avoid confusion, as the terms “serious” and “severe” are not synonymous, the following 
clarification is given: The term “severe” is often used to describe the intensity (severity) of a 
specific event (as in mild, moderate or severe myocardial infarction); the event itself; however, 
may be of relatively minor medical significance (such as a severe headache). This is not the same 
as “serious”, which is based on subject/event outcome or action usually associated with events 
that pose a threat to a subject’s life or functioning. Seriousness (not severity) serves as a guide 
for defining regulatory reporting obligations. [ICH-E2A(II)(B)] 
 
Unanticipated Adverse Device Effects (UADEs): A UADE is defined as “any serious adverse effect 
on health or safety, or any life-threatening problem, or death caused by, or associated with, a 
device; if that effect, problem, or death was not previously identified in nature, severity, or degree 
of incidence in the investigational plan, or application (including supplementary application), or 
any other unanticipated serious problem associated with a device that relates to the rights, safety, 
or welfare of subjects.” If an unanticipated adverse effect occurs, the investigator will promptly 
notify the sponsor of such an event within 24 hours of first learning of the event using the FDA 
MedWatch 3500A form. 
 
Related: An event is “related” if more likely than not it was caused by the research activity. 
 
Unexpected: An event is “unexpected” when its specificity, nature, severity or incidence is not 
accurately reflected in the ICF, protocol, or investigator’s Device Manual previously reviewed and 
approved by the IRB. Examples include a lower rate of response to treatment or a side effect that 
is more severe than initially expected. 
 
Study Period: All AEs will be recorded from the time of consent through the end of the study 
procedure. All AEs will be captured in the electronic medical record and recorded on the Case 
Report Forms (CRFs) and AE log. 
 
Monitoring, Recording and Reporting of AEs 
All AEs occurring during the study period as previously defined must be recorded. All relevant 
historical medical conditions (as determined and documented by Investigator/Clinician that are 
known/diagnosed prior to the start of the study are to be recorded as medical history. Any medical 
condition that is present at the time that the subject is screened will be considered as baseline 
and not reported as an AE. However, if the study subject’s condition deteriorates or exacerbates 
at any time during the study, it will be recorded as an AE. Pre-existing conditions should be 
recorded as adverse events only if the frequency, intensity, or the character of the condition 
worsens during the study. 
 
The clinical course of each event should be followed until resolution, stabilization, or until it has 
been determined that the study treatment or participation is not the cause. SAEs that are still 
ongoing at the end of the study period must be followed for up to 30 days to determine the final 
outcome. Any SAE that occurs after the study period and is considered to be possibly, probably, 
definitely, or related to the study treatment or study participation should be recorded and reported 
immediately to the Sponsor. 
 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
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Site: Arkansas Children’s Hospital 
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All subjects will be monitored for AEs during the study. Assessments may include monitoring the 
subject's clinical symptoms; laboratory, pathological, radiological, or surgical findings; physical 
examination; or other appropriate tests and procedures. 
 
AE data collection and reporting, which are required as part of every study, are done to ensure 
the safety of subjects enrolled in the studies and those who will enroll in future protocols. AEs are 
to be reported in a routine fashion at scheduled times during the trial, such as with the annual 
continuing review to the IRB. Certain AEs must be reported in an expedited fashion to allow for 
timely monitoring of subject safety and care. 
 
The reporting of these events depends on the characteristics of the event: 
1. Seriousness (grading of event) 
2. Relatedness to use of the investigational device or study procedure 
3. Expectedness 
 
Steps to Determine if the Event Requires Expedited Reporting: 
1. Identify the type of event 
2. Grade the event using 
3. Determine whether the adverse event is related to the investigational device. Attribution 
categories are as follows: 
• 
Unrelated 
• 
Unlikely 
• 
Possible 
• 
Probable 
• 
Definite 
4. Determine expectedness of event. Expected events are those previously identified 
resulting from administration of the investigational device. An adverse event is considered 
unexpected when the type or severity of the event is not listed in: 
• 
Protocol 
• 
Device Manual 
• 
ICF 
 
Note: This includes all events that occur within 30 days of the last protocol procedure (2nd IPA 
procedure). Any event occurring more than 30 days after the last protocol procedure that is 
possibly, probably, or definitely attributable to the investigational device must be reported 
according to the instructions above. 
 
Expedited Reporting of AEs 
Only adverse events meeting the UPIRTSO (Unanticipated Problem Involving Risks to Subjects 
or Others) will need to be reported to the UAMS IRB within the required 10-day allotment of being 
notified of the event. UPIRTSO requires that an unanticipated problem meet the following 
qualifications: a) unanticipated or unexpected; b) related to the research; and c) involves new or 
increased risk to the subject(s). All other adverse events should be recorded and reported to the 
UAMS IRB at continuing review. 
 
The Sponsor will be promptly notified of all potential SAEs/UADEs by the investigator/study staff 
using the FDA MedWatch 3500A. The Sponsor will evaluate all potential SAEs/UADEs and report 
these evaluations in accordance with 21 CFR 812. All other SAEs/UADEs not expeditiously 
reported will be reported to the Sponsor and IRB in the Annual Progress Report (APR). 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
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Site: Arkansas Children’s Hospital 
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Report all deaths to the Sponsor (ORRA) as soon as possible, preferably within 24 hours, but no 
later than 48 hours, of learning of the subject’s death, regardless of whether it is related or 
unrelated to the investigational device. A death due to a terminal condition of the research subject 
would be considered anticipated and not related to the research. 
 
The Sponsor will report deaths in accordance with 21 CFR 812. 
 
Clinical Site Monitoring 
Clinical site monitoring will be conducted by the UAMS Office of Research Regulatory Affairs 
(ORRA) to ensure that the rights and well-being of human subjects are protected, that the reported 
trial data are accurate, complete, and verifiable from source documents, and that the conduct of 
the trial is in compliance with the currently approved protocol/amendment(s), ICH GCP, and 
applicable regulatory requirements. 
 
Monitoring specialists from ORRA will conduct periodic on-site, comprehensive monitoring as 
determined by a protocol specific monitoring plan, which will be provided by the ORRA Monitoring 
Unit to the Investigator. 
 
Deviations and Violations 
Protocol Deviation: A deviation is any unintentional change, divergence, or departure from the 
study design or procedures defined in the protocol. Protocol deviations will be tracked and 
compiled in a Protocol Deviation Log. Deviations that potentially cause concern for the subject 
health, safety, or rights will be reported to the Sponsor as soon as possible for guidance on 
reporting. 
 
Protocol Violation: A violation is a change to, or non-compliance with, the IRB-approved 
procedures without prior Sponsor and IRB approval (excluding changes made to eliminate 
apparent immediate hazard to subjects). A violation may affect health, safety, or rights of a 
subject. Any violation will be reported immediately to the Sponsor for guidance on reporting. 
 
If the protocol deviation/protocol violation does not represent a significant alteration in the 
approved protocol and/or affect the safety or welfare of the subject, it will be reported to the UAMS 
IRB at the time of Continuing Review. If the protocol deviation/violation represents a significant 
alteration in the approved protocol and/or if it affects the safety or welfare of the subject, it must 
be reported to the Sponsor and UAMS IRB immediately. 
 
Data Handling and Recordkeeping 
The Principal Investigator will carefully monitor study procedures to protect the safety of research 
subjects, the quality of the data, and the integrity of the study. All study subject material will be 
assigned a unique identifying code or number. The key to the code will be kept in a password-
protected file on a secure, password-protected computer in the principal investigator’s office. Only 
the Principal Investigator (PI) will have access to the code and information that identifies the 
subject in this study. Clinical data and medical evaluation information will be obtained from the 
ACH Electronic Medical Record.  
 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
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Site: Arkansas Children’s Hospital 
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• 
Medical record information to be collected will include the subject’s name, address, telephone 
number, age, sex, race, ethnicity, head circumference, education, medical history - especially 
related to epilepsy such as epilepsy duration, results of routine EEG and imaging tests. 
 
At the conclusion of the study, the secure file containing linkages between the study ID and any 
subject identifiers (e.g., MRN, DOB) will be deleted, while the data will be stored for no more than 
10 years or until the last subject reaches the 23rd birthday. If consent was granted by the subject 
for future research then their data will be retained for an unspecified amount of time for use in 
future research which will be limited to future IRB-approved studies evaluating brain activity. All 
stored data will be de-identified. Data will be stored in the ACH MEG Center and only study 
personnel authorized to view the data will have access. Subjects may request to withdraw from 
the study by calling the PI at the number listed in the ICF or withdraw their data for future research 
use by writing a letter to the PI at the address specified in the HIPAA Authorization of the ICF. 
 
Data Analysis 
Preprocessing 
MEG data will be exported for further analysis from the acquisition computer to the signal 
processing research software, Brainstorm [66] (https://neuroimage.usc.edu/brainstorm/), which is 
an open-source application dedicated to the analysis of brain recordings. Next, data will band-
pass filtered between 0.5Hz to 100Hz and a notch filter will be applied for power-line noise 
removal (60Hz, 2nd order IIR notch filter with zero-phase lag). We will perform visual inspection 
to mark bad channels and segments. Data will be preprocessed for eye-blink and 
electrocardiogram reduction using a signal-space projection (SSP) technique [67]. The 
corresponding triggers recorded during acquisition will be used to import MEG epochs in the time 
window ranging from -200s to +800s with respect to the trigger [68, 69]. Baseline correction will 
be applied on the 200s before the trigger. Next, we will average across epochs to obtain an ERF 
waveform per subject for the language and memory tasks. Resting state data will use for baseline 
source imaging. 
 
Source Imaging 
To obtain the subject’s anatomical information for source modeling, native-space structural MRI 
data will be segmented using the research software, BrainSuite [70] (http://brainsuite.org/), to 
generate a cortical surface with a resolution of ~15,000 triangular vertices and imported into 
Brainstorm for further analysis. We will estimate empirical covariance statistics from the empty-
room recordings, to characterize instrument and environmental noise. The noise covariance 
estimates will use for subsequent inclusion into the imaging estimator of distributed cortical 
currents. Source analysis will utilize a boundary element model to compute the forward model 
with lead fields determined from elementary current dipoles distributed perpendicular to each 
individual’s segmented and tessellated cortical surface. We will apply the source modeling 
method, the minimum norm imaging (sLORETA) algorithm, to the ERFs. To obtain the most 
meaningful dipoles only source amplitudes of >=3.2 nanoAmpere-meter (nAm) will be selected. 
Dipoles meeting the above selection criteria will place on the subject’s MRI coregistered to the 
anatomic landmarks recorded during MEG collection. 
 
Statistical Analysis 
Overall: MEG and clinical parameters will be summarized as means, SD and ranges (for 
continuous and count data), as proportions (for binary and nominal data), or as proportions 
supplemented with mean scores (for Likert-scaled or other ordinal data). We will export the MEG 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
PI: 
Diana Escalona-Vargas, PhD 
Site: Arkansas Children’s Hospital 
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source analysis parameters for further statistical analysis. This is a pilot study that will provide the 
preliminary sample size estimates to support future research. 
 
Hemispheric dominance: Estimation of hemispheric dominance for language [69] and memory 
[68] will be calculated as the degree of activation of each hemisphere during performance of the 
task. We will derive an estimate of hemispheric dominance by calculating the difference in 
activation levels between the hemispheres. 
 
Group level: For this pilot research study, we will perform a preliminary statistical analysis by 
comparing MEG source activations between hemispheres (left vs. right) with α=0.05 significance 
level using a research statistical software. 
 
Ethical Considerations 
This study will be conducted in accordance with all applicable government regulations and ACH-
UAMS research policies and procedures. This protocol and any amendments will be submitted 
and approved by the UAMS IRB to conduct the study. 
 
The formal consent of each subject, using the IRB-approved ICF, will be obtained before that 
subject is submitted to any study procedure. All subjects for this study will be provided an ICF 
describing this study and providing sufficient information in language suitable for subjects to make 
an informed decision about their participation in this study. The person obtaining consent will 
thoroughly explain each element of the document and outline the risks and benefits, alternate 
treatment(s), and requirements of the study. 
 
The consent process will take place in a quiet and private room, and subjects may take as much 
time as needed to make a decision about their participation. Privacy will be maintained and 
questions regarding participation will be answered. No coercion or undue influence will be used 
in the consent process. This ICF must be signed by the subject or legally authorized 
representative and the person obtaining the consent. A copy of the signed ICF will be given to the 
subject, and the informed consent process will be documented in the research record. 
 
Dissemination of Data 
The results of this study may be used for presentations, posters, or publications. The publications 
will not contain any identifiable information that could be linked to a subject. 
 

Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
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Site: Arkansas Children’s Hospital 
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Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
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Diana Escalona-Vargas, PhD 
Site: Arkansas Children’s Hospital 
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Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
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Site: Arkansas Children’s Hospital 
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Site: Arkansas Children’s Hospital 
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Title: Pediatric Language and Memory Mapping in Refractory Epilepsy using Magnetoencephalography 
PI: 
Diana Escalona-Vargas, PhD 
Site: Arkansas Children’s Hospital 
Version 43 
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Date: 12/1309/20210 
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Study Flow Diagram 
 
Routine Clinic Visit 
-Present study to pre-identified 
eligible patients 
-Obtain informed consent 
-Confirm eligibility 
-Schedule research visit 
Research Visit 
MEG Preparation 
-Attach EOG electrodes 
-Attach indicator coils 
-Digitize landmarks, indicator coils 
& head surface points 
-Photograph landmarks and coils 
-Place MEG helmet 
Resting State Measure 
-Baseline brain activity 
No movement, eyes closed 
-5 minutes 
Receptive Language Task 
Auditory stimuli 
-Practice 
5 target words 
2-3 minutes 
-MEG recording 
5 target words, 40 distractors 
10 minutes 
Memory Task 
Visual stimuli 
-Practice 
Short version of task 
4 minutes 
-MEG recording 
96 stimuli: WM load (low, high), 
congruency (congruent, 
incongruent) 
16 minutes 
Break 
MRI 
-Only for subjects without an 
existing or suitable MRI 
-Brainstorm MEG signal 
processing 
-BrainSuite MRI image 
processing 
-Statistical analysis 
Data Analysis