Neuromodulation of Affective Valence in Humans by Amygdala Stimulation
Phase: NA
Conditions: Refractory Epilepsy
Sponsor: Dartmouth-Hitchcock Medical Center

 
 
PROTOCOL TITLE: Neuromodulation of affective valence in humans by amygdala 
stimulation 
 
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D-HH IRB OVERSIGHT: 
One of the following must be true in order to submit to the D-HH IRB. Please check all 
that apply: 
 
☒ The Principal Investigator is employed by D-H 
☒ The study will utilize any D-H data or specimens 
☒ The study will enroll D-H patients or recruit from D-H sites 
☒ The study will utilize any D-H resources, e.g. study procedures will occur at  
     D-H locations and/or use of D-H equipment or shared resources 
 
PROTOCOL TITLE: 
Modulation of emotion perception in humans via amygdala stimulation  
 
PRINCIPAL INVESTIGATOR: 
Krzysztof A. Bujarski 
Department of Neurology 
Telephone Number 603-650-5000 
Email Address Krzysztof.A.Bujarski@hitchcock.org 
Official Title: 
Neuromodulation of affective valence in humans by 
amygdala stimulation 
NCT number: 
NCT 05292183 
Document Type: 
Protocol and Statistical Plan 
Date of the 
Document: 
11/28/2023 Version Date  

 
 
PROTOCOL TITLE: Neuromodulation of affective valence in humans by amygdala 
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VERSION NUMBER/DATE: 
V5.0_12Sep2023 
 
REVISION HISTORY 
 
Revision 
# 
Version Date 
Summary of Changes 
Consent 
Change? 
V2.0 
25Jul2022 
The Differential Emotions Scale was not 
providing us with data required for this study. 
Instead, it was decided to use The Emotion 
Self-Rating Scale (ESR) that would be more 
appropriate to gather needed information 
 
Yes 
V3.0 
17Oct2022 
1. Section 14.0: added language to allow 
participants to continue their participation in 
the testing sessions on the same day even if 
they experience a single clinical seizure. The PI 
or other study personnel delegated this task 
will make the final determination.  
2. P.15: language added to reflect:” The scale 
will be administered electronically (on the 
testing computer). 
3. P.16: Updated Study Timelines 
4. Minor edits and formatting changes 
throughout the entire document. 
Yes 
V3.1 
16Nov2022 
Section 15.0: added language related to AEs 
Yes 
V4.0 
21Apr2023 
Section7.0: Data and Specimen Banking 
Section 17.0: Data Management and 
Confidentiality  
Section 24.0: HIPPA Authorization Waiver 
No 
V5.0 
12Sep2023 
Section6.0: Procedures involved. Clarification 
added in inclusion criteria 
 
Section 9.0: Study Timeline- enrollment up to 
January 1, 2024, data analysis January 2, 2024-
January 1, 2025 
 
Section 10.0: Inclusion/Exclusion Criteria: 
• “FSIQ 75 and above or any equivalent 
test of generalized intelligence as 
No 

 
 
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determined by the PI to adequately 
predict engagement in the task” 
 
V6.0 
28Nov2023 
Section 5.0: Adding clarification about the 
Blackrock stimulator 
No 
 
 

 
 
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Table of Contents 
1.0 
Study Summary ........................................................................................................ 5 
2.0 
Objectives ................................................................................................................ 6 
3.0 
Background .............................................................................................................. 7 
4.0 
Study Endpoints ..................................................................................................... 11 
5.0 
Study Intervention/Investigational Agent .............................................................. 13 
6.0 
Procedures Involved............................................................................................... 13 
7.0 
Data and Specimen Banking .................................................................................. 17 
8.0 
Sharing of Results with Subjects ........................................................................... 17 
9.0 
Study Timelines ..................................................................................................... 17 
10.0 Inclusion and Exclusion Criteria ............................................................................ 18 
11.0 Vulnerable Populations .......................................................................................... 18 
12.0 Local Number of Subjects ..................................................................................... 18 
13.0 Recruitment Methods ............................................................................................. 19 
14.0 Withdrawal of Subjects .......................................................................................... 20 
15.0 Risks to Subjects .................................................................................................... 20 
16.0 Potential Benefits to Subjects ................................................................................ 21 
17.0 Data Management and Confidentiality .................................................................. 21 
18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects .......................... 22 
19.0 Provisions to Protect the Privacy Interests of Subjects .......................................... 24 
20.0 Compensation for Research-Related Injury ........................................................... 24 
21.0 Economic Burden to Subjects ................................................................................ 24 
22.0 Consent Process ..................................................................................................... 24 
23.0 Process to Document Consent in Writing .............................................................. 25 
24.0 HIPPA Authorization Waiver ................................................................................ 25 
25.0 Setting .................................................................................................................... 26 
26.0 Resources Available............................................................................................... 27 
27.0 Multi-Site Research ............................................................................................... 29 
 
 
 

 
 
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1.0 
Study Summary 
Study Title 
Modulation of emotion perception in humans via amygdala 
stimulation 
Study Design 
Experimental  
Primary Objective 
To determine if electrical stimulation targeted to specific 
sub-nuclei of the amygdala can induce a change in 
perception of affective valence. 
Secondary Objective(s) 
1. To have a clear understanding of the safety and efficacy 
of our targeting and stimulation parameters on cognition and 
induction of undesired side effects. 
 
2. To determine if the human amygdala can be a suitable 
DBS target to treat psychiatric disorders known to involve 
the amygdala. 
Research 
Intervention(s)/ 
Investigational Agent(s)  
We will use clinically accepted and safe methods to 
understand the effects of amygdala stimulation on side 
effects and induction of electrographic discharges. 
IND/IDE #  
N/A 
Study Population 
Patients (18 years or older with normal cognition and fit all 
inclusion and exclusion criteria) who have intracranial EEG 
electrodes for evaluation of candidacy for epilepsy surgery. 
Sample Size 
16 intracranial EEG patients 
Study Duration for 
individual participants 
Approximately 2 – 3 weeks 
Study Specific 
Abbreviations/ 
Definitions  
AIC – Advanced Imaging Center 
BLN – Basolateral Nucleus  
CN – Centromedian Nucleus 
DBS – Deep-Brain Stimulation 
DHMC – Dartmouth-Hitchcock Medical Center 
EBS – Electrical Brain Stimulation 
EEG - Electroencephalogram 
EMU - Epilepsy Monitoring Unit 
ESR- The Emotion Self-Rating Scale  
GAD – Generalized Anxiety Disorder 
IAPS – International Affective Picture System 
ISM – Independent Safety Monitor 
MHMH – Mary Hitchcock Medical Hospital  
MPI – Message Passing Interface 
OASIS – Open Affective Standardized Image Set  
PTSD – Post-Traumatic Stress Disorder 

 
 
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2.0 
 Objectives 
 
The main objective of this study is to investigate how the amygdala processes affective 
valence and to determine if electrical stimulation targeted to specific sub-nuclei of the 
amygdala can be safely used to induce a change in perception of affective valence. Our 
central hypothesis is that electrical stimulation of the basolateral nuclear group (BLN) of 
the amygdala during performance of an affective valence perception task will change how 
patients perceive affective valence in pictures without causing the undesirable side effects 
of stimulation. We propose that the induction of this effect on cognition will have future 
implications for the treatment of specific psychiatric disorders that are known to involve 
the amygdala.  
 
Specific Aim 1. Characterize oscillations of the amygdala and its connections during 
judgment of valence. We will record intracranial electroencephalogram (EEG) oscillatory 
rhythms from the valence circuit, including the amygdala and, as available, the anterior 
insula, the dorsal anterior cingulate, and ventromedial prefrontal lobe during performance 
of the Affective Valence Perception Task. Our working hypothesis is that we will find 
activation and connectivity across the valence circuit, which will provide new insights into 
the representation of valence.  
 
Specific Aim 2. Determine the effect of electrical stimulation targeted to the amygdala on 
safety and cognition  
 
A. We will determine if stimulation, per new parameters and location, induces 
undesired effects or electrographic after-discharges. Our working hypothesis is 
that targeting the BLN of the amygdala and using parameters appropriate for 
long-term deep-brain stimulation (DBS) will not induce any undesired effects. 
 
B. We will measure the effect of amygdala sub-nuclei stimulation on perception of 
affective valence. Our working hypothesis is that electrical stimulation of the BLN 
will change the perceived valence of the picture presented.  
 
Research Hypothesis 
We propose that neuromodulation of the valence circuit through electrical stimulation of 
the amygdala may have therapeutic implications in treatment-resistant psychiatric 
disorders, such as generalized anxiety disorder, post-traumatic stress disorder, and 
aggression. We believe that there is a critical need to investigate specific targets within the 
amygdala and to define stimulation parameters that will allow for safe neuromodulation of 

 
 
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the human amygdala using DBS. Without this knowledge, we will miss an opportunity to 
develop an effective intervention for many disabling psychiatric conditions. 
 
3.0 
Background 
 
Studies show that the world-wide burden of psychiatric disease is immense (Whiteford, 
Ferrari et al. 2015, Rehm and Shield 2019). A 2016 study measuring global burden of 
disease points to 7% of all disability-adjusted life years lost to uncontrolled mental health 
disorders (Vigo, Thornicroft et al. 2016). Despite advances in pharmaceutical options and 
novel forms of psychotherapy, a large proportion of patients with psychiatric conditions do 
not adequately respond to standard treatment (Al-Harbi 2012). For persons with mental 
illness who have not benefited from conventional intervention, neuromodulation is an 
emerging treatment option (Altinay, Estemalik et al. 2015, Cleary, Ozpinar et al. 2015, 
Coenen, Amtage et al. 2015, Graat, Figee et al. 2017). Neuromodulation is a method used 
for the long-term alteration of pathologic neural circuits by targeted electrical stimulation, 
with the goal of improving psychiatric function. Neuromodulation can be accomplished 
using non-invasive techniques, such as transcranial magnetic stimulation, or alternatively 
by invasive techniques, such as deep-brain stimulation (DBS). Although the exact 
mechanisms of neuromodulation are uncertain, several theoretical explanations have been 
suggested, including downregulation of network activity through tonic depolarization of 
neurons, inhibition of network activity by altering the synapse, and resetting abnormal 
oscillatory activity (McIntyre, Savasta et al. 2004, Ashkan, Rogers et al. 2017).   
 
Despite the successful use of DBS in many neurological disorders, recent clinical trials of 
DBS in psychiatry have shown limited benefits (Graat, Figee et al. 2017, Widge, Malone 
et al. 2018). Currently, the only FDA-approved application of DBS in psychiatry is for the 
treatment of obsessive-compulsive disorder (Altinay, Estemalik et al. 2015). In their 2019 
review of DBS, Lozano at al. conclude that the main obstacles limiting the use of DBS in 
psychiatry include the invasive nature of the treatment and our relatively poor 
understanding of the underlying anatomy of neural networks involved in psychiatric 
disorders (Lozano, Lipsman et al. 2019). Despite its invasive nature, increasing experience 
with DBS surgical techniques have improved its safety (Deer, Lamer et al. 2017). 
Furthermore, advancements in functional imaging are providing a more complete 
understanding of the underlying neural networks involved in psychiatric disorders 
(Deckersbach, Dougherty et al. 2006). 
 

 
 
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One of the most extensively studied regions in the human brain with respect to anatomy 
and function is the amygdala (McDonald 1998, Murray 2007, Benarroch 2015, Janak and 
Tye 2015). A simplified model of the human amygdala connectivity is shown in Fig 1. 
Upstream afferent projections from cortical and subcortical regions flow into the 
basolateral nucleus (BLN). The BLN, in turn, projects to the hippocampus, the entorhinal 
cortex, and the centromedian nucleus (CN). The CN is the main source of efferent 
projections out of the amygdala mostly to the ventromedial pre-frontal cortex, the 
hypothalamus, and the brainstem. 
 
Extensive evidence from non-human and human 
animal studies implicate the amygdala in a wide 
variety of cognitive functions, including in 
affective valence and arousal (LaBar, Gatenby 
et al. 1998, Tye and Janak 2007, Fusar-Poli, 
Placentino et al. 2009, Salzman and Fusi 2010).  
Affective valence, or just valence, refers to the 
intrinsic attractiveness/”goodness” (positive 
valence) or aversiveness/”badness” (negative 
valence) of events, objects, or situations (Yee 
and Miller 1987, Garavan, Pendergrass et al. 2001, Lewis, Critchley et al. 2007, Ball, Derix 
et al. 2009, Salzman and Fusi 2010, Murray, Brosch et al. 2014). The National Institute of 
Mental Health Research Domain Criteria (RDoC) propose that affective valence is 
processed by a valence network which includes the BLN of the amygdala, the 
hippocampus, ventromedial prefrontal cortex, dorsal anterior cingulate cortex, the 
hypothalamus, and the insular cortex (Cuthbert and Insel 2013). The importance of the 
amygdala in representation of valence is evidenced by studies using functional imaging 
and in human patients with destructive amygdala lesions (Adolphs, Tranel et al. 1994, 
Hamann, Ely et al. 1999, Canli, Zhao et al. 2000, Anderson and Phelps 2001, Kilpatrick 
and Cahill 2003, Kensinger and Corkin 2004, Phelps 2004, Richardson, Strange et al. 2004, 
LaBar and Cabeza 2006, Sergerie, Lepage et al. 2006, O'Neill, Gore et al. 2018). Arousal, 
on the other hand, refers to the psychological state of wakeful attention and is important 
for detection of salience, or the relative importance and novelty of stimuli (LaBar and 
Cabeza 2006, Uddin 2017). Similar to valence, RDoC defines an arousal/salience circuit 
which includes the amygdala, insula, cingulate, and basal forebrain (Cuthbert and Insel 
2013, Uddin 2017).   
 
Fig 1. Model of the amygdala.  
BLN=basolateral nucleus; CN=central 
nucleus. 

 
 
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Mounting evidence from functional imaging studies shows that dysfunctional processing 
within the amygdala may be a common mechanism for a vast array of psychiatric illnesses, 
especially for post-traumatic stress disorder (PTSD) (Davey, Whittle et al. 2015, Dai and 
Jonnagaddala 2018). Models of PTSD propose that reduced top-down control by 
ventromedial prefrontal cortex leads to hyperactivity of the amygdala (Besnard and Sahay 
2016). Among other things, this manifests clinically in patients as dysregulated valence 
processing of environmental stimuli (Wolf, Miller et al. 2009). Indeed, studies of valence 
processing in patients with PTSD correlate exaggerated activation of the amygdala to 
negatively valenced stimuli with increasing PTSD symptom severity, and decrease in 
activation with symptom improvement (Pissiota, Frans et al. 2002, Protopopescu, Pan et 
al. 2005, Shin, Wright et al. 2005, Francati, Vermetten et al. 2007). 
 
An important source of evidence for the function of the human amygdala has come from 
studies using intracranial EEG (Guillory and Bujarski 2014). Intracranial EEG is a 
diagnostic tool used to understand the source of seizures in patients with epilepsy and 
involves the recording of EEG via depth electrodes surgically implanted directly into 
neural structures. In addition to detecting seizures, epilepsy patients undergoing an 
intracranial EEG study can be voluntarily recruited to participate in research. Despite many 
limitations, intracranial EEG has significant advantages compared to non-invasive methods 
such as fMR and PET especially with regards to temporal resolution, i.e. milliseconds for 
intracranial EEG compared to seconds for fMR and minutes for PET (Guillory and Bujarski 
2014). Intracranial EEG analysis methods such as event-related potentials, event-related 
changes in power at specific frequency ranges, and task-related network coherence have 
provided insights into amygdala function and amygdala connectivity to other brain regions 
(Halgren, Walter et al. 1978, Oya, Kawasaki et al. 2002, Krolak-Salmon, Henaff et al. 
2004, Pourtois, Spinelli et al. 2010, Sato, Kochiyama et al. 2011, Bijanki, Kovach et al. 
2014, Guillory and Bujarski 2014, Inman, Bijanki et al. 2018, Inman, Manns et al. 2018). 
 
In addition to recording brain activity, intracranial EEG can be used to deliver electrical 
brain stimulation (EBS) for the clinical purpose of functional mapping and also for research 
purposes (Guillory and Bujarski 2014). For instance, the function of the hippocampus has 
been assessed by giving patients with intracranial EEG a memory task while EBS is safely 
delivered to the hippocampus (Jacobs, Miller et al. 2016). The effect of EBS on the brain 
depends on the choice of parameters for EBS and on the specifics of neural network 
anatomy (Guillory and Bujarski 2014, Lozano, Lipsman et al. 2019). It is generally thought 
that pulse width determines the size of the region affected by stimulation; amplitude to the 
strength of the effect; and frequency to activation or inhibition of the network (Lanteaume, 

 
 
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Khalfa et al. 2007, Lozano, Lipsman et al. 2019, Mohan, Watrous et al. 2020). Recent study 
of the effect of EBS parameters showed that stimulation frequencies between 100 and 200 
Hz are most likely to cause inhibition of underlying brain tissue (Mohan, Watrous et al. 
2020). 
 
Preliminary Data/Pilot Studies   
 
We conducted 2 pilot studies in 13 epilepsy patients with intracranial EEG electrodes to  
investigate the processing of valence in the amygdala and the effect of amygdala EBS on 
valence perception (Bujarski, 2019 ). Fig 2 shows the experimental set up. Fig 3 shows the 
design of the Valence Judgment Task, where 48 pictures from the International Affective 
Picture System (Bradley 2007) of varying valence are presented to the patient.  
 
 
 
Preliminary Study #1.  We presented the 
Valence Judgment Task without EBS in 3 
patients with electrodes in the left 
amygdala and obtained event-related 
potentials.  We found activation of the 
amygdala to positively and negatively 
valenced pictures, and less so to neutral 
pictures approximately 500 ms following 
image presentation (Fig 4). These 
findings are consistent with numerous 
prior studies (Guillory and Bujarski 
2014). 

 
 
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Preliminary Study #2: We presented the 
Valence Judgment Task with block-
randomized EBS to 50% of trials in 10 
patients with electrodes in the left 
amygdala. Fig 5 shows the location of 
electrodes in the left amygdala for all 
patients. Before administering the task, we 
determined the maximum safe EBS 
intensity for each patient by gradual 
increase from 1 mA to a goal of 5 mA or 
approximately 20 µC/cm2, which is ~50% 
of maximum safe stimulation intensity.   
 
We found that 9 of 10 patients eventually developed electrographic seizures related to EBS, 
4 of which were associated with self-reported negative emotional symptoms.  The average 
afterdischarge threshold was 3.4 mA (about 17µc/cm2).  This necessitated the incremental 
reduction of EBS intensity until no electrographic seizures and no subjective symptoms 
occurred. The average final stimulation intensity was 2.8 mA (12µc/cm2). We subsequently 
administered the task. We found 
that amygdala EBS changed 
self-reported 
valence 
for 
negative 
pictures 
towards 
neutral (estimate 0.79, p<0.01), 
changed self-reported valence 
for positive pictures towards 
neutral (estimate -0.54, p<0.05), 
and did not change for neutral 
pictures 
(estimate 
0.15, 
p=0.58). Fig 6 shows the effect 
of EBS for all 48 pictures 
averaged across all 10 patients. 
 
4.0 
Study Endpoints 
 
Anticipated Outcomes 
  

 
 
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We anticipate that task-related intracranial EEG recordings will lead to better 
understanding of neural circuits responsible for processing of valence.  
• We expect to find increased power in the gamma band in the valence circuit 
(BLN > CN of amygdala).  
• We expect to find increased coherence across the valence circuit with items 
of negative and (less so) positive valence. 
  
We anticipate that targeting of stimulation to the BLN and the use of our suggested 
stimulation parameters will not result in any subjective sensations in the patient or 
electrographic after-discharges.  
• We predict that we will produce effects on reported perception of valence 
for both positive and negative pictures without affecting neutral ones by 
stimulation of the BLN as opposed to the CN.  
• We will randomize stimulation and analyze within patient effects of 
stimulation vs no stimulation.  
 
Potential Pitfalls and Alternative Strategies 
 
During an average year, 15 patients with refractory epilepsy are implanted with intracranial 
EEG electrodes at Dartmouth-Hitchcock.  
 
• We believe that 16 patients will be an appropriate number that will fit the 
inclusion and exclusion criteria over period of two years that the study is 
conducted.  
• If we cannot recruit 16 patients during this time, a no-cost extension for one 
year may be required.  
 
If stimulation done by new parameters produces untoward side effects or does not replicate 
the cognitive change in valence seen in the preliminary study, we will change stimulation 
parameters. New parameters will modulate the frequency, amplitude, and pulse duration. 
These parameters will remain within clinically-determined safety limits. Additionally, 
parameters will be reviewed after each patient and changed incrementally, one at a time 
(see below). If it is determined that a change in stimulation parameters is needed outside 
of clinically-determined safe limits, a request will be formally submitted to the IRB. 
  
• We will perform an effect-of-stimulation assessment after each patient. We 
may need to increase stimulation intensity, pulse duration, or change the 
location of stimulation. These changes will fall within clinically-determined 
safety limits: 10-200 Hz (Frequency), 0.1- 3 mA (Amplitude/Intensity), and 
30-60 microseconds (Pulse duration).  

 
 
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• Any unexpected untoward effect of the stimulation will be assessed by the 
PI and reported to the Independent Safety Monitor (ISM) and IRB as 
required.  
• Depending on the nature of the untoward effect, the stimulation parameters, 
the stimulation location, or the nature of the task will be adjusted.  
 
5.0 
Study Intervention/Investigational Agent 
 
The main objective of this study is to determine if electrical stimulation of the human 
amygdala will modulate perception of valence and arousal.  As such, our study intervention 
is electrical brain stimulation.  To accomplish our objective, we will use a Blackrock 
system, specifically Blackrock stimulator that is  able to deliver a wide range of EBS pulses 
(output voltage between 4.7-9.5 V, stimulation frequency 4 Hz to 5 kHz, pulse width 44 
µs to 65535 µs, and maximum charge density of 20 µC/cm2) and fits well within the needed 
parameters.  
This device is approved for human research. This device has been used extensively both in 
prior studies at Dartmouth-Hitchcock and other studies in epilepsy centers across the 
country. If safety concerns occur during the use of this device, such concerns will 
immediately be reported to PI, ISM, and IRB.  
 
6.0 
Procedures Involved 
 
The study will be conducted in the inpatient Epilepsy Monitoring Unit at Dartmouth-
Hitchcock Medical Center (DHMC) enrolling patients with epilepsy who are undergoing 
intracranial EEG for evaluation of possible epilepsy surgery. The study will be conducted 
in patients who do not have a specific psychiatric diagnosis, i.e. the aim is to use 
intracranial EEG in patients with epilepsy to understand amygdala electrophysiology and 
cognitive effect of EBS. The suitability of each patient for intracranial EEG is determined 
by a multidisciplinary board several months prior to the procedure. Only patients with 
appropriate electrode locations in the amygdala for clinical purposes will be identified 
during multidisciplinary epilepsy surgery conference and subsequently enrolled into the 
study. DHMC is a Level 4 Epilepsy Center with approximately 15 intracranial EEG 
patients per year. As such, we can estimate that we will enroll 16 study subjects over a 2-
year funding duration. The task will be administered as patients are waiting for seizures to 
occur.   
 

 
 
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We will include patients 18 years or older with FSIQ 75 and above or any equivalent test 
of generalized intelligence as determined by the PI to adequately predict engagement in the 
task. All study procedures, including the range of emotional content in the images 
presented, will be reviewed, and participants will give independent consent for 
participation. We will exclude patients with any additional neurological disorders and/or 
psychiatric diseases that would limit their ability to provide informed consent and/or to 
perform study tasks within normal limits. 
 
We will use the Open Affective Standardized Image Set (OASIS) for this study, as 
opposed to the International Affective Picture System (IAPS) used for the pilot (Bradley, 
2007). The OASIS image set uses more contemporary images and is well validated. It is 
composed of 900 images that have standard rankings for valence based on a large normal 
control cohort. The images selected for the task vary with regards to valence 
(positive/neutral/negative) and arousal (low arousal/high arousal). For the task, all 900 
images in the OASIS set were placed into one of the following four categories based on 
average valence and arousal ratings: Group 1: Negative Valence (<4) / Low Arousal (<4); 
Group 2: Negative Valence (<4) / High Arousal (>4); Group 3: Positive Valence (>4) / 
Low Arousal (<4); Group 4: Positive Valence (>4) / High Arousal (>4). From the 900 
images of the entire OASIS set, 48 images were selected for each Group 1–4 for a total of 
192 images. Average valence and arousal scores were calculated for each group and images 
were added and removed to optimize the two scores towards their respective extremes. 
Therefore, 192 images varying in arousal and valence were selected.  
 
The task will be divided into Part 1 and Part 2.  
• Part 1 will include 24 randomly chosen images from each of four categories (total 
of 96 images varying in valence and arousal) and will be presented without 
amygdala stimulation in Specific Aim 1 (see above).  
• Part 2 will include 24 different images from each of four categories (total of 96 
images varying in valence and arousal) and will be used in Specific Aim 2 with 
block-randomized amygdala stimulation (see above).  
 
Experimental set-up. The set-up will be similar to one used for the preliminary study (see 
Fig. 2); the main difference will be the use of a Blackrock CereStim stimulator instead of 
the Grass 12X used in the pilot, given that the Grass 12X cannot deliver the appropriate 
stimulation frequency of 100 Hz. 
 

 
 
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Electrode localization. MRI of the patient will be co-registered with the post-op CT. 
Amygdala parcellation will be obtained using FreeSurfer sub-field segmentation tool 
which gives detailed delineation of amygdala sub nuclei (Saygin, 2017).  
 
Electrode types.  The human amygdala is approximately 20 mm long on coronal images 
with the basolateral nuclear group spanning approximately 70% of its length. A standard 
EEG depth electrode has an inter-electrode spacing of 3 mm and contact length of 2.29 
mm. With proper insertion, 5 electrode contacts will span the amygdala, 3 contacts in the 
BLN, and 2 contacts in the CN (see Fig 5).  Some patient may be implanted with depth 
electrodes which have additional microelectrode contacts.  Such microelectrode contacts 
will not be used in this study.  
 
Location of EBS. We propose that EBS to the BLN of the amygdala for this study for 
several reasons.  First, the BLN is the main site of afferent projections into the amygdala 
from cortical and subcortical sites (Janak and Tye 2015). Inhibitory EBS in this location 
will has the highest chance of “blocking” information flow into the amygdala without 
affecting down-stream networks and thus causing unwanted emotional symptoms.  Second, 
the BLN takes up approximately 70% of the entire volume of the amygdala (~15 mm in 
length). The PMT 2102-14-091 EEG depth electrode used at DHMC has an inter-electrode 
spacing of 3 mm and contact length of 2.29 mm, thus resulting in likely 2 to 3 electrode 
contacts in the BLN in each patient. Therefore, we believe that targeting the BLN for 
stimulation will be feasible in most patients with amygdala for bipolar EBS.  We will target 
both the right and left amygdala. 
 
Rational choice of EBS parameters. Our intent is to deliver an EBS pulse which will inhibit 
the BLN.  Studies show that EBS in frequencies 100 to 200 Hz inhibit the function of neural 
structures (Mohan, Watrous et al. 2020).  For instance, commercial Medtronic™ DBS 
systems use frequencies of 130 Hz to inhibit neural networks in Parkinson disease.   
Furthermore, evidence from studies and our clinical experience with Neuropace™ show 
that frequencies at 200 Hz are safe to use in patients with epilepsy and inhibit seizures (Sun 
and Morrell 2014).  Lastly, our preliminary study showed that the average afterdischarge 
threshold in the amygdala is 3.4 mA (about 17µc/cm2) and final safe average stimulation 
intensity 2.8 mA (12µc/cm2). Based on this evidence from our preliminary study and the 
literature, our target stimulation parameters will be 200 Hz and intensity of 2.5 mA.  These 
EBS parameters are likely to be safe, not induce afterdischarges, and produce an inhibitory 
effect on neural structures.  If stimulation parameters used in the study result in unexpected 
effects (such as afterdischarges, seizures, experiential symptoms, or lack of clinical effect 
on perception of valence), we may determine to change stimulation parameters during the 

 
 
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course of the study.  We will adjust stimulation parameters to minimize the side effects and 
maximize the effectiveness of stimulation. We may for instance lower stimulation intensity 
or change stimulation frequency. These changes will fall within clinically-determined 
safety limits: 10-200 Hz (frequency), 0.1- 3 mA (Amplitude/Intensity), and 30-60 
microseconds (Pulse duration). If it is determined that a change in stimulation parameters 
is needed, a request will be formally submitted to the IRB.  
 
Statistical analysis of behavioral data. To account for differences among individuals, we 
will fit a linear mixed model with random intercepts and slopes to account for individual 
differences in baseline for valence judgements. In addition to valence, we will analyze the 
effect of EBS on arousal. In our preliminary study, we found an approximately 20% 
average change in valence perception in 10 patients.  Enrolling 16 patients gives us 90% 
power in seeing the effect EBS. 
 
EEG pre-processing and analysis.  To preprocess EEG data, we will exclude bad channels 
with artifact, filter line noise, and apply a high-pas filter. We will re-reference to other 
electrode contacts in the same shaft and subtract this average from each electrode in (local 
average re-referencing). EEG will be segmented using event triggers. Baseline 
normalization to -500 ms from each stimulus onset.  EEG epochs will be identified using 
event triggers and each trial will be normalized to a baseline 500 ms prior to stimulus onset. 
Time-frequency analysis using wavelet transform will be used to obtain an event-related 
time-frequency spectrogram in each recording location. We will also examine event-related 
coherence between the BLN of the amygdala, the ventromedial prefrontal cortex, the dorsal 
anterior cingulate, and anterior insula for both valence and arousal (Korzeniewska, 
Crainiceanu et al. 2008). Differences in gamma activation and coherence between 
stimulated and unstimulated trials will be assessed. 
 
The Emotion Self-Rating Scale (ESR) will be used to measure the effect of electrical brain 
stimulation (EBS) of the amygdala This is a self-reported scale of emotional experience 
which has also been used in mood-induction work (Schneider et al., 1994).  It is similar to 
other subjective ratings of emotions used in other research. Schneider et al. (1994) used it 
to assess “valence specificity” for six specific emotions.  We will administer this scale to 
understand if amygdala stimulation induces any subjective experience of emotional states. 
The scale will be administered electronically (on the testing computer) as the final 
stimulation parameters are decided for each patient but before we present the 
Valence/Arousal Task. These changes will fall within clinically-determined safety limits: 

 
 
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10-200 Hz (Frequency), 0.1- 3 mA (Amplitude/Intensity), and 30-60 microseconds (Pulse 
duration).  
 
 
 
7.0 
Data and Specimen Banking 
 
Intracranial EEG data will be de-identified and exported using secure methods to the 
analysis computer located in the Department of Neurology at DHMC.  This computer will 
have standard hospital encryption and password protection.  Data from this computer will 
not be exported to other computers or send over internet channels without appropriate 
secure protocols.  Access to this data will only be made available to the PI and other persons 
authorized by the study PI. De-identified data will be shared with NIH and/or NIMH data 
archive for use in future research. No patient identifiers will be included with this data 
sharing.  
 
Like EEG data, behavioral data and demographics will be de-identified and exported 
following standard secure protocols to a study computer located at the Department of 
Neurology.  This computer will have standard hospital encryption and password protection.  
Data from this computer will not be exported to other computers or send over internet 
channels without appropriate secure protocols.  Access to this data will only be made 
available to the PI and other persons authorized by the study PI. De-identified data will be 
shared with NIH and/or NIMH data archive for use in future research. No patient identifiers 
will be included with this data sharing  
 
8.0 
Sharing of Results with Subjects 
While the results of the daily testing sessions will not be shared with individual 
participants, we may publish the results of this research.  
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law.  
If there are negative outcomes that led to the termination of the study, these will be 
published as quickly as possible on the ClinicalTrials.gov website. This website will not 
include identifiable information. 
 
9.0 
Study Timelines 

 
 
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Participants will be enrolled for the duration of their intracranial monitoring admission, 
approximately 2 – 3 weeks.  
 
• March 31, 2022 – January 1, 2024 – Enrollment of 16 participants, data collection 
• January 2, 2024 – January 1, 2025 – Data analysis, reporting, writing manuscripts 
Due to COVID-19 pandemic and restrictions on admissions to Dartmouth-Hitchcock of 
patients with intracranial EEG, the exact timeline for this study is uncertain. 
 
 
10.0 Inclusion and Exclusion Criteria 
 
Inclusion Criteria: 
• Age of 18 years and older 
• FSIQ 75 and above or any equivalent test of generalized intelligence as 
determined by the PI to adequately predict engagement in the task 
• Able to give independent consent for participation in the study 
 
Exclusion Criteria: 
• Additional neurological disorders (such as dementia, stroke, brain tumor, etc.) 
• Any psychiatric condition that would limit their ability to provide consent and/or 
perform study tasks within normal limits. This would be based on presurgical 
psychiatric assessment.  
• Anything else that, in the opinion of the investigator, might preclude them from 
participating in the study. 
 
11.0 Vulnerable Populations 
As a standard of care, we do not perform implantation of intracranial electrodes in 
pregnant women. Additionally, we do not plan to enroll prisoners, children, or patients 
who cannot consent for themselves. We will also be screening for IQ.  
 
However, we do not exclude low-income populations from participation in this research. 
Subjects will not be compensated for participation in this study and their clinical care 
decisions will not be influenced by participation, so that will prevent financial incentive 
or coercion. 
 
12.0 Local Number of Subjects 
 

 
 
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DHMC Epilepsy Center admits approximately 15 intracranial EEG patients per year. As 
such, we estimate that we will enroll 16 study subjects over a 2-year period. If we cannot 
recruit 16 patients during this time, an extension for one year may be required. 
 
13.0 Recruitment Methods  
 
The study will recruit patients who have intracranial EEG electrodes (as described above) 
for evaluation of candidacy for epilepsy surgery to measure the effect of electrical 
stimulation of the amygdala on an original psychometric task of perception of affective 
valence. The patients who are recruited will have epilepsy which has been refractory to all 
treatment and require brain surgery. All subjects will be 18 years or older, have normal 
cognition, and will fit all inclusion and exclusion criteria. We will recruit 16 patients over 
2 years (ideally 8 males and 8 females). All patients will be recruited for Specific Aim 1, 
2A, and 2B. The study will be conducted exclusively on the Epilepsy Monitoring Unit of 
DHMC.  We will recruit patients with electrode in both the right and the left hemispheres. 
The type of electrodes implanted will be determined by the multidisciplinary team prior to 
the implant. This could include any FDA approved electrode and will be considered as a 
part of the standard implant procedure. 
 
Our study team will recruit patients with refractory epilepsy who are undergoing 
intracranial EEG for evaluation of possible epilepsy surgery. The study will be conducted 
in patients who do not have a diagnosis of aggression or PTSD, i.e. the aim is to use 
intracranial EEG in patient with epilepsy to understand amygdala physiology and cognitive 
effect of stimulation. At DHMC, the suitability of each patient with epilepsy for intracranial 
EEG and the location of implanted electrodes are determined by a multidisciplinary board 
several months prior to the procedure. As such, by far the most common brain regions 
implanted for clinical purposes are the amygdala and the hippocampus. Only patients with 
appropriate electrode locations for clinical purposes and who fulfill the inclusion and 
exclusion criteria will be enrolled in the study.  
 
All study procedures and tasks will be performed in the EMU and completed during the 
admission period. We will follow up with the participants a few months after discharge for 
a simple check in for any complications. 
 
Patients will not receive financial compensation for participation in the research. 
  

 
 
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14.0 Withdrawal of Subjects 
    
Electrographic seizures are common occurrences during electrical stimulation.  Clinical 
seizures are a rare but expected possible side effect of electrical stimulation.   
• If a patient continues to experience electrographic seizures despite maximum 
precaution with stimulation parameters (e.g. appropriate decrease of stimulation 
intensity), they will be withdrawn from the study. If changes of stimulation 
parameters are needed, these changes will fall within clinically-determined safety 
limits:10-200 Hz (Frequency), 0.1- 3 mA (Amplitude/Intensity), and 30-60 
microseconds (Pulse duration).  
• If they experience a single clinical seizure, the participant  will be approached for 
testing  some time later with new stimulation parameters (lower amplitude of 
stimulation), if judged to be appropriate. These changes will fall within clinically-
determined safety limits: 10-200 Hz (frequency), 0.1- 3 mA (Amplitude/Intensity), 
and 30-60 microseconds (Pulse duration). The participant (s) will be allowed to 
continue their participation in the study task on the same day if the PI or another 
qualified and delegated study staff determines that it is safe for the participant to do 
so. If a participant reports that the standardized emotional images are excessively 
disturbing, they will be excluded from participating in the study.  
 
15.0 Risks to Subjects 
 
Although all efforts will be taken to ensure safe stimulation parameters, untoward effects 
of electrical stimulation are the main potential risk to subjects. Risk of electrical stimulation 
includes seizures and stimulation-induced symptoms such as nausea or tingling. Patient 
will be warned about the potential risk of the stimulation prior to being enrolled in the 
study.  
 
We believe this risk will be minimal. Patients will reside in the Epilepsy Monitoring Unit 
for entire duration of the study. Electrical stimulation is used frequently in patients with 
intracranial electrodes for localization of eloquent cortex. As such, clinical and 
electrographic seizures induced by electrical stimulation for clinical purposes are common. 
Therefore, standard clinical practices exist to minimize the consequences of such seizures. 
These clinical practices include the presence of experienced physicians during stimulation, 
presence of seizure nurses, administration of rescue medication if necessary, etc. Any 

 
 
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seizures induced by stimulation will be handed by the standard protocols which already 
exist. 
• If stimulation produces subjective symptoms, alternate stimulation locations will 
be looked for.  
• If stimulation produces electrographic or clinical seizures, patient will be 
administered standard seizure treatment and per protocol of the Epilepsy 
Monitoring Unit.  
• If seizures or untoward effects occur, study PI or other physicians trained in 
epilepsy and seizure disorders will be available immediately to assist. 
 
The second potential risk to subjects is viewing of emotionally provoking images. The 
OASIS image set is composed of emotional images similar to PG-13 rated movies. 
Informed consent will be obtained from patients outlining exactly the type of images that 
patients will be viewing. The study will stop if the patient feels uncomfortable viewing any 
images. The PI will offer counseling to patients if any images produce negative effects.  
 
There is a slight risk of a breach of confidentiality; however every effort will be made to 
protect the identities of the participants and the confidentiality of the data. Study data will 
be kept on secure computers and accessible only to study staff.  Published results from the 
study will not include any identifying information. 
 
All symptoms will be assessed by qualified medical personnel throughout the participant’s 
stay in the EMU. However, for the purposes of this study, we will only record adverse 
events that occur during the study activities.  
 
 
16.0 Potential Benefits to Subjects 
We do not anticipate that knowledge gained in the study will have immediate benefits to 
patients who participate. This research may benefit patients with refractory psychiatric 
disorders. 
17.0 Data Management and Confidentiality 
 
The study will have several streams of data.  First, demographic data collected on patients.  
Second, behavioral data collected from the administered task.  Third, intracranial EEG 
data.   
 

 
 
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Behavioral data and demographics will be de-identified and exported following standard 
secure protocols to a study computer located at the Department of Neurology.  This 
computer will have standard hospital encryption and password protection.  Data from this 
computer will not be exported to other computers or sent over internet channels without 
appropriate secure protocols.  Access to this data will only be made available to the PI and 
other persons authorized by the study PI. De-identified data will be shared with NIH and/or 
NIMH data archive for use in future research. No patient identifiers will be included with 
this data sharing 
 
Intracranial EEG data will be de-identified and exported using secure methods to the 
analysis computer located in the Department of Neurology at DHMC.  This computer will 
have standard hospital encryption and password protection.  Data from this computer will 
not be exported to other computers or sent over internet channels without appropriate 
secure protocols.  Access to this data will only be made available to the PI and other persons 
authorized by the study PI. De-identified data will be shared with NIH and/or NIMH data 
archive for use in future research. No patient identifiers will be included with this data 
sharing 
 
The trial will be submitted to the ClinicalTrials.gov according to the specific timelines and 
will be compliant with the institutional policies. The trial will be published in appropriate 
clinical journal upon completion. 
 
Records will be retained for 10 years following publication of results from the study. 
 
18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects 
  
The study will be monitored by a physician who is not directly involved in the study, i.e. 
Independent Safety Monitor (ISM).   
 
• The physician chosen for this role will be a physician in the DHMC Department of 
Neurology who is not involved in the study and does not has a conflict of interest 
with this study (patent ownership, royalties, or financial gain greater than the 
minimum allowable by their institution, etc.) 
• The ISM will review the study protocol and confirm how the study will be 
monitored, including data points and the monitoring schedule.   

 
 
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• After each patient is enrolled, the PI will review the data from stimulation including 
any electrographic seizures, clinical seizures, and the any psychological impact of 
the study on the patient. These findings will be presented to the ISM on the schedule 
outlined below.    
• The ISM will monitor after the first two subjects complete the study protocol and 
then at intervals of every 6 months through study completion. 
• Serious Adverse Events will be reported to the IRB within 24 hours of study team 
awareness. Adverse events will be reported to the IRB annually and the ISM semi-
annually. 
• Unanticipated problems posing risks to subjects or others will be reported to the 
Dartmouth IRB using the form: “Unanticipated Problems Posing Risks to Subjects 
or Others Including Reportable Adverse Events” or as a written report of the event 
(including a description of the event with information regarding its fulfillment of 
the above criteria, follow-up/resolution and need for revision to consent form 
and/or other study documentation).  
 
Stopping rules  
The study will be stopped if it is determined that the stimulation parameters are inducing 
clinical seizures or undue subjective emotional phenomena.  If a seizure occurs with 
stimulation, the event will be recorded as an adverse event. The IRB will be notified of 
such adverse events annually and the ISM will be notified semi-annually. Stimulation 
parameters will be examined and adjusted as needed. If a change in parameters does not 
mitigate events, the study may be stopped for further evaluation.  
  
Risk mitigation 
This study involves two main risks to the patient.  
 
The first risk involves the images presented to the patient during the task.  The patient may 
find images from the OASIS picture set emotionally disturbing.   
• To mitigate this risk, patient will be warned and the nature of the images will be 
described in detail prior to presentation.  
• In addition, patient will be told that the images may be disturbing (e.g. “at worst as 
bad as an R rated movie”) and patient will be asked to communicate any discomfort 
with the investigators.   

 
 
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• Patient will be offered opportunity to stop taking part in the study if this occurs. 
• In the very unlikely case that study images produce severe emotional distress, the 
study PI and the hospital Behavioral Intervention Team (psychologist) will be 
available to discuss any discomfort.  
 
Second risk of the study involves the danger of induction of clinical seizures during 
electrical brain stimulation.  The PI of this study has participated in stimulation mapping 
of epilepsy patients since 2006 and has extensive experience in 100’s of patients.  
Stimulation parameters used for this study have been carefully researched and we believe 
will not produce unexpected effects.  The goal of the study is to use stimulation parameters 
designed to be of minimal risk in induction of seizures or production of any other 
unpleasant symptoms.  Despite these precautions it is still possible that a clinical seizure 
may occur during the administration of the task.  If stimulation parameters induce a clinical 
seizure: 
• The event will be reported as an adverse event, i.e. although seizures are not 
unexpected, every effort will be made to mitigate them.   
• The adverse event will be reported to the IRB annually and to the ISM semi-
annually.  The stimulation parameters for the event will be reviewed.   
• We will determine to best of our knowledge reasonable mitigation steps to prevent 
a second seizure from occurring.  
 
The entire study is conducted in the EMU, which is an inpatient unit at MHMH and 
therefore has 24-hour oversight from MD, APRN, and RN, which helps mitigate any risk. 
 
19.0 Provisions to Protect the Privacy Interests of Subjects 
 
All protected health information will be handled in a sensitive manner using standards of the D-
HH IRB. 
 
20.0 Compensation for Research-Related Injury 
N/A 
21.0 Economic Burden to Subjects 
Participants will not be charged to participate in this study. Their standard of care 
billing will not be affected by their participation in this study. 
 
22.0 Consent Process 

 
 
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Informed consent for participation in the study will be obtained prior to any study 
procedures. Commonly, this occurs at the time of clinic visit several weeks prior to the 
planned procedure. The consent will fully disclose the nature of the study, the nature of 
electrical stimulation and the risks associated with it, the nature of the images that will be 
presented. Consent for the study will be obtained exclusively by the PI. The study will 
involve patient > 18 years of age. 
Informed consent for participation in the study will be obtained following the SOP: 
Informed Consent Process for Research (HRP-090). Only patients who can consent for 
themselves will be enrolled. Cognitively impaired adults will not be enrolled. Women and 
minorities are not excluded from the study. The limiting factor in our study is our rural 
location and demographic outlay. We will recruit as many men as women and as many 
minorities or underrepresented communities as possible.  
23.0 Process to Document Consent in Writing 
We will be following SOP: Written Documentation of Consent (HRP-091).  
 
24.0 HIPPA Authorization Waiver 
 
HIPPA Waiver Authorization 
X    Waiver of HIPPA Authorization for recruitment 
 Waiver of HIPPA Authorization for study activities 
-or- 
   Alteration of HIPPA Authorization; not all required elements or statements are 
present 
 
1. The research could not practically be conducted without access to and use of PHI, nor 
without the alteration or waiver because such PHI is needed for recruitment purposes. 
While eligible participants will be referred to the study by their neurologist/epileptologist, 
participants’ health information is reviewed to determine an appropriate referral and 
collection of demographic data for the study. 
 
2.  As indicated in this protocol, there is a slight risk of a breach of confidentiality; however 
every effort will be made to protect the identities of the participants and the confidentiality 
of their PHI, including all data collected throughout the study. Study data will be kept on 
secure computers and accessible only to authorized personnel. De-identified data will be 

 
 
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shared with NIH and/or NIMH data archive for use in future research. No patient identifiers 
will be included with this data sharing. 
 
3. All data will be de-identified and kept on a secure computer and exported following 
standard secure protocols to a study computer located at the Department of Neurology. 
Only authorized personnel will have access to such data. De-identified data will be shared 
with NIH and/or NIMH data archive for use in future research. No patient identifiers will 
be included with this data sharing. 
 
4. The PHI will not be reused or disclosed to any other person or entity, except as required 
or permitted by law.  
 
25.0 Setting 
 
The study will be conducted in the inpatient EMU at DHMC enrolling patients with 
refractory epilepsy who are undergoing intracranial EEG for evaluation of possible 
epilepsy surgery. The study will be conducted in patients who do not have a specific 
psychiatric diagnosis, i.e., the aim is to use intracranial EEG in patients with epilepsy to 
understand amygdala electrophysiology and cognitive effect of stimulation. At our 
institution, the suitability of each patient with epilepsy for intracranial EEG and the 
location of implanted electrodes are determined by a multidisciplinary board several 
months prior to the procedure. As such, one of the most commonly implanted regions is 
the amygdala, and frequently also include the anterior insula, the dorsal anterior cingulate, 
the ventromedial prefrontal lobe, and the hippocampus.  
 
DHMC, a component of D–H, is New Hampshire’s only academic medical center in 
Lebanon; it includes a 396-bed hospital with the only Level 1 trauma center, and the only 
air ambulance service (DHART). The Lebanon medical center covers more than 2 million 
square feet. DHMC is composed of Mary Hitchcock Memorial Hospital (MHMH), 
originally founded in 1893, and The Hitchcock Clinic, which was founded in 1927, and is 
one of the largest multi-specialty group practices in New England. D–H employs 1,216 
physicians, as well as 500 advanced practice registered nurses and physician assistants, 
working in locations throughout New Hampshire and Vermont. DHMC is the primary 
teaching hospital for Geisel. It offers 49 accredited residency and fellowship graduate 
medical education training programs. Approximately 55% of the patients treated at DHMC 
live in New Hampshire and about 43% live in Vermont.  
 

 
 
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Department of Neurology has 62 faculty and advanced practice providers placed in nine 
teams covering all Neurological specialties. Most work is performed from the Lebanon, 
NH campus but there are also satellite practices in both New Hampshire and Vermont. The 
Department has recently expanded to include the first Neurology Intensive Care Unit at the 
medical center. Inpatient units are housed in the MHMH and outpatient offices are housed 
in the main building as well as the community health practice.  
 
The EMU is located in the hospital and is staffed by the epilepsy team at Dartmouth 
Hitchcock including residents and fellows. The unit monitors all patients with intracranial 
EEG and reads all recordings to determine epileptiform activity. This unit is often used for 
recruitment of study subjects including those with stimulation tasks.  
 
The Dartmouth-Hitchcock Epilepsy Center is the only level 4 epilepsy center in Northern 
New Hampshire, as recognized by the National Association of Epilepsy Centers (NAEC). 
Dartmouth-Hitchcock serves a rural population and covers the states of New Hampshire, 
Vermont and Maine for high-level comprehensive surgical epilepsy care. The center 
performs about 15 intracranial surgical procedures per year. The center is recognized for 
surgical care in neocortical epilepsy, responsive brain stimulation and basic and clinic 
research for cognitive impairment in epilepsy.  
 
The epilepsy center works closely with the Epilepsy Foundation of New England, the 
Epilepsy Foundation of Vermont as well as other community resource groups such as 
Outdoor Mindset to reach out to community and promote public education to eliminate the 
stigma of epilepsy. We address all aspects of epilepsy care and see approximately 1500 
unique epilepsy patients per year. All current epilepsy providers will be able to refer 
patients to the study.  
 
 
26.0 Resources Available 
 
Equipment 
For this study, we will purchase a BlackRock CereStim which has the necessary parameters 
to conduct this study. The Dartmouth College Research Computing facilities include: 
 
(1) a Dell Blade system consisting of 10-nodes, each of which consists of 2 quad-
core 2.6 GHz processors sharing 8G of RAM 

 
 
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(2) 32 dedicated processors sharing 16G of RAM on the campus-wide Discovery 
multi-processing environment at Dartmouth.  
 
All systems include MPI (message passing interface), parallel MATLAB and have 
processor-customized installations of LAPACK matrix algebra libraries. All desktops and 
servers to be used are connected to the DHMC network and are protected by the DHMC 
firewall. A 600+ node Beowulf cluster is available for shared use. 
 
 
 
Environment  
The research project leader has been provided research office space necessary for him to 
administratively oversee the completion of his research study as outlined in this 
application. He will have ample opportunity to engage the research community as well as 
collaborators through mentor meetings, research in progress meetings, journal club, and 
leadership symposium. Access to all the services at DH will provide him tools and 
resources to complete this project and expand his research knowledge. Collaboration with 
the Department of Psychology and Brain Sciences on the Dartmouth College campus will 
provide more opportunity to engage the neurosciences community more broadly and 
participate in all events.  
 
Computer  
All research personnel have assigned Lenovo ThinkPad Notebooks, which allow them to 
access patient medical records, IRB management systems, and to communicate effectively. 
All laptops are connected to secure network storage options. Dr. Bujarski uses SuperLab 6 
to program the stimulation tasks in his research studies. He also uses the FreeSurfer 
software program to assist with localizing the electrodes to the amygdala. Dr. Bujarski’ s 
computer is networked to the Natus EEG clinical acquisition system, the Epic electronic 
medical record, i2B2 cohort building software, RedCap patient database software, and 
TriNetX software program for deeper dive into patient data searches. Dr. Song uses 
BrainStorm installed on a signal processing computer. All computers have the Microsoft 
suite installed which is backed up and updated by information technology personnel in the 
medical center. High-speed connections will be used to access shared servers and database 
systems.  
 
Office  

 
 
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An office of around 125 square feet is located at DHMC. The office has space for desk, 
chairs, tables, and file storage as well as data ports to connect to the computer network and 
phone lines. Mentors will have office space adjacent to his and will have access to the 
common space for meeting with mentors and study personnel.  
 
Other  
Advanced Imaging Center (AIC) is a research resource created jointly by TSE, GSM, and 
DHMC in 2006 with infrastructure and equipment support from NIH and Philips that 
consists of 8,000 square feet of space and is directed by Dr. Paulsen. It houses two MRI 
suites, surgical prep space for animal procedures, patient exam rooms, small animal 
imaging systems, and distributed computational resources. Instrumentation includes a 
dedicated 3T MRI for whole body imaging (Philips Achieva 3.0T X-series), two microCT 
systems for in vivo small animal imaging and ex vivo specimen scanning (GE Biomedical 
eXplore Locus and eXplore Locus SP), and a microPET in vivo animal system (Philips 
MOSAIC). The AIC is physically adjacent to the Center for Surgical Innovation, and 
together, they create a contiguous space of 20,000 square feet prioritized for translational 
research that will be available to TPSI trainees. AIC is also home to clinical exam rooms, 
instrumentation development labs, and houses experimental systems undergoing clinical 
studies for breast, brain and prostate imaging and image-guidance. 
 
27.0 Multi-Site Research 
N/A 
  
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Anderson, A. K. and E. A. Phelps (2001). "Lesions of the human amygdala impair 
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