The Effects of Closed-loop TMS-EEG on Immediate Prefrontal Activity and Approach/Avoidance Behavior
Phase: NA
Conditions: Approach/Avoidance Behavior
Sponsor: University of Minnesota

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
VERSION DATE: 14/09/2024 
 
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PROTOCOL COVER PAGE 
 
Protocol Title 
Investigating the causal and phase-dependent role of 
prefrontal theta oscillations in approach/avoidance behavior 
Principal 
Investigator/Faculty 
Advisor 
Name: Alexander Opitz 
Department: Biomedical Engineering 
Telephone Number: 612-624-1094 
Email Address: aopitz@umn.edu 
Student 
Investigator 
Name: Ivan Alekseichuk 
Current Academic Status (Student, Fellow, Resident): 
 Researcher 
Department: Biomedical Engineering 
Telephone Number: 626-5004 
Institutional Email Address: ialeksei@umn.edu 
Name: Miles Wischnewski, PhD 
Current Academic Status (Student, Fellow, Resident): 
Postdoctoral Fellow 
Department: Biomedical Engineering 
Telephone Number: N/A 
Institutional Email Address: mwischne@umn.edu 
Name: Sina Shirinpour, PhD 
Current Academic Status (Student, Fellow, Resident): 
Postdoctoral Fellow 
Department: Biomedical Engineering 
Telephone Number: N/A 
Institutional Email Address: shiri008@umn.edu 
Name: Zachary Haigh 
Current Academic Status (Student, Fellow, Resident): 
Student 
Department: Biomedical Engineering 
Telephone Number: N/A 
Institutional Email Address: haigh066@umn.edu 
Name: Nipun Perera 
Current Academic Status (Student, Fellow, Resident): 
Student 
Department: Biomedical Engineering 
Telephone Number: N/A 
Institutional Email Address: perer038@umn.edu 
Name: Jonna Rotteveel 
Current Academic Status (Student, Fellow, Resident): 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
VERSION DATE: 14/09/2024 
 
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Research Assistant 
Department: Biomedical Engineering 
Telephone Number: 612-626-1118 
Institutional Email Address: jrotteve@umn.edu 
Name: Taylor Berger 
Current Academic Status (Student, Fellow, Resident): 
Graduate student 
Department: Biomedical Engineering 
Telephone Number: N/A 
Institutional Email Address: berg2944@umn.edu  
Name: Da Som Choi 
Current Academic Status (Student, Fellow, Resident): 
Graduate student 
Department: Biomedical Engineering 
Telephone Number: N/A 
Institutional Email Address: choi0908@umn.edu 
Scientific 
Assessment 
I believe Scientific Assessment is not required. 
IND/IDE # (if 
applicable) 
N/A 
IND/IDE Holder 
N/A 
Investigational Drug 
Services # (if 
applicable) 
N/A 
Version 
Number/Date: 
1.4 from 14/09/2024 
 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
VERSION DATE: 14/09/2024 
 
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ANCILLARY REVIEWS 
DO NOT DELETE.  Submit the completed checklist below with your protocol. 
Which ancillary reviews do I need and when do I need them? 
Refer to HRP-309 for more information about these ancillary reviews. 
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no 
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If yes… 
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IRB Review 
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Include Gillette resources, staff 
or locations 
Gillette Scientific review and Gillette 
Research Administration approval is 
required.  Contact: 
research@gillettechildrens.com   
Required 
prior to IRB 
submission 
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☒ No 
 
Involve Epic, or Fairview 
patients, staff, locations, or 
resources? 
The Fairview ancillary review will be 
assigned to your study by IRB staff 
Contact: ancillaryreview@Fairview.org 
Approval 
must be 
received 
prior to IRB 
committee/ 
designated 
review.   
 
Consider 
seeking 
approval 
prior to IRB 
submission. 
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☒ No 
 
Include evaluation of drugs, 
devices, biologics, tobacco, or 
dietary supplements or data 
subject to FDA inspection? 
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assigned to your study by IRB staff 
Contact: medreg@umn.edu  
 
See: 
https://policy.umn.edu/research/indide  
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sure? See guidance in the 
Investigator Manual (HRP-
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(x-ray imaging, 
radiopharmaceuticals, external 
beam or brachytherapy) 
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Application and follow instructions on 
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Approval 
from these 
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received 
prior to IRB 
approval;  
 
These 
groups 
each have 
their own 
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Use the Center for Magnetic 
Resonance Research (CMRR) 
or MR at Masonic Institute for 
the Developing Brain (MIDB) 
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Include the use of 
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eprotocol.umn.edu 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
VERSION DATE: 14/09/2024 
 
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nucleic acids, toxins, or 
infectious agents? 
application 
process.  
☐ Yes 
☒ No 
 
Include the use of human fetal 
tissue, human embryos, or 
embryonic stem cells? 
Contact OBAO for submission 
instructions and guidance 
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☒ No 
 
Include PHI or are you 
requesting a HIPAA waiver? 
If yes, HIPCO will conduct a review of 
this protocol. 
Contact: privacy@umn.edu  
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Use data from CTSI Best 
Practices Integrated 
Informatics Core (BPIC)  
Formerly the AHC Information 
Exchange (IE)? 
The Information Exchange ancillary 
review will be assigned to your study by 
IRB staff 
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received 
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approval. 
 
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groups do 
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process but 
additional 
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study team 
may be 
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Pham0435@umn.edu 
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ETHOS, the OnCore ancillary review will 
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Contact: oncore@umn.edu  
Does not 
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approval. 
 
 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
VERSION DATE: 14/09/2024 
 
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REVISION HISTORY 
 
Revision # 
Version Date 
Summary of Changes 
Consent Change? 
1.3 
07/18/2023 
New study member; two 
experimental conditions (active 
and sham) are now performed 
intermittently in blocks during the 
same experimental session. 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
VERSION DATE: 14/09/2024 
 
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Table of Contents 
 
1.0 
Objectives 
8 
2.0 
Background 
8 
3.0 
Study Endpoints/Events/Outcomes 
9 
4.0 
Study Intervention(s)/Investigational Agent(s) 
9 
5.0 
Procedures Involved 
10 
6.0 
Data and Specimen Banking 
14 
7.0 
Sharing of Results with Participants 
15 
8.0 
Study Population 
15 
9.0 
Vulnerable Populations 
16 
10.0 
Local Number of Participants 
18 
11.0 
Local Recruitment Methods 
18 
12.0 
Withdrawal of Participants 
19 
13.0 
Risks to Participants 
19 
14.0 
Potential Benefits to Participants 
21 
15.0 
Statistical Considerations 
22 
16.0 
Health Information and Privacy Compliance 
23 
17.0 
Confidentiality 
26 
18.0 
Provisions to Monitor the Data to Ensure the Safety of Participants 
26 
19.0 
Provisions to Protect the Privacy Interests of Participants 
27 
20.0 
Compensation for Research-Related Injury 
27 
21.0 
Consent Process 
28 
22.0 
Setting 
28 
23.0 
Multi-Site Research 
29 
24.0 
Coordinating Center Research 
29 
25.0 
Resources Available 
29 
26.0 
References 
30 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
VERSION DATE: 14/09/2024 
 
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ABBREVIATIONS/DEFINITIONS 
• 
(DL)PFC – (dorsolateral) prefrontal cortex 
• 
Ap/Av – approach/avoidance 
• 
EEG – electroencephalography 
• 
MEP – motor evoked potential 
• 
MR(I) – magnetic resonance (imaging) 
• 
TEP – transcranial magnetic stimulation-evoked potential 
• 
TMS – transcranial magnetic stimulation 
 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
VERSION DATE: 14/09/2024 
 
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1. 
Objectives 
1.1. Purpose: 1.1.1. to evaluate the causal link between the phase of ongoing 
theta oscillations in the prefrontal cortex and approach/avoidance (Ap/Av) 
behavior in healthy adults using phase-specific transcranial magnetic 
stimulation (TMS); 1.1.2. to investigate the electroencephalographic (EEG) 
brain responses during the Ap/Av test to TMS at peak vs. trough phases of 
ongoing prefrontal theta activity. 
 
2. Background 
2.1. Significance of Research Question/Purpose: Approach/avoidance (Ap/Av) 
behavior is a reliable marker of the emotional processes in the human 
brain (Corr & McNaughton, 2012; Bramson et al., 2020; Rolle et al., 2021). 
It presents scientific and clinical interest as a robust predictor of emotional 
disorders, such as depressive disorder (McDermott et al., 2021; Ironside et 
al., 2020; Ottenbreit et al., 2014). Ap/Av behavior can be measured in 
healthy adults using standardized computer tests. Although existing 
scientific studies found a correlation between the Ap/Av behavior and 
ongoing theta activity (3-7 Hz) in the left dorsolateral prefrontal cortex 
(DLPFC), the causal evidence of the phase-dependent role and strength of 
association between the prefrontal theta oscillations and Ap/Av behavior is 
missing. Recent advances in probing brain function using closed-loop 
transcranial magnetic stimulation with concurrent electroencephalography 
(TMS-EEG) made it possible to monitor the ongoing theta activity during 
the Ap/Av test and stimulate the theta rhythm at its specific phase 
(Shirinpour et al., 2020; Gordon et al., 2022). The phase of theta rhythm is 
important because it tracks the ongoing excitability of the brain region. The 
peaks of the oscillation indicate the most excitable time and the trough - 
the least excitable (Anastassiou et al., 2011; Anastassiou et al., 2015). We 
can monitor the excitability of theta activity in real-time non-invasively 
using EEG. Thus, we now can use the TMS-EEG system to probe the state of 
DLPFC during the Ap/Av test at the peaks vs. troughs of theta rhythm and 
examine the precise causal role and strength of association between the 
theta oscillations and Ap/Av behavior. These data will provide novel 
understanding of the mechanisms of emotional processing in human brain 
and, thus, emotional health. 
 
2.2. Preliminary Data: We have developed a real-time TMS-EEG system which 
can continuously monitor the prefrontal theta rhythm (3-7 Hz) and trigger 
TMS pulses at specific phases with high accuracy. Our system has been 
validated in computational simulations and in proof-of-concept study in 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
VERSION DATE: 14/09/2024 
 
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healthy adults (Shirinpour et al., 2020). Recently, our real-time TMS-EEG 
system was used to investigate the phase-specific role of ongoing 
oscillations in motor cortex in adult participants, demonstrating robust 
performance and no unexpected side effects (Wischnewski et al., 2022). 
 
2.3. Existing Literature: The combined application of TMS and EEG has 
established itself as a potent tool to probe and measure the causality of 
brain activity. It allows to accurate capture brain responses to the 
perturbation at specific times relative to the ongoing brain processes or 
cognitive tasks (Rogasch et al., 2016; Rogasch and Fitzgerald, 2013; Zrenner 
et al., 2016). Further, several recent studies have investigated the brain 
neurophysiology using real-time TMS-EEG for probing neural oscillations at 
different phases (Shirinpour et al., 2020; Schaworonkow et al., 2018; 
Zrenner et al., 2017). Our lab developed a novel closed-loop algorithm with 
higher accuracy compared to previous methods (Shirinpour et al., 2020). 
We recently applied the novel system to test the role of ongoing beta and 
mu oscillations in the motor cortex in healthy adults (Wischnewski et al., 
2022). Moreover, the initial efforts to utilize real-time TMS-EEG for probing 
prefrontal activity and link between the prefrontal theta and cognition 
showed effectiveness and safety of such approach (Gordon et al., 2022). 
 
3. Study Endpoints/Events/Outcomes 
3.1. Primary Endpoint/Event/Outcome: The approach/avoidance test measures 
(reaction times to positive and negative emotional stimuli) during 
concurrent probing of ongoing prefrontal theta oscillations at peaks vs. 
troughs using TMS. 
 
3.2. Secondary Endpoint(s)/Event(s)/Outcome(s): TMS-evoked potentials (TEPs) 
in concurrent EEG during the approach/avoidance test. 
 
4. Study Intervention(s)/Investigational Agent(s) 
4.1. Description: A TMS machine (MagVenture® X100 or MagStim® Rapid2) will 
be used to noninvasively stimulate the brain via a figure-8 coil. Both 
machines have FDA 510(k) clearance for several clinical indications, 
including major depressive disorder. They are developed and 
manufactured in accordance with Quality System Regulation 21 CFR 820. 
EEG will be recorded before, after, and during the whole experimental 
session using a 24-bit, battery-driven, amplifiers actiCHamp/actiCHamp 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
VERSION DATE: 14/09/2024 
 
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Plus (BrainProducts®) with the active electrode actiCap or equivalent 
(BrainProducts®). Electrooculography and heart rhythm will be recorded 
together with EEG using non-invasive sensors from BrainProducts® or 
equivalent. 
 
4.2. Drug/Device Handling: The TMS device will be stored in our laboratory in (i) 
Nils Hasselmo Hall, 312 Church St SE, University of Minnesota or (ii) 
Phillips-Wangensteen Building, 516 Delaware St SE, University of 
Minnesota. In addition, (iii) the space of the Non-invasive 
Neuromodulation Laboratory at the University of Minnesota Twin Cities 
Campus located at 717 Delaware St SE can be used. Only authorized 
personal will have accesses to the room. Application of the stimulation will 
follow the guidelines for TMS from the International Federation of Clinical 
Neurophysiology (Rossi et al., 2021). 
 
4.3. Biosafety: This study does not involve biological materials. 
 
4.4. Stem Cells: This study does not involve stem cells. 
 
4.5. Fetal Tissue: This study does not involve fetal tissues. 
 
 
5. Procedures Involved 
5.1. Study Design: Up to 26 healthy adult volunteers will be recruited for 
participation in this randomized crossover study. The study will consist of 
up to three sessions – the first session using magnetic resonance imaging 
(MRI) session and subsequent sessions with transcranial magnetic 
stimulation and concurrent electroencephalography (TMS-EEG). Informed 
consent for all study procedures and initial questionaries will be obtained 
before the first session. The 3T MRI scan will provide accurate prefrontal 
cortex anatomy for using neuronavigation for TMS. During the TMS-EEG 
sessions, we will first identify individual TMS intensity of motor threshold 
by recording motor evoked potentials. The stimulation will then be applied 
with an intensity of up to 120% of the resting motor threshold (which is a 
safe and common practice; Rossi et al., 2021). The intensity can be 
decreased for individual participants. Two TMS-EEG conditions – verum 
and sham, will occur in intermittent blocks in randomized order, and 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
VERSION DATE: 14/09/2024 
 
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volunteers will be blinded to the conditions. During each session, 
volunteers will first perform a task training and a short (approx. 5 min) 
block of the approach/avoidance task (Ap/Av) without TMS to record 
intrinsic EEG activity and use it for calibrating the real-time TMS-EEG 
system (Shrinpour et al., 2020). Then, volunteers will perform 8 main 
blocks of approach/avoidance tasks with TMS (approx. 6 minutes per block) 
in randomized order: 1. congruent task + TMS at theta peaks, 2. congruent 
task + TMS at theta troughs, 3. incongruent task + TMS at theta peaks, and 
4. incongruent task + TMS at theta troughs. During each task trial, the 
volunteer will receive a single burst of TMS (up to three pulses) at the peak 
or trough of ongoing theta rhythm. In the verum TMS-EEG condition/block, 
we will apply TMS pulses over the left DLPFC based on the left DLPFC theta 
oscillations. In the sham condition/block, TMS will be applied over the head 
vertex (which should not induce changes in the prefrontal activity but will 
induce the same sensory effects). EEG will be recorded throughout the 
TMS-EEG sessions. In addition, electrooculography and heart rate will be 
recorded together with EEG using non-invasive sensors for the accurate 
removal of ocular and cardiac artifacts. There will be 3-5 min breaks in-
between the blocks for rest. The total number of TMS pulses per day will 
not exceed 3,000 pulses, many times lower than the established safety 
limit of 90,000 pulses per day (Cole et al., 2022, 2020). 
 
Diagram 1: Experimental pipeline with timing. 
5.2. Study Procedures:  
5.2.1. Initial questionaries: during the initial visit, each volunteer will fill 
out standardized self-reported questionaries regarding their 
demographic data and emotional assessment. These include the 
Patient Health Questionnaire (PHQ-9), General Anxiety Disorder 
(GAD-7) tool, and Quick Inventory of Depressive Symptomatology – 
Self-Rated (QIDS-SR-16). Total time necessary to complete all 
questionaries is approx. 25 minutes. 
5.2.2. MRI: During the first session, 3T MRI scans will be performed at the 
Center for Magnetic Resonance Research (CMRR). Participants will 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
VERSION DATE: 14/09/2024 
 
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lay in the supine position within the scanner and be asked to relax. 
T1 and T2-weighted images will be collected to provide anatomical 
models for neural navigation during TMS. In addition, diffusion 
tensor imaging will be collected to assess structural connectivity of 
the prefrontal cortex, and BOLD fMRI contrast will be collected 
during the resting state to assess functional connectivity. All 
imaging modalities will follow standard Human Connectome Project 
(HCP) protocols (Harms et al., 2018), as routinely used in CMRR. 
Overall scanning time will be under one hour. 
5.2.3. The approach/avoidance (Ap/Av) test: In the Ap/Av task, during 
each task trial, the volunteer sees on the screen a human face with 
either positive emotion (happiness, joy), negative emotion (anger, 
fear), or neutral emotion (Figure 1). During the congruent condition, 
the volunteer has to pull a joystick towards themself when they see 
a face with positive emotions and push away when they see 
negative emotions. In the incongruent condition, the responses 
with a joystick are the opposite. Neutral emotional stimuli require 
no response. When a joystick is pulled, the image become larger on 
the screen (imitating approach), when a joystick is pushed away – it 
become smaller (imitating avoidance). The reaction times to the 
stimuli and reaction time difference between the congruent and 
incongruent conditions constitute the primary test outcomes. We 
will perform four task blocks (approx. ten minutes each): two with 
congruent conditions and two with incongruent. The emotional 
stimuli are taken from publicly available, scientifically validated 
databases of emotional facial expressions, including Karolinska 
Directed Emotional Faces (KDEF; Lundqvist et al., 1998) and 
AffectNet (Mollahosseini et al., 2017). All stimuli can legally be used 
and redistributed for research purposes. The task presentation PC 
will be synchronized with the EEG amplifier and TMS machine using 
TCP/IP, UDP, and/or TTL protocols. Total time per session is 4 blocks 
of approx. 10 minutes, with approx. 5 minutes breaks in between. 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
VERSION DATE: 14/09/2024 
 
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Figure 1. Overview of a single experimental TMS-EEG session. 
5.2.4. TMS – motor threshold: To individualize the stimulation intensity 
before every TMS-EEG session, we will apply single-pulse 
stimulation to the motor hotspot for the FDI muscle in the left 
motor cortex (M1). The volunteer will be asked to relax his right 
hand. The lowest intensity at which 3 out of 6 pulses result in the 
motor evoked potential will be considered a resting motor 
threshold. This step will take approx. 15 minutes to perform.  
5.2.5. TMS – experiment: During the Ap/Av test, we will apply single 
bursts of TMS (up to three pulses) every task trial at either peak or 
trough of prefrontal theta oscillation. The theta signal will be 
recorded in the frequency band from 3 to 7 Hz from the AF3/F3 
electrodes (according to the international 10-10 convention) using a 
Laplacian electrode-montage. The stimulation will be applied with 
the intensity of up to 120% of the resting motor threshold (which is 
a safe and common practice; Rossi et al., 2021). The intensity can be 
decreased for individual participants. In the verum TMS-EEG 
condition, we will apply TMS pulses over the left DLPFC based on 
the left DLPFC theta oscillations (Figure 2). In the sham condition, 
TMS will be applied over the head vertex (which should not induce 
changes in the prefrontal activity but will induce the same sensory 
effects). In total, 8 task/stimulation blocks will be performed per 
session, each approx. 6 minutes long with 1 burst of TMS every 2-6 
seconds (= every task trial). Stimulation will be performed by the 
investigators listed in the present protocol after safety and 
application training by the principal investigator and under his 
oversight. TMS stimulation will follow the guidelines of the 
International Federation of Clinical Neurophysiology (Rossi et al., 
2021). 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
VERSION DATE: 14/09/2024 
 
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5.2.6. Physiological recordings: EEG will be recorded throughout the 
whole experimental session at a high sampling rate (≥ 1,000 Hz) 
using a 24-bit amplifier with active electrodes and electrode caps of 
appropriate size. No hardware filtering will be used. 
Electrooculography and heart rhythm will be recorded together 
with EEG using non-invasive sensors synchronized with the EEG 
acquisition. 
5.2.7. Post-session questionary: At the end of every session the volunteer 
will be asked to fill out a written standardized questionnaire 
regarding the possible adverse effects of the stimulation procedures 
(Rossi et al., 2021). 
 
5.3. Study Duration: Before the first session, we will have an introductory 
meeting with volunteers at which point we will schedule sessions. The first 
session (3T MRI) will last approximately 2 hours, including up to 1 hour of 
MRI acquisition time. The TMS-EEG session will last up to 3-4 hours, 
including initial training and 8 blocks of approx. 6 minutes each of task and 
single-burst TMS. Thus, we anticipate that each volunteer will complete the 
three sessions in 1-3 weeks. We anticipate that we will complete the study, 
including data analysis, within two years of the first session. 
 
5.4. Individually Identifiable Health Information: We will collect personal 
information from volunteers (name, age and date of birth, biological sex at 
birth, date of enrollment, phone number, and email) as well as biomedical 
data (EEG, MRI, questionaries). Additionally, records of inclusion and 
exclusion criteria will be recorded. All biomedical data will be deidentified. 
 
5.5. Use of radiation: The participants of this study will not be exposed to 
radiation. 
 
5.6. Use of Center for Magnetic Resonance Research: During the first session of 
this study, we will collect anatomical and resting-state functional images in 
a 3T MRI scanner at the CMRR. These images will provide a precise location 
of the left dorsolateral prefrontal cortex (DLPFC) and allow us to use 
neuronavigation during our TMS experiments. 
 
6. Data and Specimen Banking 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
VERSION DATE: 14/09/2024 
 
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6.1. Storage and Access: Informed consent and paper questionaries will be 
safely secured under lock and key, and a backup copy will be saved on Box 
(box.umn.edu). Experimental data (MRI, EEG, questionaries, test measures) 
will be saved on Box and used for data analysis; additionally, backup copies 
will be stored on an encrypted external hard drive (also stored under lock 
and key). Access to Box is limited to the researchers involved in this study. 
These data will be destroyed after 6 years. In line with recent requirements 
of scientific journals and the National Institute of Health, preprocessed and 
anonymized data will be made available for the research community using 
a community-supported public repository. Data can be put in open 
repositories Zenodo (zenodo.org) and National Institute of Mental Health 
Data Archive (NDA), where it can remain for up to 20 years. 
 
6.2. Data: The MR images, EEG, questionaries, and task data will be 
preprocessed to comply with Health Information Privacy & Compliance 
Office (HIPCO) standards for a de-identified dataset. We will remove all 
information about volunteers except their age (in years), handedness, and 
biological sex. 
 
6.3. Release/Sharing: Full or partial access to the raw data will be provided 
upon the request to the faculty / research staff of recognized research, 
medical, and educational institutions for educational and scientific 
purposes. The request should be sent via an institutional email and will be 
stored with the study materials. The request should include a short 
description of the scientific or educational aims. Access is the subject of 
approval by the principal investigator. De-identified data related to the 
scientific publications can be stored in a public repository. 
 
7. Sharing of Results with Participants 
7.1. Sharing Results: The data collected in this study (MRI, EEG, task measures, 
and questionaries) will not be shared with participants. In the case of 
concerning results, the volunteer will be advised to contact their physician. 
 
7.2. Sharing Genetic Results: N/A 
 
8. Study Population 
8.1. Inclusion Criteria:  
• Age between 18 and 65 years old. 
• Stated willingness to participate and comply with all study procedures. 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Investigating the causal and phase-dependent role of prefrontal 
theta oscillations in approach/avoidance behavior 
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• Stated availability for the duration of the study. 
• Confident level of English language proficiency. 
 
8.2. Exclusion Criteria:  
• Chronic health condition that requires pharmacological treatment over 
the course of study participation. 
• History or evidence of seizures, chronic neurological or mental disorder. 
• Pregnancy or breastfeeding. 
• History or evidence of alcohol or drug addiction.  
• Metallic or electric implant in the head, neck, or chest area, or otherwise 
MRI-noncompatible implants. 
• History of metalwork. 
 
8.3. Screening: Initial screening will be conducted prior the study by the 
investigator who will ensure that the volunteer read and understood the 
consent and study forms. The investigator will explain the study protocol, 
inclusion and exclusion criteria, foreseeable risks, withdraw process, and 
compensation scheme. The volunteers will be asked to fill out the 
standardized questionnaire to assess that they meet the study criteria. 
 
8.4. Lifestyle Considerations: Participants will be asked to abstain from alcohol 
for 24 hours prior to every visit. Additionally, participants will be asked to 
abstain from nicotine-, caffeine-, and xanthine-containing products for 4 
hours prior to every visit. 
 
9. Vulnerable Populations 
9.1. Vulnerable Populations:  
Population / Group 
Identify whether any of the 
following populations will be the 
focus of the research (targeted), 
included but not the focus of the 
research or excluded from 
participation in the study.  
Children 
Excluded 
Pregnant women/fetuses/neonates 
Excluded 

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Prisoners 
Excluded 
Adults lacking capacity to consent 
and/or adults with diminished 
capacity to consent, including, but 
not limited to, those with acute 
medical conditions, psychiatric 
disorders, neurologic disorders, 
developmental disorders, and 
behavioral disorders 
Excluded 
Non-English speakers 
Excluded 
Those unable to read (illiterate) 
Excluded 
Employees of the researcher 
Excluded 
Students of the researcher 
Excluded 
Undervalued or disenfranchised 
social group 
included but not the focus 
Active members of the military 
(service members), DoD personnel 
(including civilian employees) 
included but not the focus 
Individual or group that is 
approached for participation in 
research during a stressful situation 
such as emergency room setting, 
childbirth (labor), etc. 
Excluded 
Individual or group that is 
disadvantaged in the distribution of 
social goods and services such as 
income, housing, or healthcare. 
included but not the focus 
Individual or group with a serious 
health condition for which there are 
no satisfactory standard treatments. 
Excluded 
Individual or group with a fear of 
negative consequences for not 
participating in the research (e.g. 
Excluded 

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institutionalization, deportation, 
disclosure of stigmatizing behavior). 
Any other circumstance/dynamic 
that could increase vulnerability to 
coercion or exploitation that might 
influence consent to research or 
decision to continue in research. 
Excluded 
 
9.2. Additional safeguards, if any, to ensure inclusion is appropriate: Students 
and others who directly work in the Principal Investigator's lab will be 
excluded from participation. 
 
9.3. If research holds prospect for direct benefit to participants, provide 
justification for any exclusions indicated in the table above: N/A 
 
10. Local Number of Participants 
10.1. Local Number of Participants to be Consented: We estimate that a sample 
size of 26 volunteers will allow us to reach the primary endpoints of this 
study, corresponding to medium effect size, based on previous research 
(Shirinpour et al., 2020; Gordon et al., 2022). 
 
11. Local Recruitment Methods 
11.1. Recruitment Process: Recruitment poster will be posted publicly 
throughout the Twin Cities campus of the University of Minnesota. 
 
11.2. Identification of Potential Participants: The potential participant will 
contact the investigators in this study via the institutional email provided in 
the recruitment poster. 
 
11.3. Recruitment Materials: An advertisement will be posted on advertisement 
boards in numerous buildings on the Twin Cities campus. The flyer will 
include a brief description of the study, experimental procedures, 
monetary compensation, summary of inclusion/exclusion criteria, and an 
institutional contact email. 

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11.4. Payment: The volunteers will receive a monetary compensation at the end 
of the session. The base rate of compensation is $15 per hour. We will use 
the Greenphire ClinCard system to process and track payments. 
 
12. Withdrawal of Participants 
12.1. Withdrawal Circumstances: The participant will be removed from the study 
in the following cases: (1) repeated non-appearance for experimental 
session; (2) repeated violation of the lifestyle considerations; (3) 
disrespectful behavior towards the investigators and university staff; (4) 
stated willingness of the volunteer to discontinue participation; (5) any 
legal or medical reasons for the volunteer to discontinue participation. 
 
12.2. Withdrawal Procedures: Following participant withdrawal, the volunteer 
will receive payment for their participation at the rate described in point 
11.4 according to the time spent in the study, if any. The incomplete data 
will be retained. Separately, a dedicated document with the description of 
withdrawal circumstance will be added by the principal investigator to the 
folder with study materials. No partial withdrawal is stipulated by this 
study protocol. 
 
12.3. Termination Procedures: Following the final study procedures, the 
volunteer will receive payment (point 11.4) and the data will enter the 
dataset for further analysis. 
 
13. Risks to Participants 
13.1. Foreseeable Risks:  
13.1.1. MRI machines use a strong magnet and radiofrequency magnetic fields to 
take images of your body. The scanning process is similar to an x-ray or 
CT scan, but MRI does not use ionizing radiation (high-energy radiation 
that can potentially cause damage to DNA) like x-rays or CT scans. The 
risks associated with MRI scans are:  
Projectiles:  Objects with magnetic properties can be pulled into the 
magnet and turn into projectiles. To minimize this risk, we ask that 
subjects remove all metallic items (watches, cell phones, hair pins, etc.) 
prior to entering the scanner and by controlling access to the scanner.   

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Claustrophobia:  The scanner is a long narrow tube that may cause some 
people to feel claustrophobic.  
Hearing damage:  The noise generated by the operation of the scanner 
during a study is loud enough to cause hearing damage if you do not 
wear hearing protection. Hearing protection is required and is provided 
by the investigator.  
Nerve stimulation:  Some people experience localized tingling, twitching, 
or muscle contractions during MRI scans. This is expected, but if it is 
uncomfortable, participants will be asked to notify the investigator. 
Disruption of devices:  Some devices can be damaged by magnetic fields 
and should not be brought into the scanner room. This includes some 
implanted devices such as pacemakers, cochlear implants, insulin pumps, 
nerve stimulators, etc. Participants will be screened for implanted devices 
per the CMRR procedures. 
Heating of devices:  The radiofrequency waves used in MRI can heat 
conductive materials such as metal implants (screws, plates, rods, wires, 
artificial joints, etc.), certain tattoo inks, certain clothing fabrics, jewelry, 
medication patches, wigs, etc. Participants will be asked to remove these 
items if possible. If they cannot be removed, they will be asked to provide 
more information to allow MRI staff to be able to make determination on 
the safety of proceeding with the scan.  
A thorough pre-scan questionnaire will allow us to minimize the risk of 
device disruption and heating. Subjects will be in constant contact with 
the investigator and should notify the investigator immediately, via the 
squeeze ball, if they notice anything unusual, become claustrophobic, 
think that the hearing protection is not adequate, or if nerve stimulation 
becomes uncomfortable. In addition, there is a risk of unknown effects 
related to participation in MRI research. Long-term effects of exposure to 
high magnetic fields are unknown. Most people experience no short-term 
ill effects from the strong magnetic field, but some people report 
dizziness, mild nausea, headache, a metallic taste in their mouth, or 
sensations of flashing lights. These symptoms, if present, subside shortly 
after leaving the magnet. If any sensations experienced during 
participation cause discomfort or pain, subjects will be instructed to 
notify the researcher immediately and the subject will be taken out of the 
magnetic field. 
13.1.2. TMS is FDA approved for drug-resistant depression, obsessive-compulsive 
disorder, and smoking addiction. It is a widely used technique with 
minimal risk, and there is no evidence that the procedure is harmful if 

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appropriate guidelines are followed. To protect participants from 
possible risks, we will do as follows:  
Head and neck aches: Minimize TMS intensity and avoid sensitive areas 
of scalp muscles and nerves to avoid head and neck aches. 
Transient hearing changes: Earplugs will be offered to subjects and 
investigators during TMS to prevent transient hearing shifts caused by 
TMS. 
Seizures: Screening and enrollment procedures will exclude subjects for 
whom TMS is contraindicated, those who are at increased risk of seizure, 
or those for whom the potential consequences of a seizure are increased. 
The informed consent process will note the potential risk of seizures. 
There is no evidence that a TMS-induced seizure increases the risk of 
having a second seizure in an otherwise healthy individual. In all lab 
spaces, we have a plan of action in place in the case of a seizure (based 
on NIH recommendations) as follows: 
1. Roll the person on their side to prevent them from choking on fluids 
or vomit. 
2. Cushion the individual’s head. 
3. Loosen any tight clothing around the neck. 
4. Do not restrict the person from moving or wandering unless they are 
in danger. 
5. Do not put anything in the person’s mouth – it can cause choking and 
trauma. 
6. Remove any dangerous objects the person might hit or walk into 
during the seizure. 
7. Call 911. 
8. Note how long the seizure lasts and what symptoms occurred then 
report this information to emergency personnel. 
9. Stay with the person until the seizure ends and emergency personnel 
arrive and take over. 
 
13.2. Reproduction Risks: No reproduction risks of TMS have been previously 
reported or suggested in the literature. 
 
13.3. Risks to Others: No risks to others during or after TMS have been 
previously reported or suggested in the literature. 
 
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14.1. Potential Benefits: There are no direct benefits for the participant in this 
study. 
 
15. Statistical Considerations 
15.1. Data Analysis Plan: We will analyze reaction times from the Ap/Av test 
using Hierarchical Bayesian Drift Diffusion Models (HDDM). This model is 
optimal for two alternative forced-choice cognitive tasks. It estimates 
single-trial performance in the presence of various sources of noise and 
trial-by-trial variations. The model will take reaction times as inputs and 
recover the variables of interest – speed of evidence accumulation (drift 
rate) and the decision thresholds for responding to the stimuli of positive 
and negative valence.  
EEG from the stimulation and task periods will first be preprocessed. We 
will exclude noisy trials and interpolate noise channels, bandpass filter the 
signals (0.2-80 Hz) using Butterworth noncausal filters, suppress the line 
noise, and clean the data with extended InfoMax ICA. After preprocessing 
and artifact suppression, we will epoch the data around the TMS pulses, 
and calculate the TMS-evoked potentials in the left DLPFC caused by the 
stimulation at the peak and trough of theta oscillations. 
 
15.2. Power Analysis: We estimated that medium effect size of Cohen’s d = 0.5, 
which was observed in comparable studies (Shirinpour et al., 2020; Gordon 
et al., 2022), will be reached with a sample size of 26 volunteers. 
 
15.3. Statistical Analysis:  The HDDM parameters will be compared between the 
conditions using Generalized Linear Mixed-Effect Models (GLMM) with 
model outcomes as dependent variables, stimulation conditions (real vs 
control and peaks vs trough) as categorical independent variables, and 
participant IDs as a nuance variable. Further, post-hoc pairwise 
nonparametric tests will be applied between the conditions. Latency and 
magnitude of TMS-evoked potentials (TEPs) will be comparted between the 
conditions using nonparametric cluster-based permutation test with false 
discovery rate correction for number of comparisons. Outcomes of TEPs 
and behavioral analysis will be correlated using Spearman statistics. 
 
15.4. Data Integrity: Raw data and corresponding log files will be examined by 
the principal investigator on a regular basis during the data collection 
stage. The automatic log files will be generated automatically by the 
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with the experimental lab journal. We will control the integrity of EEG data 
by checking the input impedance on the recording electrodes before and 
after each session, and by analyzing the signal-to-noise ratio in the raw 
data. 
 
16. Health Information and Privacy Compliance 
16.1. 
Select which of the following is applicable 
to your research: 
☑ My research does not require access to individual health information.   
☐ I am requesting that all research participants sign a HIPCO approved 
HIPAA 
Disclosure Authorization to participate in the research (either the 
standalone form or the combined consent and HIPAA Authorization). 
☐ I am requesting the IRB to approve a Waiver or an alteration of 
research participant authorization to participate in the research. 
Appropriate Use for Research:  
 
 
16.2. Identify the source of Private Health Information you will be using for 
your research (Check all that apply)   
☐ I will use the Informatics Consulting Services (ICS) available through 
CTSI (also referred to as the University's Information Exchange (IE) or 
data shelter) to pull records for me 
☑ I will collect information directly from research participants. 
☐ I will use University services to access and retrieve records from the 
Bone Marrow Transplant (BMPT) database, also known as the HSCT 
(Hematopoietic Stem Cell Transplant) database. 
☐ I will pull records directly from EPIC. 
☐ I will retrieve record directly from axiUm / MiPACS 
☐ I will receive data from the Center for Medicare/Medicaid Services  
☐ I will receive a limited data set from another institution  
☐ Other.  Describe:  
16.3. Explain how you will ensure that only records of patients who have 
agreed to have their information used for research will be reviewed: N/A 
16.4. Approximate number of records required for review: N/A 

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16.5. Please describe how you will communicate with research participants 
during the course of this research.  Check all applicable boxes 
☐ This research involves record review only. There will be no 
communication with research participants. 
☐ Communication with research participants will take place in the course 
of treatment, through MyChart, or other similar forms of 
communication used with patients receiving treatment.  
☑ Communication with research participants will take place outside of 
treatment settings. If this box is selected, please describe the type of 
communication and how it will be received by participants. 
We will use email communications for scheduling purposes. The 
recruitment materials, which will solicit participants, include our 
institutional email address. A prospective volunteer will write to us on 
this email, and we will continue communications using the email from 
which we were contacted. No health information will be shared via 
email. 
16.6. Explain how the research team has legitimate access to 
patients/potential participants: No medical records will be reviewed. 
Other personal information will be collected directly from the 
participants in the laboratory room. Screening questionnaires will be 
administered in person during enrollment to assess eligibility as a 
volunteer. 3T MRI scans will be collected to obtain structural brain 
images using the University facilities. EEG, questionaries, and Ap/Av test 
data are collected during the main experiment in the laboratory room, 
and these will be the primary outcome measure. 
16.7. Location(s) of storage, sharing and analysis of research data, including 
any links to research data (check all that apply).   
☐ In the data shelter of the Information Exchange (IE)  
 
☐ Store 
☐ Analyze 
☐ Share 
☐ In the Bone Marrow Transplant (BMT) database, also known as the 
HSCT (Hematopoietic Stem Cell Transplant) Database  
 
☐ Store 
☐ Analyze 
☐ Share 
☐ In REDCap (recap.ahc.umn.edu)  
 
☐ Store 
☐ Analyze 
☐ Share 
☐ In Qualtrics (qualtrics.umn.edu) 
 
☐ Store 
☐ Analyze 
☐ Share 

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☐ In OnCore (oncore.umn.edu)  
 
☐ Store 
☐ Analyze 
☐ Share 
☑ In the University’s Box Secure Storage (box.umn.edu) 
 
☑ Store 
☑ Analyze 
☑ Share 
☐ In an AHC-IS supported server. Provide folder path, location of server 
and IT Support Contact: 
 
☐ Store 
☐ Analyze 
☐ Share 
☐ In an AHC-IS supported desktop or laptop.  
Provide UMN device numbers of all devices:  
1. Product model: Dell Inc. - xps, asset id: bme-opitz-112 
 
☐ Store 
☑ Analyze 
☐ Share 
☐ Other: 
Indicate if data will be collected, downloaded, accessed, shared or stored 
using a server, desktop, laptop, external drive or mobile device (including 
a tablet computer such as an iPad or a smartform (iPhone or Android 
devices) that you have not already identified in the preceding questions 
☐I will use a server not previously listed to collect/download research data 
☐I will use a desktop or laptop not previously listed 
☐I will use an external hard drive or USB drive (“flash” or “thumb” drives) 
not previously listed  
☐I will use a mobile device such as an tablet or smartphone not previously 
listed 
 
16.8. Consultants. Vendors. Third Parties: No information will be collected, 
stored, analyzed or shared using a consultant, vendor, or third-party 
software application, system, device or technology (other than University 
of Minnesota provided REDCap or OnCore). 
 
16.9. Links to identifiable data: Identifiable data sharing, if necessary, will 
happen only through Box Secure Storage (box.umn.edu). No links will be 
used. 
 
 

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16.10. Sharing of Data with Research Team Members: Research data, that is, EEG, 
MRI, questionaries, and task data will be stored on University’s Box Secure 
Storage (box.umn.edu) and shared with relevant team members if 
necessary.  
 
 
16.11. Storage of Documents: Screening forms, questionaries, and informed 
consents will be stored under lock and key for 6 years in accordance with 
the HIPAA guidelines. 
 
 
16.12. Disposal of Documents: After 6 years screening and informed consents will 
be destroyed. 
 
17. Confidentiality 
17.1. Data Security: The consent and study forms, as well as any other 
documents that contain Protected Health Information, will be stored in the 
office of the principal investigator at the Department of Biomedical 
Engineering, University of Minnesota. We will assign a new study identifier 
to every participant. This identifier will be used during the data collection 
and for the purpose of any other documentation. Thus, all datasets will be 
pseudo-anonymized. The data will be recorded and temporarily stored on 
the computers at the research sites (see point 16), all of which have 
restricted access by the authorized personal only. The data will be 
transferred from the research sites to the computers of the investigators 
by using an encrypted hard drive. All computers are encrypted and 
password protected. A copy of the data will be deposited to a secured Box 
account of the laboratory which was organized in accordance with HIPCO 
regulations. We will not supply a copy of the consent form or any other 
documentation that contains PHI to any third party, and will not place it in 
the participants’ medical, employment, or educational records. 
 
18. Provisions to Monitor the Data to Ensure the Safety of Participants 
18.1. Data Integrity Monitoring: The principal investigator will be responsible for 
the data integrity monitoring in this study. The principal investigator will 
biweekly oversee the collected data, equipment log files, laboratory 
journal, consent forms, and standardized questionnaires to ensure that all 
procedures are executed on time and according to the present regulation. 
 

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18.2. Data Safety Monitoring: The principal investigator in the study will 
biweekly monitor (1) the original standardized questionnaires for possible 
adverse effects, which will be filled out by the volunteers at the end of the 
experimental session; and (2) aggregated data on the volunteers’ reports 
regarding potential adverse effects. The investigators will inform IRB within 
24 hours if a volunteer reports side effects during the experimental 
procedure or will otherwise inform the investigators about the potential 
adverse effect. 
18.3.  Unblinding procedures: This study follows a crossover design, with verum 
and sham conditions administered in intermittent blocks in randomized 
order. Thus, each participant will experience all study procedures. The 
exact sequence of procedures is stored in a computer file. In an unlikely 
case of adverse events, the study’s principal investigator will access the 
specific file and reveal the sequence of procedures preceding the event to 
the response team and overseeing bodies. 
 
19. Provisions to Protect the Privacy Interests of Participants 
19.1. Protecting Privacy: We will obtain personal information about the 
volunteer necessary for the study (day of enrollment, name, age and date 
of birth, biological sex at birth, handedness, phone number, email, 
screening results regarding study criteria) and store it in paper form and in 
an encrypted electronic form in the Department of Biomedical Engineering 
separately from other data. This information will not be shared with any 
3rd party, and the volunteers’ enrollment in the study will not be disclosed 
to anyone outside the investigation group. The investigators in the study 
will contact volunteers through the course of the study to arrange the 
experimental session via the volunteers’ phone or email. The volunteers 
will be informed prior to their participation that the application of 
physiological recordings and transcranial magnetic stimulation will require 
an investigator to touch their head, face, arms, and hands while setting up 
the equipment. 
 
19.2. Access to Participants: We will not collect PHI about the volunteers from 
their medical records or any other sources outside this study. The 
information that is necessary for the study will be obtained by the 
investigators directly from the participants during the initial meeting and 
the experimental sessions. 
 
20. Compensation for Research-Related Injury 

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20.1. Compensation for Research-Related Injury: No specific compensation 
scheme for research-related injury is planned. 
 
20.2. Contract Language: N/A 
 
21. Consent Process 
21.1. Consent Process (when consent will be obtained): The consent process will 
take place at the research sites (see point 22.1) in the presence of the 
investigator who is involved in this study. The investigator will be 
responsible to ensure that the volunteer understands the content of the 
consent and study forms, and all study procedures. After that, written 
informed consent will be obtained. The volunteer will be asked to fill out 
the standardized questionnaire at every session. At this point, the 
volunteer will verbally indicate the ongoing consent to participate in the 
study. 
 
21.2. Waiver or Alteration of Consent Process (when consent will not be 
obtained): N/A 
 
21.3. Waiver of Written/Signed Documentation of Consent (when written/signed 
consent will not be obtained): N/A 
 
21.4. Non-English Speaking Participants: N/A 
 
21.5. Participants Who Are Not Yet Adults (infants, children, teenagers under 18 
years of age): N/A 
 
21.6. Cognitively Impaired Adults, or adults with fluctuating or diminished 
capacity to consent: N/A 
 
21.7. Adults Unable to Consent: N/A 
 
22. Setting 

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22.1. Research Sites: All research procedures will be conducted in the 
laboratories of the Department of Biomedical Engineering at the University 
of Minnesota Twin Cities Campus: (1) at Nils Hasselmo Hall, 312 Church St 
SE and/or (2) Phillips-Wangensteen Building, 516 Delaware St SE. Besides, 
research can be performed at (3) the Non-invasive Neuromodulation 
Laboratory at the University of Minnesota Twin Cities Campus located at 
717 Delaware St SE. Only authorized personnel have access to the 
laboratories. 
 
22.2. International Research: N/A 
 
 
23. Multi-Site Research 
23.1. Study-Wide Number of Participants: N/A 
 
23.2. Study-Wide Recruitment Methods: N/A 
 
23.3. Study-Wide Recruitment Materials: N/A 
 
23.4. Communication Among Sites: N/A 
 
23.5. Communication to Sites: N/A 
 
24. Coordinating Center Research 
24.1. Role: N/A 
 
24.2. Responsibilities: N/A 
 
24.3. Oversight: N/A 
 
24.4. Collection and Management of Data: N/A 
 
25. Resources Available 
25.1. Resources Available: MRI and TMS-EEG experiment will be conducted by 
the (co-)investigators. 3T MRI scans will be measured at the Center for 

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Magnetic Resonance Research (CMRR). The TMS-EEG main experiment will 
be performed at our lab in the Nils Hasselmo Hall, 312 Church St SE, 
University of Minnesota or Phillips-Wangensteen Building, 516 Delaware St 
SE, University of Minnesota. This facility is fully equipped for the TMS-EEG 
experiment. Co-investigators will primarily dedicate their work efforts in 
completing the study. 
 
26. References 
Anastassiou CA, Koch C. Ephaptic coupling to endogenous electric field activity: 
why bother? Curr Opin Neurobiol 2015;31:95–103. 
https://doi.org/10.1016/j.conb.2014.09.002. 
Anastassiou CA, Perin R, Markram H, Koch C. Ephaptic coupling of cortical 
neurons. Nat Neurosci 2011;14:217–23. https://doi.org/10.1038/nn.2727. 
Bramson B, den Ouden HE, Toni I, Roelofs K. Improving emotional-action control 
by targeting long-range phase-amplitude neuronal coupling. Elife 2020;9:. 
https://doi.org/10.7554/eLife.59600. 
Cole EJ, Phillips AL, Bentzley BS, Stimpson KH, Nejad R, Barmak F, et al. Stanford 
neuromodulation therapy (SNT): a double-blind randomized controlled trial. 
Am J Psychiatry. 2022;179:132–41. 
Cole EJ, Stimpson KH, Bentzley BS, Gulser M, Cherian K, Tischler C, et al. Stanford 
accelerated intelligent neuromodulation therapy for treatment-resistant 
depression. Am J Psychiatry. 2020;177:716–26. 
Corr PJ, McNaughton N. Neuroscience and approach/avoidance personality 
traits: A two stage (valuation–motivation) approach. Neurosci Biobehav Rev 
2012;36:2339–54. https://doi.org/10.1016/j.neubiorev.2012.09.013. 
Gordon PC, Belardinelli P, Stenroos M, Ziemann U, Zrenner C. Prefrontal theta 
phase-dependent rTMS-induced plasticity of cortical and behavioral responses 
in human cortex. Brain Stimul 2022:118159. 
https://doi.org/10.1016/j.brs.2022.02.006. 
Harms M et al. Extending the Human Connectome Project across ages: Imaging 
protocols for the Lifespan Development and Aging projects. Neuroimage 2018 
Dec;183:972-984. PMID: 30261308 DOI: 10.1016/j.neuroimage.2018.09.060 
Ironside M, Amemori K, McGrath CL, Pedersen ML, Kang MS, Amemori S, et al. 
Approach-Avoidance Conflict in Major Depressive Disorder: Congruent Neural 
Findings in Humans and Nonhuman Primates. Biol Psychiatry 2020;87:399–
408. https://doi.org/10.1016/j.biopsych.2019.08.022. 
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