Modulating Human Cortical Plasticity With Transcranial Electrical Stimulation
Phase: NA
Conditions: Healthy, Schizophrenia
Sponsor: University of Minnesota

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PROTOCOL COVER PAGE 
Protocol Title 
Modulating Human Cortical Plasticity with Transcranial 
Electrical Stimulation 
Principal 
Investigator/Faculty 
Advisor 
Name: Kelvin O. Lim 
Department: Psychiatry 
Telephone Number: (612) 273-8700 
Email Address: kolim@umn.edu 
Student 
Investigator 
Name: Elias Boroda 
Current Academic Status (Student, Fellow, Resident): 
 Graduate Student 
Department: Neuroscience 
Telephone Number: 7634984176 
Institutional Email Address: borod002@umn.edu 
Scientific 
Assessment 
HRPP facilitated scientific assessment 
IND/IDE # (if 
applicable) 
N/A 
IND/IDE Holder 
N/A 
Investigational Drug 
Services # (if 
applicable) 
N/A 
Version 
Number/Date: 
V1 
NCT: NCT03114488

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REVISION HISTORY 
 
Revision # 
Version Date 
Summary of Changes 
Consent Change? 
 
 
Crossover to new template 
n/a 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
 
1.0 
Objectives................................................................................................................. 5 
2.0 
Background .............................................................................................................. 5 
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 .................................................................................. 12 
7.0 
Sharing of Results with Participants ...................................................................... 13 
8.0 
Study Population .................................................................................................... 13 
9.0 
Vulnerable Populations .......................................................................................... 14 
10.0 Local Number of Participants................................................................................. 14 
11.0 Local Recruitment Methods ................................................................................... 14 
12.0 Withdrawal of Participants .................................................................................... 15 
13.0 Risks to Participants ............................................................................................... 15 
14.0 Potential Benefits to Participants .......................................................................... 16 
15.0 Statistical Considerations ....................................................................................... 16 
16.0 Confidentiality ........................................................................................................ 16 
17.0 Provisions to Monitor the Data to Ensure the Safety of Participants ................... 16 
18.0 Provisions to Protect the Privacy Interests of Participants ................................... 17 
19.0 Compensation for Research-Related Injury ........................................................... 17 
20.0 Consent Process ..................................................................................................... 17 
21.0 Setting .................................................................................................................... 18 
22.0 Multi-Site Research ................................................................................................ 18 
23.0 Resources Available ............................................................................................... 18 
24.0 References ............................................................................................................. 19 
 

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ABBREVIATIONS/DEFINITIONS 
 
• tDCS – Transcranial Direct Current Stimulation 
• EEG – Electroencephalograph  
• ERP – Event Related Potential  
• SSP – Stimulus Specific Plasticity  
• AEP – Auditory Evoked Potential 
 

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1.0 
Objectives 
1.1 Purpose: Experience dependent plasticity is a fundamental property of the 
brain. It allows neural systems to adapt in response to environmental input 
and subserves the vital functions of learning and memory. Deficits in 
plasticity are also thought play a causal role in the pathophysiology of 
several psychiatric disorders, specifically schizophrenia (SZ). Treatments 
that can probe or even enhance plasticity have potential to be of great 
clinical and research value. Non-invasive neuromodulation via transcranial 
direct current stimulation (tDCS) is a promising method for modulating 
neural plasticity. tDCS delivers low-intensity direct current to cortical areas, 
thereby facilitating or inhibiting neural activity in a polarity specific manner. 
Due to its low cost and safety, tDCS has been employed in a wide variety of 
studies, but much remains unknown regarding its mechanism of action in 
humans. Experiments carried out in animal and tissue models indicate that 
tDCS modulates synaptic plasticity mechanisms of long term potentiation 
and depression (LTP/D), however, these findings have never been translated 
to human subjects, limiting the practical utility of the research. Recently 
developed electroencephalographic (EEG) based measures now allow the 
interrogation of synaptic plasticity non-invasively in humans, making it 
possible to explore the effects of tDCS on human brain plasticity. 
 
Specific Aims: 
 1. Evaluate the effects of Anodal tDCS vs. Sham in enhancing the 
induction of plasticity in the auditory cortex in healthy participants.  
 
Hypothesis: Anodal tDCS will enhance the induction of LTP (as measured 
by potentiation of AEP’s) compared to Sham. 
2.0 
Background 
2.1 Significance of Research Question/Purpose: Experience dependent plasticity 
is generally defined as the ability of a nervous system to dynamically shift 
functional or structural states in response to extrinsic and intrinsic factors. 
Research over the past 50 years demonstrates that experience dependent 
plasticity is a fundamental property of the brain and is critical for everyday 
functioning. It allows us to learn and recall patterns, predict and obtain 
reward, and guides response selection for adaptive behavior (Cooke and 
Bliss, 2006; Ganguly and Poo, 2013). Given its fundamental role in brain 
dynamics, maladaptive experience dependent plasticity can lead to 
debilitating conditions. Disrupted synaptic plasticity is thought to play a 
significant role in the pathophysiology of several severe psychiatric 
disorders, including schizophrenia (SZ), bipolar disorder and major 
depressive disorder (Elvsåshagen et al., 2012; Normann et al., 2007; 
Stephan et al., 2006). The contribution of disrupted plasticity is most clearly 

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implicated in SZ, a serious neuropsychiatric illness that impacts 1% of the 
population and presents with a host of positive, negative and cognitive 
symptoms. Therefore, treatments that can assess or even enhance plasticity 
have the potential to be of great clinical value.  
 
Non-invasive neuromodulation via transcranial direct current stimulation 
(tDCS) is a promising method for modulating plasticity. Due to its low cost, 
tolerability and simplicity, the use of tDCS in both research and clinical 
settings has grown substantially. The beneficial effects of tDCS have been 
reported on a wide range of faculties, including learning and various 
cognitive abilities (Hill et al., 2016). Clinically, it has been used to treat a 
plethora of symptoms, from cognitive deficits to psychotic symptoms (Kekic 
et al., 2016). Despite the positive effects however, significant issues, such as 
moderate effect sizes and a high degree of variability in outcomes, limit the 
clinical potential of tDCS. One factor that contributes to these issues is the 
paucity of research that has investigated the mechanism of action of tDCS 
in humans. The vast majority of studies looking at this question have been 
conducted in animal or tissue models. Findings from these studies clearly 
demonstrate that tDCS effects are mediated by modulating plasticity 
mechanisms. However, due to the invasive techniques used to gather this 
data, recapitulating these findings in human subjects has not been possible. 
Techniques that can parallel the experimental procedures used in animal 
models are necessary to bridge the translational gap. A recently developed 
paradigm, termed stimulus specific plasticity (SSP), is a close parallel to the 
high frequency electrical stimulation protocols used in studies that 
investigated the impacts of tDCS on plasticity in animals and tissue slices. 
SSP utilizes sensory stimuli to evoke neural responses that can be recorded 
via the electroencephalogram (EEG), and has been shown to be functionally 
equivalent to the plasticity inducing paradigms used in model systems. This 
project has a strong translational application due to the paradigms that will 
be utilized. We will be translating much of the work that has been 
conducted in animal and tissue models which shows the modulatory effect 
of tDCS on synaptic plasticity. Translation of these findings to humans is 
necessary to better understand the mechanisms of tDCS and also to 
validate the animal models themselves. In addition, tracking tDCS effects 
with SSP allows the probing of neural plasticity in the sensory cortices, 
something that has generally been limited to the motor cortex in the past 
(via Transcranial Magnetic Stimulation). Given the fact that sensory 
processing is disrupted in psychiatric illnesses such as SZ, monitoring 
plasticity in these regions may also has a strong clinical significance. Finally, 
SSP allows the non-invasive assessment of the efficacy of treatments that 
are aimed at enhancing brain plasticity. In that sense, this project will serve 
as a proof of concept for studies that seek to assess effectiveness of tDCS 
intervention.  

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TDCS Modulates Synaptic Plasticity: tDCS is a neuromodulatory technique in 
which low-intensity direct current is conducted to the brain through scalp 
electrodes. Most commonly, two electrodes are utilized, an anode and a 
cathode. Anodal stimulation produces a shift in excitability that depolarizes 
neurons, while cathodal stimulation has opposite effects. These 
assumptions are only generalizations however, as it has been demonstrated 
that neuronal activity and morphology play a greater role in directionality 
of effects than previously thought (Kronberg et al., 2016). Though current 
spread from tDCS is rather diffuse, a degree of focality can be achieved as 
current density is highest directly underneath the electrodes (Bikson et al., 
2012; Datta et al., 2009). Though the cellular mechanisms of tDCS are still 
under investigation, it is known that stimulation changes resting membrane 
potential (in a polarity specific manner), and modulates synaptic plasticity 
mechanisms of long term potentiation and depression (LTP/D). LTP refers to 
the lasting functional (or structural) enhancement of synaptic connections 
that occurs through coincident pre and postsynaptic activity. This concept, 
first postulated by Donald Hebb (Hebb, 1949), has several properties that 
make it an attractive candidate for serving as the substrate for learning and 
memory (Rioult-Pedotti et al., 2000). First, LTP is persistent, lasting from 
several minutes to months (Abraham et al., 2002). Second, it is input 
specific, in that the potentiation is restricted to active synapses only. Third, 
it is associative and cooperative, meaning that weakly stimulated synapses 
can still be potentiated if associated in time with other inputs that 
depolarize the postsynaptic cell (Kitajima and Hara, 1991). Lastly, LTP relies 
on the coincidence detecting mechanism provided by the NMDAR and is 
thus dependent on NMDAR activation (Rioult-Pedotti et al., 2000). 
Investigations of the effects of direct current stimulation on LTP/D have 
primarily been carried out in excised tissue samples from the hippocampus 
or the motor cortex of mice (Fritsch et al., 2010; Kronberg et al., 2016). In 
these studies, LTP is induced by applying a high frequency train of electrical 
impulses (HFS) to an afferent pathway. This causes the coincident activation 
of pre and postsynaptic cells, leading to enhancement of synaptic strength 
as measured by the slope of excitatory postsynaptic potentials (ESPS). 
Multiple studies have shown that when applied during this protocol, direct 
current stimulation acts to modulate the potentiation of EPSPs. Anodal 
stimulation was found to enhance potentiation (Fritsch et al., 2010; 
Kronberg et al., 2016; Ranieri et al., 2012), while cathodal stimulation had 
varying effects depending on location of the recording electrode (Kronberg 
et al., 2016). It is important to note that direct current stimulation provides 
only a subthreshold change in membrane potential and does not on its own 
induce LTP. Thus tDCS relies on concurrent synaptic activity to enhance 
plasticity (Fritsch et al., 2010). The facilitation of LTP via tDCS has also been 
demonstrated in vivo in animal models. Here, learning of a motor task was 

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used to induce LTP in behaving mice who were treated with anodal or sham 
(placebo) stimulation over the motor cortex (Fritsch et al., 2010). 
Immediately after learning the task, LTP was assayed by eliciting EPSPs 
from the layers II/III of the motor cortex. Mice who had received tDCS while 
learning the task displayed enhanced elevation of EPSPs compared to sham 
stimulated mice. In addition, the rate of learning on the motor task was 
significantly higher in the active stimulation group. These works 
demonstrate that tDCS effects on the brain are emergent from a 
modulation of plasticity mechanisms. 
 
Very little work has been done that translates the findings from the 
aforementioned studies to human subjects. The only studies that have 
probed the effects of tDCS on plasticity in humans have done so in the 
motor cortex. These studies use Transcranial Magnetic Stimulation (TMS) 
triggered motor evoked potentials (MEP) as measures of synaptic 
potentiation. This method of probing plasticity is lacking in several regards. 
First, MEP’s are not a direct measure of brain activity. Second, due to 
reliance on MEP’s, these investigations are confined to the motor cortex, 
restricting the scope and the applicability of findings. Finally, the paradigm 
does not induce LTP and is not a close parallel to the HFS protocols used in 
animal/tissue models, thus limiting translational relevance.  
 
SSP is a Non-Invasive Measure of Synaptic Plasticity: Recently developed 
techniques utilizing the EEG now enable the non-invasive interrogation of 
synaptic plasticity in the human cortex. As demonstrated first by Clapp et 
al., (2005), and since then by others (Teyler et al., 2005; Zaehle et al., 2007), 
it is possible to induce LTP in the human sensory cortices by the rapid 
presentation of sensory stimuli. It has been shown that a rapidly presented 
checkerboard pattern (a photic tetanus) can induce long lasting changes in 
evoked potentials (Teyler et al., 2005), spectral features (Clapp et al., 
2006a), and hemodynamic response (Clapp et al., 2005a) in the visual 
cortex. Similar findings have been reported in the auditory cortex with rapid 
presentation of auditory tones (Clapp et al., 2005b). Here, the N100 
component of the auditory evoked potential (AEP) was potentiated post 
auditory tetanus. The N100 component is a negative peak that emerges just 
anterior of the Cz electrode and is thought to emanate from the bilateral 
superior temporal gyri (Ford et al., 2016; Zaehle et al., 2007). The 
potentiation of the AEP post tetanus was independent of arousal state and 
persisted for over an hour without decrease. Studies of SSP in rats 
demonstrate that the potentiation effect is long lasting, NMDAR dependent 
and input specific, supporting the theory that SSP is indeed inducing LTP 
(Clapp et al., 2006b). This paradigm is thus a close parallel to the high 
frequency electrical stimulation that is used to induce LTP in animal and 
tissue models. These properties make SSP an ideal translational tool for 

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recapitulating the work done in models regarding the effects of tDCS on 
neural plasticity. To date no one has used SSP to analyze tDCS effects. 
 
The fact that SSP allows the interrogation of plasticity in the sensory 
cortices is relevant from a clinical perspective as well. Several psychiatric 
disorders present with disrupted functioning of the sensory areas. This is 
especially notable in SZ, where disruptions of synaptic plasticity in the 
auditory cortex result in deficits of auditory perception and can lead to 
hallucinations (Gaebler et al., 2015; Sweet et al., 2009). A pertinent study 
by Mears and Spencer (2012) utilized the auditory SSP paradigm to assay 
LTP induction in SZ patients, finding a lack of potentiation in the N100 
component (compared to healthy controls). A more recent paper utilized 
visual SSP to evaluate the effectiveness of D-cycloserine (an agonist of the 
NMDAR) on enhancing plasticity (Forsyth et al., 2015). Together these 
studies demonstrate that SSP can be used to both assay the integrity of the 
brain to support LTP, and as a tool to gauge the efficacy of treatments that 
are aimed at enhancing plasticity. Demonstrating the effects of tDCS on 
plasticity measures in healthy humans, is a necessary step prior to carrying 
this study out in a clinical population. 
2.2 Preliminary Data: N/A 
2.3 Existing Literature: See Section 2.1  
3.0 
Study Endpoints/Events/Outcomes 
3.1 Primary Endpoint/Event/Outcome: Change in amplitude of AEP as recorded 
by the EEG. Change in AEP is a proxy for brain plasticity. 
3.2 Secondary Endpoint(s)/Event(s)/Outcome(s): N/A 
4.0 
Study Intervention(s)/Investigational Agent(s) 
4.1 Description: Transcranial Direct Current Stimulation (tDCS) is a noninvasive 
method of neuromodulation which applies low levels of electrical current to 
the scalp. TDCS can modulate plasticity and has been used for a variety of 
clinical and research purposes. We will apply tDCS bilaterally to the 
auditory cortex.   
4.2 Drug/Device Handling: We will be using the StarStim8 (Neuroelectrics) 
device for tDCS and EEG recording. This device has been approved for use in 
research without an investigational device exemption due to meeting 
criteria for non- significant risk (NSR). In addition, the device has built in 
safety mechanisms which allow for the immediate cessation of stimulation 
should the subject become uncomfortable or if the impedance of the 
stimulation electrodes is too high. Stimulating electrodes will be placed over 
the auditory cortex and return electrodes will be placed over the 
supraorbital bone. 1 mA of current will be delivered for the duration of 

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stimulation. The device will be stored in a locked cabinet in our lab space. 
Our lab space on the 5th floor of the secure 717 Delaware Research 
Building. Only trained team members who are on the IRB protocol will have 
access to the locked cabinet.  
4.3 Biosafety: N/A  
 
4.4 Stem Cells: N/A 
 
5.0 
Procedures Involved 
5.1 Study Design: The study will be conducted in a blinded, within-groups 
design involving two separate study sessions. The two sessions will consist 
of simultaneous tDCS and EEG recording. Each participant will receive both 
active and sham tDCS over the course of the two sessions (but not within a 
single session). Order of stimulation type will be counterbalanced across 
participants. The two sessions will be spaced at least 24 hours apart. The 
consent process will be done at the first study session. The primary outcome 
measure will be the difference in the amplitude of the ERP’s (specifically the 
N100 component) recorded before and after tDCS. This difference is 
reflective of the capacity of the sensory cortex to support synaptic plasticity. 
5.2 Study Procedures:  
• Screening Visit: The screening process will happen over email or phone 
(depending on how participant makes contact). Potential participants 
will be provided with information about the study using an established 
script and will be asked a series of questions to determine if they meet 
basic inclusion/exclusion criteria (see below). They will be told about the 
basic aims of the study, and those interested in participating will be 
scheduled for the study. 
• Study visits: Visits will take place at our 717 Delaware Street SE offices, 
the Ambulatory Research Center (ARC) at the department of Psychiatry, 
or at the clinical spaces at our St. Louis Park location. At the first study 
session, the participants will complete the informed consent process. 
The participant will also be told that this is not a treatment study and 
no benefits to the participant are expected from the study. After, and if, 
they complete the process, the participant will fill out the tDCS Side 
Effect Questionnaire (TSEQ), and the Edinburgh Handedness Inventory. 
These two brief questionnaires ask about potential side-effects of tDCS 
and the subject’s handedness respectively. After the paperwork has 
been completed, the participant will undergo EEG and either active or 
sham tDCS (see embedded figure). The stimulation and the recording 
will be provided using the StarStim Neurostimulator (Neuroelectrics, 
Inc.). This device has been approved for use in research in the United 

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States without an investigational device exemption due to meeting 
criteria for non-significant risk. The device utilizes standard Ag/Cl 
electrodes embedded in an easy to use neoprene cap. A small amount 
of conductive gel is applied to each electrode before insertion into the 
head cap. Electrodes will be positioned on the subject's scalp according 
to the international 10/20 electrode placement system. During EEG 
recording, all electrodes will be utilized to record brain signal. The 
session will begin with EEG recording while the participant engages in a 
visual search task. Immediately after, either a passive Auditory Oddball 
paradigm or a passive Visual Oddball paradigm (these tasks are 
described in detail in the instruments section) will begin. They will be 
seated in front of a monitor as the observe visual stimuli or will be 
wearing insert headphones through which auditory stimuli will be 
delivered. After the first Oddball task, simultaneous EEG and tDCS will 
commence for a period of 10 min. During simultaneous EEG and tDCS, 
two electrodes will be used to deliver stimulation, while the remaining 
electrodes continue to record EEG. The two stimulation electrodes will 
be positioned bilaterally over the auditory cortex (T3/T4). In the anodal 
group the device will deliver 1mA of current through each stimulating 
electrode. The current is initiated in a ramp like fashion over a 10 sec 
period from 0mA to 1mA. Once at 1mA, the current is held constant for 
the duration of the session. Should the participant not be able to 
tolerate a current of 1mA due to pain or irritation, the current will be 
decreased down to a minimum of 0.5mA. If 0.5 mA is still not tolerable, 
the participant will be removed from the study. The sham procedure 
involves only 40 sec stimulation at 1mA and then drops to 0mA with 
15ms pulses every 550ms. This simulates the tingling sensations that 
are often associated with active stimulation. 15min into the stimulation 
session the sensory tetanus will commence. The auditory tetanus 
involves the presentation of a 1000Hz tone at a rate of 13Hz for a 
period of approximately 5min. The visual tetanus involves the 
presentation of the visual stimulus (either a horizontal or vertical 
grating) at a rate of 9Hz). Sensory tetanus and tDCS will end at the 
same time. Briefly after tetanus and tDCS, the participants will perform 
the second oddball task as well as a final visual search task.30 min after 
the cessation of tDCS, a final oddball task will be conducted. After the 
completion of the EEG recording, the head cap will be removed and the 
participant will be given the opportunity to wash their hair (towels and 
shampoo provided). The two study sessions will be identical, differing 
only in type of tDCS applied (sham or active). 
• Precautions Taken: tDCS is considered to be a safe brain stimulation 
technique that rarely result in adverse events. There is currently no 
evidence of serious side-effects. We will discontinue any participant who 
experiences sores at the tDCS administration site, headaches that 

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impair global functioning, and worsening psychosis. Mild side-effects 
typically resolve upon discontinuation tDCS. The participant may choose 
to discontinue stimulation at any time during the session if experiencing 
discomfort or side effects. No other risks are anticipated. Nonetheless, 
in order to minimize risks, study staff will be using standards of 
administration that have been shown to be safe in numerous other 
studies and across more than 2000 studies (Liebetanz et al., 2009; 
Nitsche et al., 2007; Poreisz, Boros, Antal, & Paulus, 2007) using tDCS; 
this includes length of administration, magnitude of the current, size of 
electrode sponges used, and method of applying stimulation. Any 
unanticipated problems or adverse events will be reported according 
the University of Minnesota IRB standard operating procedure. 2. 
Participants will be informed that they are not required to answer any 
questions or participate in any activities which make them 
uncomfortable. 3.The results of this study may be published or 
presented but the participant's identity and records will not be revealed 
unless required by Federal Law. A Federal Law allows the U.S. Food and 
Drug Administration, Office for Human Research Protections, 
Government Accountability Office and other Federal agencies, the 
Research and Development Committee, representatives of USAMRMC, 
Henry M. Jackson Foundation, the University of Health & 
Biological/Medical Application Form 11 Minnesota Institutional Review 
Board (IRB), and/or the Institutional Review Board (IRB)/Human Studies 
Subcommittee of the VA Medical Center to review records. Because of 
the need for these inspections, absolute confidentiality cannot be 
guaranteed. However, every effort would be made to minimize these 
risks by providing the participant with a unique numerical identifier at 
the beginning of the study in order to protect their actual identification 
and maintain complete confidentiality. 
 
5.3 Study Duration: We plan on enrolling participants through May 2019. Data 
analysis should be completed by December 2019.   
5.4 Individually Identifiable Health Information: Basic information regarding 
participants, name, email, phone number, address and DOB will be 
collected. See the HIPCO form for more details.  
 
5.5 Use of radiation: N/A  
5.6 Use of Center for Magnetic Resonance Research: N/A  
6.0 
Data and Specimen Banking 
6.1 Storage and Access: All participants will receive a unique numerical ID 
which will be used in lieu of identifiable information whenever possible. All 
source data containing identifiers will be stored in locked cabinets in locked 

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rooms. All digital identifiable data will be stored on access-controlled, 
password-protected databases. 
6.2 Data: Deidentified Neuroimaging data (EEG recordings) will be the only 
data stored 
7.0 
Sharing of Results with Participants 
7.1 Results of the study will not be shared with participants. The findings of the 
study will be shared via publication or presentation at a conference once all 
data has been collected/analyzed.  
8.0 
Study Population 
8.1 Inclusion Criteria: Participants will be recruited from the University and 
surrounding community. No vulnerable populations will be recruited for this 
study. Specific inclusion criteria are listed below: 
• Between 18-50 years old 
• Normal hearing ability 
• No psychiatric medication prescription 
• No clinically significant head injury or neurological disease 
• No drug dependence past 6 months or no substance abuse in the 
past month 
• Sufficient spoken English to understand study procedures  
• Ability to give informed consent   
8.2 Exclusion Criteria: Exclusion criteria are listed below:  
• History or tDCS or other cortical energy exposure within past 12 
months 
• History of seizures or epilepsy  
• Cranial metallic plates/screws 
• Implanted devices 
• History of craniotomy 
• History of eczema on scalp 
• Bipolar disorder or Depression diagnosis  
• Cornrows or dreadlocked hair 
• Impaired hearing 
8.3 Screening: The screening process will happen over email or phone 
(depending on how participant makes contact). Potential participants will 

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be provided with information about the study using an established script 
and will be asked a series Health & Biological/Medical Application Form 7 
of questions to determine if they meet basic inclusion/exclusion criteria. 
They will be told about the basic aims of the study, and those interested in 
participating will be scheduled for the study. At the study visit, the 
participants will first complete the informed consent process 
9.0 
Vulnerable Populations 
9.1 Vulnerable Populations:  
☐ Children 
☐ Pregnant women/Fetuses/Neonates 
☐ Prisoners 
☐ 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 
☐ Approached for participation in research during a stressful situation such 
as emergency room setting, childbirth (labor), etc. 
☐ Disadvantaged in the distribution of social goods and services such as 
income, housing, or healthcare 
☐ Serious health condition for which there are no satisfactory standard 
treatments 
☐ Fear of negative consequences for not participating in the research (e.g. 
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 
☐ Undervalued or disenfranchised social group 
☐ Members of the military 
☐ Non-English speakers 
☐ Those unable to read (illiterate) 
☐ Employees of the researcher 
☐ Students of the researcher 
☐ None of the above 
9.2 Additional Safeguards: N/A 
10.0 Local Number of Participants 
10.1 Local Number of Participants to be Consented: Up to 80 participants will be 
consented for the study. The goal is to have 35 complete the study.    
11.0 Local Recruitment Methods 

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11.1 Recruitment Process: Recruitment will be conducted using posted flyers as 
well as ads posted on Craigslist. Flyers will be posted around campus both 
outside and inside buildings. Ads will be placed on Craigslist under “part 
time gigs”.  
11.2 Identification of Potential Participants: Interested participants will get in 
contact with study staff using email or phone calls. Initial contact will be 
made primarily by the student investigator. No medical records will be 
asked for/collected as a part of this study.  
11.3 Recruitment Materials: Recruitment materials include posted flyers and ads 
on craigslist.  
11.4 Payment: We will use the Greenphire ClinCard System to pay our 
participants. Participants will receive the card with $20 preloaded at the 
end of the first study session. $20 more will be loaded onto the card at the 
completion of the second study session. Research experience points may 
also be awarded 
12.0 Withdrawal of Participants 
12.1 Withdrawal Circumstances: If we cannot collect quality EEG data from the 
subject due to the following reasons, the participant will be withdrawn 
from the study 
• Excessively thick hair  
• Small earlobe (cannot place earclip electrode) 
• Excessive movement during EEG 
• Excessive blinking during EEG 
• Issues with lack of alertness (falling asleep) 
12.2 Withdrawal Procedures: In the case that a participant withdraws, the PI will 
be notified and data collection from that subject will immediately cease. 
Records will be updated to reflect a withdrawal. No partial withdrawal 
option is given for this study.  
12.3 Termination Procedures: N/A 
13.0 Risks to Participants 
13.1 Foreseeable Risks: There is currently no evidence of serious side-effects 
associated with tDCS. Criteria for discontinuation that may rarely occur are 
sores at the tCS administration site, headaches that impair global 
functioning, and worsening psychosis. Mild side-effects that typically 
resolve upon discontinuation tDCS include light itching under the electrode 
at the beginning of administration, headache, fatigue, and nausea. 
13.2 Reproduction Risks: N/A 

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13.3 Risks to Others: N/A 
14.0 Potential Benefits to Participants 
14.1 Potential Benefits: No benefits expected for participating in the study 
15.0 Statistical Considerations 
15.1 Data Analysis Plan: Data analyses will include traditional statistical analyses 
for within-groups differences in EEG neuroimaging data.  
15.2 Power Analysis: 35 participants in a within-groups design will 
provide the statistical power (1- β = 0.80) necessary to detect effect 
sizes greater than d’ = 0.450. Based on the large effect sizes (d’ > 
0.68) reported by Clapp et al. (2005) we expect to be sufficiently 
powered with the aforementioned sample size.  
15.3 Statistical Analysis: Data will be analyzed in a 2-way ANOVA with correction 
for multiple comparisons 
15.4 Data Integrity: EEG data will be subjected to standard quality control 
measures (both automated and manual) including measuring and 
controlling for artefacts.  
16.0 Confidentiality 
16.1 Data Security: Data will be handled by trained research staff members. 
Paper records will be stored in locked file drawers and electronic data 
storage will meet University security requirements (password protection, 
encryption, controlled access, audit trails of access, etc.). Protected Health 
Information will be separated from research data. Research data will be 
coded and, thus, de-identified. De-identified data will be stored in a local 
HIPAA-compliant RedCap database or Box Storage managed by the 
University of Minnesota. Signed consent forms will be scanned into the 
OnCore system as required by the University. Research information will not 
be placed into the individual’s electronic medical record. 
 
17.0 Provisions to Monitor the Data to Ensure the Safety of Participants 
17.1 Data Integrity Monitoring: The principal investigator will monitor 
safety and data quality for this study. They will ensure that adverse 
events are reported accordingly and that data are generated, 
documented (recorded), and reported - in compliance with this 
protocol, with Good Clinical Practice, and any other applicable 
regulatory requirements. In addition, independent research 
monitoring will be conducted by the Clinical and Translational 
Science Institute (CTSI). A CTSI staff member, Lisa Hostetler, will act 
as the regulatory monitor for this study. Her duties will include 

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reviewing regulatory binders and patient files to make sure that the 
research is being conducted properly 
17.2 Data Safety Monitoring. N/A 
18.0 Provisions to Protect the Privacy Interests of Participants 
18.1 Protecting Privacy: Participants are free to contact the study team and will 
not be directly contacted unless they indicate an interest. During screening 
and consent, participants will be given the option to not participate at any 
point. Before the start of the first and second study sessions, the participant 
will again be given an option to discontinue. We will stress that if at any 
point anything feels uncomfortable, they can let us know and we will 
quickly resolve the situation.    
18.2 Access to Participants: No medical records will be assessed 
19.0 Compensation for Research-Related Injury 
19.1 Compensation for Research-Related Injury: In the event that this research 
study results in an injury, we will provide treatment including first aid, 
emergency care, and follow-up as needed. Care for injuries would be billed 
in the ordinary manner and costs would not be covered by the research 
study itself. 
19.2 Contract Language: N/A 
20.0 Consent Process 
Note: The process and documentation plan must follow “SOP: Informed Consent 
Process for Research (HRP-090)” and “SOP: Written Documentation of Consent 
(HRP-091).” 
20.1 Consent Process (when consent will be obtained): Consent will be obtained 
in our lab spaces in the 717 Delaware Research Building. Participant and 
study team member will go through the entirety of the document together, 
then the participant will be given as much time as needed to review the 
document on his/her own. Questions regarding the study/consent form will 
be encouraged. The study team member may ask the participant if he/she 
understands the study procedures and may ask to have the participant 
relay the major items in the consent form. The voluntary nature of the study 
will be stressed at all times.  
20.2 Waiver or Alteration of Consent Process (when consent will not be 
obtained): N/A 
20.3 Non-English Speaking Participants: Non-English speaking participants will 
not be recruited for the study 
20.4 Participants Who Are Not Yet Adults (infants, children, teenagers under 18 
years of age): N/A 

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20.5 Cognitively Impaired Adults, or adults with fluctuating or diminished 
capacity to consent: N/A 
20.6 Adults Unable to Consent: N/A  
21.0 Setting 
21.1 Research Sites: Participants will be recruited from around the University 
campus areas as well as in the greater Twin Cities area via Craigslist 
postings. Study visits will take place at our 717 Delaware Street SE offices, 
the Ambulatory Research Center (ARC) at the department of Psychiatry, or 
at the clinical spaces at our St. Louis Park location.  
 
21.2 International Research: N/A 
 
22.0 Multi-Site Research N/A 
 
23.0 Resources Available 
23.1 Resources Available:  
• 
Dr. Kelvin Lim has a wealth of experience carrying out tDCS studies 
and will have direct oversight of this study. He will train and have 
weekly interactions with the student investigator. The weekly 
meetings will involve review of data, reporting of any adverse effects 
and continued training on tDCS and EEG.   
• 
We have recruited healthy participants from the University in the past 
using similar techniques and have has no issues meeting our required 
sample sizes. 
• 
Dr. Lim will be devoting about 15% of his time to this study, Elias 
Boroda, the student investigator, will devote 65% of his time to the 
study. 
• 
Study visits will take place at our 717 Delaware Street SE offices, the 
Ambulatory Research Center (ARC) at the department of Psychiatry, 
or at the clinical spaces at our St. Louis Park location. All 3 of these 
locations have designated rooms for EEG data collection and are all 
suited for tDCS studies. These locations provide laundry services for 
towels (needed for cleanup) as well as technical support for 
troubleshooting EEG.  
• 
Though we do not anticipate any adverse effects requiring medical 
intervention, we do have licensed medical professionals working on 
the same floor as all of our 3 locations.  
• 
Dr. Lim will ensure that all study team members are trained on the 
protocol and are appropriately overseen.  
 

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