Combining Neuro-Imaging and Non-Invasive Brain Stimulation for Clinical Intervention in Alcohol Use Disorder
Phase: NA
Conditions: Alcohol Use Disorder, Eligible to go Into the MRI Scanner, Short-term Abstinence From Alcohol Use (2 Week Abstinent)
Sponsor: University of Minnesota

PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
PROTOCOL TITLE: 
Effects of Neuromodulation and Cognitive Training on Brain Networks Associated with 
Relapse in Alcohol Use Disorder 
PRINCIPAL INVESTIGATOR or FACULTY ADVISOR: 
Investigator: Y. Jazmin Camchong, PhD 
717 Delaware St SE, Suite 516 
Minneapolis, MN 55414 
(612) 624-0134 
camch002@umn.edu 
Co-Investigator: Kelvin O. Lim, MD 
Department of Psychiatry 
Medical School 
F282/2A 2450 Riverside Ave 
Minneapolis, MN 55455-1495 
(612) 273-9765 
kolim@umn.edu 
Co-Investigator: Matt Kushner, PhD 
Department of Psychiatry 
Medical School 
2450 Riverside Ave. 
F282/2A West 
Minneapolis, MN 55454 
(612) 273-9806 
kushn001@umn.edu 
STUDENT INVESTIGATOR: 
N/A 
VERSION NUMBER/DATE: 
10-25-2021 version 
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PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
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PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
REVISION HISTORY 
Revision #
Version Date
Summary of Changes
Consent 
Change?
1
10/03/2017
detailing recruitment methods, consent 
process, inclusion/protection of vulnerable 
populations
No
2
05/14/2018
Adding new recruitment site: Boynton 
Health Services
Yes
3
08/02/2018
Changing title, new K01 funding
Yes
4
08/30/2018
Adding sample size to 50
No
5
12/10/2018
Adding assessment tasks, hotline 
information cards, and expanding inclusion 
Yes
6
05/01/2019
More detailed plan in case of acute mental 
health. Compensation no longer mentioned 
under benefits section. 
No
7
04/09/2019 
Re-submitted 
05/14/2019
Recruitment changes under the CAR 
Recruitment Registry, increasing sample 
size to 70, adding an acceptable time 
window for completion of follow-up visits, 
and indicating participants will be 
compensated with ClinCard. 
No
8
06/06/2019
Addition of an MRI scan at ~1-month 
follow-up with updated compensation. 
Addition of optional saliva collection for 
genotyping. Exclusion criteria regarding 
psychiatric diagnosis changed to only 
exclude those with psychosis. Modify 
definition of follow-up visits with more 
flexible timepoints. Indication of how data 
will be collected for missed visits. Removal 
of Boynton as a recruiting site. Addition of 
optional informed consent to communicate 
through unencrypted email and/or 
Yes
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PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
9
08/05/2019
Addition of form to assess and record more 
detailed understanding of informed consent
Yes
10
02/19/2020
Increase number of consented participants 
to 100. Test for alcohol use at in-person 
follow-up visit on an as-needed basis. 
Yes
11
04/08/2020
COVID19: Only during the COVID19 
crisis, research staff will take subject 
material home.
No
12
05/08/2020
Addition of optional decision-making 
computerized task; Option to complete 
follow-up assessments remotely; Updated 
Set Shifting task stimuli. 
Yes
13
09/10/2020
Modifications related to COVID19 crisis, 
statement saying study will follow Sunrise 
Plan; Addition of research-dedicated room 
in Lodging Plus treatment program.
Yes
14
03/09/2021
Modifications related to routine audit. 
Modifications related to optional ecological 
momentary assessment (EMA) survey.
Yes
15
06/03/2021
Parking reimbursement for participants
Yes
16
08/31/2021
Modification related to maintaining 
COVID19 changes permanently, for having 
the option of either in-person or remote 
visits.
Yes, only 
change is 
new lab 
phone 
number
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PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
Table of Contents 
1.0 
Objectives 
6 
2.0 
Background 
6 
3.0 
Study Endpoints/Events/Outcomes 
7 
4.0 
Study Intervention(s)/Investigational Agent(s) 
8 
5.0 
Procedures Involved 
9 
6.0 
Data and Specimen Banking 
17 
7.0 
Sharing of Results with Participants 
18 
8.0 
Study Duration 
18 
9.0 
Study Population 
18 
10.0 Vulnerable Populations 
20 
11.0 Local Number of Participants 
23 
12.0 Local Recruitment Methods 
23 
13.0 Withdrawal of Participants 
25 
14.0 Risks to Participants 
25 
15.0 Potential Benefits to Participants 
27 
16.0 Data Management 
27 
17.0 Confidentiality 
28 
18.0 Provisions to Monitor the Data to Ensure the Safety of Participants 
28 
19.0 Provisions to Protect the Privacy Interests of Participants 
29 
20.0 Compensation for Research-Related Injury 
29 
21.0 In Case of Acute Mental Health                                                                              29 
22.0 Consent Process 
30 
23.0 Setting 
31 
24.0 Multi-Site Research 
32 
25.0 Resources Available 
32 
26.0 References 
34 
17
10/25/2021
To directly collect EMA data on factors that 
can mediate clinical outcomes (influencing 
Aims 2 and 3), participants will be given the 
option of using a wearable device that 
passively tracks stress and sleep when they 
leave the addiction treatment program. 
Passive data collected from the wearable 
device will be useful to complement and 
compare with the self-report EMA data 
collected through surveys.
Yes
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PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
ABBREVIATIONS/DEFINITIONS 
●
DLPFC - Dorsolateral Prefrontal Cortex
●
NAcc - Nucleus accumbens
●
FC - Functional connectivity
●
AUD - Alcohol use disorder
●
fMRI - Functional magnetic resonance imaging
●
tDCS - Transcranial direct current stimulation
●
CMRR - Center for magnetic resonance research
●
HCP - Human Connectome Project
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PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
STUDY SUMMARY 
Study Title
Effects of Neuromodulation and Cognitive Training 
on Brain Networks Associated with Relapse in 
Alcohol Use Disorder
Study Design
Double-blind, within subject, and sham-controlled
Primary Objective
The overall objective of this proposal is to enhance 
FC between DLPFC and NAcc as a therapeutic 
intervention to enhance cognitive flexibility.
Secondary Objective(s)
Reduce craving in addiction.
Exploratory Objective(s)
Explore associations between genotype/epigenetic 
changes and intervention response.
Research Intervention(s)/
Investigational Agents
Transcranial direct current stimulation and magnetic 
resonance imaging.
IND/IDE # (if applicable)
N/A
Investigational Drug Services 
# (if applicable)
N/A
Study Population
Individuals with alcohol use disorder
Sample Size (number of 
participants)
100 consented
Study Duration for Individual 
Participants
8 months, up to 4-month extension available 
depending on participant availability for follow-ups
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PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
1.
Objectives 
2.
The overarching goal of this project is to expand the traditional expertise in 
non-invasive neuromodulation at the University of Minnesota towards 
developing novel paired-neuromodulation approaches using tDCS for new 
addiction treatments that support long-term abstinence.  This study will allow 
us to investigate whether the pairing of DLPFC stimulation and cognitive 
flexibility training can enhance FC between DLPFC and NAcc.  We have 
identified higher FC between DLPFC and NAcc in alcoholics that have 
successfully maintained abstinence for extended periods of time (7 years). 
This paired-neuromodulation approach can potentially be used as a 
therapeutic intervention to decrease relapse probability in addiction. The long 
term goal is to develop new addiction treatments that support long-term 
abstinence.  The overall objective of this proposal is to enhance FC between 
DLPFC and NAcc as a therapeutic intervention to enhance cognitive 
flexibility and reduce craving in addiction. 
3.
Exploratory objectives: To associate genotypes and epigenetic changes with 
variations in intervention response and clinical outcome. 
2.
Background  
1.
Significance of Research Question/Purpose: The relapsing nature of 
alcoholism is a major obstacle to successful treatment.  About 60% of those 
entering treatment will relapse within one year. To improve treatment 
outcome, new interventions targeting the underlying brain biomarkers of 
relapse vulnerability hold significant promise in reducing this critical public 
health problem. 
2.
Preliminary Data: Using resting functional magnetic resonance imaging 
(fMRI) we have identified brain biomarkers that support long-term 
abstinence. Our cross-sectional and longitudinal findings provide evidence 
that higher functional connectivity (FC), particularly between nucleus 
accumbens (NAcc) and dorsolateral prefrontal cortex (DLPFC), is a potential 
brain biomarker that supports abstinence. Long-term abstinent alcoholics (7 
years of abstinence) have higher resting FC between NAcc and DLPFC when 
compared to controls. Short-term abstinent alcoholics (11 weeks of 
abstinence) have intermediate FC (lower than long-term abstinent alcoholics 
and higher than controls) (Camchong, Stenger, and Fein 2013c, [a] 2013). 
Further, lower FC between NAcc and DLPFC at 11 weeks of abstinence can 
be a predictor of subsequent relapse (with 74% accuracy) (Camchong, 
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PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
Stenger, and Fein 2013b). Moreover, in a pilot longitudinal FC study 
examining resting FC of NAcc at 5 and 13 weeks of abstinence in individuals 
with substance use disorder, we found that FC between NAcc and DLPFC 
decreased from 5 to 13 weeks of abstinence in subsequent relapsers, while it 
increased in subsequent abstainers (Camchong et al. 2014). Based on the 
above, we believe that long-term abstinence is supported by a compensatory 
mechanism that mediates proper executive function over reward (mediated 
by DLPFC-NAcc FC), a potential brain biomarker that could be an 
intervention target. These findings provide a compelling case to explore 
whether this brain biomarker can be modulated to enhance patients’ ability to 
remain abstinent.  There is a need to investigate methods that can be used to 
increase FC between DLPFC and NAcc. 
3.
Existing Literature: Cognitive flexibility, the ability to change maladaptive 
behavior, depends on DLPFC input to NAcc (Gruber, Hussain, and 
O’Donnell 2009). DLPFC transmits reward representations to NAcc through 
glutamatergic projections that guide goal-directed behavior (Ballard and 
Knutson 2009). If DLPFC fails to activate when required, a common 
observation in substance use disorder, target neurons in the NAcc core do not 
receive critical information needed to select the appropriate outcome, causing 
acquired maladaptive response patterns to persist (e.g. drug consumption) 
(Gruber, Hussain, and O’Donnell 2009). Higher FC between DLPFC and 
NAcc may be achieved by stimulating DLPFC while subjects perform a task 
that requires cognitive flexibility, the reversal learning task. Transcranial 
direct current stimulation (tDCS) is a non-invasive brain stimulation 
technique that can modulate brain connectivity. DLPFC stimulation may 
increase input to NAcc to facilitate proper selection of goal-directed behavior 
and may also decrease craving in individuals with substance use disorder 
(Boggio et al. 2008). Genetics and treatment response: A source of treatment 
response variability could stem from differences between participants in 
baseline genetic profiles or epigenetic changes over the course of treatment. 
Genetic polymorphisms, especially in genes important for neuroplasticity, 
may also mediate neuroplastic changes underlying the effects of tDCS 
(Chhabra et al., 2016), as has been demonstrated with gene BDNF (Antal et 
al., 2010; Fritsch et al., 2010). In light of these genetic influences on key 
tenants of our study - i.e. treatment response in alcohol use disorder and 
physiological effects of tDCS - we will collect genetic samples from 
participants to determine whether genetic or epigenetic variations may affect 
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PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
response to the cognitive training and tDCS intervention. This information 
may help inform the development of more individually-tailored treatment 
protocols in the future. As this is a secondary aim, participants will be given 
the choice in the consent form to opt in or out of the genetic sampling 
procedure.
4.
There is preclinical data suggesting that sleep alterations are associated with 
increased alcohol consumption (Garcia-Garcia et al 2021). We have 
preliminary clinical data showing that sleep alterations are associated with 
vulnerability to relapse. The nature of these associations may be specific to 
an individual, so that not enough sleep or too much sleep can be associated 
with relapse vulnerability depending on the individual. Moreover, sleep 
alterations, which are common in alcohol use disorder are associated with 
brain alterations (Zhang et al 2021). It is important to determine whether 
sleep disturbances are a factor that affects treatment outcome in alcohol use 
disorder.
3.
Study Endpoints/Events/Outcomes 
1.
Primary Endpoint/Event/Outcome: In a double-blind randomized design, 100 
abstinent (~2 weeks abstinent) individuals with alcohol use disorder (AUD) 
recruited from Lodging Plus Program will receive 10 sessions (2 sessions per 
day for 5 days) of either (i) transcranial direct current stimulation (tDCS) to 
the PFC or (ii) sham-tDCS. All subjects will perform the reversal learning 
task during tDCS intervention (active or sham) to prime the engagement of 
the NAcc-PFC brain circuit that mediates cognitive flexibility. Rest fMRI and 
craving measures will be collected before the first and after the last day of 
tDCS sessions, and about one month after the last fMRI (timepoint 
depending on participant availability). Monthly follow-up interviews will be 
conducted for approximately 8 months after intervention completion to query 
relapse status. Dependent variables will be (i) change in NAcc-PFC FC 
between 2,3 weeks of abstinence and one month later, (ii) change in craving 
scores between 2 and 3 weeks of abstinence and (iii) relapse status ~8 months 
after study participation. Aim 1: To investigate whether NAcc-PFC FC can 
be modulated, we will compare magnitude and durability of change in NAcc-
PFC FC between active-tDCS and sham-tDCS groups. Aim 2: To determine 
if PFC stimulation has a short-term effect on behavior related to clinical 
outcome, we will compare change in craving scores (difference in craving 
scores between 2 and 3 weeks of abstinence) between active-tDCS and sham-
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PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
tDCS groups. Aim 3: To correlate neuromodulation intervention with long-
term clinical outcome, we will record craving and relapse status during the 
~8 months following treatment discharge.  We will examine the relationship 
between change in NAcc-PFC FC between 2 and 3 weeks of abstinence and 
subsequent (i) monthly craving scores and (ii) relapse status. Aim 4: Examine 
relationships between genetic variants, epigenetic changes and treatment 
outcome (e.g. durability, functional connectivity). 
4.
Study Intervention(s)/Investigational Agent(s) 
1.
Description: As in previous clinical studies that achieved treatment response 
and reduction of relapse probability (Klauss et al. 2014), patients will receive 
two 13 minute daily sessions with a rest interval (no stimulation) of 20 
minutes in between (13:20:13 schedule; as in (Klauss et al. 2014; Monte-
Silva et al. 2013)) of either active (2-mA) or sham transcranial direct current 
stimulation (tDCS) every day for five consecutive days. This study will add 
to the literature by having patients practice the reversal learning task (D’Cruz 
et al. 2011) during tDCS intervention, to enhance paired neuromodulation. 
While patients practice the reversal learning task, half of the patients will 
receive active tDCS stimulation to the left DLPFC to enhance top-down 
control and improve the tuning or gating of the extraneous information and 
the other half will receive sham tDCS.   
2.
The tDCS will be performed with Neuroelectrics Starstim Enobio 20 
(Neuroelectrics Barcelona, Spain).  This device has been approved for use in 
research without an investigational device exemption due to meeting criteria 
for non-significant risk.  In addition, the device has built in safety 
mechanisms which allow for the immediate cessation of stimulation should 
the subject become uncomfortable or impedance levels too high.  The current 
will be administered via two saline soaked electrode sponges (approximately 
25cm²) for two 13 minute blocks.  The current strength during each 
administration will be 2 mA. These administration procedures are in line with 
other protocols that have outlined safe administration (Nitsche et al. 2008, 
2007).  Across more than 2000 subjects no side-effects have been reported 
with the exception of slight itching under the electrode and occasional 
occurrence of headache, fatigue, or nausea (Poreisz et al. 2007).  The anodal 
electrode will be placed over left DLPFC and the cathodal electrode will be 
placed over right DLPFC. 
3.
Drug/Device Handling: We will use transcranial direct current stimulation 
(tDCS) to stimulate dorsolateral prefrontal cortex (DLPFC).  TDCS is a non-
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PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
invasive brain stimulation technique that can modulate brain connectivity. 
TDCS involves applying a weak electrical current (2mA or less) to the scalp 
via anodal and cathodal electrode sponges, causing either increases or 
decreases in cortical excitability, respectively. Research has shown in both 
healthy subjects and patients (e.g. Alzheimer’s disease, Parkinson’s disease, 
stroke, and depression) that tDCS has the potential to modulate synaptic 
strengthening and neurotransmitter-dependent plasticity underlying changes 
in behavior and learning (Lang et al. 2005). 
4.
IND/IDE: N/A 
5.
Biosafety: N/A 
6.
Stem cell research: N/A 
1.
Procedures Involved 
1.
Study Design: This study is double-blind, within subject, and sham-
controlled. The scientific integrity of the trial and the credibility of the data 
from the trial depend substantially on the trial design.  A description of the 
trial design includes: In a double-blind randomized design, 100 abstinent 
(approximately 2 weeks abstinent) individuals with alcohol use disorder 
(AUD) recruited from Lodging Plus Program will receive 10 sessions (2 
sessions per day for 5 days) of either (i) active transcranial direct current 
stimulation (tDCS) to DLPFC or (ii) sham-tDCS. All subjects will perform 
the reversal learning task during tDCS intervention (active or sham) to 
prime the engagement of the NAcc-PFC brain circuit that mediates 
cognitive flexibility (D'Cruz et al., 2011). Rest fMRI and craving measures 
will be collected before the first and after the last day of tDCS sessions. 
Follow-up interviews will be scheduled for each month, but may not happen 
exactly every month, depending on the participant’s availability. Follow-ups 
will be conducted for approximately 8 months after study completion to 
query relapse status. Dependent variables will be (i) change in NAcc-
DLPFC FC between 2 and 3 weeks of abstinence, (ii) change in craving 
scores between 2 and 3 weeks of abstinence and (iii) monthly queries on 
relapse status for the next 6 months after intervention completion. Aim 1: To 
investigate whether NAcc-DLPFC FC can be modulated, we will compare 
magnitude of change in NAcc-DLPFC FC between active-tDCS and sham-
tDCS groups. Aim 2: To determine if DLPFC stimulation has a short-term 
effect on behavior related to clinical outcome, we will compare change in 
craving scores (difference in craving scores between 2 and 3 weeks of 
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PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
abstinence) between active-tDCS and sham-tDCS groups. Aim 3: To 
correlate neuromodulation intervention with long-term clinical outcome, we 
will record monthly craving and relapse status ~8 months after intervention 
completion.  We will examine the relationship between change in NAcc-
DLPFC FC between 2 and 3 weeks of abstinence and subsequent (i) 
monthly craving scores and (ii) relapse status.  Patients will be asked to 
complete these scales monthly for ~8 months after intervention completion 
to examine long-term effects.  Patients will be asked to come back for 3 in-
person (or remote) visits scheduled approximately 1, 4 and 8 months later, 
with the actual date of each visit varying depending on participant 
availability. On a case-by-case basis, follow-ups may be scheduled up to 3 
months after each timepoint (1, 4, and 8 month timepoints) depending on 
participant availability. In these in-person (or remote) visits the participants 
will complete the same assessments and fill out questionnaires assessing 
behavior, personality and substance use metrics as in the baseline 
appointment. At the ~1-month follow-up timepoint, the participant will also 
complete a third MRI session, which could be on the same day of the 
assessments and questionnaires or on a different day, depending on 
participant availability. 
2.
Study Procedures: Randomization:  Participants will be randomly assigned 
to either active or sham tDCS. Blinding:  Participants will not be informed 
on their assigned protocol.  During consent, they will be informed that there 
is a 50% chance of receiving active tDCS or sham tDCS every day for five 
consecutive days. Study appointments will be conducted either in-person, or 
remotely.  
3.
Participants who consent to the study and meet study criteria as per the 
screening evaluation will be asked to participate in an 8-day session study, 
be available for monthly phone follow-up measures after study completion 
to query relapse status and for 3 in-person (or remote) follow-up visits. At 
any of the in-person follow-up visits, research staff may test participants for 
recent alcohol use using a Breathalyzer (will not be administered if 
assessments are remote). Participants will be informed of alcohol level, but 
will not be excluded from the study if test shows recent alcohol use. If 
Breathalyzer shows alcohol level of > 0.08%, participant will be asked to 
reschedule visit. While the target will be to conduct follow-up phone calls 
every month, plus in-person/remote assessments at 1, 4 and 8 months 
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PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
timepoints, the actual date for these follow-up sessions will vary depending 
on participant availability.  
The participants who are referred to our study by the Consortium of 
Addiction Research (CAR; approved under IRB protocol 
#STUDY00005170) will be asked if they are interested in participating. 
Participants will be informed about the study via the “1406M51241 Invite,” 
which informs them that they need to be available for 8 appointments during 
their stay at the treatment program. They also need to be available for 
monthly (depending on subject availability) phone follow-up measures after 
study completion to query relapse status and for the 3 in-person (or remote) 
follow-up visits. 
Baseline Interview: A research staff member will meet the participant either 
in person or through a virtual video conference to complete the informed 
consent process with the participant and administer surveys assessing 
behavior, personality and substance use, and alcohol craving levels. 
Understanding of informed consent will be assessed with the “Assessment 
of Informed Consent” form. Participants will also complete a screening 
questionnaire for contraindications of MRI scanning. Females who could 
potentially be pregnant will be tested for pregnancy and, if positive, will not 
be allowed to participate.  If testing is refused, participation will not be 
allowed. Baseline assessments will take about 1.5 hours total. 
MRI #1: The participant will undergo an MRI scan (3T), which takes about 
75 to 80 minutes. MRI involves taking pictures of the participant's brain, 
from which the properties of certain brain tissues can be measured.  While 
sometimes MRI scans are done for clinical purposes, the scans the 
participant will receive are being done for research purposes.  Since these 
scans are not designed for clinical or medical reading, the participant's scans 
will not receive a clinical or medical interpretation. For the scan, the 
participant will be asked to lie down quietly on a bed, and the bed will slide 
into the scanner. Once the participant is inside the scanner, it will start to 
take the pictures. During the scan, the participant will simply lie quietly in 
the scanner with eyes closed while the scanner takes images of the 
participant's brain. The MRI scan will be performed at the University of 
Minnesota’s Center for Magnetic Resonance Research.  Day 2 assessments 
will take about 1.5 hours total. 
Interventions Days 1-5: Will involve reversal learning task training and two 
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PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
tDCS interventions. We will first explain to the participant what the reversal 
learning task is, and the participant will perform one trial/practice run.  
During the reversal learning task the participant will be presented with four 
identical stimuli.  The participant will be required to choose the stimulus 
that is in the correct location (correct location is randomly determined and 
changes across trials).  Before and after completion of all tDCS 
interventions (pre-intervention and post-intervention), the participant will 
perform the following two tasks:  
Before and after completion of all tDCS interventions (pre-intervention and 
post-intervention), the participant will perform the following two tasks:  
1. Computerized dimensional set shifting task (available in jspsych https://
expfactory.github.io/experiments/): this will measure whether changes in 
cognitive flexibility generalize to a task similar to the task that is practiced 
(reversal learning task, IRB approved) jspsych  
https://expfactory.github.io/experiments/ (additional 7 minutes).  
The Computerized Dimensional Set Shift task is a test of rule acquisition 
and reversal. It involves visual discrimination and attentional set formation 
maintenance, shifting and flexibility of attention. This test is sensitive to 
changes in the fronto-striatal areas of the brain and is a computerized 
analogue of the Wisconsin Card Sorting test. 
Task Description: In this task, participants must use feedback to work out 
a rule that determines which stimulus is correct. After a variable number 
of correct responses, the stimuli and/or rule changes. Initially the task will 
involve simple stimuli which are made up of just one of the dimensions, 
i.e. different geometric shape or line. Later on in the task, compound 
stimuli are used: different types of geometric shapes and different types of 
lines. The shifts in rule are initially intra-dimensional (i.e. shape remain 
the only relevant dimension) and then later extra-dimensional (i.e. line 
become the relevant dimension).  
2.Risk Task (Gilmore et al. 2018; Rogers et al. 1999): 
To evaluate whether there is a generalization effect, the 
Risk task will be administered before and after the 
complete course of intervention.  
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PROTOCOL TITLE: Effects of Neuromodulation and Cognitive Training on Brain 
Networks Associated with Relapse in Alcohol Use Disorder  
VERSION DATE: 10-25-2021
 
The Risk Task is a computerized behavioral measure of the propensity for 
risk-taking within a decision-making task, wherein participants must make 
a choice between high- and low-risk options determined by the ratio of 
blue or red colored boxes potentially hiding a single token; the higher-risk 
option being associated with the higher value reward. 
Two typical displays from the decision-making task 
are shown below, Figures A and B. The subject is told 
that the computer has hidden a yellow token inside 
one of the red or blue boxes arrayed at the top of the 
screen and that he has to decide whether this token is 
hidden inside a red box or a blue box. However, this 
decision involves gambling a certain number of points 
associated with each choice. In the Figure A and B 
examples, if the subject chooses red, then he/she 
gains 30 points if the yellow token is indeed hidden 
inside a red box, but he/she loses 30 points if the token is hidden inside a 
blue box. On the other hand, if the subject chooses blue, then he/she gains 
70 points if the token is hidden inside a blue box, but loses 70 points if it is 
hidden inside a red box. The subject is told that there is an equal 
probability that the token would be hidden inside any of the six boxes.  
The subject indicates his decision by touching one of the two square 
response panels, located at the bottom of the display, containing the 
associated “stake” written in either red or blue ink. Immediately after a 
selection, one of the boxes opens to reveal the location of the token, 
accompanied by either a “You win!” or a “You lose!” message written in 
large yellow font. If the subject chooses the correct color, the stake 
associated with that color is added to the total points score; if the subject 
chooses the wrong color, the same stake is subtracted. No monetary 
significance is attached to the points accumulated by the end of the task. 
At the start of each sequence, the subject is given 100 points and 
instructed to make whatever choices thought necessary to increase this 
score by as much as possible. It is emphasized that these choices might 
involve either conservative or risk-taking behavior. The ratio of colored 
boxes (5:1, 4:2, and 3:3) and the balance between the associated rewards 
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(10 vs 90, 20 vs 80, 30 vs 70, 40 vs 60, and 50 vs 50) vary independently 
from trial to trial according to a fixed pseudorandom sequence. This 
sequence ensures that each balance of reward and each ratio of colored 
boxes co-occurs an equal number of times, with the restriction that on all 
trials with an unequal ratio of red and blue boxes (i.e., 5:1 or 4:2), the 
larger reward is always associated with the least likely outcome (i.e., the 
color with the fewest number of boxes; see Figures A and B), thus 
capturing the conflict inherent in risk-taking situations. 
After the last tDCS day, the participant will be given the same behavior, 
personality, craving and substance use questionnaires as baseline. 
MRI #2:  Follow-up MRI scan with the same procedures as baseline will be 
collected.  Total participation time for MRI #2 will be about 3 hours. 
4.
Optional Procedures 
Optional Ecological Momentary Assessment (EMA) self-report surveys. 
We will gather information related to whether or not the participant has 
experienced: craving, mood states, stressful events, or has used any alcohol 
or drugs. The purpose of adding optional daily EMA surveys is to obtain a 
more granular picture of the timing of events leading to a return to alcohol 
or drug use following treatment. Participants will have the option to fill out 
the EMA survey both (i) at each visit with research staff while they are in 
the treatment program if time allows (once for each visit) and (ii) for the 30 
days following their residential addiction treatment completion (up to three 
daily surveys spaced out throughout the day). Surveys will take about five 
minutes to complete and will be completed via a secure internet enabled 
REDCap survey. Only participants who will have a cell phone that receives 
text messages after discharge from the addiction treatment program will be 
able to opt in the EMA procedure. 
During visits with our research staff while staying in the Lodging Plus 
treatment program. EMA surveys (up to one per day) will be completed on a 
computer via REDCap. REDCap version of the paper survey in ETHOS 
may appear different because of formatting within REDCap. Study staff will 
be available at each of these appointments to answer questions participants 
have about the EMA survey. Participants will be compensated $1 for each 
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EMA completed. Participants will only complete the EMA surveys if time 
allows while in the treatment program. 
After discharge from Lodging Plus, participants will receive text messages 
for 30 days with an embedded link to complete a REDCap survey assessing 
mood, substance use/urges, and use of coping skills. Participants will 
receive a text message at 9am, 2pm, and 7pm including the embedded link 
to the REDCap survey. The survey will be open until midnight that day and 
participants will receive reminders every 1.5 hours or until it is complete. 
Daily reminders will stop at 8:30pm in the evening (or earlier if completed). 
Participants will be compensated $1 for each survey completed. Payment 
will be given weekly and these payments will be processed on the business 
day following each 7-day window. At each weekly payment, participants 
will get a $5 bonus if they have completed at least 2 EMA assessments per 
day in the past week. 
Text messages will be generated through the REDCap and Twilio 
integration with all data stored in REDCap’s secure server. Data will be 
entered directly into the REDCap survey and REDCap ensures that SMS 
transcriptions are not stored in Twilio servers, but are shortly removed after 
completing for security reasons. REDCap version of the paper survey in 
ETHOS may appear different because of formatting within REDCap. 
During the first week of the EMA procedure, study staff will monitor 
completion rates and may contact a participant if two days in a row are 
missed. Participants will be informed that EMA data is not being monitored 
and will be provided mental health resources at the end of every survey. 
Once a participant completes a survey, they will not be able to open it 
again.  
Optional Wearable Device. To collect objective data about sleep, activity 
and other physiology information that may affect treatment outcome, we 
will use a consumer wearable device, the Garmin VivoSmart4 device. This 
device is worn on the wrist and is equipped with an accelerometer, an 
optical heart rate monitor, barometric altimeter, ambient light sensor, and a 
blood oxygenation saturation monitor. The device provides measures on 
sleep, physical activity, heart rate (every sec), and stress level. If the 
participant agrees to this optional portion, they will install the Garmin 
Connect App on their mobile device with a Garmin Connect account and 
then the participant authorizes Garmin to transfer data directly to our 
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secured HST-maintained UMN server. Garmin Connect App will connect 
with the VivoSmart4 device at least once a day to pull data to the 
GarminConnect server. Garmin then pushes the data to the UMN server. 
This will allow us to monitor that data is being received and that the device 
is being charged. Participants who agree to this optional portion will wear 
the device after recruitment and during the complete 8-month follow-up 
period of this study. The participant will be paid $80 for wearing the device 
during the 8-month follow-up period. Besides the upfront App installation 
and authorizing data sharing, there is no additional burden to the participant. 
All data stored in the HST-maintained UMN server will be secured, will 
only be accessible to IRB-approved research staff via password, and will be 
kept for a total of 6 years. At the end of the 8-month follow-up period the 
participant will have the choice of returning the wearable device or keeping 
it for personal use. Research staff will no longer access information 
collected from the wearable device after the 8-month follow-up period is 
over. 
Optional Genetic Sampling Procedure. All participants will be given the 
option to provide one saliva sample for genetic analyses. This sample may 
be collected at any point during participation of the study. A study staff 
member will provide the participant with written step-by-step instructions 
for the collection of a saliva sample using the Oragene DISCOVER saliva 
self-collection kit (DNA Genotek, Ottawa, ON, Canada, Catalog number 
OGR-500) and ask the participant to not eat, drink, smoke or chew gum for 
30 minutes before giving a saliva sample. The total amount of saliva 
collected is approximately 2 milliliters (about half a teaspoon) and will take 
approximately 5 minutes to complete.  
Nucleic Acid (DNA) Extraction: 
Collected samples will be stored in the laboratory of Dr. Jeffrey R. Bishop at 
the University of Minnesota (516 Delaware Street S.E. Phillips-
Wangensteen Building room B150 Minneapolis, MN 55455). Saliva samples 
will be processed for DNA using the prepIT extraction kit following the 
manufacturer’s standard protocol (DNA Genotek, Ottawa, ON, Canada, 
catalog number PT-L2P-5). Extracted DNA will be quantified by the Quant-
iT™ PicoGreen™ dsDNA Assay Kit (Invitrogen, Waltham, MA USA, 
Catalog number P7589) using the Synergy HTX multi-mode plate reader 
(BioTek Instruments, Winooski, VT, USA). 
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Genetic analyses: 
DNA extracted from saliva specimens will be standardized to a working 
concentration of 10-25ng/l prior to analyses. Targeted gene variants will 
be genotyped using TaqMan SNP Genotyping assays and the Applied 
Biosystems 7500 Real Time PCR system (Applied Biosystems, Foster 
City, CA, USA), Restriction Fragment Length Polymorphism (RFLP) 
performed by fragment analysis on the 3730 Genetic Analyzer (Applied 
Biosystems), or multiplexed genotyping assays performed on the 
MassARRAY System (Agena Bioscience) at the University of Minnesota 
Genomics Core facility (UMGC). Genome-wide scale genotyping will be 
performed using microarray or sequencing techniques in consultation with 
the University of Minnesota Genomics Core (UMGC)  For methylation 
detection studies, DNA extracted from saliva specimens will be bisulfite-
converted using the EZ DNA Methylation Kit (Zymo Research, Irvine, 
CA, USA). Bisulfite-modified DNA will be PCR-amplified using primers 
designed to cover target gene regions for CpG site DNA methylation 
detection, and sequenced using the Illumina MiSeq system following a 
standardized protocol at the University of Minnesota Genomics Core 
facility (UMGC). Genome-wide methylation assessments will be 
performed using the Infinium MethylationEPIC BeadChip Kit (Illumina) 
(or comparable alternative) which interrogates over 850,000 methylation 
sites quantitatively across the genome at single-nucleotide resolution. 
Optional computerized decision-making task. Participants will be given 
the option of completing a novel computerized task that measures decision-
making in the context of the neuroeconomics of addiction, the Websurf task. 
The Web-Surf Task provides a rich behavioral economics data space to 
explore complex variables that capture multiple aspects of reward valuation 
and decision-making processes (Sweis et al 2018; Abram et al 2016; Abram 
et al 2019a; Abram et al 2019b).  During this task, participants will be asked 
to make a series of economic choices on a computer for ~ 30 minutes 
simulating the experience of surfing the web for entertaining video clips. 
The participant will be paid $20 for completing this task. The task can be 
completed at any visit (remote or in-person) while in Lodging Plus, and/or at 
any in-person follow-up timepoint. This data may be collected at any point 
(as many as 3 times) during participation of the study. All data collected 
using this task will be encrypted and stored on box.umn.edu or on an AHC-
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IS maintained server (cnc2.med.umn.edu) that is secured and accessible 
only via password to research staff.  
5.
Follow-Up: TELEPHONE FOLLOW-UP:  Monthly follow-up phone 
interviews, for which timing may vary depending on subject availability, 
will be conducted until the 3rd in-person (or remote) follow-up visit is 
completed to query relapse status.  We will ask the participant to provide the 
phone number of a good friend or relative who will know the participant's 
whereabouts to help us re-contact the participant if needed.  IN PERSON 
(OR REMOTE) FOLLOW-UP:  The participant will be asked to complete 
follow-up assessments about 1, 4 and 8 months later (in person or remotely), 
with the actual date of each timepoint varying depending on participant 
availability. The participant will be given the option to complete these 
follow-up assessments over the phone and follow-up questionnaires through 
RedCap. Follow-up timepoints may be conducted up to 3 months after each 
timepoint to maximize scheduling flexibility. At the first follow-up 
timepoint, the participant will undergo a follow-up MRI scan with the same 
procedures as the baseline scan.  At all 3 in-person (or remote) follow-up 
visits, the participant will complete the same assessments and fill out the 
same behavior, personality and substance use questionnaires as baseline. At 
any of the in-person follow-up visits, research staff may test participants for 
recent alcohol use using a Breathalyzer. Participants will be informed of 
alcohol level, but will not be excluded from the study if test shows recent 
alcohol use. If Breathalyzer shows alcohol level of > 0.08%, participant will 
be asked to reschedule visit. At the first in-person timepoint, which will 
happen approximately 1 month after the post-intervention MRI, will be 
about 3 hours. Because of the length, participants will have the choice to 
complete the scan and questionnaire/assessments on separate days. The 
second and third follow-up timepoints will be about 1.5 hours each. 
MISSED VISITS: In the case that a participant misses a telephone or in-
person follow-up assessment, research staff will attempt to collect as much 
missing data as possible at the next contact with the participant.  
6.
Individually Identifiable Health Information: Participants will be probed for 
personal information during the interviewing process. As noted in the 
consent form, participants will be told that all diagnostic and other sensitive 
raw data will be kept in a locked file and available only to authorized 
investigators involved in this study. 
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Trained research staff will be instructed to keep the content of the records 
confidential. During the initial consent process subjects will be told that 
they have the right to refuse to answer questions; however, this may affect 
whether they continue in the study. At all points in the study subjects will 
be warned at the beginning of procedures which involve the disclosure of 
personal and sensitive information. These warnings will occur in the 
introductory comments of interviews or in the instructions of 
questionnaires and surveys. 
Only research staff will have access to subject information. Data contained 
on paper records and computer files will not include names or other 
identifying information of subjects. Records containing identifying 
information will be stored in a private research office in a locked file 
cabinet and be accessible only by the principal investigator and the study 
coordinator. The study coordinator or the principal investigator will review 
and remind research staff of this guideline on a regular basis. Paper and 
electronic records will be kept for 3 years or longer. Paper records not 
under use will be stored in locked file cabinets in a private research space. 
Any identifying information on magnetic or optical media will be stored in 
a similar manner or be password protected. The password for accessing 
this information will be available to only select staff that need access to the 
information to conduct their research duties. All other data will not contain 
identifying information. All other data will be stored on encrypted 
magnetic or optical media that is secured or on computer systems 
accessible only by research staff and computer system administrators via 
password. There is a slight possibility that data (without identifiers) will be 
requested by reviewers and other scientists when study data is presented to 
the scientific community. 
Individuals will complete a screening questionnaire for contraindications 
of MRI scanning. Any affirmative responses on the questionnaire will 
result in an interview regarding the possible contraindication. An attempt 
will be made to secure any records of the nature of the possible 
contraindication and this information will be reviewed by the PI and 
CMRR staff at the University of Minnesota. A determination will be made 
regarding the level of risk to the subject and whether they are approved for 
scanning. If approved for scanning by professionals, all risks to the subject 
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will be conveyed to him or her so they can deliberate as to whether or not 
they want to complete the procedure. Any concerns from the review 
committee will be conveyed to the participant at that time. If the subject 
has certain problematic iron or steel implants in their body that cannot be 
removed, the subject may not have the scan and will be excluded from that 
part of the study. 
There are no known risks to humans due to the static magnetic field.  
Since the risks to fetuses are unknown, pregnant women are excluded 
from the study.  Female subjects in child-bearing years will be informed 
that their consent to participate indicates that they are willing to complete 
a urine pregnancy test to demonstrate that they are not pregnant. Subjects, 
operators, and guests are carefully screened prior to entering the magnetic 
environment, and frequently reminded of the potential danger of 
introducing magnetic objects to the controlled area.  Subjects are 
carefully screened and excluded from the study if they have any 
implanted devices.  Subjects are always accompanied when near the 
magnet, and reminded to move slowly and carefully as they enter and 
leave the magnet. 
The risk of tissue damage by energy emitted by the MRI device is 
controlled by compliance with FDA guidelines for commercial MRI 
devices.  Safety devices are in place so that the magnet will cease to 
operate should any parameters begin to exceed their preset safety limits. 
The risk of peripheral nerve stimulation by dB/dt is limited by safety 
devices. The noise levels generated by each scan are monitored to ensure 
adherence to guidelines. In addition, subjects are provided with earplugs 
and secondary protection (foam covering or headphones) to increase 
comfort during the scan. 
All information obtained from the subject will be strictly for research 
purposes. Our procedures for obtaining this information will conform to 
HIPAA policies.  
7.
Use of radiation: N/A 
8.
Use of Center for Magnetic Resonance Research: This study has CMRR 
(PARS) Project Application Review System (application # 4528)  
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1.
Data and Specimen Banking 
1.
Storage and Access: Only research staff will have access to subject 
information. Records containing identifying information will be stored in a 
private research office in a locked file cabinet and be accessible only by the 
principal investigator and the study coordinator. The study coordinator or 
the principal investigator will review and remind research staff of this 
guideline on a regular basis. Paper and electronic records will be kept for 3 
years or longer. Paper records not under use will be stored in locked file 
cabinets in a private research space. Any identifying information on 
magnetic or optical media will be stored in a similar manner or be password 
protected. The password for accessing this information will be available to 
only select staff that need access to the information to conduct their research 
duties. All other data will not contain identifying information. All other data 
will be stored on encrypted magnetic or optical media that is secured or on 
computer systems accessible only by research staff and computer system 
administrators via password. There is a slight possibility that data (without 
identifiers) will be requested by reviewers and other scientists when study 
data is presented to the scientific community. 
To comply with retention requirements, records including HIPAA and 
consent forms will be retained for at least six years after completion of the 
research. 
 
All biological specimens for genetic analyses collected through this protocol 
will be stored in the laboratory of Dr. Jeffrey R. Bishop at the University of 
Minnesota (516 Delaware Street S.E. Phillips-Wangensteen Building room 
B150 Minneapolis, MN 55455). All specimens will be labeled and stored 
with a study specimen number, not with any personal or protected health 
information. 
•
Data: All diagnostic and other sensitive data will be kept in a locked file and be 
available only to authorized investigators involved in this study.  Identifiers will 
include name, birthdate, address, and telephone numbers.  The PI will keep the 
data file containing the link between subject number and identity.  This will be 
kept in a password-protected computer file and also in printed form in a locked 
file cabinet. Research staff will have access to the identifiers only after a subject 
has agreed to participate in the study. They will use this information only for 
making contact to schedule visits, etc.  
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COVID19: To be able to work remotely during the COVID19 crisis, research staff 
will take subject material home.  
o
Subject material will be kept behind two locked doors. 
o
When transporting equipment and documents, employees will take the 
same precautions as they would when transporting any kind of extremely 
valuable item. The items should be kept out of sight in a closed bag and 
will not be left unattended at any time. The research staff will go straight 
home without any stops, during transportation, the items will be locked 
securely and out of sight in the trunk of their car before they stop. 
o
While the work items are in the research staff’s home, research staff will 
take care that other people in their home are not able to view any 
confidential information. Papers with confidential or sensitive information 
will be kept out of sight of other people in their home. 
o
Items will be returned to the University worksite when employees are able 
to return. Items will not be left at home indefinitely or destroyed/discarded 
at home. 
o
Any loss or theft of PHI or University owned devices will be reported 
immediately to the employee’s supervisor and privacy@umn.edu. 
2.
Genetic data may be banked for future studies. Participants will choose on 
the consent form whether or not they wish for their specimens to be banked 
for future studies. 
3.
If a participant is found to be eligible for this study and completes the 
consent process for this study, all information provided at the CAR 
screening appointment will be made available to us via REDCap access. 
4.
Release/Sharing: The data collected may represent a unique resource for 
some investigators. Following HHS/CDC (Department of Health and 
Human Services/Centers for Disease Control and Prevention) policy, we 
will make the de-identified data available to interested investigators who 
contact us for access to the data. As the proposed work is a clinical trial, the 
most appropriate database for our collected data appears to be 
clinicaltrials.gov.  The investigator, co-investigator, and research staff will 
permit trial-related monitoring, audits, IRB/IEC(s) review and regulatory 
inspection(s) by providing direct access to source data/documentation. 
7.
Sharing of Results with Participants 
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1.
The consent form states that the benefits to the participants as: “There is no 
direct benefit to you to participate in this study. Learning more about brain 
function in psychiatric disorders could aid in directing patient treatment in 
the future”.  No results are shared with participants.
2.
Should participants be interested in up to three screenshots of their MRI 
images for souvenir purposes, they must sign a release of information 
authorizing us to send these photos by mail or through the University of 
Minnesota’s preferred encrypted email service. No identifying details will 
be in the subject line or other non-encrypted text areas.
8.
Study Duration 
1.
Describe:
1.
The anticipated duration an individual participant’s participation in 
the study is ~8 months since recruitment with up to 4-month later 
depending on participant availability for follow-ups.
2.
The duration anticipated to enroll all study participants: 
Anticipated end date Fall 2022.
3.
The duration anticipated to complete all study procedures and data 
analysis: Anticipated end date Winter 2022.
1.
Study Population 
1.
Inclusion Criteria: Abstinent individuals (18-65 years old; ~2 weeks of 
abstinence) who meet DSM-V criteria for alcohol use disorder (AUD) will 
be recruited from the Lodging Plus Program, part of the University of 
Minnesota Medical Center. This 28-day program provides a supervised 
environment to treat alcoholism in which patients receive random drug/
alcohol screenings daily. Lodging Plus has 50 beds and admits an average of 
20 patients per week and 59% of patients admitted have a diagnosis of 
alcohol use disorder. Inclusion criteria: (i) ability to provide written consent 
and comply with study procedures; (ii) meet the Diagnostic and Statistical 
Manual of Mental Disorders (DSM-V) diagnostic criteria for AUD. Subjects 
may have current comorbid drug use, but their primary substance use 
disorder diagnosis needs to be based on alcohol use. Subjects must have the 
intention to remain in the Lodging Plus program until the end of the 
intervention portion of the study. Vulnerable populations will not be 
included. 
2.
Exclusion Criteria: (i) Any medical condition or treatment with neurological 
sequelae (i.e. stroke, tumor, loss of consciousness>30 min, HIV); (ii) a head 
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injury resulting in a skull fracture or a loss of consciousness exceeding 30 
minutes (i.e., moderate or severe TBI); (iii) any contraindications for tDCS 
or MRI scanning (tDCS contraindication: history of seizures; MRI 
contraindications; metal implants, pacemakers or any other implanted 
electrical device, injury with metal, braces, dental implants, non-removable 
body piercings, pregnancy, breathing or moving disorder); (iv)  any primary 
psychotic disorder (e.g. schizophrenia, schizoaffective disorder). 
Participants with other treated and stable psychiatric disorders will be 
included ; (v) presence of a condition that would render study measures 
difficult or impossible to administer or interpret; (vi) age outside the range 
of 18 to 65; (vii) primary current substance use disorder diagnosis on a 
substance other than alcohol except for caffeine or nicotine; (viii) clinical 
evidence for Wernicke-Korsakoff syndrome; (ix) left handedness, (x) 
entrance to the treatment program under a court mandate. Nicotine use will 
be recorded. 
The study staff person will thoroughly describe the study at the baseline 
appointment, either in-person or remotely. Then the patient will be given 
time to read the consent form and ask questions of study staff. If the patient 
agrees they will sign the consent with the study staff person looking on. Part 
of the consent involves asking questions of the patient and having him or her 
record their responses in the Assessment of Informed Consent to ensure they 
understand the study and that they can terminate participation at any point. 
To protect vulnerable populations, if the patient does not seem to fully 
understand the nature of the study (including procedures, risks, 
confidentiality, voluntary nature), they will not be included in the study. 
They are also informed that study staff may terminate study participation at 
any point if they are concerned about the patient’s welfare or behavior.  
3.
Screening: Individuals recruited under the CAR registry have undergone a 
combined screening process, approved as IRB protocol #STUDY00005170.  
Participants referred to our study are asked if they are still interested in 
participating. If they agree, the informed consent process starts. After 
informed consent, individuals will complete a screening questionnaire for 
contraindications of MRI scanning. Any affirmative responses on the 
questionnaire will result in an interview regarding the possible 
contraindication. CMRR staff will need to approve any affirmative response 
before participant can undergo MRI scanning. 
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1.
Vulnerable Populations 
1.
Vulnerable Populations: 
! Children 
! Pregnant women/Fetuses/Neonates 
! Prisoners 
X! 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 
2.
Adults lacking capacity to consent and/or adults with diminished capacity to 
consent 
1.
Study will recruit abstinent individuals (18-65 years old; ~2 weeks of 
abstinence) who meet DSM-V criteria for alcohol use disorder (AUD; 
a psychiatric disorder) will be recruited from the Lodging Plus 
Program, part of University of Minnesota Medical Center. Potential 
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participants will self-identify based on response to a flyers posted on 
IRB approved boards within the treatment program distributed to all 
incoming patients. 
2.
Alcohol use disorder is considered a psychiatric disorder (listed in 
10.1), capacity to consent will be evaluated thoroughly by research 
staff as detailed below.  
3.
Part of the consent involves asking questions of the subject and 
having him or her record their responses in the Assessment of 
Informed Consent form to ensure they understand the study and that 
they can terminate participation at any point. Participants are 
explained the study in detail before giving informed consent and 
evaluated on their capacity to consent with a form that contains the 
following items: 
•
Participant was given time to review the consent form 
•
The Consent document was explained, discussed, and 
reviewed 
•
Study explanation and discussion was completed (check all 
that apply) 
•
The participant’s comprehension was assessed to ensure 
that he/she understands the research and the risks and 
benefits involved in the study 
•
Participant’s questions were answered satisfactorily and 
concerns were addressed 
•
Upon completion of conversation participant did Not have 
any additional questions or concerns 
•
The participant has agreed to participate in the study, and 
has signed and /dated the most current, IRB-approved 
consent form prior to the start of any study procedures. 
•
Written consent was obtained with most recent IRB 
approved consent form 
•
Participant was given a copy of the consent form 
•
The original signed and dated consent form was placed in 
the research record or participant study binder 
4.
To protect vulnerable populations, if the patient does not seem to 
fully understand the nature of the study (including procedures, 
risks, confidentiality, voluntary nature), they will not be included 
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in the study. They are also informed that study staff may terminate 
study participation at any point if they are concerned about the 
patient’s welfare or behavior.
5.
Importance of knowledge to be gained: There are increasing data 
supporting specific cognitive and brain functional connectivity 
abnormalities in alcohol use disorder.  An understanding of 
whether these specific abnormalities can be modulated with 
cognitive training and non-invasive brain stimulation interventions 
will hold significant promise in designing new targeted 
interventions that can reduce vulnerability to relapse and improve 
treatment outcome. The knowledge derived from this research will 
allow us to gather crucial evidence supporting the therapeutic use 
of interventions targeting both cognitive and underlying neural 
mechanisms that support alcohol abstinence. The knowledge 
gained from this study may eventually help guide further research 
in the area and future studies to improve addiction treatment 
programs.
6.
Protection against risk: Trained research staff will be instructed 
to keep the content of the records confidential. During the initial 
consent process subjects will be told that they have the right to 
refuse to answer questions; however, this may affect whether they 
continue in the study. At all points in the study subjects will be 
warned at the beginning of procedures which involve the 
disclosure of personal and sensitive information. These warnings 
will occur in the introductory comments of interviews or in the 
instructions of questionnaires and surveys.
7.
Additional safeguards: 
i. To protect vulnerable populations, if the patient does not seem to 
fully understand the nature of the study (including procedures, 
risks, confidentiality, voluntary nature), they will not be included 
in the study. They are also informed that study staff may terminate 
study participation at any point if they are concerned about the 
patient’s welfare or behavior. 
ii. No neonates, prisoners, individuals who have not attained legal age 
for consent. 
1.
Local Number of Participants 
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1.
Local Number of Participants to be Consented: 100 
1. Local Recruitment Methods
1.
Recruitment Process: Participants recruited under the Consortium of 
Addiction Research (CAR) registry and referred to this study will be 
recruited. CAR research staff will give qualifying participants the 
“1406M51241 Invite,” which provides a brief study description, a study 
appointment time, and a Consent Form to review before their appointment if 
they are interested in completing the study.
2.
If participants cannot make it to the appointment but do wish to learn more 
about the study, they are instructed to return the note requesting another 
appointment date. If participants do not show up at the appointment time 
and no note is returned, research staff will assume they are not interested in 
the study and will not try to look for them. 
3.
If participants do show up to their appointment, research staff will give them 
detailed information about the study. If participants are still interested in 
participating in the study after learning all details of the study, research staff 
will ask them if they would like to answer confidential questions to confirm 
that they qualify to be in the study.
4.
If participants do not qualify to be in the study, research staff will thank 
them for their time. . If participants do qualify to be in the study, research 
staff will let them know that they do qualify to be in the study and ask them 
if they are still interested to be in the study. If so, research staff will proceed 
(e.g. consent, HIPAA, etc).
5.
When a subject arrives for their first study appointment they will complete a 
consent process. A trained and IRB-approved study staff person will carry 
out the process. The study staff person will describe the study, consent form, 
and the required signatures if the individual agrees to commence with the 
study. Then the subject will be given time to read the consent form and ask 
questions of study staff. If the subject agrees they will sign the consent form 
with the study staff person looking on. Part of the consent involves asking 
questions of the subject and having him or her record their responses to 
ensure they understand the study and that they can terminate participation at 
any point. They are also informed that study staff may terminate study 
participation at any point if they are concerned about the subject’s welfare or 
behavior.
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6.
Source of Participants: Only participants recruited under the Consortium 
of Addiction Research (CAR) will be recruited.
7.
Identification of Potential Participants: Only participants recruited under the 
Consortium of Addiction Research (CAR) and referred to our study by the 
CAR will be recruited. Participants will not be recruited based on 
information contained in private/protected records (e.g., medical records, 
student records; note that this also includes participants who will be 
recruited from the PI’s or Co-PI’s patient or student population.)
1. No private/protected records will be used. 
2. Potential participants will self-identify and express their interest 
after learning about the study through the CAR registry. 
3. No MEDICAL records will be used.  
4. HIPAA form states that the participant does agree to have research 
staff communicate with treatment program staff that they are 
participating in research so that they know their whereabouts 
during their break time. 
8.
Recruitment Materials: Only participants recruited under the Consortium of 
Addiction Research (CAR) and referred to our study by the CAR will be 
recruited. 
9.
Payment: There is no cost for the participant to be in the study.  Participant 
will be compensated at the end of each of each day of participation (8 
potential days plus three follow-up timepoints).  Participants will be 
compensated $25 for Baseline questionnaires completed; $25 at the end of 
the second MRI scan; $10 for tDCS interventions days 1-5; $25 on MRI #2 
for questionnaires completed; and $25 for the scan.  For the first follow-up 
timepoint   the participant will be compensated with $100 ($50 for the 
questionnaires/assessment session and $50 for the MRI scan). For the 
second and third follow-up timepoints, the participant will be compensated 
with $100. To summarize, if a participant completes all participation days, 
they can receive up to $450 for participating in this study. Additionally, if 
participants choose to complete the optional Websurf task (~30 minutes), 
they will be compensated with $20 for each task completion (Participants 
can complete this task up to three times during their participation in this 
study). If participants choose to complete the daily optional Ecological 
Momentary Assessment survey during their visits while they are in the 
treatment program, they will receive $1 per completed EMA assessment. 
(EMA payment will be given weekly and these payments will be processed 
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on the business day following each 7-day window. At each weekly EMA 
payment during the follow-up period, participants will get a $5 bonus if they 
have completed at least 2 EMA assessments per day in the past week). If 
participants choose to complete the wearable device optional portion of the 
study, they will receive $80. All compensation will be awarded through a 
reloadable Greenphire ClinCard. 
Parking expenses up to $7 will be reimbursed to the participant if they need 
to pay parking at each in-person follow-up visit. 
No Research Experience Points will be awarded. 
1.
Withdrawal of Participants 
1.
Withdrawal Circumstances: The prospective participants will be able to 
discontinue study participation at any time. The participants may choose to 
discontinue stimulation at any time during the session if experiencing 
excessive discomfort or side effects. Criteria for discontinuation related to 
intervention: i) sores at the tDCS administration site; ii) headaches that 
impair global functioning.  If subjects choose to stop their participation, they 
will be released from the study. To protect vulnerable populations, if a 
patient that was deemed capable of providing consent goes through 
unforeseeable situations that may affect their capacity to consent, their 
capacity will be reassessed, and if not deemed capable, they will not be 
withdrawn from the study. Participants are also informed that study staff 
may terminate study participation at any point if they are concerned about 
the patient’s welfare or behavior.  
2.
Withdrawal Procedures: If participants withdraw from procedures, all their 
data collected until the withdrawal data will be retained.  No new data will 
be collected from any private/protected record.  
3.
Termination Procedures: If at any point research staff is concerned about 
participant’s welfare or behavior, they will notify the participant that their 
participation in the study needs to terminate because of safety reasons.  The 
participant will be paid for their time as per 12.5 until their last active 
participation day. Data collected until the termination date will be used and 
considered incomplete.  
1.
Risks to Participants 
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1.
Foreseeable Risks: tDCS is considered to be a non-invasive investigational 
device that involves applying a weak electrical current to the scalp. This 
device has been labeled as a non-significant risk device by the FDA for 
investigational purposes. There is currently no evidence of serious side-
effects. Mild side-effects that typically resolve upon discontinuing tDCS 
include light itching under the electrode at the beginning of administration, 
headache, fatigue, and nausea. The subject may choose to discontinue 
stimulation at any time during the session if experiencing excessive 
discomfort or side effects. Although seizures are not a known risk of tDCS 
intervention (Fregni et al., 2006), anyone with a history or a risk for seizures 
will be excluded from the study.  No other risks related to tDCS are 
anticipated. To minimize risks regarding tDCS, study staff will be using 
standards of administration that have been shown as safe in numerous other 
studies using transcranial direct current stimulation.  The length of 
administration of the current, size of electrode sponges used, and method of 
applying stimulation are the same as methods of administration that have 
been demonstrated as safe.  
2.
The other potential risks pertain to the maintenance of confidentiality. 
Participants will be probed for personal information during the interviewing 
process. As noted in the consent form, participants will be told that all 
diagnostic and other sensitive raw data will be kept in a locked file and 
available only to authorized investigators involved in this study. To 
minimize confidentiality risks, as noted in the consent form, all diagnostic 
and other sensitive raw data will be kept in a locked file and be available 
only to authorized investigators involved in this study. Genetic and 
epigenetic information will be for research purposes only and will not be 
included in participants’ medical records. Genetic specimens and data will 
be labeled with the participant’s study ID number and will not contain 
personally identifying information. Confidentiality is not absolute. Research 
staff are mandated reporters and are legally required to report suspicion of 
child or vulnerable adult abuse or neglect to the relevant authorities.  
3.
MRI risks. Individuals will complete a screening questionnaire for 
contraindications of MRI scanning. Any affirmative responses on the 
questionnaire will result in an interview regarding the possible 
contraindication. An attempt will be made to secure any records of the 
nature of the possible contraindication and this information will be reviewed 
by the PI and CMRR staff at the University of Minnesota. A determination 
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will be made regarding the level of risk to the subject and whether they are 
approved for scanning. If approved for scanning by professionals, all risks to 
the subject will be conveyed to him or her so they can deliberate as to 
whether or not they want to complete the procedure. Any concerns from the 
review committee will be conveyed to the participant at that time. If the 
subject has certain problematic iron or steel implants in their body that 
cannot be removed, the subject may not have the scan and will be excluded 
from that part of the study. 
1.
There are no known risks to humans due to the static magnetic 
field. Subjects, operators, and guests are carefully screened prior to 
entering the magnetic environment, and frequently reminded of the 
potential danger of introducing magnetic objects to the controlled 
area.  Subjects are carefully screened and excluded from the study 
if they have any implanted devices.  Subjects are always 
accompanied when near the magnet, and reminded to move slowly 
and carefully as they enter and leave the magnet. 
2.
The risk of tissue damage by energy emitted by the MRI device is 
controlled by compliance with FDA guidelines for commercial 
MRI devices.  Safety devices are in place so that the magnet will 
cease to operate should any parameters begin to exceed their preset 
safety limits. The risk of peripheral nerve stimulation by dB/dt is 
limited by safety devices. The noise levels generated by each scan 
are monitored to ensure adherence to guidelines. In addition, 
subjects are provided with earplugs and secondary protection 
(foam covering or headphones) to increase comfort during the 
scan. 
3.
Reproduction Risks: Since the MRI risks to fetuses are unknown, 
pregnant women are excluded from the study.  Female subjects in 
child-bearing years will be informed that their consent to 
participate indicates that they are willing to complete a urine 
pregnancy test to demonstrate that they are not pregnant.  
4.
Risks to Others: N/A. 
15. Potential Benefits to Participants 
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1.
Potential Benefits: There is no direct benefit to you to participate in this 
study. Learning more about brain function in psychiatric disorders could aid 
in directing patient treatment in the future. 
16. Data Management 
1.
Data Analysis Plan: A mixed model analysis of variance will be conducted 
with between-group measures (sham vs active tDCS) and within-group 
measures (FC and craving reports before and after cognitive flexibility 
training and tDCS intervention).  This mixed model analysis will examine 
main effects and interaction effects. To examine the long-term effects of 
cognitive flexibility training and tDCS, we will conduct a repeated measures 
analysis using longitudinal data collected monthly for 6 months after 
intervention completion.  A Log-rank (Mantel-Cox) Test (used in Klaus et al 
2014) will be conducted to establish the efficacy of cognitive flexibility 
training and active tDCS vs. cognitive flexibility training and sham tDCS in 
the time domain. 
2.
Power Analysis: The study in reference is a pilot study for which a power 
analysis is not applicable. 
3.
Data Integrity: The principal investigator and co-investigator will monitor 
data quality for this study.  They will ensure that data are generated, 
documented (recorded), and reported, in compliance with this protocol, with 
Good Clinical Practice, and any other applicable regulatory requirements. 
17. Confidentiality 
1.
Data Security: Trained research staff will be instructed to keep the content of 
the records confidential. During the initial consent process subjects will be 
told that they have the right to refuse to answer questions; however, this may 
affect whether they continue in the study. At all points in the study subjects 
will be warned at the beginning of procedures which involve the disclosure 
of personal and sensitive information. These warnings will occur in the 
introductory comments of interviews or in the instructions of questionnaires 
and surveys. 
Only research staff will have access to subject information. Data contained 
on paper records and computer files will not include names or other 
identifying information of subjects. Records containing identifying 
information will be stored in a private research office in a locked file cabinet 
and be accessible only by the principal investigator and staff. The study 
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coordinator or the principal investigator will review and remind research 
staff of this guideline on a regular basis. Paper and electronic records will be 
kept for 3 years or longer. Paper records not under use will be stored in 
locked file cabinets in a private research space. Any identifying information 
on magnetic or optical media will be stored in a similar manner or be 
password protected. The password for accessing this information will be 
available to only select staff that need access to the information to conduct 
their research duties. All other data will not contain identifying information. 
All other data will be stored on encrypted magnetic or optical media that is 
secured or on computer systems accessible only by research staff and 
computer system administrators via password.  
No copy of the consent form or other research study information will be 
placed in the participants’ medical, employment, or educational records. 
1.
Optional Unencrypted Digital Communication With Participants: 
Participants have the option to provide informed consent for the 
study team to contact them using unencrypted email and/or 
unencrypted text message. This communication would primarily be 
used for appointment scheduling purposes. Souvenir MRI 
screenshots will not be sent using unencrypted communication 
means.  
18. Provisions to Monitor the Data to Ensure the Safety of Participants 
N/A 
19. Provisions to Protect the Privacy Interests of Participants 
1.
Protecting Privacy: Only research staff will have access to subject 
information. Data contained on paper records and computer files will not 
include names or other identifying information of subjects. Records 
containing identifying information will be stored in a private research office 
in a locked file cabinet and be accessible only by the principal investigator 
and the study coordinator. The study coordinator or the principal 
investigator will review and remind research staff of this guideline on a 
regular basis. Paper and electronic records will be kept for 3 years or longer. 
Paper records not under use will be stored in locked file cabinets in a private 
research space. Any identifying information on magnetic or optical media 
will be stored in a similar manner or be password protected. The password 
for accessing this information will be available to only select staff that need 
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access to the information to conduct their research duties. All other data will 
not contain identifying information. All other data will be stored on 
encrypted magnetic or optical media that is secured or on computer systems 
accessible only by research staff and computer system administrators via 
password. 
2.
As part of study interviews, questions may be asked which touch on 
sensitive or private issues which the subject may feel uncomfortable 
discussing. Although there is a potential for disclosure of sensitive personal 
information, every effort will be made to lessen the risk. The subject may 
refuse to answer any questions they do not wish to answer at any time; 
however, this may lead to their discontinuation from the study protocol. 
3.
Access to Participants: Research team will not access any medical records 
from participants.  
1.
Compensation for Research-Related Injury 
1.
Compensation for Research-Related Injury: There is no compensation in the 
event of research-related injury.  The consent form states: “In the event that 
this research activity results in an injury, treatment will be available, 
including first aid, emergency treatment and follow-up care as needed.  Care 
for such injuries will be billed in the ordinary manner, to you or the 
participant's insurance company.  If you think that you have suffered a 
research-related injury, please let us know right away.”  
2.
Contract Language: N/A 
21.0
In Case of Acute Mental Health   
1.
If a participant endorses thoughts of suicide (SCID-IV screening), the 
action(s) taken will depend on the level of risk.  
For low risk, research staff will encourage the participant to speak with 
their treatment program (e.g. Lodging Plus) therapist and give an IRB 
approved resource card with the following information:  
•
Thoughts of suicide: National Suicide Prevention Lifeline, 
1-800-273-8255
•
Feeling like a threat to yourself or others: 911
•
Addiction and mental health services referral: Substance Abuse 
and Mental Health Services Administration, 1-800-662-4357
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For medium risk, research staff will consult with the PI and/or the study 
clinicians prior to the participant leaving the appointment to determine 
best steps to take. Recommended steps include continued monitoring, 
encouraging use of the suicide hotline as needed, and consulting the 
participant's therapist. 
For high risk, research staff will immediately alert the PI and/or study 
clinicians to ensure proper steps are taken. Research staff will inform 
treatment staff (e.g. Lodging Plus) directly. If neither is available, research 
staff will bring the participant to the Fairview-Riverside UMMC 
Emergency Department for care. 
2.
If a participant is suffering from active and/or unstable Axis I disorders, 
suicidal ideation, and/or homicidal ideation mid-study, their participation 
will be discontinued.   
1.
Consent Process 
1.
Consent Process (when consent will be obtained): Consent will take place 
either in a private room in the Ambulatory Research Center housed in the 
Department of Psychiatry at the University of Minnesota (in person) or in a 
private research-designated area within the Lodging Plus addicDon 
treatment program (remotely). Depending on locaDon, consent will be 
completed in person or remotely (through a video conference). If consent is 
completed remotely, an eConsent form will be completed in RedCap while 
using Zoom or a phone call.  
COVID-19 AdaptaDons: The following modiﬁcaDons to consent procedures 
may be used to miDgate pandemic-related risks while parDcipaDng in this 
study. These modiﬁcaDons may stay in place even aOer the pandemic-
related risks are considered to have diminished:  
•
Consent procedures will be completed remotely 
using REDCap, while also using Zoom or a phone call to 
communicate to the parDcipant who will be in a private 
research-designated area within the Lodging Plus addicDon 
treatment program. The physical consent form will be available 
to the parDcipant at the Lodging Plus addicDon treatment 
program and then a copy with all required emailed to them.  
•
The electronic versions of forms in REDCap may be 
formaRed slightly diﬀerent than the paper versions, due to 
limited formaTng opDons in REDCap. The content will be the 
same.  
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The study research staff will thoroughly describe the study and read the 
consent form. Then the patient will be given time to read the consent form 
and ask questions of study staff. If the patient agrees, they will sign the 
consent with the study staff person looking on. Part of the consent involves 
asking questions of the patient and having him or her record their responses 
in the Assessment of Informed Consent form to ensure they understand the 
study and that they can terminate participation at any point. To protect 
vulnerable populations, if the patient does not seem to fully understand the 
nature of the study (including procedures, risks, confidentiality, voluntary 
nature), they will not be included in the study. They are also informed that 
study staff may terminate study participation at any point if they are 
concerned about the patient’s welfare or behavior.  
2.
To ensure ongoing consent: After consent is provided and at each 
intervention day, participants are monitored for any concerns they have 
about the intervention with the Treatment Side Effect Questionnaire. 
Participants who agree to continue in the study will sign this questionnaire 
daily. 
3.
Waiver or Alteration of Consent Process (when consent will not be 
obtained): N/A 
4.
Non-English Speaking Participants: We will not enroll participants who do 
not speak English. 
5.
Participants Who Are Not Yet Adults (infants, children, teenagers under 18 
years of age): We will not recruit participants under 18 years of age. 
6.
Cognitively Impaired Adults, or adults with fluctuating or diminished 
capacity to consent: We will record the informed consent process in the 
“Documentation of the Informed Consent Process” to ensure full 
understanding of study procedures and voluntary nature. In addition to the 
informed consent assessment, participants will complete the Montreal 
Cognitive Assessment (MoCA), which has been modified to be administered 
remotely (Blind – Version 8.1). This will be administered at the baseline 
visit after Informed Consent. If a participant has a score of 14 or below (out 
of 22 possible points), they will not be included in the study because of 
potential cognitive impairment.  
7.
Adults Unable to Consent: We will not recruit any individual unable to 
consent for themselves.  
1.
Setting 
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1.
Research Sites:  
1.
This study has been approved by Fairview after following research 
approval procedures. Participants will be recruited from Lodging 
Plus treatment program for addiction, part of the University of 
Minnesota Medical Center. 
2.
Screening, consent, interview, assessments and tDCS intervention 
will take place either at the Ambulatory Research Center in the 
Psychiatry Department (2nd floor, same building as Lodging Plus 
treatment program) or at a research-dedicated room within the 
Lodging Plus treatment program. These procedures will be done in 
person or remotely. 
3.
Only brain scans will be conducted at the Center for Magnetic 
Resonance Research (CMRR). 
4.
Biological samples for genetic analyses will be stored and 
processed at the laboratory of Dr. Jeffrey R. Bishop at the 
University of Minnesota (516 Delaware Street S.E. Phillips-
Wangensteen Building room B150 Minneapolis, MN 55455). 
24.
Multi-Site Research 
N/A 
25.
Resources Available 
1.
Resources Available:  
1.
To collect complete data for 70 participants, we expect to screen 
and consent approximately 100 participants with alcohol use 
disorder.  We estimate to have a 25% attrition rate which will yield 
data collection from 70 participants.   
2.
30% of PIs effort will be dedicated to completing the research. 
3.
Facilities: 
i. Laboratory of Neuropsychiatric Imaging (LNPI; led by Dr. 
Lim). Dr. Camchong is part of the LNPI, a multidisciplinary 
research group that studies the biological underpinnings of 
neuropsychiatric disorders by combining imaging techniques with 
neurocognitive assessments and genetics. The facility is a fully 
equipped and secure research laboratory supported by the UMN 
Medical with private offices and conference rooms, full computer 
and telecommunication systems and support, secure entrance and 
file storage, private research testing rooms, a reception desk and 
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waiting area for research subjects, and physical space to house 
multiple research staff and support graduate student research 
efforts. All of these resources are currently and will continue to be 
available to the P.I. 
ii. Center for Magnetic Resonance Research (CMRR). The CMRR 
is located on the UMN campus. This imaging center was 
established in 1991 as a result of the rapidly growing and 
successful in vivo magnetic resonance imaging (MRI). CMRR is 
an interdepartmental and interdisciplinary research laboratory that 
provides state-of-the-art instrumentation, expertise, and 
infrastructure to carry out biomedical research utilizing the unique 
capabilities provided by high field MRI and MRS methodology. 
The central aim of the research conducted in CMRR is to non-
invasively obtain functional, physiological, and biochemical 
information in intact biological systems, and use this capability to 
probe biological processes in health and disease. The CMRR is 
currently equipped with nine high field magnets for humans with 
magnetic field strength of 3 Tesla and greater, with the most 
notable being a 10.5 Tesla/89cm. MRI data (resting, task-evoked 
and high-resolution structural scans) will be collected using a 32-
channel head coil on a Siemens Prisma FIT 3T scanner (Siemens 
Medical Solutions, Erlangen, Germany). The Prisma was inspired 
by the success of the Connectome 3T systems, in particular the 
one-of-a-kind modified Siemens Skyra system that was built 
specifically for the WU-Minn Human Connectome Project (HCP) 
consortium (Connectome Skyra). The HCP is from the 16 NIH 
Institutes and Centers that support the NIH Blueprint for 
Neuroscience Research. The consortium led by Washington 
University, University of Minnesota, and Oxford University (the 
WU-Minn HCP consortium) is comprehensively mapping human 
brain circuitry in a target number of 1200 healthy adults using 
cutting-edge methods of non-invasive neuroimaging. The unique 
features of the Prisma system are based on an integrated system 
that combines a high strength gradient system with capability of 80 
mT/m @ 200 T/m/s (FDA approved mode, but capable of 100 mT/
m in research mode), an advanced RF receiver system that provide 
better signal-to-noise performance, 64 channel receive capability. 
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Accelerated data collection provides improved signal in resting 
state networks (Griffanti et al 2014). HCP has developed and 
supports multiband acquisition sequences for the Prisma, which 
accelerate data acquisition by a factor of up to 12. These fMRI 
sequences use MB factor of 8, allowing us to collect 32 slices in 
1/8 TR, which is 8 simultaneous slices in one TR. 
iii. Biological samples for genetic analyses will be stored and 
processed at the laboratory of Dr. Jeffrey R. Bishop at the 
University of Minnesota (516 Delaware Street S.E. Phillips-
Wangensteen Building room B150 Minneapolis, MN 55455). 
iv. Kelvin O. Lim, MD will be available in case of unanticipated 
issues. 
v. All research staff will undergo protocol training. Only trained 
research staff will obtain consent.
1.
References 
Abram S. V., Hanke M., Redish A. D., MacDonald A. W. (2019) Neural signatures 
underlying deliberation in human foraging decisions. Cognitive, Affective, & 
Behavioral Neuroscience, 19(6):1492-1508. 
Abram S. V., Redish A. D., MacDonald A. W. (2019) “Learning from loss after risk: 
Dissociating reward pursuit and reward valuation in a naturalistic foraging task” 
Frontiers in Psychiatry 
Abram S. V., Breton Y. A., Schmidt B., Redish A. D., MacDonald III A. W. (2016) “The 
Web-Surf Task: A translational model of human decision-making” Cognitive, 
Affective, and Behavioral Neuroscience 16(1):37-50. 
Ballard, Kacey, and Brian Knutson. 2009. “Dissociable Neural Representations of Future 
Reward Magnitude and Delay during Temporal Discounting.” NeuroImage 45 (1): 
143–50. 
Boggio, Paulo S., Natasha Sultani, Shirley Fecteau, Lotfi Merabet, Tatiana Mecca, Alvaro 
Pascual-Leone, Aline Basaglia, and Felipe Fregni. 2008. “Prefrontal Cortex 
Modulation Using Transcranial DC Stimulation Reduces Alcohol Craving: A 
Double-Blind, Sham-Controlled Study.” Drug and Alcohol Dependence 92 (1-3): 
55–60. 
Camchong, Jazmin, Angus W. Macdonald 3rd, Bryon A. Mueller, Brent Nelson, Sheila 
Specker, Valerie Slaymaker, and Kelvin O. Lim. 2014. “Changes in Resting 
Functional Connectivity during Abstinence in Stimulant Use Disorder: A 
Preliminary Comparison of Relapsers and Abstainers.” Drug and Alcohol 
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