Mindful Breathing and Neuromodulation for Depression in Young People
Phase: NA
Conditions: Depression, Depressive Disorder
Sponsor: University of Minnesota

PROTOCOL TITLE: STUDY00004214 Mindful Breathing and Neuromodulation for 
Depression in Young People 
 
VERSION DATE: 03/11/2021 
 
 
Page 1 of 53 
Revised: 1/19/2018 
 
PROTOCOL COVER PAGE  
 
 
 
 
 
 
Protocol Title 
Mindful Breathing and Neuromodulation for Depression in 
Young People 
Principal 
Investigator/Faculty 
Advisor 
Name: Kathryn Cullen 
Department: Psychiatry 
Telephone Number: (612) 273-9762 
Email Address: rega0026@umn.edu 
Student 
Investigator 
Name: Michelle Thai 
Current Academic Status (Student, Fellow, Resident): 
 Student 
Department: Psychology 
Telephone Number:  612-626-7065 
Institutional Email Address: thaix049@umn.edu 
Scientific 
Assessment 
HRPP facilitated scientific assessment 
IND/IDE # (if 
applicable) 
N/A. 
IND/IDE Holder 
N/A. 
Investigational Drug 
Services # (if 
applicable) 
N/A. 
Version 
Number/Date: 
Version 17    3/11/2021 
 

PROTOCOL TITLE: STUDY00004214 Mindful Breathing and Neuromodulation for 
Depression in Young People 
 
VERSION DATE: 03/11/2021 
 
 
Page 2 of 53 
Revised: 1/19/2018 
 
REVISION HISTORY 
 
 
Version # 
Version Date 
Summary of Changes 
Consent Change? 
1 
9/16/18 
Initial submission 
No 
2 
1/23/19 
Removed pre-/post-EEG during 
tDCS sessions 1-10, questionnaire 
updates, changing total at-home 
MBT training to 4 weeks, changes 
in recruitment and assessments  
Yes 
3 
2/4/19 
Added new titles corresponding 
with grants, updating times and 
adding procedure details, added 
PSQI, removed emotion regulation 
task. 
 
Yes 
4 
3/4/19 
Expanded age range, updated 
payment, added future re-contact. 
 
5 
3/21/19 
Added recruitment from clinic, re-
administering the MINI depression 
module post-intervention, clarified 
study details, changed 
randomization to be based on sex 
only 
 
6 
4/26/19 
Made MRI optional and clarified 
procedures in the case of poor 
data quality and technical errors, 
updated outcomes to be 
consistent with aims, clarified 
details about MBT, added stress 
biology measurements, updated 
compensation, and added new 
recruitment material  
Yes 
7 
8/1/19 
Updates to recruitment materials 
and increased flexibility about 
rescheduling sessions  
No 
8 
8/14/2019 
Changed procedure for MRI 
toxicology screen to reflect that 
participants will be scanned if 
No 

PROTOCOL TITLE: STUDY00004214 Mindful Breathing and Neuromodulation for 
Depression in Young People 
 
VERSION DATE: 03/11/2021 
 
 
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Revised: 1/19/2018 
results are positive, and we have 
taken out language that stated the 
PI will be called if results are 
positive since recent drug use is 
not a safety issue.  
9 
9/11/2019 
Remote completion option for 
REDCap self-report online 
questionnaires has been added to 
increase flexibility with 
questionnaire completion when 
participants have time constraints 
at in-person appointments. 
No 
10 
10/18/2019 
1) Change in phone screen process 
involves the addition of an online 
eligibility survey link (MADRS-S 
via REDCap). Completion of 
MADRS-S during the phone screen 
will help reduce participant and 
staffing burden by allowing staff to 
know which participants meet the 
basic requirement of eligibility 
(MADRS-S score of 13 or more). 
2) Added standardized language 
provided by CMRR, approved by 
the IRB regarding usage of CMRR 
subject safety screening forms. 
3) Change in procedure for 
completing 3 weeks of mindful 
breathing training- participants will 
be given the option of doing it in 
person only if the study team 
determines it would be helpful for 
the participant.  
No 
11 
 
 
 
 
 
 
1/16/2020 
1) Added language regarding the 
risks of using text messaging and 
email communication with 
participants. 
2) REDCap questionnaire (Cash 
Choice Task) added.  
3) Clarified that the post-tDCS EEG 
and MRI will be completed within 
1-2 business days, instead of 1-2 
days.  
No 

PROTOCOL TITLE: STUDY00004214 Mindful Breathing and Neuromodulation for 
Depression in Young People 
 
VERSION DATE: 03/11/2021 
 
 
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Revised: 1/19/2018 
4) Added clearer language stating 
that participants are not required 
to complete all five mindful 
breathing sessions during the 
ramp-up period in order to begin 
in-person tDCS and mindful 
breathing. 
5) Added new location 
(Department of Psychiatry at Park 
Plaza) for consenting and 
conducting clinical intervNAiews. 
Clarified that the Center for 
Neurobehavioral Development is 
used for consenting and clinical 
interviews.  
12 
3/18/2020 
 
 
 
1) Changed study exclusion 
criteria- removed “family history of 
epilepsy” as this is not a safety 
concern for tDCS. 
2) Changed inclusion criteria 
regarding study population to 
Female, 17 to 24 year old, in order 
to decrease sample heterogeneity.  
No 
13 
3/24/2020 
Remote completion option for 
study procedures due to COVID-19. 
No 
14 
6/8/2020 
Took out language stating that 
participants will be randomized 
according to sex since the study is 
now recruiting females only. 
Added language regarding 
withdrawal of participants who 
appear to be unduly stressed 
(section 12.1). 
 
Yes 
15 
8/28/2020 
Included language to allow 
flexibility about repeating visits if 
there is a delay between baseline 
visits and the start of tDCS and 
MBT.  
Yes  
16 
11/04/2020 
Included language to allow 
participants to be screened using 
Yes 

PROTOCOL TITLE: STUDY00004214 Mindful Breathing and Neuromodulation for 
Depression in Young People 
 
VERSION DATE: 03/11/2021 
 
 
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Revised: 1/19/2018 
 
 
 
REDCap surveys. Updated 
recruitment materials for phone 
number.  
17 
3/11/2021 
Clarified in the protocol that the 
MADRS-S may be repeated if 
clinically indicated  
No  

PROTOCOL TITLE: STUDY00004214 Mindful Breathing and Neuromodulation for 
Depression in Young People 
 
VERSION DATE: 03/11/2021 
 
 
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Revised: 1/19/2018 
Table of Contents 
 
1.0 
Objectives................................................................................................................ 8 
2.0 
Background ............................................................................................................. 8 
3.0 
Study Endpoints/Events/Outcomes ...................................................................... 11 
4.0 
Study Intervention(s)/Investigational Agent(s) .................................................... 11 
5.0 
Procedures Involved ............................................................................................. 12 
6.0 
Data and Specimen Banking ................................................................................. 25 
7.0 
Sharing of Results with Participants ..................................................................... 25 
8.0 
Study Population ................................................................................................... 26 
9.0 
Vulnerable Populations ......................................................................................... 28 
10.0 
Local Number of Participants................................................................................ 29 
11.0 
Local Recruitment Methods .................................................................................. 29 
12.0 
Withdrawal of Participants ................................................................................... 30 
13.0 
Risks to Participants .............................................................................................. 31 
14.0 
Potential Benefits to Participants ......................................................................... 35 
15.0 
Statistical Considerations ...................................................................................... 35 
16.0 
Confidentiality ....................................................................................................... 38 
17.0 
Provisions to Monitor the Data to Ensure the Safety of Participants .................. 38 
18.0 
Provisions to Protect the Privacy Interests of Participants .................................. 39 
19.0 
Compensation for Research-Related Injury .......................................................... 40 
20.0 
Consent Process .................................................................................................... 40 
21.0 
Setting ................................................................................................................... 41 
22.0 
Multi-Site Research ............................................................................................... 42 
23.0 
Resources Available .............................................................................................. 42 
24.0 
References ............................................................................................................ 43 
 

PROTOCOL TITLE: STUDY00004214 Mindful Breathing and Neuromodulation for 
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ABBREVIATIONS/DEFINITIONS 
 
AAI: Alpha asymmetry Index  
 
DLPFC: Dorsolateral prefrontal cortex 
 
DMN: Default Mode Network  
 
ECG: Electrocardiographic  
 
EEG: Encephalography  
 
ERN: Error-related negativity  
 
ERP: Event-Related Potential 
 
HRV: Heartrate variability  
 
LPP: Late Positive Potential  
 
MDD: Major Depressive Disorder  
 
MRI: Magnetic Resonance Imaging  
 
MBT: Mindful Breathing Training  
 
RSFC: Resting state functional connectivity  
 
tDCS: Transcranial Direct Current Stimulation  
 
 
 

PROTOCOL TITLE: STUDY00004214 Mindful Breathing and Neuromodulation for 
Depression in Young People 
 
VERSION DATE: 03/11/2021 
 
 
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1.0 
Objectives 
1.1 
Purpose: This study will investigate whether transcranial direct current 
stimulation (tDCS) targeting the dorsolateral prefrontal cortex (DLPFC) can 
enhance the therapeutic effect of mindful breathing training (MBT) for 
adolescent depression. The objective is to enhance connectivity between the 
DLPFC with the amygdala and Default Mode Network (DMN) circuits as well as to 
enhance emotion regulation abilities and decrease rumination to reduce 
symptoms of depression. This will aid in the development of novel treatments 
for depression.  
1.2 
This study will investigate the following aims:  
Aim 1: To demonstrate the feasibility of recruiting and randomizing adolescents 
with depression to a research protocol involving MBT and tDCS. We expect that 
adolescents will be willing to enroll in a randomized trial involving MBT and tDCS.  
Aim 2: To test the tolerability of MBT and tDCS in adolescents. We expect that 
MBT will be well-tolerated and that active tDCS will show no difference in 
tolerance compared to sham stimulation.  
Aim 3: To examine whether tDCS can enhance the effects of MBT. We expect the 
MBT + tDCS group will show greater reduction in depressive symptoms 
compared to the MBT + sham stimulation group.  
Aim 4: To examine the mechanisms of MBT +/- tDCS treatment. We expect that 
depression symptom improvement will be associated with decreased 
rumination, improvements in emotion regulation, increased task-based and 
resting state DLPFC-DMN and DLPFC-amygdala connectivity, as well as increased 
DLPFC activation and reduced amygdala activation during rumination and 
emotion processing tasks. We also expect reduced alpha asymmetry and 
reduced LPP amplitude during emotion regulation and emotion processing. We 
expect these changes will be greatest in the active tDCS + MBT group. 
2.0 
Background 
2.1 Significance of Research Question/Purpose:  
Depression, the main contributor to disability globally and a significant risk 
factor to premature deaths due to suicide (Friedrich, 2017), commonly 
arises in adolescence (Kessler et al., 2005). Forty percent of depressed 
adolescents do not adequately respond to existing treatments (March et 
al., 2004), emphasizing the urgent need to identify novel, biologically-based 
treatments. Recent neuroscience research has begun shed light on the 
pathophysiology of depression, implicating impairments in frontolimbic 
circuitry, including 1) an underactive dorsolateral prefrontal cortex (DLPFC), 
a region that supports executive control and emotion regulation (Disner, 

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Depression in Young People 
 
VERSION DATE: 03/11/2021 
 
 
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Beevers, Haigh, & Beck, 2011; Koenigs & Grafman, 2009) and 2) an 
overactive amygdala, a region implicated in the experience of negative 
affect (Drevets, 2006). Connectivity between DLPFC and amygdala is also 
reduced in depression (Lu et al., 2012). Abnormal hypothalamic pituitary 
adrenal (HPA) functioning has been found in depression (Burke, Davis, 
Otte, & Mohr, 2005; Vreeburg et al., 2009) and with rumination (Zoccola & 
Dickerson, 2012). Since these brain systems are still undergoing 
development during adolescence (Luciana, 2013), the adolescent years 
represent a critical time during which to advance understanding of the 
neural basis both of depression and of novel treatments.  
Transcranial direct current stimulation (tDCS) is a non-invasive 
neuromodulation technique that can modulate neural activity. If paired 
with MBT, tDCS may be able to enhance learning and neural changes 
associated with MBT. This study will test the efficacy of a novel treatment 
comprised of MBT and tDCS and will be the first to implement tDCS in 
adolescent depression. We propose that for patients with depression, 
where the core feature is persistent negative mood, a training task that 
engages the DLPFC’s role in regulating emotion may optimally reduce 
symptoms of depression. Mindful breathing training (MBT) may be a 
suitable task to down-regulate negative affect and prime the fronto-limbic 
circuit. Further, this work will advance our understanding the synergistic 
effects of combining MBT with tDCS to target the connections between the 
DLPFC with the default mode network (DMN) and limbic regions.  If 
successful, this study will aid in the development of novel treatments for 
adolescent depression and improve the ability of neuromodulation to treat 
depression. This would improve public health by promoting remission, 
reducing poor outcomes like suicide, and reducing the economic burden of 
depression.  
2.2 
Preliminary Data:  
Drs. Cullen, Klimes-Dougan, Mueller and Lim have conducted foundational 
research identifying possible targets of intervention. Using resting-state 
fMRI, we previously showed in 43 unmedicated adolescents with 
depression versus 35 controls that patients had greater resting-state 
functional connectivity between amygdala (a brain region that is critically 
involved in negative emotion) and the precuneus (a key node of the default 
mode network) (Cullen et al., 2014). These findings inspired us to further 
pursue the interactions between DMN and salience network in adolescents 
at risk for suicide as proposed here.  
Drs. Cullen and Klimes-Dougan’s collaborations have documented the 
feasibility for conducting intervention studies, including those employing 

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Depression in Young People 
 
VERSION DATE: 03/11/2021 
 
 
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neuromodulation techniques (transcranial magnetic stimulation; TMS), in 
adolescents with depression (Cullen et al., 2016). Notably, this TMS 
protocol required 30-daily TMS intervention visits in addition to pre- and 
post- MRI and assessment visits.  
2.3 
Existing Literature:  
Mindfulness-based interventions (MBI), which include MBT, involve 
focusing on the present experience. During MBI, one becomes aware of 
mind-wandering, disengages and shifts attention back to the present 
experience. In depression, this can serve to regulate emotion by redirecting 
attention away from spontaneous thoughts, which tend to be negative and 
ruminative in nature.  MBI has been shown to improve emotion regulation 
abilities and to reduce negative affect (Keng, Smoski, & Robins, 2011). 
Neurally, MBI may be able to prime the connections between the DLPFC 
with limbic and DMN regions as mindfulness has shown to activate the 
DLPFC (Hasenkamp & Barsalou, 2012), reduce amygdala activation (Goldin 
& Gross, 2010), increase connectivity between the DLPFC and the amygdala 
(Hölzel et al., 2013) and increase connectivity between the DLPFC and the 
DMN (Jang et al., 2011; King et al., 2016).   
Transcranial direct current stimulation (tDCS) is a safe and cost-effective 
technique that has been studied in adult depression, typically targeting the 
DLPFC (Kalu, Sexton, Loo, & Ebmeier, 2012). Notably, the DLPFC subserves 
multiple regulatory functions, including emotional and non-emotional 
behavior. Prior neuroimaging studies have shown that tDCS stimulating the 
left DLPFC upregulates DLPFC activity, can decrease amygdala activity 
(Ironside et al., 2017) and increase connectivity between the DLPFC and the 
DMN (Keeser et al., 2011). Although tDCS has been shown to be safe for 
adolescents (Krishnan, Santos, Peterson, & Ehinger, 2015), its efficacy for 
adolescent depression has yet to be explored (Vicario & Nitsche, 2013). 
Further, while adult depression studies have demonstrated effectiveness of 
tDCS versus sham, the effect size has been only small to moderate (Hedge’s 
g = 0.74), with response rates, ranging from 0-80% and only an average of 
8.5% of patients achieve full remission with tDCS (Kalu et al., 2012), 
highlighting significant room for improvement with this treatment.  
An important advance in this line of work shows that the effects of MBT 
and tDCS may interact synergistically. tDCS establishes a neuroplastic state 
which can accelerate the learning and neural effects of mindful breathing 
(Fritsch et al., 2010). The effects of tDCS can be augmented by priming the 
targeted neural networks by having participants perform a task that 
requires activation of the targeted neural system in conjunction with 
stimulation (Romei, Thut, & Silvanto, 2016). In adult depression, cognitive 

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Depression in Young People 
 
VERSION DATE: 03/11/2021 
 
 
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control training has been combined with tDCS to enhance DLPFC activity 
with a response rate of 25-44% (Brunoni et al., 2014; Segrave, Arnold, Hoy, 
& Fitzgerald, 2014).  
3.0 
Study Endpoints/Events/Outcomes 
3.1 
Primary Endpoint/Event/Outcome: Primary outcome measures of 
feasibility and tolerability include side-effects, number of participants enrolled, 
and dropout rate. The primary clinical outcome measure will be change in 
depression symptoms and DLPFC connectivity with the salience network and the 
default mode network.   
3.2 Secondary Endpoint(s)/Event(s)/Outcome(s): Additional outcomes may 
include mindfulness, rumination, cortisol, cognition as assessed by 
executive functioning tasks, change in biological measures (e.g., RSFC, task-
based neural activation, alpha asymmetry, and LPP amplitude),  
4.0 
Study Intervention(s)/Investigational Agent(s) 
4.1 Description:  
Mindful Breathing Training (MBT): All participants will undergo mindful 
breathing training (MBT). MBT is a mindfulness-based intervention that 
guides participants to pay attention to the present experience. Participants 
will be trained to become aware of mind-wandering, disengage, and shift 
attention back to the present experience. Participants will practice mindful 
breathing using a computerized application that they will be able to access 
on the web. This training will be administered through a University of 
Minnesota server on an internet browser (e.g., Google Chrome). During 
this task, participants will close their eyes and focus on their breath, 
tapping at the end of each breath. Participants will first complete five 
sessions (for 10, 12.5, 15, 17.5, and 20 minutes) of mindful breathing 
training at home using a personal laptop, tablet, or cell phone over five 
days. Following this training, participants will be randomized to undergo 
either ten 20-minute sessions of active or sham tDCS concurrent with MBT 
across two weeks in lab. Participants are not required to complete all five 
mindful breathing sessions prior to starting in-person treatment. Following 
lab MBT training with either active or sham tDCS, participants will 
complete 15 sessions of MBT training across three weeks at home or in-
person.  
tDCS: We will use transcranial direct current stimulation (tDCS), a non-
invasive brain stimulation technique that can modulate brain activity and 
connectivity, to stimulate the dorsolateral prefrontal cortex (DLPFC). Weak 
electrical current (~2mA) is applied to the scalp using anodal and cathodal 

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Depression in Young People 
 
VERSION DATE: 03/11/2021 
 
 
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electrode sponges, which increase or decrease cortical excitability 
respectively. Research has shown in both healthy participants and patients 
(e.g. Alzheimer’s disease, Parkinson’s disease, 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). Sham stimulation will serve as a control 
condition with current applied only for the first and last 30 seconds of the 
20-minute session. 
4.2 Drug/Device Handling:  
 
tDCS will be applied with a StarStim Enobio system (Neuroelectrics, 
Barcelona, Spain) using a bipolar stimulation montage.  
 
This device has been approved for use in research without an 
investigational device exemption due to meeting criteria for non- 
significant risk (NSR).  
 
In addition, the device has built in safety mechanisms which allow for 
the immediate cessation of stimulation should the participant 
become uncomfortable or if the impedance of the stimulation 
electrodes is too high.  
 
The current will be administered via two saline soaked electrode 
sponges during each intervention session, using a current strength of 
2.0 mA.  
 
These administration procedures are in line with other protocols that 
have outlined the safe use of tDCS in pediatric populations (Krishnan 
et al., 2015).  
 
The tDCS cap and stimulation electrodes/sponges will be washed and 
disinfected after each intervention session and stored under lock and 
key in 717 Delaware Street SE.  
4.3 Biosafety: N/A IND/IDE 
 
5.0 
Procedures Involved 
5.1 
Study Design: Participants will undergo ten daily sessions of one of two 
conditions: 1) active tDCS + Mindful Breathing Training or 2) sham tDCS + 
Mindful Breathing Training (approximate final n of 15 per group). A randomized 
block design will be used to assign each subject to a condition (sham or active 
tDCS). This study will be double-blind to +/- tDCS stimulation.  
 

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Revised: 1/19/2018 
5.2 
Study Procedures: Participants will complete a baseline assessment 
(including a diagnostic interview, clinical assessments, behavioral tasks, 
questionnaires, an EEG/ECG visit, and an optional MRI scan) prior to 
intervention, an interim assessment (clinical assessments and questionnaires) 
after 5 intervention sessions, a post-intervention assessment (including clinical 
assessments, behavioral tasks, questionnaires, an EEG/ECG session, and an 
optional MRI scan) after the tDCS intervention, and a final assessment (clinical 
Baseline 
Visits 
MBT at 
home 
Active tDCS + 
MBT 
Sham tDCS + 
MBT 
Post tDCS  
Visits 
MBT at 
home / in-
person 
Final  
Visits  
Randomized 
Figure 1 

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assessments, behavioral tasks, questionnaires, and an EEG/ECG session) 
following the at-home/in-person MBT intervention. The intervention will consist 
of MBT completed at home or in-person and MBT completed in the laboratory 
concurrent with active or sham tDCS (see Figure 1 and Table 1 for an outline of 
study activities). All self-report questionnaires will be administered online 
through REDCap, a HIPAA-compliant survey system, or on paper. All online self-
report questionnaires administered through REDCap will be completed by 
participants either in-person or remotely. Participants who are unable to 
complete all online self-report questionnaires in-person due to time constraints 
will be emailed an access code for each questionnaire and a link to the REDCap 
website. Upon opening the website link, they will be prompted to enter their 
access code in order to fill out questionnaires. Questionnaires administered on 
paper will be entered into REDCap by research staff.  
Remote Conduct of Study Procedures- In the interest of disease containment and 
prevention, study staff will use HIPAA-compliant communication platforms approved for 
use at the University of Minnesota (e.g., Zoom) at their discretion to conduct necessary 
study procedures when possible during the period of heightened public health concern 
due to COVID-19. This will allow for participants to be given the option for remote study 
visits when deemed necessary by either the participant or by research staff.  
 

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Week 
 
1 
1, 5, 
and 9 
1 and 
5 
3-4 
3 
5 
9 
 
Time 
Baseline 
Assessment 
EEG 
1, 2, 
& 3 
MRI 
1 & 2 
tDCS + 
MBT 
Visits 1-
10 
Interim 
Assessment 
Post-tDCS 
Assessment 
 
Final 
Assessment 
Consent 
 
X 
 
 
 
 
 
 
tDCS Safety 
Screen 
 
X 
 
 
 
 
 
 
MINI 
20 min 
X 
 
 
 
 
 
 
MINI 
Depression 
Module 
 
 
 
 
 
 
X 
X 
MADRS-S 
 
X 
 
 
 
X 
X 
X 
C-SSRS (LV or 
SLV) 
 
X 
 
 
 
X 
X 
X 
MAAS 
 
X 
 
 
 
X 
X 
X 
FMI 
 
X 
 
 
 
X 
X 
X 
RSS 
 
X 
 
 
 
 
X 
X 
IDAS-II 
 
X 
 
 
 
 
 
 
DAS 
 
X 
 
 
 
 
X 
X 
DERS 
 
X 
 
 
 
 
X 
X 
AAQ-II 
 
X 
 
 
 
 
X 
X 
Cash Choise 
Task 
 
X 
 
 
 
 
X 
X 
Side Effects 
Questionnaire 
 
 
 
 
X 
 
 
 
tDCS 
Perceptions 
Questionnaire 
 
X 
 
 
 
 
X 
X 
PSQI 
 
X 
 
 
 
 
X 
X 
CRT 
20 min 
X 
 
 
 
 
X 
X 
Rest Eyes 
Open/closed + 
ECG 
6 min 
 
X 
 
 
 
 
 
Rumination 
3 min 
 
X 
 
 
 
 
 
Distraction 
3 min 
 
X 
 
 
 
 
 
Mindful 
Breathing + 
ECG 
10 min 
 
X 
(only 
EEG
 
 
 
 
 

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 
Baseline Visit (2 Hours) 
o Participants will complete a diagnostic interview, self-
report clinical measures, and behavioral tasks.  
 
Active/Sham tDCS and MBT Intervention Visits (10 sessions; 45 
minutes each)  
o 20 minutes to set up  
o 22 minutes of mindful breathing training with 20 minutes 
of active or sham tDCS 
o 5 minutes of assessments  
 
tDCS Description 
o 20 minutes of active or sham stimulation will be applied at 
2.0 mA in parallel with mindful breathing training using the 
StarStim Enobio 8 system (Neuroelectrics, Barcelona, 
2 & 
3) 
Flanker 
20 min 
 
X 
 
 
 
 
 
Go/No-Go 
10 min 
 
X 
 
 
 
 
 
Manipulation 
Check 
Questionnaires 
 
 
X 
X 
X 
 
 
 
Safety Screen 
 
 
 
X 
 
 
 
 
UTox 
 
 
 
X 
 
 
 
 
Pregnancy Test 
 
 
 
X 
 
 
 
 
Anatomical 
Scan 
15 min 
 
 
X 
 
 
 
 
RSFC 
12 min 
 
 
X 
 
 
 
 
Mindful 
Breathing Scan 
12 min 
 
 
X 
(only 
MRI 
2) 
 
 
 
 
Harari Task 
5 min 
 
 
X 
 
 
 
 
Rumination 
Task 
20 min 
 
 
X 
 
 
 
 
Active/Sham 
tDCS + MBT 
 
 
 
 
X 
 
 
 
PANAS 
 
 
X 
X 
X 
 
 
 
Pre-/Post tDCS 
Questions 
 
 
 
 
X 
 
 
 
Saliva Samples 
 
X 
 
 
 
 
X 
 
Table 2: Schedule of activities 

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Spain) using a bipolar stimulation montage with the anode 
over the left DLPFC (F3 10-20 position) and the cathode 
over the right orbitofrontal cortex (FP2 10-20 position).  
o The sham condition will apply stimulation only for the first 
and last 30 seconds of the 20-minute session.  
o Stimulation will be double-blinded using StarStim settings.  
 
Mindful Breathing Training Description  
 30 sessions of MBT: Participants will be instructed to practice 
mindfulness and will complete a guided computerized task. During 
the computerized task, they will be asked to focus on the sensations 
of their breaths. They will tap at the end of each breath and receive 
feedback. Participants will be trained to use the mindful breathing 
program after their last in-person baseline visit. Training will involve 
a brief overview of mindful breathing and a one-minute training to 
introduce the task. The first 5 sessions will be competed at home 
for 10, 12.5, 15, 17.5, and 20 minutes respectively. The first session 
may be completed in person during the mindful breathing training 
to ensure participants understand how to use the training program. 
Participants are not required to complete all five breathing sessions 
prior to starting in-person treatment. The next 10 sessions will last 
22 minutes and will be done concurrent with active or sham tDCS. 
The remaining 15 sessions will last 20 minutes and participants will 
be given the option of completing these either in-person (only if the 
study team determines that it would be helpful for the participant 
to complete these sessions in-person) or at home using a personal 
laptop, tablet, or cell phone. This app will collect data about the 
quality of focus during MBT and session completion information. 
See Figure 1.  
 
Clinical Assessments:  
o MINI: The Mini-International Neuropsychiatric Interview 
(MINI) (D. V. Sheehan et al., 1998; D. Sheehan et al., 1997; 
Lecrubier et al., 1997; Amorim, Lecrubier, Weiller, 
Hergueta, & Sheehan, 1998; D. V. Sheehan et al., 2010) is a 
brief structured interview designed to quickly diagnose 
major DSM-5 Axis I disorders.  The mean completion time 
of the MINI is 26 minutes (12 to 60 minutes). The 
diagnostic interview will be clinician administered with the 
participant by trained research staff and overseen by a 
licensed psychologist. Diagnoses will be based on the MINI 

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evaluation, case discussion during weekly research team 
meetings and biweekly group supervisions, and brief 
report reviewed by a licensed psychologist. Diagnoses will 
be confirmed by the research team prior to randomization. 
The MINI depression module will be repeated at the post-
tDCS and final assessments to assess changes in 
depression.  
o MADRS: Montgomery-Åsberg Depression Rating Scale – 
self-assessment (MADRS-S) (Bondolfi et al., 2010; 
Montgomery & Asberg, 1979). As in antidepressant trials, 
a ≥50% reduction in depression severity will be used to 
indicate treatment response. Total scores range from 0 to 
27. The MADRS-S is strongly correlated with the clinician 
administered MADRS and has shown to be sensitive to 
change. Although it has not been validated in adolescents, 
it has been used in several previous treatment studies of 
adolescent depression (Berard et al., 2006; von Knorring et 
al., 2006). A cutoff score of 13 will be used to determine 
the presence of mild depression (Svanborg & Ekselius, 
2003).  The MADRS-S may be repeated over the course of 
the study if clinically indicated.  
o Ruminative Response Scale (RRS) focuses on thoughts 
related to depressive symptoms 10/2/2022 10:46:00 PM  
o Freiburg Mindfulness Inventory (FMI) assesses curious 
attitude toward the mindfulness experience (Walach, 
Buchheld, Buttenmüller, Kleinknecht, & Schmidt, 2006) 
o Mindful Attention and Awareness Scale (MAAS) 
measures presence or absence of awareness of what is 
happening in the present (Brown & Ryan, 2003).  
o Difficulties in Emotion Regulation Scale (DERS) assesses 
dimensions of emotion regulation (Gratz & Roemer, 2003).  
o tDCS Safety Screen: We will administer a question to 
assess for tDCS contraindications at the baseline visit  
o We will use a questionnaire developed to assess side 
effect of tDCS (Gillick et al., 2018) before and after each 
tDCS session.  
o We will use a questionnaire to assess perceptions of tDCS 
treatment.  

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o Columbia-Suicide Severity Rating Scale (C-SSRS) assesses 
the presence and severity of suicidal ideation and behavior 
(Posner et al., 2011). The C-SSRS will be clinician 
administered with the participant by trained research staff 
and overseen by a licensed psychologist. Answers will be 
reviewed by trained clinical assessors who are supervised 
by a licensed psychologist. This will be administered at 
baseline for inclusion criteria, at the interim visit, at the 
post-tDCS and at final assessment visits to monitor 
suicidality.  
o Inventory of Depression and Anxiety Symptoms (IDAS) 
assesses symptoms of depression and anxiety (Watson et 
al., 2007).  
o Positive and Negative Affect Schedule (PANAS) is a mood 
scale that assesses positive and negative affect (Watson, 
Anna, & Tellegen, 1987). This will be administered at the 
beginning of each tDCS session and before and after each 
MRI and EEG session as a manipulation check and to assess 
participant mood at the end of the scans to ensure 
participants are not leaving sessions in a distressed mood. 
A study investigator will be contacted if the participant 
endorses a 5 (“Extremely”) for being “upset,” “guilty,” 
“distressed,” or “ashamed” at the end of the session. 
o Dysfunctional Attitude Scale (DAS) assesses maladaptive 
beliefs associated with depression (Weissman & Beck, 
1978)  
o Action and Acceptance Questionnaire – II assesses 
psychological inflexibility and experiential avoidance (Bond 
et al., 2011).  
o Pittsburgh Sleep Quality Index (PSQI) assesses sleep 
quality (Buysse, Reynolds, Monk, Berman, & Kupfer, 1989).  
o Cash Choice Task is a single-item survey assessing delay of 
gratification, impulsivity, and motivation (Wulfert et al., 
2002).  
o Participants will be asked at the beginning of each 
intervention session to rate the degree of rumination they 
experienced the day before. At the end of each MRI scan 
and EEG scan, participants will be asked to rate the degree 
of rumination they experienced during each scan (e.g., 

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resting scan). They will rate the quality of mindfulness, 
rumination, neutral thinking, and rest, thoughts, and mood 
after respective EEG, MRI, and tDCS task completion.  
o At the end of each intervention session and when they 
engage in MBT for the EEG and the MRI, participants will 
be asked to rate how successful they were at engaging in 
the MBT (see attached).  
o Additionally, at the end of the treatment, participants will 
be asked whether they think they were in the active or 
sham condition.  
 
Behavioral Tasks 
o Choice Reaction Time (CRT) Task is an established 
thought-probe task in which participants are instructed to 
engage in a task with low cognitive demand, and 
periodically queried during the task about 6 dimensions of 
their thoughts (past/future, self/other, negative/positive) 
(Hoffmann, Banzhaf, Kanske, Bermpohl, & Singer, 2016). 
 
MRI  
o Acquisition: All participants meeting MRI criteria to 
participate in the study following the clinical interview will 
be scanned using a 3T Siemens Prisma MR system at 
CMRR. The MRI scan is optional, and participants may 
choose to complete other study-related activities without 
undergoing the MRI scan. The Prisma is a fully-clinical 
derivation of the Connectome MRI scanner developed by 
Siemens and UMN at CMRR for the WashU-UMinn Human 
Connectome Project. All participants will be scanned at 
baseline, and 1-2 business days following the last day of 
the tDCS intervention. Participants will complete MRI 
safety screening. High-resolution T1 and T2 images will be 
collected. We will also collect a field map to correct the 
fMRI data for the geometric distortion caused by magnetic 
field inhomogeneity. This will take approximately 15 
minutes.  
o The research team will utilize the CMRR Center’s screening 
tools and adhere to the screening SOP during enrollment 
of all research participants in this protocol. The CMRR 
Center’s screening tools and SOP are IRB approved under 
the CMRR Center’s Grand (HSC# 1406M51205) and 

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information regarding screening procedures is publically 
available on the CMRR website (CMRR Policies/ 
Procedures).   
o Resting State and Mindful Breathing Scans: Whole-brain 
T2*-weighted functional volumes will be obtained during 
rest, with eyes open while viewing a fixation cross (12 min) 
and while practicing mindful breathing (12 min). The 
duration and the choice of fixation cross as the resting 
condition are selected to optimize reliability. The mindful 
breathing scan will only be conducted at the post-
intervention scan.  
o Rumination Task: Participants will be instructed to think 
about a series of 30 statements (30 seconds each, 
interspersed by 10 seconds of fixation cross) that are 
designed to induce either rumination, non-ruminative 
abstract thinking, and non-ruminative concrete thinking (5 
statements of a single category per block, after which 
participants rate the valence of their thoughts during the 
block and current feelings) (Cooney, Joormann, Eugène, 
Dennis, & Gotlib, 2010). This task will last approximately 
20 minutes.  
o Hariri Task: Participants will be asked to match angry or 
sad emotional faces or horizontal and vertical ellipses 
(Hariri et al., 2002). This task will last approximately 5 
minutes.  
o If the MRI data collected is not of high enough quality 
(e.g., due to excessive motion) or if MRI data is not 
acquired due to technical difficulties, the participant may 
be invited to repeat the MRI scan and will be compensated 
for the repeated MRI scan.  
 
EEG  
o We will obtain EEG to quantify band power, alpha 
asymmetry, entropy, coherence, the late positive 
potential, and phase-amplitude coupling. EEG data will be 
collected at baseline, within 1-2 business days following 
the tDCS intervention, and within 1-2 business days 
following the 3-weeks of MBT training at home/in-person. 
Lab staff will place a 32-channel EEG cap on each of the 
participants for a baseline and post-intervention EEG 

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(done at the beginning of treatment session 1 and the end 
of treatment session 10).  The leads will be positioned to 
optimally obtain frontal and midline regions.  All 
participants will undergo 2 3-minute rest EEG scans with 
their eyes open and closed. Participants will also be asked 
to describe a negative and neutral thought they have and 
fixate on this thought for 3 minutes each. Participants will 
also be asked to practice mindful breathing for 10-minutes 
at the post-intervention EEG.   
o Flanker task assesses interference processing. Participants 
are asked to indicate the direction of a central arrow that 
is flanked by two arrows on each side that are either 
pointing in the same direction (congruent) or the opposite 
direction (incongruent) as the central arrow (Albrecht et 
al., 2008). This will be administered using Eprime.  
o Go/no-go task assesses attention and inhibition. 
Participants see letters and are asked not to respond to 
one letter and respond to all other letters (Wodka et al., 
2007). This will be administered using Eprime. 
o If the EEG data collected is not of high enough quality (e.g., 
due to excessive motion) or if EEG data is not acquired due 
to technical difficulties, the participant may be invited to 
repeat the EEG scan and will be compensated for the 
repeated EEG scan.  
 
Electrocardiographic (ECG)  
o ECG data will be collected to quantify heart rate variability 
(HRV). ECG data will be collected concurrent with EEG data 
collection under rest (6 minutes), under rumination and 
neutral thinking conditions, and mindful breathing 
conditions (10 minutes). ECG data will be collected during 
the EEG sessions at baseline, within 1-2 business days 
following the tDCS intervention, and within 1-2 business  
days following the 3-weeks of MBT training at home/in-
person.  
 
Saliva Collection Procedures 
o We will also be asking participants to provide home saliva 
samples prior to participating in MBT to measure cortisol 
levels. We will ask participants to complete eight saliva 
samples at home, over the course of two days. Four 

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samples should be collected each day following this 
schedule: right when waking up, 15 minutes after waking 
up, and 30 minutes after. The fourth sample is to be taken 
at bedtime (approximately 10:00PM). 
o We will have participants document the times that they 
collected their at home saliva samples, as well as any 
medications, caffeine, or events that occurred during the 
day that could affect their saliva samples via a “Daily 
Diary”- a type of self-report form for the day. We will 
compensate participants for their time spent collecting 
and documenting the saliva samples. 
o Participants will be asked to repeat these procedures 
following the tDCS sessions.  
o Saliva samples will be stored without any identifying 
information in a freezer and sent as a complete batch to 
Trier, Germany to be analyzed. 
5.3 Study Activities and Schedule: After an initial phone screen, participants 
will undergo an initial visit where they will complete a series of assessment 
and tDCS and MBT visits. At the first visit, participants will undergo a 
diagnosis assessment (MINI) and behavioral and cognitive assessments and 
questionnaires (see Table 1). Participants who are not eligible at the time 
of the baseline assessment but based on their history and responses are 
expected to meet eligibility criteria at a later point in time (e.g., depression 
scores as assessed by the MADRS-S are too low) may be re-contacted 
within 3 months of their baseline assessment to be re-assessed.  
Eligible participants will undergo: 
1)  an EEG/ECG session (visit 2) and an optional MRI scan (visit 3)  
2) Participants will be instructed to complete 5 MBT sessions using a 
personal laptop, tablet, or cell phone at home. Following the in-
person training after all the baseline visits are completed, the first 
MBT session (10 minutes) will completed during the last in-person 
visit (MRI or EEG visit) to ensure that participants understand how 
to use the training program.  
3) Participants will then be randomly assigned to one of two 
conditions: active tDCS + MBT and sham tDCS + MBT. Participants 
will undergo 10 daily sessions of tDCS across two weeks (visits 4-
13). Missed sessions may be rescheduled. If there is a month or 
longer delay between the last baseline assessment visit (e.g., 

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initial assessment, EEG, or MRI), participants may be asked to 
repeat some or all of the baseline research visits and will be paid 
accordingly.  
4) Following the treatment, participants will complete a post-tDCS 
MRI scan, EEG/ECG session, and assessment visits (visit 14-16) 
that will include behavioral and cognitive assessments as well as 
questionnaires.  
5) Participants will then complete 15 sessions of MBT either at home 
or in-person (only if the study team determines that it would be 
helpful for the participant to complete these sessions in-person) 
across 3 weeks. After they complete the home-based MBT 
training, all participants will complete a final EEG/ECG session and 
final assessment (visits 17 and 18), irrespective of how many at-
home/in-person MBT sessions were completed.  
In total, this study will require 18 in-person visits and 20 online MBT 
sessions that can be completed at home (see Figure 1 for an overview of 
study activities). For participants who complete the 3-weeks of MBT in-
person, there will be an addition of 15 in-person visits and a total of 4 
online MBT sessions.  
Randomization: A randomized block design will be used to assign each 
subject to undergo either active or sham tDCS in a 1:1 ratio. Randomization 
will occur after completion of the 5 at-home MBT sessions before their first 
tDCS + MBT laboratory visit.  
5.4 Study Duration: The total duration of research activities for individual 
participants will involve 18 in-person visits and 20 MBT sessions that can be 
completed at home or in person (only if the study team determines that it 
would be helpful for the participant to complete these sessions in-person) . 
Research-related activities will occur over the duration of up to 10 weeks. 
The anticipated duration to complete all study-related activities, include 
data analysis and publications is 4 years (present to 2022). It is anticipated 
that year 1 and year 2 will involve data collection and year 3 and 4 will 
involve data analysis, presentations, and publications., 
5.5 Individually Identifiable Health Information: Study staff may collect 
individually identifiable health information (e.g., medical history, mental 
health diagnoses, treatment history, demographic information) during 
research-related procedures (e.g., diagnostic interview, questionnaires). 
See attached HIPCO Ancillary Review Form and HIPAA Authorization form. 
HIPAA Authorization may be obtained on paper or using REDCap. All 
individually identifiable health information will be stored as described in 

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the Confidentiality section. Data analyses will be conducted on deidentified 
data on University computers and laptops and the CMRR servers. 
Participants will be contacted by phone call and/or email. Email contact 
with participants will not contain PHI (otherwise, emails will be encrypted).  
  
5.6  Use of radiation: The research does not involve the use of radiation.  
5.7 Use of Center for Magnetic Resonance Research: The study uses the CMRR 
and follows all CMRR protocols and procedures.  
6.0 
Data and Specimen Banking 
Storage and Access: Study data will be managed by Co-Investigator 
Michelle Thai. Data will be deidentified using an arbitrary identification 
number assigned to each participant. Personally-identifiable information, 
including participant names, birthdates, and contact information, will be 
maintained in order to contact patients. This personally identifiable 
information will be kept separately in an encrypted, password-protected 
file kept separate from study data. A separate file linking identifiers with 
identification numbers will be stored separately. Phone screen information 
will only be kept for participants who participate in the consent visit; this 
will be stored in locked cabinets. Phone screen information from 
individuals who do not qualify based on the phone screen or who decide 
not to enroll will be shredded.  
Data: Include clinical assessments, self-report measures, behavioral task 
performance data, technical aspects of neuromodulation sessions, MRI 
scan data, EEG data, and ECG data. De-identified neuroimaging data will be 
stored locally on servers supported by the Center for Magnetic Resonance 
(CMRR). De-identified clinical, EEG, ECG, and behavioral data will be stored 
in a secure, HIPAA-compliant REDCap database and Box Secure Storage 
supported by the university of Minnesota or on local servers. 
Release/Sharing: Data will only be released in deidentified form to research 
collaborators.  
7.0 
Sharing of Results with Participants 
7.1 Study results and individual participant results may be shared with 
participants at their request at the conclusion of the study to preserve 
study blinding. Individual diagnostic results from the initial visit may be 
shared with participants at their request. Incidental findings from the MRI 
scan will be first shared with a trained radiologist after the scan to be 
assessed for abnormalities. The images will not include identifying 
information about the patient. If the radiologist recommendation is to 

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further investigate unusual results from the images, the investigator will 
contact the participant. Consent and assent may be obtained from parents 
and participants to share this information with the participant’s primary 
care physician. 
8.0 
Study Population 
8.1 Inclusion Criteria:  
 Female, Aged 17-24 years old 
 Diagnosis of major depressive disorder (MDD), Dysthymia, or Other 
specified/Unspecified Depressive Disorder based on MINI.  
 Experiencing current symptoms of depression as indexed by a MADRS-S 
score ≥ 13 
 Ability to access the MBT online-based application (e.g., on a personal 
laptop, tablet, or cell phone)  
 Fluent in English  
8.2 Exclusion Criteria:  
 Any participant with a current diagnosis of epilepsy (must be 
seizure-free during the 2 years prior to consent to be included) 
 Any participant with a clinically defined neurological disorder or 
insult indicating, but not limited to, a condition likely to increase the 
risk of seizure; such as, space occupying brain lesion; history of 
cerebrovascular accident; transient ischemic attack within two 
years; cerebral aneurysm; dementia; brain surgery; history of stroke 
 Any participant with an increased risk of seizure for any reason, 
including prior diagnosis of increased intracranial pressure or 
history of significant head trauma with loss of consciousness for  5 
minutes. 
 Participants with active or inactive implants (including device leads), 
including deep brain stimulators, cochlear implants, and vagus 
nerve stimulators 
 Participants with pre-existing sores or lesions at the site of tDCS or 
EEG electrode placement 
 A hair style that would impede EEG and tDCS electrode contact 
(e.g., dread locks) 
 Any participant with a current or possibility of current pregnancy  
 Participants unable to give informed consent.  
 Participation in any investigational drug trial within 4 weeks of the 
baseline visit 

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 Clinically significant laboratory abnormality or medical condition, 
that in the opinion of the investigator would hinder the participant 
in completing the procedures required by the study 
 Currently actively suicidal with intent and plan determined by the C-
SSRS at the baseline visit. 
 A diagnosis of current or recent substance use disorder (within the 
past 12 months) 
 A diagnosis of Schizophrenia, Bipolar Disorder, or Autism 
 Unstable psychotherapy (therapy must be for at least 3 months 
prior to entry into the study, with no anticipation of change in the 
frequency or treatment focus of the therapeutic sessions over the 
duration of the study) 
 Recent change in dose of antidepressant medication (within 6 
weeks prior to entry into the study). This includes all 
antidepressants and any adjunctive psychotropic medications that 
are being used to address problems related to mood or anxiety (e.g. 
antipsychotic medications, mood stabilizers) 
 Refusal to cooperate with study procedures 
MRI Exclusion Criteria: If participants meet MRI exclusion criteria, they 
may not participate in the MRI scan but may still choose to participate in 
other study visits  
 Participants with conductive, ferromagnetic, or other 
magnetic-sensitive metals implanted in the head excluding the 
mouth that cannot safely be removed. Examples include 
cochlear implants, implanted electrodes/stimulators, 
aneurysm clips or coils, stents, bullet fragments, jewelry and 
hair barrettes 
8.3 
Screening: Potential participants (if age 18 or older) or parents of 
potential participants (if under age 18) will first complete an initial, brief 
telephone interview with a member of the research team. Prior to the phone 
screen, potential participants will be informed that they will need to fill out a 
short online survey to determine their eligibility and so they would need email 
access during the phone call. During the phone call, the study will be explained 
to the participant and/or their parent and will include questions about the 
participant’s medical history, their mood, and behavior. A REDCap survey link for 
the MADRS-S, a depression rating scale, will be emailed to potential participants 
or to parents of potential participants during the phone call. The phone screen 
MADRS-S will not include item 9 (“Zest for life”) in order to reduce any risk of 
triggering suicidal thoughts or ideation. The phone screen and MADRS-S will 
serve to select participants likely to meet inclusion criteria and to screen out 

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participants who meet exclusionary criteria. The REDCap survey will be linked to 
a dummy ID that will not be attached to a name. Potential participants/parents 
will be told that it is recommended that they/their child fill out their responses 
while the study staff remains on the phone. The survey will take about 3 to 5 
minutes to complete. Participants who are interested in continuing with the 
study and who have a score of 13 or more on the MADRS-S will be eligible to 
schedule in-person visits. Participants or parents (if under age 18) will provide 
verbal consent for the screen to be completed. See the attached phone screen. 
Participants may also be screened using a REDCap survey that the participant (if 
age 18 or older) or parent will complete.  
9.0 
Vulnerable Populations 
9.1 Vulnerable Populations:  
☒ Children 
☐ Pregnant women/Fetuses/Neonates 
☐ Prisoners 
☐ Adults lacking capacity to consent and/or adults with diminished 
capacity to consent, including, but not limited to, those with acute 
medical conditions, psychiatric disorders, neurologic disorders, 
developmental disorders, and behavioral disorders 
☐ Approached for participation in research during a stressful situation such 
as emergency room setting, childbirth (labor), etc. 
☐ Disadvantaged in the distribution of social goods and services such as 
income, housing, or healthcare 
☐ Serious health condition for which there are no satisfactory standard 
treatments 
☐ Fear of negative consequences for not participating in the research (e.g. 
institutionalization, deportation, disclosure of stigmatizing behavior) 
☐ Any other circumstance/dynamic that could increase vulnerability to 
coercion or exploitation that might influence consent to research or 
decision to continue in research 
☐ Undervalued or disenfranchised social group 
☐ Members of the military 
☐ Non-English speakers 
☐ Those unable to read (illiterate) 
☐ Employees of the researcher 
☐ Students of the researcher 
☐ None of the above 

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9.2 Additional Safeguards: Adolescents are the focus of this study because 
adolescence represents a critical period of brain development and because 
depression commonly arises in adolescence. Adolescents under the age of 
18 will complete written assent and parents will undergo an informed 
consent process. Consent and assent may also be obtained using REDCap. 
Participants will be checked for capacity to consent using the UCSD Brief 
Capacity to Consent (UBACC).  
 
 
10.0 Local Number of Participants 
10.1 Local Number of Participants to be Consented: 75 people will be consented 
and undergo the initial assessment for a minimum target of 30 participants 
completing the study.  
11.0 Local Recruitment Methods 
11.1 
Recruitment Process: Participants will be recruited through the Research 
Experience Participation (REP) program in the Psychology Department at the 
University of Minnesota. Study information will be available on the REP website. 
Research staff may introduce the study in relevant UMN courses and emails with 
study information may be distributed in relevant UMN courses. No students 
from Dr. Klimes-Dougan’s courses will be directly recruited by Dr. Klimes-Dougan 
or her graduate students, including Michelle Thai. Flyers and advertisements will 
be posted around the University of Minnesota campus, clinics, and hospitals, and 
surrounding area. Letters and brochures may be sent to local clinicians. 
Descriptions of the study may also be posted on websites, like ClinicalTrials.gov, 
StudyFinder, and http://radlab.umn.edu, and the University of Minnesota’s 
Department of Psychiatry website 
(https://sites.google.com/umn.edu/psychiatryresearch/home/depression/mindfulne
ss-tdcs). We will also post advertisements on social media outlets (e.g., 
Facebook). Our recruitment materials may include a QR code or a link 
(https://z.umn.edu/mbttdcs) to our landing page. Upon scanning the QR code or 
clicking the link, users will be brought to a REDCap survey that describes the 
study and asks for contact information and birthdate. The REDCap landing page 
survey will be managed by project coordinators and will be independent from 
REDCap projects used for data collection. We will recruit participants from the 
Riverside Behavioral Health Outpatient Clinic using multiple strategies. First, 
patients in this clinic are invited to participate in a research recruitment registry. 
Our research staff will use the research registry to contact potential participants 
who have indicated they are interested in research using the contact information 
provided in the registry. Secondly, we will use a direct, in-person recruitment 
approach. Research staff will connect with providers in the clinic to discuss 

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patients who could be potential participants. For specific patients we will ask the 
provider to give an IRB-approved study brochure to the patient, along with a 
general introduction about the study. The research staff will be available to meet 
with the patient and their parent in the clinic to provide further information 
about the study; interested families will have the option to meet briefly with a 
researcher in person to allow face-to-face discussion, or to have the researcher 
follow up with them by phone. The Behavioral Health Research Recruitment 
Committee has approved this process. 
 
11.2 Identification of Potential Participants: Potential research participants will 
self-identify in response to REP postings, flyers and advertisements, 
brochures, or other recruitment methods as listed above. Following this 
initial contact, a member of the research staff will screen the potential 
participant.  
11.3 Recruitment Materials: See attached.  
11.4 Payment: Participants will be compensated $20 for the initial visit 
(consent/HIPAA & baseline assessment), $15 for the baseline and post-
tDCS, and final EEG/ECG session, $40 for the baseline and post-treatment 
MRI scan, $5 for completing the home saliva samples and dairy at baseline 
and post-tDCS, $10 for the post-tDCS assessment visit, $15 for the final 
assessment, and $5 for a week 1 assessment for a maximum total of $185.  
If participants have to repeat a visit for any reason (e.g., poor data quality), 
they will be compensated accordingly for any repeated visits. Participants 
will not be compensated for intervention visits. If participants complete all 
in-person visits of the study, they will be entered into a $50 raffle. A winner 
will be selected each time 3 participants complete the study. Participants 
may also choose to receive course extra credit as partial or total payment 
instead of cash (Research Experience Points) for their participation in this 
study (each ½ hour of assessment is worth 1 REP point). Cash payments will 
be made via institutional standard Greenphire ClinCard, a prepaid debit 
card that we can continue to load with money as the participants complete 
studies. In the case of early termination, the participant will receive partial 
payment. Parking passes will be provided when available.  
12.0 Withdrawal of Participants 
12.1 Withdrawal Circumstances: Participants who have MRI or tDCS 
contraindications or participants who experience severe adverse events 
(e.g., seizure, suicide attempt, acute suicidality with plan of intent) or any 
unanticipated problem where the principal investigator feels it would be 
unsafe for the participant to continue may be withdrawn from certain 

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study activities or withdrawn from the entire study without their consent. 
In the case of other serious adverse events, the principal investigator or 
research staff will decide with the participant whether it would be safe or 
prudent for the participant to continue in the study based on their 
situation. Participants who experience mild to moderate adverse events 
(e.g., discomfort or other side effects like headache) will be allowed to 
discontinue at any point if they choose. Participants withdrawn from study 
participation due to an adverse event may be replaced to reach intended 
sample size. Participants will be withdrawn from the study if they appear to 
be unduly stressed.  
12.2 Withdrawal Procedures: Participants may withdraw from the study at any 
time and study staff can withdraw a participant at any time if there are any 
serious adverse events. In the event of participant withdrawal, research 
staff may ask participants some questions about the study and/or to 
participate in some procedures or tests to help participants leave the study 
safely and/or to collect more information for the study. Information 
already collected prior to participant withdrawal will still be used. 
Participants who withdraw or do not qualify for the study after the phone 
screen may choose to receive referrals for psychological assessments.  
12.3 Termination Procedures: In the case of a serious adverse event, research-
related activities may be terminated immediately and appropriate 
treatment will be provide to the participant (e.g., first aid, emergency 
treatment, and follow-up care as needed). Care for such injuries will be 
billed in the ordinary manner to the participant or the participant’s 
insurance company. Following termination, research staff may ask 
participants some questions about the study and/or to participate in some 
procedures or tests to help participants leave the study safely and/or to 
collect more information for the study. Information already collected prior 
to participant withdrawal will still be used. 
13.0 Risks to Participants 
13.1 Foreseeable Risks:  
Transcranial Direct Current Stimulation (tDCS): tDCS has shown to be a 
safe brain stimulation technique. Adverse events are rare with tDCS, and 
serious side effects have not been found following tDCS application. tDCS 
has been safely applied in psychiatry populations and in child and 
adolescent populations. The most common side effects are mild, including 
itching or discomfort under the electrode at the beginning of 
administration, headache, fatigue, dizziness, and nausea, which typically 
resolve at the end of stimulation. Our stimulation parameters will be within 

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established safety guidelines (Brunoni et al., 2011). There have been 
reported incidents of treatment-emergent hypomania and mania in 
unipolar and bipolar depression patients following tCS (Matsumoto et al., 
2017). As such, we will rule out participants with bipolar disorder and will 
use the MINI to screen out participants with symptoms of mania and to 
monitor participants for any change in manic symptoms over the course of 
the study. These risks will be described to the participants during the 
consent process and participants may choose whether to participate or 
not.  Participants may decide to withdraw from the study at any point.  
MRI Scanning: MRI scanning will be conducted using a 3 Tesla Siemens 
Prisma MRI machine. The magnet in the scanner may cause electronic 
devices like watches to malfunction, and some metal objects can be pulled 
into the scanner. Participants will be screened prior to the scan to make 
sure they have nothing in their body which could be magnetic or affected 
by the magnetic field of the scanner. Participants will be asked to change 
into scrubs to ensure they have no metal on their person. 
 
It may be uncomfortable lying still in the scanner for the amount of time 
required. The participant may experience some stiffness and soreness in 
the muscles from being still. To make participants as comfortable as 
possible, we will provide soft pads to help support the next, back, and legs. 
The scanner itself makes a lot of noise while it is running. This can be 
uncomfortable and may affect the participant's hearing. Participants will be 
asked to wear ear plugs which will significantly reduce the amount of noise. 
Participants will also be wearing headphones in addition to the earplugs to 
allow them to hear the investigators and listen to music. 
 
Some people may become uncomfortable in the scanner because they are 
not comfortable being in enclosed spaces. We will screen for 
claustrophobia before we bring the participant to the scan center. They will 
have the option of using a mock scanner prior to going into the scanner to 
assess their level of comfort. They will not be required to participate in the 
scan or continue the scan if they are uncomfortable. 
 
If a participant has a positive pregnancy test, they will not be scanned. We 
will not inform the participant's parent of the results unless we feel the 
pregnancy would cause serious problems for the participant.  Adult 
participants will be notified of their pregnancy test results, if positive. We 
may also obtain a false positive with the urine toxicology screen or 
pregnancy test. We will inform participants of the risk of obtaining a false 
positive and encourage them to follow up with their primary care 

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physician. If the toxicology screen is positive, results will be noted on the 
MRI CRF form and the participant will continue on with the MRI scan. 
 
There is a chance we might find something abnormal when we look at the 
images of the participant's brain. We will send all images to a trained 
radiologist after the scan so they can be assessed for abnormalities. These 
images will not have any identifying information about the patient. If the 
radiologist recommendation is to further investigate the unusual results of 
the pictures, the investigator will contact the participant. The participant is 
responsible for further evaluation and follow-up in response to any MRI 
incidental findings.  
Clinical Assessments: Participants may also experience mild stress, 
discomfort, or fatigue during the clinical assessment or while completing 
self-report or behavioral assessments.  The assessments may involve 
questions about feelings, past experiences, and family history. Participants 
are encouraged to only share what they feel comfortable with and will not 
be induced to discuss anything that will make them too uncomfortable. The 
results of this study may be published and/or presented, but identifying 
information about participants will not be released unless required by 
Federal Law. 
Behavioral Tasks: These tasks may be tiring. Some tasks may ask 
participants to think about negative thoughts or involve negative stimuli 
that may cause mild stress, discomfort, or fatigue.  
Suicide/Self-Injury Risk: The population being researched in this study has 
a higher risk for suicidal ideation, suicide attempts, and serious injury due 
to depression. The research team will monitor depression (MADRS-S), 
suicidal ideation (C-SSRS), and self-harm behaviors (C-SSRS) at baseline, 
midway through the intervention assessments at the interim assessment, 
and post-intervention. Answers will be reviewed by the clinical assessor 
who is trained and supervised by a licensed psychologist. Participants who 
indicate suicidal ideation or significantly increased self-harm behaviors 
based on the C-SSRS will be asked to meet with one of the investigators of 
the study to assess risk. 
 
Participants with suicidal ideation with no plan or intent who agree to 
a safety plan (either developed with the investigator or a pre-existing 
safety plan) will be allowed to continue in the study. The investigator 
will inform parents of the discussion and safety plan (if applicable). 
 
Participants with severe self-harm (requiring stitches or 

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hospitalization), suicidal ideation with intent, or those who cannot or will 
not agree to a safety plan will be escorted to the Emergency 
Room located 1 floor below the Ambulatory Research Center (ARC) in 
the West Building of the Fairview Riverside Hospital. 
EEG/ECG: Mild skin irritation may occur at the electrode placement site 
(e.g., redness). 
 
13.2 Reproduction Risks:  The effects of tDCS, EEG and MRI scans on the unborn 
fetus are not known, and participating females should not be pregnant.  
Pregnant participants will not undergo the stimulation, EEG or MRI scans. 
Participants and parents if participants are under the age of 18 will be told 
that the participant should not undergo study procedures if there is a 
pregnancy or possibility of a pregnancy. Participants will be informed about 
pregnancy risks during the consent process and will be encouraged to use a 
reliable form of birth control. Participants will take a mandatory pregnancy 
test before each MRI scan. If the urine pregnancy test is positive, the 
participant will not undergo the MRI scan or any tDCS sessions. If the 
pregnancy test is positive at the post-tDCS session, participants will not 
undergo the MRI scan but may choose to complete the 3-week at-home / 
in-person MBT training and clinical assessments. Participants will be asked 
to inform study staff at any other point of the MRI and tDCS visits if they 
have any concerns that they may be pregnant. Additional pregnancy tests 
can be offered at any point during other visits. Pregnancy and toxicology 
screens will be conducted at the CMRR by research staff. Participants will 
provide urine samples and we will use a pregnancy test strip (Clarity 
Diagnostics; Manufacturer # DTG-HCG100) to test for pregnancy and an 
Integrated E-Z Split Key Cup Urine Drug Screening with Adulteration for 5 
Drugs for the toxicology screen (Manufacturer # DUD157023019). Both of 
these tests have a CLIA waiver (see attached materials for more details on 
the tests and for CLIA waiver documentation). These tests will be 
purchased through UMarket. Results will be recorded on CRF forms for MRI 
scanner sessions. Urine will be disposed of by being flushed down the toilet 
and used testing materials will be disposed of in the garbage. 
13.3 Risks to Others: There are no anticipated risks to others who are not 
participants.  
13.4 Email Risks: Participants will be able to opt in to communicating with study 
staff via unencrypted email to arrange their appointments and receive 
study instructions. There are risks associated with email communication, 
and these risks increase when the emails are sent without an encryption 

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service. Risks of sending or receiving emails without encryption include, but 
are not limited to: 
 Others can intercept messages. 
 If messages are sent or received on an employer-owned device, 
the employer may have the right to save and read the messages. 
The internet or cell-phone provider may also have the right to 
save and read email messages.  
 A copy of the messages may be saved on a device or computer 
system, even if it is deleted. 
 If an email address is not typed correctly, it can be sent to the 
wrong person. 
 Emails can spread computer viruses. 
 Others may be able to access messages on devices that were lost, 
stolen, or thrown away. 
 If a user changes emails without notifying study staff, they may 
miss communications.  
13.5 
Text Message Risk: Participants will be able to opt in to communicating 
with stud staff via text message to arrange their appointments and receive study 
instructions. There are risks associated with communication via text message. 
Risks of sending or receiving text messages include, but are not limited to: 
 Others can intercept messages 
 Text messages may be viewed by University of Minnesota staff 
depending on the nature and timing of said messages, and may be 
monitored by the University to ensure appropriate use.  
 If messages are sent or received on an employer-owned device, 
the employer may have the right to save and read the messages. 
The cell-phone provider may also have the right to save and read 
text messages.  
14.0 Potential Benefits to Participants 
14.1 Potential Benefits:   It is possible that a participant may have an 
improvement in depressive symptoms from this treatment but there are no 
anticipated direct benefits to participation in this research project. The 
contribution to general knowledge on the research topic may be a societal 
benefit.   
15.0 Statistical Considerations 

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15.1 Data Analysis Plan:  
Effectiveness analyses: Repeated measures ANOVAs will examine the effect 
of condition (active tDCS + MBT and sham tDCS + MBT) on pre- and post-
intervention MADRS scores, rumination scores, mindfulness scores, and 
emotion regulation scores. EEG outcomes will include alpha asymmetry, 
LPP amplitude, coherence, and entropy at rest, during rumination, during 
mindfulness, and during emotion processing. ECG outcomes will include 
heartrate variability. MRI outcomes will include DLPFC-DMN, DLPFC-limbic 
system, and within-DMN RSFC, as well as DLPFC, limbic, and DMN 
activation to rumination and emotional processing tasks. Additional 
analyses will be conducted to assess whether changes in emotion 
regulation, mindfulness, and rumination moderate changes in depression 
symptoms. Regression analyses will be run on baseline measures to identify 
predictive biomarkers of MBT/tDCS treatment response. Correlation 
analyses will be conducted between the degree of change in clinical scores 
(depression symptoms, rumination, emotion regulation) with degree of 
change in neuroimaging and mindfulness indices. 
Neuroimaging data analysis: We will optimize components from the HCP 
minimum processing pipeline to fit our imaging protocols and will include 
gradient non-linearity distortion corrections, distortion correction caused 
by magnetic field inhomogeneity, co-registration of functional and 
anatomical images, non-linear registration to MNI template brain, intensity 
bias corrections, highpass filtering, re-sampling of the data onto the cortical 
mesh (surface analyses), and denoising of the data using ICA-fix (Griffanti et 
al., 2014). Network Analysis. We will quantify RSFC within fronto-limbic and 
default mode networks as described in our prior work.  
EEG: Change in alpha band asymmetry: Eyes-open and eyes-closed resting-
state EEG alpha power (8-13 Hz) will be calculated for left and right 
prefrontal electrodes using a fast-fourier transform approach. We will 
define the alpha asymmetry index (AAI) as the ratio of the left prefrontal 
alpha power to the right prefrontal alpha power. A similar AAI analysis will 
be carried out for the rumination EEG data. Coherence Analysis: We will 
investigate resting-state EEG correlates of DMN functional connectivity by 
computing the coherence between posterior and prefrontal cortical 
regions. In order to specifically assess alpha and beta band coherence 
changes within the DMN, we will choose channel Pz to represent the 
precuneus/posterior cingulate and channel Fz to represent the medial 
prefrontal cortex/anterior cingulate. We will further assess changes in 
coherence between the DMN (channels Fz, Pz) and the DLPFC (channels F3, 
F4). P300 Amplitude. P300 ERP responses will be measured during the 

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Go/No-Go and Flanker tasks and will be compared across different types of 
trials (e.g., go versus no-go trials and congruent versus incongruent trials). 
ERN Amplitude. Error Related Negativity (ERN) ERP responses will be 
measured during the Go/No-Go and Flanker tasks and will be compared 
across different types of trials (e.g., trials after correct versus incorrect 
responses). 
ECG: Estimates of HRV will be calculated based on recommendations by an 
international committee (Malik et al., 1996). Power spectral analyses will 
be used to estimate contributions from sympathetic (low frequency) and 
parasympathetic (high frequency) components. 
Number of study visits completed may be used as a covariate in analyses.  
15.2 
Power Analysis: 
Since we do not have pilot data with adolescents using either of 
these interventions, we were unable to conduct a power analysis to 
calculate an appropriate sample size. Budget and time constraints 
necessitate a relatively small sample size. While some studies in the 
literature have reported significant effects using similarly small 
samples, we cannot be certain that the study is powered 
appropriately to confirm or refute our hypotheses. Therefore, we 
have framed the project with a primary goal of establishing 
feasibility (our ability to recruit, adolescents' acceptance of 
randomization, adolescents' tolerability of the interventions) and of 
collecting data that will allow a power calculation to determine the 
sample size necessary for the federal grant to follow this work. 
15.3 Statistical Analysis: A p-value of .05 will be used to determine significance 
for behavioral measures and a p-value of .005 will be used to determine 
significance for neuroimaging measures. Paired t-tests will be used to 
compare baseline versus post-tDCS and post-MBT intervention for both 
intervention groups for biological, clinical, and behavioral measures. 
Between-group t-tests will be conducted on the side-effects to examine 
group differences in prevalence of side effects. Feasibility will be 
determined by looking at descriptive statistics about enrollment and 
eligibility of people that express interest in the study and enroll as well as 
retention of enrolled participants. Correlation analysis will be conducted to 
assess how changes in clinical and behavioral relate to biological measures 
following intervention. Mixed repeated measures ANOVAs will test our 
hypothesis that the active tDCS group will show greater change than the 
sham tDCS group with condition (active or sham) as the between 
participant measures; within-participant measures will include behavioral, 

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clinical, and biological indices. Regression models will also be conducted on 
baseline measures (e.g., RSFC, task activation, trait mindfulness and 
emotion regulation) to assess biomarkers of treatment response. 
Behavioral indices include performance on the GoGreen, Middle Fish, and 
CRT. Biological indices include EEG (e.g., AAI, coherence, entropy at rest 
and during mindful breathing, as well as LPP amplitude during the Emotion 
Regulation Task, P300 and ERN during the GoGreen and Middle Fish tasks), 
ECG data (HRV), and MRI data (e.g., DMN, DLPFC, and Limbic activation to 
Hariri and Rumination Tasks and functional connectivity at rest and during 
mindful breathing). Clinical measures include depression symptoms, 
rumination scores, and mindfulness scores.  
15.4 Data Integrity: Outlier analyses will be conducted and data values that 
exceed three standard deviations will be removed or winsorized. 
Neuroimaging data will also be examined for excessive motion. Data will be 
checked by Michelle Thai.  
16.0 Confidentiality 
Data Security:  
16.1 All participants will be identified by a research identification number. All 
research data will be de-identified using ID numbers. Hard copies of 
documents will be stored in a locked cabinet. The participants name will be 
retained on consent and assent forms and these forms will be stored in a 
separate, locked cabinet. Both cabinets will only be accessible to the 
research team on the protocol. Behavioral and clinical data will be entered 
electronically using the ID numbers onto the HIPAA-compliant REDCap 
database that is managed by the University of Minnesota. Clinical data and 
questionnaires may be completed using REDCap or paper documents. Raw 
behavioral and EEG/ECG data will be stored on the HIPAA-compliant Box 
Secure Storage. Data may also be stored on password protected databases 
and files on AHC-IS servers (cnc2.med.umn.edu). De-identified 
neuroimaging data will be stored locally on servers supported by the 
Center for Magnetic Resonance (CMRR). Access to these electronic 
directories will be limited to the research staff. Copies of the consent form 
and other research study information will not be included in their medical, 
employment, or educational records to maintain confidentiality.  
17.0 Provisions to Monitor the Data to Ensure the Safety of Participants 
 
  
17.1 Data Integrity Monitoring: The principal investigator and/or co-investigator 
will monitor data quality for this study. They will ensure that data are 
generated, documented (recorded), and reported - in compliance with this 

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protocol, with Good Clinical Practice, and any other applicable regulatory 
requirements. Data will be stored in de-identified format. Study staff will 
monitor side effects forms and the CSSR-S for safety upon collection. 
Confidentiality may be broken in situations such as active suicidal ideation 
or other situations required by law.  
17.2 
Data Safety Monitoring. During all stimulation sessions, a member 
of the research staff will constantly monitor participants to ensure 
comfort and safety. A licensed clinical psychologist (Dr. Bonnie Klimes-
Dougan) or a supervising psychiatrist (Dr. Kathryn Cullen) will be 
contacted in the case of a clinical emergency to determine whether 
intervention is necessary. Emergency incidents will be documented and 
reported to the IRB. Documentation will include a description of the 
incident, action taken, and individuals involved. A 0 (No adverse event or 
within normal limits) to 5 (Fatal adverse event) rating scale will be used to 
evaluate the severity of adverse events and a 0 (Unrelated: The adverse 
event is clearly not related to investigational agent(s)) to 5 (Definite: The 
adverse event is clearly related to investigational agent(s)) will be used to 
determine the relationship between the adverse event and the proposed 
intervention. Any events rated 2 or higher will result in a notification to 
the supervising psychologist and events rated 3 or higher may warrant 
breaking the blind. Intervention will be determined by the supervising 
psychologist. Examples of incidents requiring immediate intervention and 
discontinuation from the study include active suicidal or homicidal 
ideation with plan, current self-harm requiring medical intervention, and 
a seizure. Data and safety monitoring will be discussed during weekly 
staff meetings with members of the research team to ensure that all 
adverse events are reported in compliance with the protocol, Good 
Clinical Practice, and other applicable regulatory requirements. 
 
 
18.0 Provisions to Protect the Privacy Interests of Participants 
18.1 
Protecting Privacy:  
The records of this study will be kept private. In any publications or 
presentations, participants will not be identified by name or any other 
identifiable information. Any records, results, or publications related to the 
study will remain as confidential as possible and will be disclosed only with 
participant permission. Each participant will be provided with a unique 
numerical identifier at the beginning of the study in order to protect their 
actual identification and maintain complete confidentiality.  
Mental health professionals are mandated reporters, and as such, are 
obliged to report alleged or probable abuse, as well as known abuse. Any 

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concerns about maltreatment will be reported in accordance to the law. If 
research staff learn that someone (including the participant) is in danger of 
serious harm), research staff may need to obtain outside assistance. 
Only research staff associated with this study and authorized personnel will 
have access to the records. Research records will be kept in a locked file. 
Any publications from this study will not include any information that can 
identify participants. Data will be stored on a password protected 
electronic database.  
A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov, as required by U.S. Law. This website will not 
include any information that can identify participants. At most, this website 
will include a summary of the results.   
18.2 
Access to Participants: The research team will not access any medical 
records or other sources of private information outside of information without 
the participants written consent. HIPAA Authorization will be obtained for all 
participants.  
19.0 Compensation for Research-Related Injury 
19.1 Compensation for Research-Related Injury: In the event that research-
related activities result in an injury, treatment will be provided to the 
participant (e.g., first aid, emergency treatment, and follow-up care as 
needed). Care for such injuries will be billed in the ordinary manner to the 
participant or the participant’s insurance company.  
19.2 
Contract Language:  
“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 your 
insurance company. If you think that you have suffered a research related injury 
let the study doctor or study staff know right away. You do not give up any of 
your legal rights by signing this form. Be aware that your health-care 
payer/insurer might not cover the costs of study-related injuries or illnesses.” 
20.0 Consent Process 
20.1 
Consent Process (when consent will be obtained): Consenting will take 
place in a private office in the Department of Psychology, or the Ambulatory 
Research Center (ARC), or at the Center for Neurobehavioral Development, or at 
the Department of Psychiatry (Park Plaza) at the University of Minnesota. 
Consent will be documented in writing or electronically through REDCap. For 
participants 18 years-old or over, one of the members of the research staff will 
review the study procedures, risks and benefits as described in the consent form 

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with the potential participant. Participants will be given time to read the 
materials and ask any questions they have about the study. The research staff 
member will pose a set of questions to the participant to ensure that they fully 
understand the procedures, risks, and voluntary nature of the study. The 
participant and research staff will sign the document to complete the consent 
process. Research staff will have completed human participants research 
training, and this information will be maintained on file. For participants under 
the age of 18, one of the members of the research staff will review the study 
procedures, risks and benefits as described in the consent form with the 
parent/guardian and in the assent form with the adolescent. The families will be 
given time to read the materials and ask any questions they have about the 
study.  
20.2 Waiver or Alteration of Consent Process (when consent will not be 
obtained): We are requesting a waiver of documentation of the consent for 
only the phone screen portion of the study. Participants would be 
consented prior to any other study activities. We need to collect sensitive 
information from the parent/guardian prior to the first visit and 
documented consent process in order to determine basic eligibility. All 
parents will be read the attached script and asked to verbally consent to 
the phone screen only. If participants are screened using REDCap, they will 
be presented the same script on the survey and indicate their consent to 
the screen on the survey.  
20.3 Non-English Speaking Participants: N/A 
20.4 Participants Who Are Not Yet Adults (infants, children, teenagers under 18 
years of age): Participants in this study may include minors (under 18 years 
of age) at the time of enrollment. Parental consent (from at least one 
parent) and child assent will be obtained in applicable cases at enrollment 
and documented with a signed form.  
20.5 Cognitively Impaired Adults, or adults with fluctuating or diminished 
capacity to consent: N/A 
 
20.6 Adults Unable to Consent: N/A  
21.0 Setting 
21.1 
Research Sites: Potential participants will be recruited by flyers and 
advertisements posted around the University of Minnesota campus and 
surrounding local areas, including local clinics that allow research postings, and 
through the REP system. Clinical and behavioral assessments may be completed 
in the Department of Psychology, the Ambulatory Research Center, or at the 
Center for Neurobehavioral Development, or at the Department of Psychiatry 

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(Park Plaza) at the University of Minnesota. Stimulation and EEG/ECG visits will 
take place on the University of Minnesota, Twin Cities Campus, at 717 Delaware 
St. MRI scanning will take place at the Center for Magnetic Resonance Research 
(CMRR).  
 
21.2 International Research: N/A 
22.0 Multi-Site Research 
N/A 
23.0 Resources Available 
23.1 Resources Available: We will recruit participants from the University of 
Minnesota’s undergraduate population of over 30,000 students (21% of 
whom have a lifetime diagnosis of depression and 8% of whom have been 
diagnosed with depression in the last year; 2015 College Student Health 
Survey Report: Health Related Behaviors, University of Minnesota—Twin 
Cities Students). We will have access to tDCS equipment and MRI scanners 
through the Neuromodulation laboratory and the Center of Magnetic 
Resonance Research on campus, it is feasible that we will be able to reach 
recruitment targets. Research staff will meet on a weekly basis to discuss 
study progress. Approximately 20 hours/week of Michelle Thai’s time will 
be dedicated to this study, and more time will be dedicated to this study as 
needed. Michelle Thai will coordinate day-to-day logistics of the study with 
research staff and investigators.  
Research-related activities will be conducted in dedicated lab space within 
the Departments of Psychology and Psychiatry. Dr. Cullen has office space 
in Psychiatry. Dr. Klimes-Dougan has laboratory space on the 3rd floor of 
Elliott Hall. Michelle Thai and Dr. Klimes-Dougan have office space on the 
4th floor of Elliott Hall.  
Dr. Cullen has access to office space within the Ambulatory Research 
Center. This research space will be used to conduct consent, clinical and 
behavioral assessments.  
MRI scans will be conducted at the Center for Magnetic Resonance 
Research (CMRR). The CMRR houses state of the art MR instrumentation 
with experts in imaging physics, engineering, and signal processing. The 
interdisciplinary experts and advanced MR technology will ensure quality 
imaging data to be collected. 
tDCS will be applied at the Neuromodulation Laboratory. The 
Neuromodulation Laboratory was established to support research using 
noninvasive neuromodulation The Neuromodulation Laboratory has state 

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of the art equipment, including electroencephalography (EEG) equipment 
and the Neuroelectrics StarStim transcranial current stimulation system.  
Data may be stored and analyzed using the Minnesota Supercomputing 
Institute (MSI). MSI has software, hardware, and experts to support the 
proposed neuroimaging analyses.  
Research related activities may also be conducted at the Center for 
Neurobehavioral Development (CNBD). The CNBD is a research center that 
supports research on brain development in relation to cognitive and 
behavioral development. The CNBD has research space as well as brain 
imaging equipment, tDCS equipment, and software. EEG and tDCS sessions 
may also be conducted at the CNBD.     
Dr. Cullen is a licensed child and adolescent psychiatrist with expertise in 
adolescent depression. Dr. Klimes-Dougan is a licensed psychologist who 
runs a practicum for clinical psychology trainees and will oversee clinical 
assessments and training in clinical assessments. Either Dr. Cullen or 
Klimes-Dougan will be available to provide consult in the case of any 
adverse events. All study staff will complete appropriate IRB and 
institutional trainings.  
 
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