A Pilot Study of the Immediate Effects of DLPFC tDCS on Attention Bias in Depression
Phase: NA
Conditions: Depression
Sponsor: NYU Langone Health

 
 
Page i 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
 
 
 
A Pilot Study of the Immediate Effects of DLPFC tDCS on Attention Bias in 
Depression 
 
Principal Investigator: 
 
Leigh Charvet, PhD 
NYU Langone Health 
Department of Neurology 
222 East 41st Street, 10th Floor 
New York, NY 10017 
Leigh.Charvet@nyumc.org  
929-455-5141 
Additional Investigators: 
 
 
 
 
 
 
 
 
Hyein Cho, PhD 
NYU Langone Health 
Department of Neurology 
222 East 41st Street, 10th Floor 
New York, NY 10017 
Hyein.Cho@nyulangone.org  
929-455-5319 
 
Giuseppina Pilloni, PhD 
Department of Neurology, NYU Langone Health 
222 East 41 Street, 10th Floor 
New York, NY, 10017 
Giuseppina.pilloni@nyulangone.org  
(929) 455-5568 
NYULMC Study Number: 
S21-01461 
Funding Sponsor:  
NYU Langone Department of Neurology 
 
Initial Version: November 18, 2021 
Amended: December 2, .2021 
Amended: June 27, 2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study number: s21-01461 
 
Page ii 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
 
Statement of Compliance 
 
This study will be conducted in accordance with the Code of Federal Regulations on the Protection of 
Human Subjects (45 CFR Part 46), any other applicable US government research regulations, and 
institutional research policies and procedures. The Principal Investigator will assure that no deviation from, 
or changes to the protocol will take place without prior agreement from the sponsor and documented 
approval from the Institutional Review Board (IRB), except where necessary to eliminate an immediate 
hazard(s) to the study participants. All personnel involved in the conduct of this study have completed 
Human Subjects Protection Training. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study number: s21-01461 
 
Page iii 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
 
Table of Contents 
PROTOCOL SUMMARY .............................................................................................................................. 1 
SCHEMATIC OF STUDY DESIGN ............................................................................................................... 2 
KEY ROLES ................................................................................................................................................. 3 
1 
INTRODUCTION, BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ....................... 3 
1.1 
BACKGROUND INFORMATION AND RELEVANT LITERATURE ................................................................ 3 
RATIONALE ................................................................................................................................................. 4 
2 
POTENTIAL RISKS & BENEFITS ....................................................................................................... 4 
2.1 
KNOWN POTENTIAL RISKS .............................................................................................................. 4 
2.2 
KNOWN POTENTIAL BENEFITS ......................................................................................................... 5 
3 
OBJECTIVES AND PURPOSE ........................................................................................................... 5 
3.1 
PRIMARY OBJECTIVE ...................................................................................................................... 5 
3.2 
SECONDARY OBJECTIVE ................................................................................................................. 5 
4 
STUDY DESIGN AND ENDPOINTS .................................................................................................... 5 
4.1 
DESCRIPTION OF STUDY DESIGN .................................................................................................... 5 
4.2 
PRIMARY ENDPOINTS ..................................................................................................................... 6 
4.3 
SECONDARY ENDPOINTS ................................................................................................................ 6 
5 
STUDY ENROLLMENT AND WITHDRAWAL .................................................................................... 6 
5.1 
INCLUSION CRITERIA ...................................................................................................................... 6 
5.2 
EXCLUSION CRITERIA ..................................................................................................................... 6 
5.3 
VULNERABLE SUBJECTS ................................................................................................................. 7 
5.4 
STRATEGIES FOR RECRUITMENT AND RETENTION ............................................................................ 7 
5.5 
TOTAL NUMBER OF PARTICIPANTS AND SITES .................................................................................. 7 
5.5.1 
Use of Epic Information for Recruitment Purposes ................................................................. 7 
5.6 
DURATION OF STUDY PARTICIPATION .............................................................................................. 7 
6 
STUDY SCHEDULE............................................................................................................................. 7 
6.1 
PRE-SCREENING ............................................................................................................................ 7 
6.2 
SCREENING/STUDY VISIT ............................................................................................................... 8 
7 STUDY PROCEDURES/EVALUATIONS .................................................................................................. 8 
7.1 
SCREENING ................................................................................................................................... 8 
7.2 
MOOD AND DEPRESSION QUESTIONNAIRES ..................................................................................... 8 
7.3 
ATTENTION BIAS TASKS ................................................................................................................. 8 
7.3.1 
Dot Probe Task........................................................................................................................ 8 
7.3.2 
Visual Search Task ................................................................................................................. 9 
7.4 
TDCS SESSION ............................................................................................................................. 9 
7.5 
REPEAT QUESTIONNAIRES & ATTENTION BIAS TASKS .................................................................... 10 
8 
STUDY QUESTIONNAIRES .............................................................................................................. 10 
9 
SAFETY AND ADVERSE EVENTS ................................................................................................... 10 
9.1 
DEFINITIONS ................................................................................................................................ 10 
9.2 
RECORDING OF ADVERSE EVENTS ................................................................................................ 11 
9.3 
REPORTING OF SERIOUS ADVERSE EVENTS AND UNANTICIPATED PROBLEMS ................................. 12 
9.3.1 
Investigator reporting: notifying the IRB ................................................................................ 12 
10 
STUDY OVERSIGHT ......................................................................................................................... 13 
10.1 
DATA SAFETY MONITORING .......................................................................................................... 13 

Study number: s21-01461 
 
Page iv 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
10.2 
MEDICAL MONITORING ................................................................................................................. 13 
10.3 
CLINICAL MONITORING ................................................................................................................. 13 
10.4 
STUDY HALTING RULES ................................................................................................................ 13 
THERE ARE NO PREDEFINED STOPPING RULES FOR THIS STUDY. ................................................ 13 
10.5 
PARTICIPANT WITHDRAWAL OR TERMINATION ................................................................................ 13 
10.5.1 
Reasons for Withdrawal or Termination............................................................................ 13 
10.5.2 
Handling of Participant Withdrawals or Termination ......................................................... 13 
10.5.3 
Premature Termination or Suspension of Study ............................................................... 13 
11 
STATISTICAL CONSIDERATIONS .................................................................................................. 14 
11.1 
STUDY HYPOTHESES .................................................................................................................... 14 
11.2 
SAMPLE SIZE DETERMINATION ...................................................................................................... 14 
11.3 
STATISTICAL METHODS ................................................................................................................ 14 
12 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ................................. 14 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................................. 15 
13.1 
ETHICAL STANDARD ..................................................................................................................... 15 
13.2 
INSTITUTIONAL REVIEW BOARD ..................................................................................................... 15 
13.3 
INFORMED CONSENT PROCESS .................................................................................................... 15 
13.3.1 
Consent and Other Informational Documents Provided to Participants ........................... 15 
13.3.2 
Consent Procedures and Documentation ......................................................................... 15 
13.3.3 
Posting of Clinical Trial Consent Form .............................................................................. 16 
13.4 
PARTICIPANT AND DATA CONFIDENTIALITY .................................................................................... 16 
13.4.1 
Research Use of Data ....................................................................................................... 16 
14 
DATA HANDLING AND RECORD KEEPING ................................................................................... 17 
14.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES .............................................................. 17 
14.2 
STUDY RECORDS RETENTION ....................................................................................................... 17 
14.3 
PROTOCOL DEVIATIONS ............................................................................................................... 17 
14.4 
PUBLICATION AND DATA SHARING POLICY ..................................................................................... 17 
15 
STUDY FINANCES ............................................................................................................................ 17 
15.1 
FUNDING SOURCE ........................................................................................................................ 17 
15.2 
COSTS TO THE PARTICIPANT ......................................................................................................... 17 
15.3 
PARTICIPANT REIMBURSEMENTS OR PAYMENTS ............................................................................ 17 
16 
STUDY ADMINISTRATION ............................................................................................................... 18 
16.1 
STUDY LEADERSHIP ..................................................................................................................... 18 
16.1.1 
Non-traditional Volunteers ................................................................................................ 18 
17 
CONFLICT OF INTEREST POLICY .................................................................................................. 18 
18 
REFERENCES ................................................................................................................................... 18 
 
 
 

Study number: s21-01461 
 
Page v 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
 
List of Abbreviations 
 
AB 
Attention Bias 
ACC 
Ambulatory Care Center 
AE 
Adverse Event/Adverse Experience 
AMS 
Analog Mood Scale 
BAI 
Beck Anxiety Inventory 
BDI-II 
Beck Depression Inventory 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DLPFC 
Dorsolateral Prefrontal Cortex 
FFR 
Federal Financial Report 
FPN 
Frontroparietal network 
FWA 
Federalwide Assurance 
HAM-D 
Hamilton Depression Rating Scale 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
IRB 
Institutional Review Board 
MDD 
Major Depressive Disorder 
N 
Number (typically refers to participants) 
NIH 
National Institutes of Health 
OHRP 
Office for Human Research Protections 
OHSR 
Office of Human Subjects Research 
PANAS- SF 
Positive and Negative Affect Schedule 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SMDDS 
Symptoms of Major Depressive Disorder Scale 
SOP 
Standard Operating Procedure 
tDCS 
Transcranial direct current stimulation 
US 
United States 
WRAT-4 
Wide Range Achievement Test-4 Fourth Edition 

Study number: s21-01461 
 
Page 1 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
Protocol Summary 
Title 
A Pilot Study of the Immediate Effects of Single-Session DLPFC tDCS on 
Attention Bias in Depression 
Short Title 
Change in Depressive Attention Bias with DLPFC tDCS  
Brief Summary 
Depression and other psychiatric conditions are marked by exaggerated, 
preferential processing (or attention bias) of negative information relative to 
neutral or positive information. This depression-related attention bias can be 
measured using the Dot Probe task and Visual Search task, that allow 
assessment of the degree to which one shows bias toward negative infromation 
in the presence of neutral or positive information. A clinically effective treatment 
for depression is noninvasive brain stimulation with transcranial direct current 
stimulation (tDCS), targeting the dorsolateral prefrontal cortex (DLPFC), 
delivered in repeated sessions across a period of time. Here, we will test the 
effect of a single session of DLPFC tDCS on attention bias in individuals with 
mild to moderate depression. We predict that a single session DLPFC tDCS will 
alter depression-related, negative attention bias. Further, we compare this effect 
across the mild to moderate depression to healthy controls. 
Objectives 
To test if we can modify or reduce negative attention bias in depression 
following a single session of left anodal DLPFC tDCS. 
Methodology 
Prospective 
Endpoint 
Attention bias and subjective depressive symptoms (affect/mood) at before 
and after a single-session tDCS. 
Study Duration 
One year  
Participant Duration 
A single 2.5 hour research visit  
Population 
Female participants, ages of 18-45, with mild to moderate depression for 
depression group, no to minimal depression for healthy control groups. 
Study Sites 
222 E 41st street, 10th Floor, NY, NY 10017 – NYU Dept. of Neurology 
Number of participants 
N=75 participants  
Study Product 
Transcranial direct current stimulation 
Statistical Analysis 
Pre-post tDCS comparison analyses using t-tests and correlations 
 
 
 

Study number: s21-01461 
 
Page 2 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
Schematic of Study Design  
 
Pre-Screen 
 
 
 
 
 
 
 
 
 
Study Visit 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-tDCS Administration 
 
 
 
 
 
 
 
 
tDCS Admnistration 
 
 
 
 
 
 
 
Post-tDCS Admnistration 
 
 
 
 
 
 
 
 
 
 
 
• 
Eligibility pre-screen to determine general eligibility including 
BDI-II screen 
 
• 
Obtain Informed Consent 
• 
Mini International Neuropsychiatric Interview (MINI) 
(Screening) 
• 
Beck Depression Inventory (BDI-II) (Screening) 
• 
Beck Anxiety Inventory (BAI) 
• 
Hamilton Depression Rating Scale (HAM-D) 
• 
Symptoms of Major Depressive Disorder Scale (SMDDS) 
• 
Healthy controls will complete a brief computer-based word 
puzzle task before the tDCS session, assigned to one of two 
conditions: difficult/unsolvable or easier 
 
• 
PANAS 
• 
AMS 
• 
DP and VS Tasks  
• 
Positive and Negative Affect Schedule-SF (PANAS); 
• 
Analog Mood Scale (AMS) 
• 
Dot Probe Task (DP) and Visual Search (VS) Task 
• 
tDCS tolerability test 
• 
30 minutes of tDCS (up to 2.0mA)  

Study number: s21-01461 
 
Page 3 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
Key Roles 
Principal Investigator: 
Leigh Charvet, PhD 
NYU Langone Health 
Department of Neruology 
222 East 41st Street, 10th Floor 
New York, NY 10017 
Leigh.Charvet@nyumc.org 
929-455-5141 
 
Sub-Investigators: 
Hyein Cho, PhD 
NYU Langone Health 
Department of Neurology 
222 East 41st Street, 10th Floor 
New York, NY 10017 
Hyein.Cho@nyulangone.org 
929-455-5319 
 
Giuseppina Pilloni, PhD 
Department of Neurology, NYU Langone Health 
222 East 41 Street, 10th Floor 
New York, NY, 10017 
Giuseppina.pilloni@nyulangone.org  
(929) 455-5568 
1 Introduction, Background Information and Scientific Rationale 
1.1 
Background Information and Relevant Literature 
 
Depression is characterized by distinct cognitive and emotional disruptions (Mathews & MacLeod, 2005; 
Winer & Salem, 2016), and the symptom burdens associated with the disease are tremendously debilitating to 
those who are affected (Lorenzo-Luaces, 2015). Depression is highly prevalent globally, and occurs twice as 
often in females than in males consistently in almost every part of the world (Culbertson, 1997; Nolen-
Hoeksema & Hilt, 2009; Weissman & Klerman, 1977). Cognitive models of depression have shown depression-
related attention bias (AB), a selective and exaggerated preferential processing toward negative information 
and stimuli, as a key mechanism in the etiology and maintenance of depression pathology (Bar-Haim et al., 
2007; Mathews & Macleod, 1985, 2002; Peckham et al., 2010. Particularly, AB is presented as increased 
attention to negative, mood congruent stimuli and reduced attention to positive, mood-incongruent stimuli in 
depression (Trapp et al., 2018). Furthermore, this negative AB, which could be measured and quantified by 
various cognitive tasks such as the Dot Probe Task (Mathews & Macleod, 1985, 2002), has shown significant 
difference between depressed versus non-depressed individuals, indicating that negative AB is a robust 
measure of depression-related cognitive disruptions (Peckham et al., 2010). Other tasks such as the Visual 
Search (VS) Task (Wolfe & Horowitz, 2017), which is a task that measures facilitation and interference effects 
of attention that are disrupted in emotional and stress-related disorders, have shown robust findings in anxiety 
and PTSD (e.g., Pineles et al, 2009), but less is known about depression (Bodenschatz et al., 2021; Rinck & 
Becker, 2005). Importantly, negative AB was shown in clinical depression, non-clinical dysphoria, research 
subjects undergoing depressive mood induction, and in those who have recovered from depressive episodes 
(Joormann & Gotlieb, 2007; Peckham et al., 2010; Trapp et al., 2018). 
Noninvasive brain stimulation (NIBS) is an effective treatment for depression when applied in repeated 
sessions targeting the DLPFC.  tDCS is one type of NIBS with a large body of clinical evidence supporting its 
PRIMSA Level A recommendation as “definitely effective” for the treatment of a major depressive episode 
(Fregni et al., 2021; Razza et al.,2020). In tDCS, low amplitude current is delivered through electrodes placed 

Study number: s21-01461 
 
Page 4 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
on the scalp to the target regions of interest. tDCS has been extensively demonstrated to be a safe and tolerable 
treatment, with no serious adverse events reported across clinical trials to date (Bikson et al., 2016). 
In treatment of MDD, the use of tDCS is based on evidence of an interhemispheric functional asymmetry 
in depressive states that leads to a hypoactivation of the left dorsolateral prefrontal cortex (DLPFC) and 
hyperactivation of the right DLPFC (Grimm et al., 2008). The DLPFC is connected to the frontoparietal network 
(FPN), which has been found to be underactivated in depression (Korgaonkar et al., 2013). Most importantly, 
past studies suggest that the use of tDCS over the DLPFC may increase cognitive performance of people with 
depression, mainly due to the fact that DLPFC is involved in complex cognitive processes and attentional 
network (Brunoni & Vanderhasselt, 2014; Dedoncker et al., 2016). This further implies that application of tDCS 
in the DLPFC may also modulate attention associated with negative attention bias associated with depression, 
as well as potentially reducing depressive symptoms.  
Recent studies have noted that a single session of DLPFC tDCS administration can reduce AB in patients 
with anxiety disorders (Heeren et al., 2017), but more research is needed to support the impact of short-term 
(i.e., single-session) tDCS in modifying or reducing AB, more specifically in depression.  
In summary, tDCS has an extensive record of safety and tolerability. A large body of research has 
demonstrated its efficacy in reducing depressive symptoms following cumulative daily treatment sessions (e.g., 
20 or more). While there is no clinical treatment benefit expected from a single session of tDCS, no study to 
date has yet to evaluate the immediate effect of single-session DLPFC tDCS in depression-related AB. This 
study will be one of the first studies to evaluate the efficacy of the single-session tDCS on depression-related 
attention bias and depressive mood and symptoms.  
Rationale 
 
 
We will test the effects of a single-session of DLPFC tDCS to alter negative attention bias in individuals with 
mild to moderate depression. In addition, for comparison, we will include healthy control participants 1:1 
assigned to one of two pre-task conditions, where they will complete either difficult/unsolvable or easier 
computer-based word puzzles. The difficult/unsovleable condition will serve as a situational stressor. The easier 
word puzzle condition will provide neutral condition normative data. Findings will inform future studies and have 
the potential to inform the use of tDCS reducing symptoms of depression. Findings will inform future studies 
and have the potential to inform the use of tDCS reducing symptoms of depression.  
 
2 Potential Risks & Benefits 
2.1 Known Potential Risks 
 
Risks associated with tDCS:  
 
MINDD STIM (ybrain, South Korea) is medical-grade non-invasive brain stimulation system that uses weak 
electrical current to stimulate brain region of interest. MINDD STIM system has been used in over 33,200 
sessions and 1,000 patients, without any serious adverse event reported. The side effects reported are similar 
to the ones reported (e.g., tingling, itching, warmth sensation) in other studies using other tDCS devices.  
 
According to literature and the extensive experience of our lab (> 11,000 tDCS sessions delivered so far), 
there are no major risks associated with tDCS. Some people report tingling, itchiness and warmth sensation 
at the site of the electrodes. Rarely, the use of saline-soaked sponge electrodes can provoke skin dryness. 
tDCs do meet criteria for non-significant risk (Bikson et al., 2016). Additionally, there are no known serious 
adverse events associated with this type of stimulation. The current intenisity for this study will be set at 2.0 
mA. The safety and tolerability of tDCS current intensity at 2.0 mA has been assessed in multiple studies in 
which a single session of tDCS was found to be safe and well-tolerated. 
 
For the reasons referenced above, tDCS meets the criteria for an abbreviated IDE (non-significant risk medical 
device): 

Study number: s21-01461 
 
Page 5 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
1. It is not intended as an implant and does not present a potential for serious risk to the health, safety, 
or welfare of a subject 
2. It is not purported or represented to be for a use in supporting or sustaining human life and does not 
present a potential for serious risk to the health, safety, or welfare of a subject. 
3. It is not for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or 
otherwise preventing impairment of human health and does not present a potential for serious risk to 
the health, safety, or welfare of a subject: the device will not be used for subject treatment and 
subjects standard medical treatment will continue regardless of their participation in the study 
4. It does not otherwise present a potential for serious risk to the health, safety, or welfare of a subject. 
 
Risks Associated with Mood Questionnaires: Completing questionnaires may produce some emotional distress 
in some participants. While we do not anticipate this to be a significant issue, participants will be allowed to take 
breaks as needed and may stop answering questions at any time without affecting their enrollment. 
 
Risks Associated with Computer-Based Word Puzzle Task: If participants are assigned to the 
diffficult/unsobleable condition, they may experience situational frustration or emotional discomfort. While we 
expect any discomfort to be  brief and transitory, participants will be able to stop if the task at any point.  
 
Risks Associated with Attention Bias Task: There are no anticipated risks from completing a computerized 
attention bias tasks. 
 
Other risks: 
 
There is minimal risk of breach of confidentiality. All data will be kept strictly confidential and stored in locked 
cabinets located at NYU Ambulatory Care Center (ACC), 222 East 41st Street, 10th Floor, New York, NY 10017. 
Electronic data will be stored on secure, password-protected, NYU Langone computers. Participants will be 
assigned a unique ID that will be used on all data collection instruments. 
 
Unforseeable risks: There may be risks associated with tDCS that are currently not known. 
2.2 Known Potential Benefits 
There is no direct expected benefit to the participants expected from the tDCS protocol as established. It is 
hoped that the knowledge gained from this study will help inform future research projects and ultimately help 
patients in the future. 
3 Objectives and Purpose 
3.1 Primary Objective 
The researchers aim to test if a single-session tDCS targeting the DLPFC (left anodal) can modulate negative 
attention bias associated with depression  and in comparison to helathy controls with and without 
experiencing a situational stressor. 
3.2 Secondary Objective 
Secondary objectives include evaluation of improvement in affect, reduction in depressive symptoms, and 
generation of primary data for future grant applications and basis of larger-sample studies. 
4 Study Design and Endpoints 
4.1 Description of Study Design 
In this prospective pilot study we will recruit 25 female participants, ages 18-45 (inclusive), with mild to moderate 
depression (based on BDI-II score range 14-19 for mild and 20-28 for moderate) as well as 50 healthy control 
(defined by a BDI > 14) females of the same age range (18-45) to determine if a single-session of tDCS can 
alter negative attention bias. With the healthy control group, the recruited participants will be assigned to either 

Study number: s21-01461 
 
Page 6 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
the easy (n = 25) or difficult/unsolvable (n = 25) pre-tDCS word puzzle task condition. The group assignment 
will be pseudo-randomized (counterbalanced; e.g., alternating easy and difficult anagram conditions).The 
primary objective is to study if single-session tDCS will affect attention bias in depression and is not meant to 
treat depression. Subjects may or may not be receiving treatment for mild-moderate depression. If potential 
participant is severly depressed during the screening, standard clinical procedures will be used such as advising 
them to contact their treating physician and/or providing them a crisis hotline number (SAMHSA’s National 
Helpline: 1-800-662-HELP (4357), or to NYU Langone Psychiatry Associates at (212) 263-7419.  
 
For this initial pilot study, we are measuring subtle changes in response time latency at the millisecond level for 
attention bias. Because demographic factors of both age and sex are known to influence response times on 
attention tasks (Dykiert, Der, & Deary, 2012; Joormann & Gotlieb, 2007), we will limit the contribution of these 
factors in this initial pilot study. 
 
The study will consist of a single 2.5 hour research visit that will take place at the NYU Ambulatory Care Center 
(222 East 41st Street, 10th Floor, New York, NY 10017). After written informed consent is obtained (outlined in 
section 13.1), participants will have an eligibility screening which will include a semi structured interview (MINI). 
Eligible participants will complete depression and mood self-report questionnaires, two attention bias tasks (dot-
probe and visual ), and a single 30-minute tDCS session. Total study duration (including analysis, etc.) will be 
1 year. 
4.2 Primary Endpoints 
 
We will examine if a single-session tDCS will reduce depression-related negative attention bias before and after 
the stimulation using the attention bias scores generated using reaction-time based data during the dot probe 
and visual search task. We will also compare this difference across conditions.   
4.3 Secondary Endpoints 
 
Measure if tDCS administration can improve negative/depressive mood and affect measured using self-
reported questionnaires before and after tDCS, as well as across conditions.  
5 Study Enrollment and Withdrawal 
5.1 Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
1. Aged 18-45 
2. Female  
3. Depression group only: Mild to moderate depression (determined by BDI-II scores of 14-19 and 20-
28, respectively). 
4. If taking antidepressants, medication must be stable ≥ 30 days prior to screening 
5. Health control group only: Minimal depression (determined by BDI-II scores of 0-13). 
5.2 Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this study: 
1. Wide-Range Achievement Test-Fourth Edition (WRAT-4) Reading Subtest standard score <85 (to 
ensure understanding of test procedures) 
2. Insufficient visual and motor ability to operate the intervention and assessments as judged by treating 
neurologist or study staff 
3. Primary neurologic condition that would prevent ability to participate  
4. History of head trauma in the last year 
5. Medical device implants in the head or neck 
6. History or current uncontrolled seizure disorder 

Study number: s21-01461 
 
Page 7 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
7. Current substance abuse disorder  
8. Pregnant or lactating women 
9. Skin disorder/sensitive skin near stimulation locations  
10. Depressed participants only: 
11. Primary psychiatric disorder other than depression (based on MINI, only for the mild to moderate 
depression group) 
 
 
Source documents for inclusion/exclusion criteria can include subject self-report, medical records, case report 
forms, and eligibility checklists. Criteria asked during the phone pre-screen will be reconfirmed after consent 
is obtained. 
 
5.3 Vulnerable Subjects 
Vulnerable subjects will not be recruited for this study. 
5.4 Strategies for Recruitment and Retention 
Subjects will be recruited through NYU Langone’s iConnect, clinicaltrials.gov, word of mouth, and research 
flyers placed in the NYU Langone and NYC community. We will also use email blasts (e.g., listserv) to NYC 
schools and community (an email script attached separately). Interested participants will be able to contact a 
study team member via phone or e-mail. A team member will respond by phone to provide potential participants 
an overview of the study, including study procedures, and risks and benefits, using an IRB-approved phone 
script. Potential participants will be clearly informed that they have the right not to participate in the study. If 
interested, subjects can complete a general eligibility pre-screen over the phone.  Subjects will additionally 
verbally confirm if they meet eligibility criteria. 
5.5 Total Number of Participants and Sites  
Recruitment will end when approximately 25 participants are enrolled for each condition (Total N = 75). It is 
expected that approximately 25 participants will be enrolled in order to produce 20 evaluable participants per 
each group (Total N = 60) for this pilot study. 
5.5.1 Use of Epic Information for Recruitment Purposes 
N/A 
5.6 Duration of Study Participation 
Subject participation will consist of a single visit lasting approximately 2.5 hours and will include: 
 
• 
Obtain written consent (~25 minutes) 
• 
Eligibility screening (15 minutes) 
• 
Mood Questionaires (30 minutes) 
• 
Attention Bias Tasks (DP & VS, 60 minutes) 
• 
tDCS session (30 minutes) 
 
6 Study Schedule 
6.1 Pre-Screening 
• 
Team member conducts phone pre-screening (including BDI-II) to determine general eligibility based 
on inclusion/exclusion criteria. Participants who meet the BDI-II criteria during the phone screen will 
not be required to repeat it if they schedule their visit within 2 days of the phone screen. Completing 
the BDI-II over the phone is a practical option that helps screen out those who are ineligible before 

Study number: s21-01461 
 
Page 8 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
they travel to clinic and it is suitable for phone use as participants can verbally rate the BDI-II 
statements on a scale from 0-4.  
Those who score in the severly depressed range (29-63) will be offered to contact the NYU Langone 
Psychiatry Associates at (212) 263-7419, or if outside the NY area the Substance Abuse and Mental 
Health Services Administration (SAMHSA) hotline at 800-662-HELP (4357). 
All data collected for the purposes of the eligibility pre-screening will be destroyed immediately if the 
potential subject is ineligible or does not sign an informed consent form at their baseline.  
6.2 Screening/Study Visit 
• 
Obtain written informed consent (25 minutes or however much time is needed). 
• 
Conduct eligibility screening/MINI/BDI-II (15 minutes)  
• 
tDCS tolerability test (2 minutes) 
• 
Administer depression surveys (BAI, HAM-D, and SMDDS) (15 minutes) 
• 
Administer computerized attention bias dot-probe and visual search task (30 minutes) 
• 
Administer pre-tDCS measures (PANAS and AMS; 10 minutes) 
• 
Complete tDCS session (30 minutes) 
• 
Repeat PANAS and AMS (10 minutes) 
• 
Repeat attention bias dot-probe task and visual search (30 minutes)  
 
7 Study Procedures/Evaluations 
After participants provide written informed consent, the following study procedures will take place during a single  
2.5 hour research visit: 
7.1 Screening 
The PI (or team members with PhD or MA in a related field who are trained by the PI) will meet with the 
participant to review eligibility according to the inclusion/criteria including and administer the mood disorders 
portion of the Mini International Neuropsychiatric Interview (MINI). Data from screen failures will be deleted 
immediately after the recruitment period ends. 
7.2 Mood and Depression Questionnaires  
Participants will be asked to complete self-report questionnaires to assess their baseline depressive symptoms 
and mood.  
7.3 Word Puzzle (Anagram) Task 
Half of the healthy control participants (n = 25) will receive a difficult anagram task, consisted of medium to 
difficult mixed letter words (i.e., anagrams; e.g, TAEIGNS = TEASING). The other half (n = 25) will receive an 
easy anagram task for comparison). The task has been well-validated and used successfully in previous 
research to induce mild stress in healthy controls and those who are at risk for affective disorders (Bishop, 
2009; Mogg et al., 1990; Wen & Yoon, 2019). Some of the words in the difficult anagram task are not solvable 
as real words. Participants will be instructed to solve 40 anagrams as accurately and quickly as possible and 
they will have 3 minutes to complete the task. The participants will be given a paper and pencil to write down 
their solutions, and all words will be programmed into present one word at a time on a laptop screen.  
7.4 Attention Bias Tasks  
Participants will be asked to complete two attention bias assessments: Dot-Probe Task and Visual Search Task. 
7.4.1 Dot Probe Task 
The dot probe task is an established procedure for measuring and manipulating biases in attention associated 
with depression in adults and children (MacLeod, Mathews, & Tata, 1986; Eldar et al., 2008, Joormann & 

Study number: s21-01461 
 
Page 9 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
Gotlieb, 2007; Pekham et al., 2010). The dot-probe task will be used to assess depression-related attention 
bias before and after tDCS administration. 
 
To complete the Dot-Probe task, participants will be shown two emotional images (e.g., sad and neutral pair 
or happy and neutral pair) simultaneously followed by a target in the location of one of the emotional images. 
Response latencies to targets replacing either the negative/positive or neutral images will be measured before 
and after training which will be the primary study outcome. Emotional stimuli used are a selection of negative, 
positive, and neutral pictures taken from a standardized and often used set of emotional faces called the 
racially diverse affective expression [RADIATE; Conley et al., 2018].  
7.4.2 Visual Search Task 
In addition, the Visual Search task (e.g., Wolf & Horowitz, 2017) will be administered to further assess 
attention bias, particularly examining the interference and facilitation effects in attention using emotional 
stimuli (Rinck & Becker, 2005). The task uses emotional faces or words as stimuli, where the participant is 
instructed to search for the face that does not fit into the search set with respect to gender (i.e., the only male 
under three female faces, or the only female under three male faces), where the target and distractors are 
expressing different or same emotions (i.e., neutral-neutral, sad-neutral, happy-neutral, neutral-sad, neutral-
happy, sad-sad, and happy-happy). Studies have shown that individuals with emotional and stress-related 
disorders show interference effect (i.e., emotional stimuli being the distractor) and facilitation effect (i.e., 
emotional stimulus being the search target), but less is known about depression (Bodenschatz et al., 2021; 
Rinck & Becker, 2005; Pineles et al., 2009). This study will use this task as an outcome measure of AB 
alongside the DP task. For this task, mean response time (the time between display onset and button press) 
to the target stimulus for each stimulus type is measured as the main outcome variable. 
7.5 tDCS Session 
tDCS Dose Selection and Tolerability: Participants will undergo a tolerability test to ensure tolerance of the 
stimulation intensity. In under 2 minutes, the tDCS device ramps up to the target stimulation of 2.0mA and 
ramps back down to 0mA. The tolerability test can be aborted at any time if the participant is uncomfortable. If 
2.0mA stimulation is not tolerated, the participant will be given the option to proceed with a second tolerability 
test at a lower stimulation amperage (1.5 mA). Participants who cannot tolerate 1.5mA will be excluded as a 
screen failure. 
tDCS settings: The MINDD STIM tDCS system is composed of a management component, treatment module, 
single-use sponge patches and supporting patches, a headband to hold in position the sponge patches, and 2 
cables. A trained study technician will program the stimulation device through the management component 
setting to the following stimulation parameters: 
 
• 
Stimulation intensity: 2.0 mA or 1.5 mA 
• 
Stimulation duration: 30 minutes 
• 
Ramp up duration: 30 seconds (beginning of stimulation) 
• 
Ramp down duration: 30 seconds (end of stimulation) 
 
Participant preparation for tDCS session: The trained study technician will prepare the stimulation electrodes 
as detailed below:  
 
- Two single-use sponge patches will be (1) inserted in the patch supporters and (2) soaked with saline solution.  
  
- The patches will be then attached to the headband in the positions corresponding to the frontal region. The 
red patch (anode) will be located on the left frontal region while the blue patch (cathode) on the right region 
frontal region.   
 
- The headband will be then positioned on the participant’s head. 
 
- The stimulation module will be then attached to the electrode cables.  

Study number: s21-01461 
 
Page 10 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
  
- The study technician will connect the stimulation module via Bluetooth to the management station and then 
will be ready to initiate the stimulation session.   
  
tDCS session: Participants will complete a single 30 minutes tDCS session targeting the left DLPFC while sitting 
in a comfortable position. At the end of the tDCS session possible side effects experienced during the tDCS 
session will be recorded along with their intensity (rated using the visual analogue scale, 0-10) and duration. 
The session can be aborted at any time for any reason if the participant wishes. 
7.6 Repeat Questionnaires & Attention Bias Tasks  
After the tDCS session participants will repeat two of the questionnaires (PANAS and AMS) and both attention 
bias tasks.  
8 Study Questionnaires  
 
Participants will be asked to complete the following self-report questionnaires: 
 
• 
Beck Depression Inventory (BDI-II): a brief, criteria-referenced assessment for measuring depression 
severity. The BDI-II consists of 21 items to assess the intensity of depression. Each item is a list of four 
statements arranged in increasing severity about a particular symptom of depression. 
 
• 
Beck Anxiety Inventory (BAI): a brief, criteria-referenced assessment for measuring anxiety severity and 
level. Participants respond to 21 items rated on a scale from 0 to 3. Each item is descriptive of subjective, 
somatic, or panic-related symptoms of anxiety. BAI has been found to discriminate well between anxious 
and non-anxious diagnostic groups in a variety of clinical populations. 
 
• 
Hamilton Depression Rating Scale (HAM-D): 17-item measure that was designed to assess frequency 
and intensity of depressive symptoms in patients with MDD. This measure contains somatic and suicidal 
ideation items and has demonstrated reliability, validity, and efficiency in adult populations 
• 
Symptoms of Major Depressive Disorder Scale (SMDDS): a brief measure for adults with MDD and  
measures specific symptom dimensions. The measure has good psychometric properties including high 
reliablity and validity.   
 
• 
Analog Mood Scale (AMS): is a brief measure of positive and negative mood consisting of three questions 
(i.e., “How anxious are you?”, “How sad are you?”, and “How happy are you?”). Participants were told to 
indicate their present mood by identifying a location on a horizontal line divided into 30 equally distanced 
segments labeled 1 (not at all) to 30 (very much). 
 
• 
Positive and Negative Affect Schedule (PANAS-SF): a self-report questionnaire that consists of two 10-
item scales (20 items total) to measure both positive and negative affect. 
 
9 Safety and Adverse Events 
9.1 Definitions 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria:  
• Unexpected in nature, severity, or frequency  (i.e. not described in study-related documents such as the 
IRB-approved protocol or consent form, the investigators brochure, etc) 
• Related or possibly related to participation in the research (i.e. possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research) 

Study number: s21-01461 
 
Page 11 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
• Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
 
Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity during 
the course of the study. Intercurrent illnesses or injuries should be regarded as adverse events.  Abnormal 
results of diagnostic procedures are considered to be adverse events if the abnormality: 
• results in study withdrawal 
• is associated with a serious adverse event 
• is associated with clinical signs or symptoms 
• leads to additional treatment or to further diagnostic tests 
• is considered by the investigator to be of clinical significance 
 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is:  
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• an important medical event 
Important medical events are those that may not be immediately life threatening, but are clearly of major clinical 
significance.   They may jeopardize the subject, and may require intervention to prevent one of the other serious 
outcomes noted above.  For example, drug overdose or abuse, a seizure that did not result in in-patient 
hospitalization, or intensive treatment of bronchospasm in an emergency department would typically be 
considered serious.  
 
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious adverse 
events.  
 
Preexisting Condition 
A preexisting condition is one that is present at the start of the study.  A preexisting condition should be recorded 
as an adverse event if the frequency, intensity, or the character of the condition worsens during the study period. 
 
General Physical Examination Findings 
At screening, any clinically significant abnormality should be recorded as a preexisting condition.  At the end of 
the study, any new clinically significant findings/abnormalities that meet the definition of an adverse event must 
also be recorded and documented as an adverse event.  
 
Post-study Adverse Event 
All unresolved adverse events should be followed by the investigator until the events are resolved, the subject 
is lost to follow-up, or the adverse event is otherwise explained.  At the last scheduled visit, the investigator 
should instruct each subject to report any subsequent event(s) that the subject, or the subject’s personal 
physician, believes might reasonably be related to participation in this study.  The investigator should notify the 
study sponsor of any death or adverse event occurring at any time after a subject has discontinued or terminated 
study participation that may reasonably be related to this study.  The sponsor should also be notified if the 
investigator should become aware of the development of cancer or of a congenital anomaly in a subsequently 
conceived offspring of a subject that has participated in this study.  
9.2 Recording of Adverse Events 
At each contact with the subject, the investigator must seek information on adverse events by specific 
questioning and, as appropriate, by examination.  Information on all adverse events should be recorded 
immediately in the source document, and also in the appropriate adverse event module of the case report 
form (CRF). All clearly related signs, symptoms, and abnormal diagnostic procedures results should recorded 
in the source document, though should be grouped under one diagnosis. 

Study number: s21-01461 
 
Page 12 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
 
All adverse events occurring during the study period must be recorded.  The clinical course of each event 
should be followed until resolution, stabilization, or until it has been determined that the study treatment or 
participation is not the cause.  Serious adverse events that are still ongoing at the end of the study period 
must be followed up to determine the final outcome.  Any serious adverse event that occurs after the study 
period and is considered to be possibly related to study participation should be recorded and reported 
immediately. 
9.3 Reporting of Serious Adverse Events and Unanticipated Problems 
For Narrative Reports of Safety Events 
If the report is supplied as a narrative, the minimum necessary information to be provided at the time of the 
initial report includes: 
• 
Study identifier 
• 
Study Center 
• 
Subject number 
• 
A description of the event 
• 
Date of onset 
• 
Current status 
• 
Whether study treatment was discontinued 
• 
The reason why the event is classified as serious 
• 
Investigator 
assessment 
of 
the 
association 
between the event and study treatment 
9.3.1 Investigator reporting: notifying the IRB 
Federal regulations require timely reporting by investigators to their local IRB of unanticipated problems posing 
risks to subjects or others. The following describes the NYULMC IRB reporting requirements, though 
Investigators at participating sites are responsible for meeting the specific requirements of their IRB of record.  
 
Report Promptly, but no later than 5 working days: 
Researchers are required to submit reports of the following problems promptly but no later than 5 working days 
from the time the investigator becomes aware of the event: 
• 
Unanticipated problems including adverse events that are unexpected and related 
– Unexpected: An event is “unexpected” when its specificity and severity are not accurately reflected 
in the protocol-related documents, such as the IRB-approved research protocol, any applicable 
investigator brochure, and the current IRB-approved informed consent document and other relevant 
sources of information, such as product labeling and package inserts.  
– Related to the research procedures: An event is related to the research procedures if in the opinion 
of the principal investigator or sponsor, the event was more likely than not to be caused by the 
research procedures.  
– Harmful: either caused harm to subjects or others, or placed them at increased risk 
 
Other Reportable events: 
The following events also require prompt reporting to the IRB, though no later than 5 working days: 
• Complaint of a research subject when the complaint indicates unexpected risks or the complaint 
cannot be resolved by the research team. 
• Protocol deviations or violations (includes intentional and accidental/unintentional deviations from 
the IRB approved protocol) for any of the following situations:  
– one or more participants were placed at increased risk of harm  
– the event has the potential to occur again 
– the deviation was necessary to protect a subject from immediate harm 
• Breach of confidentiality 
• Incarceration of a participant when the research was not previously approved under Subpart C and 
the investigator believes it is in the best interest of the subject to remain on the study. 

Study number: s21-01461 
 
Page 13 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
• New Information indicating a change to the risks or potential benefits of the research, in terms of 
severity or frequency. (e.g. analysis indicates lower-than-expected response rate or a more severe or 
frequent side effect; Other research finds arm of study has no therapeutic value; FDA labeling change 
or withdrawal from market) 
Reporting Process 
The reportable events noted above will be reported to the IRB using a Reportable New Information submission 
and will include a description of the event with information regarding its fulfillment of the above criteria, follow-
up/resolution, and need for revision to consent form and/or other study documentation. Copies of each report 
and documentation of IRB notification and receipt will be kept in the Clinical Investigator’s study file. 
10 Study Oversight 
10.1 Data Safety Monitoring 
It is the responsibility of the Principal Investigator to oversee the safety of the study. This safety monitoring will 
include careful assessment and appropriate reporting of adverse events as noted above. Data safety monitoring 
will occur at least every 4 months and will include PI review of reports of tDCS side effects including skin 
irritation, itching, warming, and discomfort, emotional distress, protocol adherence, regulatory documentation, 
enrollment (e.g. rate of enrollment, screen fails, withdrawals, etc.), unanticipated problems, and any issues that 
may arise during the course of research. 
10.2 Medical Monitoring 
Dr. Lauren Krupp, MD, Director of the NYU MSCCC, will serve as medical monitor for this study. Dr. Krupp will 
be responsible for determing SAE severity and relatedness. 
10.3 Clinical Monitoring 
N/A 
10.4 Study Halting Rules 
There are no predefined stopping rules for this study.   
10.5 Participant Withdrawal or Termination 
10.5.1 Reasons for Withdrawal or Termination 
Participants are free to withdraw from participation in the study at any time upon request. An investigator may 
terminate participation in the study if: 
• 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation occurs 
such that continued participation in the study would not be in the best interest of the participant 
• 
The participant meets an exclusion criterion (either newly developed or not previously recognized) that 
precludes further study participation 
• 
The participant is non-compliant with study procedures 
10.5.2 Handling of Participant Withdrawals or Termination 
Data of participants who withdraw or are terminated from the study may be kept for analysis if the data is usable 
(as determined PI).   
10.5.3 Premature Termination or Suspension of Study 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause. If 
the study is prematurely terminated or suspended, the PI will promptly inform the IRB and will provide the 
reason(s) for the termination or suspension. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 

Study number: s21-01461 
 
Page 14 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping 
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, data quality are addressed and satisfy 
the IRB. 
11 Statistical Considerations 
11.1 Study Hypotheses 
A single-session tDCS to the left DLPFC will reduce negative attention bias in people with mild to moderate 
depression. There will be cohort differences across mildy depressed vs. healthy controls with easy anagram 
vs. healthy controls with difficult anagram (situational stressor) where the reduction of negative attention bias 
would be greatest in the depressed group compared to the healthy controls.  
The primary objective of this study is exploratory data collection. These pilot study findings will be the 
necessary first step to inform future study design and hypotheses. We are collecting the healthy control pilot 
data to better interpret the pilot findings in patients with depression, and to provide us with expected ranges of 
change in our task measures. This inclusion of the anagram task is exploratory to inform future study designs. 
The use of the challenging anagram task is based from literature where the same paradigm has been used in 
healthy controls to study temporary states of negative affect (e.g., frustration, anxiety; Myruski et al., 2021). 
11.2 Sample Size Determination 
The primary objective of this study is to test change in negative attention bias in people with mild to moderate 
depression following a single session of DLPFC tDCS, and see if their outcomes differ from that of healthy 
controls.  
This is a pilot study to assess the feasibility of a single-session tDCS in a small sample, and the findings will 
provide preliminary evaluation of effect and inform power analyses for use in a clinical trial design.  
A total of N = 75 (n=25 participants for each group) will be enrolled to obtain evaluable target of N=60 (n = 20 
for each group) based on the estimated number of eligible participant for each group contacts across the study 
period.  
11.3 Statistical Methods 
For the study hypothesis to examine the preliminary effect of a single-session tDCS on depression on negative 
attention bias, we will use the calculated latency response times pre-tDCS and post-tDCS using the DP and VS 
tasks and compare change using a paired sample’s t-test for each measure. Further, to compare across the 
groups, we will use ANOVA for before and after effect of tDCS on negative attention bias across the three 
groups. 
As secondary and exploratory, we will also test change in pre- to post- ratings of depressive symptoms and 
affect.  These findings will be collected to inform the power analyses for a larger controlled trial. 
12 Source Documents and Access to Source Data/Documents 
Source data is all information, original records of clinical findings, observations, or other activities in a study 
necessary for the reconstruction and evaluation of the study.  Source data are contained in source documents.  
Examples of these original documents, and data records include: hospital records, clinical and office charts, 
laboratory notes, memoranda, evaluation checklists, pharmacy dispensing records, recorded data from 

Study number: s21-01461 
 
Page 15 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
automated instruments, copies or transcriptions certified after verification as being accurate and complete, 
subject files.  
 
The study case report form (CRF) is the primary data collection instrument for the study.  All data requested on 
the CRF must be recorded.  All missing data must be explained.  If a space on the CRF is left blank because 
the procedure was not done or the question was not asked, write “N/D”.  If the item is not applicable to the 
individual case, write “N/A”.  All entries should be printed legibly in blue or black ink.  If any entry error has been 
made, to correct such an error, draw a single straight line through the incorrect entry and enter the correct data 
above it.  All such changes must be initialed and dated.  DO NOT ERASE OR WHITE OUT ERRORS.  For 
clarification of illegible or uncertain entries, print the clarification above the item, then initial and date it. 
 
Access to study records will be limited to IRB-approved members of the study team. The investigator will permit 
study-related monitoring, audits, and inspections by the IRB, government regulatory bodies, and University 
compliance and quality assurance groups of all study related documents (e.g. source documents, regulatory 
documents, data collection instruments, study data etc.). The investigator will ensure the capability for 
inspections of applicable study-related facilities. 
 
Participation as an investigator in this study implies acceptance of potential inspection by government regulatory 
authorities and applicable University compliance and quality assurance offices. 
13 Ethics/Protection of Human Subjects 
13.1 Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with Regulations for the Protection of 
Human Subjects of Research codified in 45 CFR Part 46. 
13.2 Institutional Review Board 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be submitted to 
the IRB for review and approval. Approval of both the protocol and the consent form must be obtained before 
any participant is enrolled. Any amendment to the protocol will require review and approval by the IRB before 
the changes are implemented to the study. All changes to the consent form will be IRB approved; a 
determination will be made regarding whether previously consented participants need to be re-consented. 
13.3 Informed Consent Process 
13.3.1 Consent and Other Informational Documents Provided to Participants 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting intervention. The 
following consent materials are submitted with this protocol: informed consent form. 
13.3.2 Consent Procedures and Documentation 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study and 
continues throughout the individual’s study participation. Extensive discussion of risks and possible benefits of 
participation will be provided to the participants and their families. Consent forms will be IRB-approved and 
the participant will be asked to read and review the document. The investigator will explain the research study 
to the participant and answer any questions that may arise. All participants will receive a verbal explanation in 
terms suited to their comprehension of the purposes, procedures, and potential risks of the study and of their 
rights as research participants. Participants will have the opportunity to carefully review the written consent 
form and ask questions prior to signing. The participants should have the opportunity to discuss the study with 
their surrogates or think about it prior to agreeing to participate. The participant will sign the informed consent 
document prior to any procedures being done specifically for the study. The participants may withdraw 
consent at any time throughout the course of the study. A copy of the signed informed consent document will 
be given to the participants for their records. The rights and welfare of the participants will be protected by 

Study number: s21-01461 
 
Page 16 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
emphasizing to them that the quality of their medical care will not be adversely affected if they decline to 
participate in this study. 
 
A copy of the signed informed consent document will be stored in the subject’s research record. The consent 
process, including the name of the individual obtaining consent, will be thoroughly documented in the 
subject’s research record. Any alteration to the standard consent process (e.g. use of a translator, consent 
from a legally authorized representative, consent document presented orally, etc.) and the justification for 
such alteration will likewise be documented.  
 
Subject capacity to provide written informed consent will be determined by the PI, or a team member trained 
by the PI, during the semi-structured screening interview (MINI). In addition, the WRAT-4, a cognitive 
measure for reading comprehension, will also be administered. A clinician is not required to administer the 
WRAT-4 because it is scored with normative values.  
13.3.3 Posting of Clinical Trial Consent Form 
N/A 
13.4 Participant and Data Confidentiality 
Information about study subjects will be kept confidential and managed according to the requirements of the 
Health Insurance Portability and Accountability Act of 1996 (HIPAA). Those regulations require a signed subject 
authorization informing the subject of the following:  
• What protected health information (PHI) will be collected from subjects in this study 
• Who will have access to that information and why 
• Who will use or disclose that information  
• The rights of a research subject to revoke their authorization for use of their PHI.  
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, retains 
the ability to use all information collected prior to the revocation of subject authorization. For subjects that have 
revoked authorization to collect or use PHI, attempts should be made to obtain permission to collect at least 
vital status (i.e. that the subject is alive) at the end of their scheduled study period. 
 
Participant confidentiality is strictly held in trust by the participating investigators and their staff. This 
confidentiality is extended to cover clinical information relating to participants. Therefore, the study protocol, 
documentation, data, and all other information generated will be held in strict confidence. No information 
concerning the study or the data will be released to any unauthorized third party without prior written approval. 
The study participant’s contact information will be securely stored on NYU Langone servers for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as long a 
period as dictated by local IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be 
securely stored at the NYU Langone Health Ambulatory Care Center. This will not include the participant’s 
contact or identifying information. Rather, individual participants and their research data will be identified by a 
unique study identification number. The study data entry and study management systems used by research 
staff will be secured and password protected. At the end of the study, all study databases will be de-identified 
and archived at NYU Langone Health Ambulatory Care Center . 
 
Identifying information will not be presented or published to maintain participant privacy and confidentiality. 
13.4.1 Research Use of Data 
Consent forms, source documents, and research data will be stored in locked filing cabinets at the NYU 
Langone Health ACC, 222 East 41st Street, 10th Floor, New York. NY 10017. 
 
Collected study data, including demographic information and research questionnaires, will be obtained 
electronically through TrialMaster, a HIPAA and 21 CFR Part 11-compliant database designed specifically for 

Study number: s21-01461 
 
Page 17 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
this study. An anonymous database number will be assigned to each participant. The following study personnel 
will have access to the collected data and study documents: Principal Investigator, Sub-Investigators, and 
Research Coordinators who are specifically assigned to work on this study. 
 
If participants request to leave the study, no additional data from the date of request will be collected. Any 
existing data which was previously collected will continue to be stored. 
14 Data Handling and Record Keeping 
14.1 Data Collection and Management Responsibilities 
Data collection is the responsibility of the study staff at the site under the supervision of the site PI. The 
investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data 
reported. All source documents should be completed in a neat, legible manner to ensure accurate interpretation 
of data. Black ink is required to ensure clarity of reproduced copies. When making changes or corrections, cross 
out the original entry with a single line, and initial and date the change. DO NOT ERASE, OVERWRITE, OR 
USE CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and maintained for recording 
data for each participant enrolled in the study. Data reported in the eCRF derived from source documents 
should be consistent with the source documents or the discrepancies should be explained and captured in a 
progress note and maintained in the participant’s official electronic study record. 
14.2 Study Records Retention 
Study documents will be retained for the longer of 3 years after close out or 5 years after final 
reporting/publication. These documents should be retained for a longer period, however, if required by local 
regulations. 
14.3 Protocol Deviations 
A protocol deviation is any noncompliance with the study protocol. The noncompliance may be either on the 
part of the participant, the investigator, or the study site staff. As a result of deviations, corrective actions are to 
be developed by the site and implemented promptly. 
 
It is the responsibility of the site to use continuous vigilance to identify deviations within 7 working days of the 
scheduled protocol-required activity. Protocol deviations will be reported to the local IRB at the time of study 
Continuation. The site PI/study staff is responsible for knowing and adhering to IRB requirements. 
14.4 Publication and Data Sharing Policy 
At the end of the study, the PI will make results of the research available to the research community and 
public at large. 
15 Study Finances 
15.1 Funding Source 
This study is departmentally funded by the NYU Department of Neurology. 
15.2 Costs to the Participant 
There are no costs to the participant in order to take part in this study. 
15.3 Participant Reimbursements or Payments 
Participants will be compensated $100 for participating in this study in the form of check or GreenPhire 
Clincard. 

Study number: s21-01461 
 
Page 18 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
16 Study Administration 
16.1 Study Leadership 
The PI will oversee the conduct of this study, in coordination with sub-investigators as applicable. 
16.1.1 Non-traditional Volunteers 
Non-traditional volunteers who are approved by the IRB to work on this study will not consent nor have direct 
interaction with research participants.  
17 Conflict of Interest Policy 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical industry, 
is critical. Therefore any actual conflict of interest of persons who have a role in the design, conduct, analysis, 
publication, or any aspect of this study will be disclosed and managed. Furthermore, persons who have a 
perceived conflict of interest will be required to have such conflicts managed in a way that is appropriate to their 
participation in the study. The study leadership has established policies and procedures for all study group 
members to disclose all conflicts of interest and will establish a mechanism for the management of all reported 
dualities of interest.  
 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial gain 
greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by the NYU 
Langone Conflict of Interest Committee with a Committee-sanctioned conflict management plan that has been 
reviewed and approved by the study sponsor prior to participation in this study. All NYULMC investigators will 
follow the applicable conflict of interest policies. 
 
 
 
18 References 
 
Bar-Haim, Y., Lamy, D., Pergamin, L., Bakermans-Kranenburg, M. J., & Van Ijzendoorn, M. H. (2007). Threat-
related attentional bias in anxious and nonanxious individuals: a meta-analytic study. Psychological 
Bulletin, 133(1), 1. 
 
Bikson, M., Grossman, P., Thomas, C., Zannou, A. L., Jiang, J., Adnan, T., ... & Woods, A. J. (2016). Safety of 
transcranial direct current stimulation: evidence based update 2016. Brain stimulation, 9(5), 641-661. 
 
Bodenschatz, C. M., Czepluch, F., Kersting, A., & Suslow, T. (2021). Efficient visual search for facial emotions 
in patients with major depression. BMC Psychiatry, 21(1), 1-12. 
 
Boggio, P. S., Rigonatti, S. P., Ribeiro, R. B., Myczkowski, M. L., Nitsche, M. A., Pascual-Leone, A., & Fregni, 
F. (2008). A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation 
for the treatment of major depression. International Journal of Neuropsychopharmacology, 11(2), 249-
254. 
 
Borrione, L., Bellini, H., Razza, L. B., Avila, A. G., Baeken, C., Brem, A. K., ... & Brunoni, A. R. (2020). Precision 
non-implantable neuromodulation therapies: a perspective for the depressed brain. Brazilian Journal of 
Psychiatry, 42, 403-419. 
 
Brunoni, A. R., Amadera, J., Berbel, B., Volz, M. S., Rizzerio, B. G., & Fregni, F. (2011). A systematic review 
on reporting and assessment of adverse effects associated with transcranial direct current 
stimulation. International Journal of Neuropsychopharmacology, 14(8), 1133-1145. 
 

Study number: s21-01461 
 
Page 19 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
Brunoni, A. R., & Vanderhasselt, M. A. (2014). Working memory improvement with non-invasive brain 
stimulation of the dorsolateral prefrontal cortex: a systematic review and meta-analysis. Brain and 
Cognition, 86, 1-9. 
 
Brunoni, A. R., Valiengo, L., Baccaro, A., Zanão, T. A., de Oliveira, J. F., Goulart, A., ... & Fregni, F. (2013). 
The sertraline vs electrical current therapy for treating depression clinical study: results from a factorial, 
randomized, controlled trial. JAMA psychiatry, 70(4), 383-391. 
 
Charvet, L. E., Kasschau, M., Datta, A., Knotkova, H., Stevens, M. C., Alonzo, A., ... & Bikson, M. (2015). 
Remotely-supervised transcranial direct current stimulation (tDCS) for clinical trials: guidelines for 
technology and protocols. Frontiers in Systems Neuroscience, 9, 26. 
 
Charvet, L. E., Shaw, M. T., Bikson, M., Woods, A. J., & Knotkova, H. (2020). Supervised transcranial direct 
current stimulation (tDCS) at home: a guide for clinical research and practice. Brain Stimulation, 13(3), 
686-693. 
 
Conley, M. I., Dellarco, D. V., Rubien-Thomas, E., Cohen, A. O., Cervera, A., Tottenham, N., & Casey, B. J. 
(2018). The racially diverse affective expression (RADIATE) face stimulus set. Psychiatry 
research, 270, 1059-1067. 
 
Culbertson, F. M. (1997). Depression and gender: an international review. American Psychologist, 52(1), 25. 
 
Dedoncker, J., Brunoni, A. R., Baeken, C., & Vanderhasselt, M. A. (2016). A systematic review and meta-
analysis of the effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal 
cortex in healthy and neuropsychiatric samples: influence of stimulation parameters. Brain 
Stimulation, 9(4), 501-517. 
 
Dykiert, D., Der, G., Starr, J., & Deary, I. (2012). Sex differences in reaction time mean and intraindividual 
variability across the life span. Dev Psychol. Sep;48(5):1262-76. doi: 10.1037/a0027550. Epub 2012 
Mar 5. PMID: 22390656. 
 
Eldar, S., Ricon, T., & Bar-Haim, Y. (2008). Plasticity in attention: Implications for stress response in 
children. Behaviour Research and Therapy, 46(4), 450-461. 
 
Fregni, F., Boggio, P. S., Nitsche, M. A., Marcolin, M. A., Rigonatti, S. P., & Pascual-Leone, A. (2006). 
Treatment of major depression with transcranial direct current stimulation. 
 
Fregni, F., El-Hagrassy, M. M., Pacheco-Barrios, K., Carvalho, S., Leite, J., Simis, M., ... & Brunoni, A. R. 
(2021). Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct 
Current 
Stimulation 
in 
Neurological 
and 
Psychiatric 
Disorders. International 
Journal 
of 
Neuropsychopharmacology, 24(4), 256-313. 
 
Grimm, S., Beck, J., Schuepbach, D., Hell, D., Boesiger, P., Bermpohl, F., ... & Northoff, G. (2008). Imbalance 
between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional 
judgment: an fMRI study in severe major depressive disorder. Biological Psychiatry, 63(4), 369-376. 
 
Heeren, A., Billieux, J., Philippot, P., De Raedt, R., Baeken, C., de Timary, P., ... & Vanderhasselt, M. A. (2017). 
Impact of transcranial direct current stimulation on attentional bias for threat: a proof-of-concept study 
among individuals with social anxiety disorder. Social cognitive and affective neuroscience, 12(2), 251-
260. 
 
Jones, B. D., Weissman, C. R., Razza, L. B., Husain, M. I., Brunoni, A. R., & Daskalakis, Z. J. (2021). Protocol 
for a systematic review and meta-analysis of the placebo response in treatment-resistant depression: 
comparison of multiple treatment modalities. BMJ open, 11(2), e041349. 
 

Study number: s21-01461 
 
Page 20 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
Joormann, J., & Gotlib, I. H. (2007). Selective attention to emotional faces following recovery from 
depression. Journal of Abnormal Psychology, 116(1), 80. 
 
Korgaonkar, M. S., Grieve, S. M., Etkin, A., Koslow, S. H., & Williams, L. M. (2013). Using standardized fMRI 
protocols to identify patterns of prefrontal circuit dysregulation that are common and specific to cognitive 
and emotional tasks in major depressive disorder: first wave results from the iSPOT-D 
study. Neuropsychopharmacology, 38(5), 863-871. 
 
Lorenzo-Luaces, L. (2015). Heterogeneity in the prognosis of major depression: from the common cold to a 
highly debilitating and recurrent illness. Epidemiology and Psychiatric Sciences, 24(6), 466-472. 
 
MacLeod, C., Mathews, A., & Tata, P. (1986). Attentional bias in emotional disorders. Journal of Abnormal 
Psychology, 95(1), 15. 
 
Mathews, A., & Macleod, C. (1985). Selective processing of threat cues in anxiety states. Behaviour Research 
and Therapy, 23(5), 563-569. 
 
Mathews, A., & MacLeod, C. (2002). Induced processing biases have causal effects on anxiety. Cognition & 
Emotion, 16(3), 331-354. 
 
Mathews, A., & MacLeod, C. (2005). Cognitive vulnerability to emotional disorders. Annu. Rev. Clin. Psychol., 1, 
167-195. 
 
Mogg, K., Mathews, A., Bird, C., & Macgregor-Morris, R. (1990). Effects of stress and anxiety on the processing 
of threat stimuli. Journal of personality and Social Psychology, 59(6), 1230. 
 
Myruski, S., Cho, H., Bikson, M., & Dennis-Tiwary, T. A. (2021). Transcranial direct current stimulation (tDCS) 
augments the effects of gamified, mobile attention bias modification. Frontiers in Neuroergonomics, 2, 
652162. 
 
Nolen-Hoeksema, S., & Hilt, L. M. (2009). Gender differences in depression. 
 
Padberg, F., Bulubas, L., Mizutani-Tiebel, Y., Burkhardt, G., Kranz, G. S., Koutsouleris, N., ... & Brunoni, A. R. 
(2021). The intervention, the patient and the illness–Personalizing non-invasive brain stimulation in 
psychiatry. Experimental Neurology, 341, 113713. 
 
Peckham, A. D., McHugh, R. K., & Otto, M. W. (2010). A meta‐analysis of the magnitude of biased attention in 
depression. Depression and Anxiety, 27(12), 1135-1142. 
 
Pineles, S. L., Shipherd, J. C., Mostoufi, S. M., Abramovitz, S. M., & Yovel, I. (2009). Attentional biases in 
PTSD: More evidence for interference. Behaviour Research and Therapy, 47(12), 1050-1057 
 
Razza, L. B., Palumbo, P., Moffa, A. H., Carvalho, A. F., Solmi, M., Loo, C. K., & Brunoni, A. R. (2020). A 
systematic review and meta‐analysis on the effects of transcranial direct current stimulation in 
depressive episodes. Depression and Anxiety, 37(7), 594-608. 
 
Rigonatti, S. P., Boggio, P. S., Myczkowski, M. L., Otta, E., Fiquer, J. T., Ribeiro, R. B., ... & Fregni, F. (2008). 
Transcranial direct stimulation and fluoxetine for the treatment of depression. European 
Psychiatry, 23(1), 74-76. 
 
Rinck, M., & Becker, E. S. (2005). A comparison of attentional biases and memory biases in women with social 
phobia and major depression. Journal of Abnormal Psychology, 114(1), 62. 
 
Rosenblat, J. D., Kurdyak, P., Cosci, F., Berk, M., Maes, M., Brunoni, A. R., ... & Carvalho, A. F. (2020). 
Depression in the medically ill. Australian & New Zealand Journal of Psychiatry, 54(4), 346-366. 
 

Study number: s21-01461 
 
Page 21 
Version:  27 June 2021 
 
 
CONFIDENTIAL 
This material is the property of the NYU Langone. Do not disclose or use except as authorized in writing by the study sponsor 
Study Template Version: 5 MAY 2017 
Trapp, W., Kalzendorf, C., Baum, C., Hajak, G., & Lautenbacher, S. (2018). Attentional biases in patients 
suffering from unipolar depression: results of a dot probe task investigation. Psychiatry Research, 261, 
325-331. 
 
Weissman, M. M., & Klerman, G. L. (1977). Sex differences and the epidemiology of depression. Archives of 
general psychiatry, 34(1), 98-111. 
 
Wen, A., & Yoon, K. L. (2019). Depression and affective flexibility: A valence-specific bias. Behaviour Research 
and Therapy, 123, 103502. 
 
Winer, E. S., & Salem, T. (2016). Reward devaluation: Dot-probe meta-analytic evidence of avoidance of 
positive information in depressed persons. Psychological Bulletin, 142(1), 18. 
 
Wolfe, J., & Horowitz, T. (2017). Five factors that guide visual attention. Nature Human Behavior, 1(0058), 10-
1038.