Transcranial Direct Current Stimulation for the Treatment of Deficits After Traumatic Brain Injury
Phase: NA
Conditions: Traumatic Brain Injury, Post Concussive Symptoms, Depression, Executive Dysfunction
Sponsor: University of New Mexico

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 1 of 49
Version Date: January 29, 2019
PROTOCOL TITLE:
Transcranial direct current stimulation for treatment of deficits after traumatic brain 
injury. 
PRINCIPAL INVESTIGATOR:
Davin Quinn, MD
Department of Psychiatry
SPONSOR:
Davin Quinn, MD
FUNDING SOURCE:
National Institutes of Health (NIH)/NIGMS
VERSION NUMBER:
#9
DATE:
01/09/2019
REGULATORY FRAMEWORK:
Please indicate all that apply:
DOD (Department of Defense)
DOE (Department of Energy)
DOJ (Department of Justice)
ED (Department of Education)
EPA (Environmental Protection Agency)
x
FDA (Food and Drug Administration)
x
HHS (Department of Health and Human Services)
VA
Other:      
Is this a clinical trial under ICH-GCP E6?   
 Yes   
X No
If yes, please confirm that the research team is familiar with and agrees to comply 
with the investigator requirements cited in ICH-GCP E6.  
 Yes   
 No 
ICH-GCP E6 can be accessed by copying and pasting this URL into your 
browser: http://www.fda.gov/downloads/Drugs/Guidances/ucm073122.pdf

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 2 of 49
Version Date: January 29, 2019

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 3 of 49
Version Date: January 29, 2019
Table of Contents
1.
Objectives.....................................................................................................................4
2.
Background ..................................................................................................................4
3.
Study Design ................................................................................................................7
4.
Inclusion and Exclusion Criteria ..................................................................................7
5.
Number of Subjects ....................................................Error! Bookmark not defined.
6.
Study Timelines............................................................................................................9
7.
Study Endpoints .........................................................................................................10
8.
Research Setting.........................................................................................................11
9.
Resources Available...................................................................................................11
10.
Prior Approvals.......................................................................................................13
11.
Multi-Site Research ................................................................................................13
12.
Study Procedures ....................................................................................................14
13.
Data Analysis..........................................................................................................18
14.
Provisions to Monitor the Data to Ensure the Safety of Subjects...........................18
15.
Withdrawal of Subjects...........................................................................................19
16.
Data Management/Confidentiality..........................................................................19
17.
Data and Specimen Banking...................................................................................21
18.
Risks to Subjects.....................................................................................................21
19.
Potential Benefits to Subjects .................................................................................22
20.
Recruitment Methods..............................................................................................22
21.
Provisions to Protect the Privacy Interests of Subjects ..........................................23
22.
Economic Burden to Subjects.................................................................................24
23.
Compensation .........................................................................................................25
24.
Compensation for Research-Related Injury............................................................25
25.
Consent Process......................................................................................................25
26.
Documentation of Consent .....................................................................................26
27.
Study Test Results/Incidental Findings ..................................................................26
28.
Sharing Study Progress or Results with Subjects...................................................26
29.
Inclusion of Vulnerable Populations ......................................................................26
30.
Community-Based Participatory Research.............................................................27
31.
Research Involving American Indian/Native Populations .....................................27
32.
Transnational Research...........................................................................................27
33.
Drugs or Devices ....................................................................................................27
Checklist Section ...............................................................................................................29

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 4 of 49
Version Date: January 29, 2019
1. Objectives
Our long-term goal is to develop safe and effective treatments for symptoms of mild to moderate TBI 
(mmTBI) that restore patients to higher levels of functioning, decrease disability, and promote brain 
healing.  The objective of this application is to investigate the use of transcranial direct current 
stimulation (tDCS) to treat symptoms of executive dysfunction and depression in patients with 
mmTBI. Our central hypotheses are (1) tDCS paired with relevant cognitive training facilitates 
improves executive function on NIH-approved neuropsychological measures, (2) tDCS reduces 
depression scores on NIH Common Data Elements for TBI, (3) that these improvements in emotion 
and cognition will be detectable up to one year after stimulation, (4) (4) certain clinical variables will 
reliably predict response to tDCS, such as age, education level, injury severity, and magnetic 
resonance imaging (MRI) evidence of structural/functional/metabolic abnormalities and (5) 
quantitative electroencephalography (EEG) will demonstrate changes in frontal midline theta band 
power and theta band synchrony, markers of cognitive control, in responders. These objectives were 
formulated based on our clinical experience with Dr. Ronald Yeo (project mentor) characterizing 
symptomatic patients with mmTBI in the post-acute setting, groundbreaking research led by Dr. 
Vincent Clark (project mentor) that has demonstrated robust increases in attention and learning 
with tDCS, and extensive evidence accumulated by co-junior investigator on the grant application Dr. 
James Cavanagh on EEG measures of executive dysfunction.
Specific Aim 1: tDCS for executive dysfunction in mmTBI
Experiments in this aim will test the hypothesis that in patients with mmTBI, left prefrontal anodal 
tDCS concurrent with cognitive training for up to ten consecutive weekdays will result in significantly 
more improvement in executive function compared to sham stimulation.  Patients with cognitive 
complaints 3 months to 15 years after mmTBI will be recruited from local emergency departments 
and brain injury clinics.  Healthy controls will also be recruited through flyers, advertisements and 
word of mouth.  Aim 1.1: tDCS will be paired with computer-based cognitive training tasks of 
response inhibition, set shifting, and working memory, while executive function will be measured 
with the NIH Examiner battery before, immediately after, and one month after stimulation. Pre-and 
post-stimulation EEG and MRI may be obtained. During EEG and MRI participants may be asked to 
rest quietly or perform simple tasks. Aim 1.2: Persistence of post-traumatic symptom reduction and 
quality of life improvement will be assessed with Common Data Elements instruments via telephone 
interview at 6 months and one year.  Aim 1.3: Clinical predictors of tDCS response including EEG 
frontal theta synchrony, injury severity, presence of neuroimaging abnormalities, premorbid 
intelligence, and post-traumatic symptom burden will be determined with linear mixed-models 
analysis.
Specific Aim 2: tDCS for depressive symptoms in mmTBI
Experiments in this aim will test the hypothesis that left prefrontal anodal tDCS in patients with 
mmTBI will significantly reduce depressive symptoms compared to sham stimulation. Aim 2.1: 
Patients will be assessed for symptoms of depression via self-report instruments and clinician-
administered scales from NIH Common Data Elements before, immediately after, and one month 
after the stimulation protocol.  Aim 2.2: Persistence of antidepressant benefit will be assessed via 
telephone interview at 6 months and one year.  Aim 2.3: clinical predictors of tDCS response such as 
EEG frontal theta synchrony, injury severity, premorbid intelligence, neuroimaging abnormalities, 
and symptom burden will be determined.
2. Background

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 5 of 49
Version Date: January 29, 2019
Traumatic brain injury (TBI) is a significant public health problem. An estimated 1.7 million TBI-
related deaths, hospitalizations, and emergency department (ED) visits occur in the United States 
each year,1 costing an estimated $76.5 billion in 2000 alone.2 Among 34 states in a 2004 survey New 
Mexico had the 2nd highest TBI fatality rate, with approximately 10,000 ED visits and 1400 
admissions for TBI, making this an important regional problem to be addressed for our 
communities.3 Even after mild TBI, up to 22% of patients will report functional impairment at one 
year post-injury.4 Much of this loss of function is due to the fact that the majority of TBIs affect the 
frontal lobes and cause damage to the frontal-subcortical circuits that are responsible for the 
complex thought processes required to navigate contemporary life,5,6 including comportment and 
social behavior, mood and motivation, and especially cognitive control.7 
These deficits in cognition and emotion compound one another, as the neural circuits mediating 
them are closely interconnected.8,9 Within the first year after TBI 33% of patients will suffer a major 
depressive disorder,10 which may exacerbate any separate post-traumatic cognitive deficits and 
effectively render a “double-hit” to patients’ abilities to manage their lives’ daily activities.9 
Conversely, deficits in the domain of cognitive control can be seen even after only mild TBIs,11 
affecting executive functions such as response inhibition, working memory impairment, and set 
shifting and leading to further depression as patients spend long periods functionally disabled.7,8 
Unfortunately, few effective treatments exist for the post-acute neurobehavioral sequelae of TBI.  
Current strategies for cognitive rehabilitation are both time- and resource intensive but yield only 
small effect sizes.12 Non-FDA approved treatments such as methylphenidate are coarse in their 
mechanism of action and carry adverse consequences such as irritability, addiction, and 
cardiovascular effects.13 Dopamine agonists have had mixed results in improving function after 
TBI,14,15 and little evidence currently exists to recommend any other class of medication.16 Treatment 
approaches for mood symptoms in TBI are understudied, nonspecific, and have even been shown to 
worsen cognition.17,18 Novel rehabilitation approaches that simultaneously and holistically address 
both the cognitive and emotional post-traumatic deficits of TBI are needed.
The current proposal represents a major step towards a solution for post-TBI symptoms that 
harnesses the intact brain’s neuroplastic potential to overcome a variety of deficits.  Transcranial 
direct current stimulation (tDCS) is a non-invasive form of brain stimulation utilizing low amounts of 
current to modulate neuronal activity and improve neuropsychiatric symptoms across diverse 
disorders, including post-stroke aphasia and motor learning, working memory in dementia, and 
major depression.19,20–22 We will attempt to demonstrate that tDCS produces similar gains in 
cognitive symptoms among mmTBI patients as we have seen in our lab,23 as well as improvements in 
depressive symptoms others have found in depressed patients.19 We will then correlate response to 
tDCS with EEG measures of cognitive control and brain connectivity so as to better identify patients 
likely to benefit from tDCS, as well as clarify the mechanism of therapeutic action of tDCS. Due to its 
low cost, minimal side effects, and the ease with which it can be integrated with existing 
rehabilitation approaches, empirical support for tDCS would be a “game-changer” in the field of TBI.  
Successful completion of our specific aims will have a major impact on research and clinical practice 
regarding the management of debilitating TBI symptoms. Toxic effects of medications could be 
avoided; visits to rehabilitation facilities could be reduced; and treatment could be provided in 
diverse settings. Future studies would elucidate optimal electrode placements and stimulation 
parameters for specific cognitive symptoms and in specific types of brain injury, as well as provide a 
rational mechanism of therapeutic action in terms of improved functional brain connectivity. 
Integration with emerging multimodal neuroimaging techniques may reveal exactly which type of 
patient benefits from which type of tDCS, personalizing clinical interventions.
Review of relevant literature
tDCS can improve brain function. Anodal tDCS typically has an excitatory neuronal effect due to a shift 
toward depolarization, while cathodal stimulation elicits a hyperpolarization.24 tDCS-induced 
changes last from minutes to hours, and multiple stimulation sessions over the course of days to 
weeks can lead to cumulative long-lasting effects.25–27 This powerful neuroplastic effect of tDCS has 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 6 of 49
Version Date: January 29, 2019
already been applied to injured brain in patients recovering from stroke, with observed benefits in 
motor control, neglect, vision, and aphasia, without adverse consequences such as seizures or 
worsening of deficits.27,28,29,30 Anodal stimulation of the dorsolateral prefrontal cortex (DLPFC) has 
become a standard protocol in the cognitive tDCS literature because of its ability to improve multiple 
dimensions of cognitive functioning,31–33 including cognitive control and working memory,31,32,34, 
attention,35 improved decision making,36 and enhanced memory.37 Reduction of impulsivity has been 
demonstrated with anode over right DLPFC.38,39
 tDCS is understudied in TBI.  Application of this therapy to TBI is a logical next step, but tDCS has not 
been extensively studied in this disorder as it has for stroke rehabilitation and depression.19,40 
Several animal studies have shown that anodal tDCS is potentially neuroprotective after brain 
injury.41,42 Only three studies have attempted tDCS for cognition in TBI, all utilizing left prefrontal 
anodal stimulation. Angelakis et al. treated 5 severe TBI patients with 5 days of anodal 1 mA tDCS for 
20 minutes then 5 days of 2 mA.  Age of injury ranged from 6 months to 10 years, and electrode 
positioning was at left DLPFC or left sensorimotor cortex (C3) in alternating order.  There were no 
adverse events, and no clear advantage from either electrode position. Three patients of the five 
experienced benefit by 1 year followup. 
Kang et al, in a one-session protocol43 involving 9 patients with moderate-severe TBI 2-18 months 
from date of injury, administered 2mA tDCS for 20 minutes while they performed a computerized 
cognitive rehabilitation program.  Significant benefits in set-switching and reaction time were 
detected immediately after and up to 24 hours later.  There were no adverse events and the 
treatment was well tolerated, despite all subjects having known left frontal lobe pathology. In 
contrast, Lesniak et al. administered tDCS at 1 mA for 10 minutes to 23 TBI patients for fifteen 
sessions over a 3-week protocol.  All patients had severe TBI between 4 and 92 months from date of 
injury, 16 of whom had known left frontal pathology. Their group found the treatments safe and well 
tolerated, but failed to find any significant benefit in a multitude of attentional domains.44 Our 
correspondence with studies registered in clinicaltrials.gov for tDCS in TBI (Spaulding, NYU, U. Leige) 
did not discover any occurrence of seizures or serious adverse events.
We conclude the following from these studies:  (1) anodal tDCS over left DLPFC at various current 
densities, durations, and over multiple sessions in TBI patients of moderate and severe degree is 
safe; (2) the presence of pre-treatment brain abnormalities, even at the site of anodal electrode, does 
not necessarily increase risk nor impede benefit, and (3) the severity of injury and current 
density/stimulation protocol used may influence the efficacy of tDCS. 
Choice of study population.  Our research strategy is focused on the mild to moderate range of TBI 
severity. Importantly, this range of severity captures the vast majority of TBI patients.  Though we 
believe patients with severe injuries may also benefit from tDCS, we are concerned that their greater 
burden of neuropathology may compromise plasticity.44 Our research strategy calls for patients to be 
beyond the acute phase of injury with a minimum of a three-month period since injury. Our clinical 
experience suggests that patients are medically stable at this time but often struggling with 
persisting cognitive and emotional sequelae of mmTBI. By applying the technique in patients with 
mild to moderate severity the likelihood of intact neural circuits undergoing a robust adaptive 
neuroplastic change is maximized. An ongoing controversy in the TBI literature is the high rate of 
postconcussive symptoms that occur in healthy non-TBI populations, calling into question the 
validity of these symptoms.  By simultaneously recruiting healthy controls as a comparator group, we 
will be able to demonstrate that there are clear cognitive control deficits in mmTBI patients, and 
whether tDCS is more or less efficacious in a clinical versus nonclinical population.
tDCS is effective in clinical studies at UNM.  Our group at UNM has experimented with a number of 
different variables regarding tDCS to determine optimal effects on attention and learning.23 Using a 
paradigm of a threat detection task for learning, Clark and colleagues found activation on fMRI in 
right inferior frontal cortex and right parietal cortex, which were then used as targets for stimulation.  

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 7 of 49
Version Date: January 29, 2019
Higher current densities, up to 2 mA for 30 minutes, applied to these localized networks produced 
greater increases in learning on the threat detection task in a dose-response manner that were still 
detectable one hour later (Figure 2). Using the same paradigm, we then demonstrated a prolonged 
effect on alerting attention with the Attention Network Task after just one 30 minute session of 
anodal tDCS to right inferior frontal cortex.45 Variables that most enhanced task performance were 
exposure to task stimuli during stimulation and repetition of the various stimulus response 
contingencies. Therefore there is ample experience at our center to conduct intensive studies of tDCS 
for mmTBI and to determine optimal stimulation paradigms and patient characteristics. In addition, 
the PI of the current project has written several reviews of safety of neuromodulation therapies in 
various patient populations and treated hundreds of clinical patients with electrical stimulation.46,47 
Established expertise in neuroimaging of TBI.  Our group has also been very active in the longitudinal 
study of TBI patients, utilizing multimodal neuroimaging and neuropsychological testing to assess 
biomarkers of injury and recovery.48,49 In adult and pediatric mTBI populations we have documented 
deficits 
in 
attention,50 
post-traumatic 
symptoms,48 
diffusion 
tensor 
abnormalities,51 
neurometabolites,49 and fMRI differences,52 both in the semi-acute phase and in the chronic phase (4 
months post-injury). We have used fMRI to examine attentional dysfunction in patients with TBI, 
observing decreased activation in both sub-cortical and cortical networks. The PI of this project has 
been providing clinical care for brain injured patients on an inpatient neurosurgical service and in an 
outpatient neuropsychiatry clinic for the past five years, and has ample experience with retention, 
characterization, and treatment of this clinical population.53,54 MRI sequences for characterization of 
TBI may be obtained as part of baseline and post-stimulation assessment in a subgroup of mmTBI 
subjects.  The advantage of obtaining neuroimaging in this study is three-fold: 1) structural 
abnormalities may affect current flow and alter the effectiveness of TDCS; 2) TDCS has been shown 
by our group to increase glutamate under the anodal electrode, and use of MRS to characterize 
neurometabolite flux before and after stimulation could add important evidence to this theory; 3) 
mmTBI may cause functional brain activation abnormalities independent of structural lesions that 
can be correlated and localized with EEG.  
EEG is a candidate biomarker for tDCS effect in TBI.  Co-Junior investigator Cavanagh has extensive 
experience analyzing EEG measures of frontal midline theta band synchrony in various populations 
as a phenomenon underlying cognitive control.55,56 Task-related EEG abnormalities have been found 
to distinguish patients with mmTBI from healthy controls, and correlate with executive 
dysfunction.57,58  PI Cavanagh’s co-occurring study will investigate whether functional EEG variables 
such as theta band phase synchrony will correlate with the common disturbances of cognitive control 
during the semi-acute stage of recovery from mmTBI. We will apply this technique to investigate 
whether chronic post-concussive symptoms are associated with these same EEG abnormalities, and 
what effect tDCS may have to increase frontal theta synchrony. 
3. Study Design
This study is a randomized placebo-controlled clinical trial.  Investigators will be blinded to the type 
of stimulation given (sham versus active) through use of a computer-assisted pre-programmed tDCS 
stimulator. Subjects will be blinded to sham versus active through the use of low-current (up to 0.2 
mA) sham stimulation, which provides a tactile sensation similar to active 2.0 mA stimulation.  
Ramping up and down the current at the beginning of stimulation also prevents subjects from 
distinguishing sham from active.   The duration of an individual subject’s participation in the 
research may range up to 1 year. The duration anticipated to enroll all subjects is 3 to 4 years. The 
expected duration for the investigators to complete the study (complete analysis) is 5 years.

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 8 of 49
Version Date: January 29, 2019
Inclusion and Exclusion Criteria 
Human participants who have suffered mmTBI (ages 18-55) will be recruited from the UNM Hospital 
ED and from other local Emergency Departments via CTSC patient recruitment services.  Healthy 
controls will be recruited from the greater Albuquerque area via flyers and online ads. If a participant 
shows interest in participating in our study, a brief prescreening will be done over the telephone 
prior to initiating informed consent procedures.  The prescreening procedures will assure that each 
potential participant meets study inclusion and exclusion criteria.  If, after prescreening, the patient 
remains interested and eligible, the project will be described in great details and the potential 
participant and their caregivers will be invited to come to the investigation site to ask questions prior 
to providing consent.  Consent forms will be provided, as well as forms that again describe the study 
procedures and potential risks in detail.  If potential participants are unsure about participation, they 
will be given a copy of the consent form with our contact information and be invited to call if they 
decide to participate.  Once informed consent is obtained and the appropriate forms signed, the 
complete procedures of the study, as described in the consent forms, are provided to prospective 
subjects.  We review the forms, and file them away in a locked file cabinet in a locked office, away 
from any material with personal or sensitive study data.
Inclusion Criteria
Patients seen the emergency department (ED) will be enrolled in this study if they 1) are aged 18-55, 
2) have suffered a TBI with documented evidence of loss of consciousness (LOC) which was less than 
24 hours, 3) were injured between 3 months and 15 years ago, 4) received a Glasgow coma scale 
(GCS) score of between 9 and 15 upon ED admission, 5) experienced less than 1 week of post-
traumatic amnesia (PTA), and 6) have post-traumatic cognitive symptoms as evidenced by endorsing 
at least 1 out of 4 cognitive symptoms on the Neurobehavioral Symptom Inventory (NSI), a measure 
of post-traumatic symptoms from the NIH Common Data Elements, and 7) have been on stable doses 
of any psychotropic medications for the past 2 months..  Healthy controls will be between the ages of 
18-55.   
Exclusion Criteria
Potential participants will be excluded from participation in this study if there is 1) a prior history of 
other neurological disease or any history of seizures, 2) history of psychosis  3) history of current or 
recent (within two years) substance/alcohol dependence, 4) any discontinuity in skull electrical 
conductivity (i.e., unhealed burr holes in scalp) or artificially constructed (metal or plastic) 
craniotomy cover; 5) presence of any implanted electrical device (e.g. pacemaker), 6) recent medical 
instability (within three weeks), 7) any condition that would prevent the subject from completing the 
protocol, 8) appointment of a legal representative, as assessed via direct inquiry of the subject and a 
designated trusted other. Because our population will have only mild to moderate TBIs, and be well 
beyond the subacute phase of injury (> 3 months), ongoing complications from the injury itself such 
as skin infection, bleeding, ischemia, swelling, increased intracranial pressure, seizures, and 
hyponatremia will be extremely unlikely.  However, these would be considered exclusionary criteria 
if present over the previous three weeks prior to enrollment.  Adults unable to consent, individuals 
who are not yet adults (infants, children, teenagers), pregnant women, and prisoners are specifically 
excluded from the study. Persons not fluent in English will be excluded, as the neuropsychological 
test batteries are administered in English.
 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 9 of 49
Version Date: January 29, 2019
TARGETED/PLANNED ENROLLMENT: Number of Subjects
Sex/Gender
Ethnic Category
Females
Males
Total
Hispanic or Latino
26
38
64
Not Hispanic or Latino
38
58
96
Ethnic Category: Total of All Subjects *
64
96
160
Racial Categories
American Indian/Alaska Native
4
4
8
Asian
2
2
4
Pacific Islander 
2
2
4
Black or African American 
2
2
4
White 
46
66
112
Other races 
10
16
26
Two or more races
2
4
6
Racial Categories: Total of All Subjects *
64
96
160

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 10 of 49
Version Date: January 29, 2019
4. Study Timelines
 
GOAL
YEAR 1
YEAR 2
YEAR 3
YEAR 4
YEAR 5
Project 
Progress
Human Subjects Review 
Board approval 
completed
Equipment purchased 
Biostatistical training 
completed
Clinical Supervisor and 
Research Assistant 
training completed
Begin participant 
recruitment (targeted 
enrollment of 10
active tDCS patients 
and 10 controls)
Progress reported to 
Human Research 
Protections Office 
(HRPO), PI, and NIH.
Recruited 20 active 
tDCS patients and 20
controls
Preliminary data
analyses on tDCS 
effects completed, in 
preparation for NIH 
grant submission
Progress reports 
submitted to
to HRPO, PI and NIH
Recruited 10 active 
tDCS patients and 10 
controls
Completed  
preliminary data 
analyses of group 
differences in tDCS 
effects across groups
Progress reports 
submitted to
to HRPO, PI and NIH
Progress reports 
submitted to
to HRPO, PI and 
NIH
Complete all data 
analysis
Progress reports 
submitted to
to HRPO, PI and 
NIH
Closure Report 
submitted to HRPO

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 11 of 49
Version Date: January 29, 2019
5. Study Endpoints
Primary endpoint:  change in scores on the EXAMINER battery from before to after stimulation.
Secondary endpoints:  change in score on the Neurobehavioral Symptom Inventory, Beck Depression 
Inventory-II, Hamilton Rating Scale for Depression, change in frontal midline theta synchrony on 
EEG, change in MRI abnormalities, and quality of life measure from time 0 to 1 year.
6. Research Setting
All testing, analytical, and research activities will take place at the Clinical Core, UNM Center for Brain 
Injury Recovery and Repair, located in Domenici Hall, MIND Research Network.
Subjects will be identified and recruited from the UNM ED and other local EDs via the CTSC patient 
recruitment service, as well as coordination with ED providers and posted advertisements.  Healthy 
controls will be recruited through online advertisements, word of mouth and flyers.  As the only 
Level 1 trauma center for the state of New Mexico and the community hospital for Bernalillo County 
and the city of Albuquerque, which is the most populous city in the state, UNM treats the majority of 
TBIs presenting in the state.  Approximately 10,000 New Mexicans receive treatment for a TBI in 
hospitals annually, and the majority of these injuries (~9000) are mild in nature; therefore, 
recruiting 80 TBI subjects and 80 healthy controls over 3 years is felt to be a feasible goal.  
7. Resources Available

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 12 of 49
Version Date: January 29, 2019
Principal Investigator
As a junior PI in the UNM Center for Brain Recovery and Repair, Dr. Quinn’s goal is to establish an 
independent NIH-funded research program in neurorehabilitative and neurostimulatory therapies 
for affective, behavioral, and cognitive sequelae of traumatic brain injury (TBI).  The current proposal 
will study the administration of transcranial direct current stimulation to patients with mild to 
moderate traumatic brain injury (TBI) to ameliorate chronic cognitive and emotional deficits, and 
represents an exciting opportunity for him to bring together several of his academic interests in one 
scientific endeavor. Dr. Quinn has made the treatment of TBI the focus of his clinical work for the past 
several years, achieving board-certification in neuropsychiatry and behavioral neurology in 2012, 
and establishing a neuropsychiatry clinic in the UNM Clinical Neurosciences Center in 2013 to better 
serve the undertreated population of TBI patients in New Mexico. Serving as the consultant 
psychiatrist for the University of New Mexico Hospital since 2009, Dr. Quinn evaluates patients 
admitted to the hospital to the neurological and neurosurgical services.  As UNMH is the only Level 1 
trauma center in the state, the vast majority of TBIs receive care at this institution, and Dr. Quinn 
treats many patients with post-traumatic amotivational, dysexecutive, disinhibition, and 
psychomotor syndromes resulting from damage to cortical-subcortical circuits.  He has followed 
these patients after their hospitalizations as well, and published several case reports highlighting 
theoretical and practical dilemmas in treating TBI. 
During this same period Dr. Quinn has become involved in brain stimulation therapies, at 
first through their important role in the treatment of the catatonic syndrome, on which he has 
published several reviews and case reports.  Dr. Quinn joined the UNM Electroconvulsive Therapy 
(ECT) Service in 2012 after becoming certified in ECT, and in 2013 became the consultant 
psychiatrist for the UNM Movement Disorders Clinic and their associated deep brain stimulation 
(DBS) team.  He has co-authored a review of longitudinal neuroimaging studies of ECT, a review of 
psychiatric symptoms after DBS, and reported the first successful use of right unilateral ECT for 
catatonia in a patient with a deep brain stimulator.   
To assist him in carrying out the proposed research Dr. Quinn has assembled an experienced 
team of advisors.  Of his mentors, Dr. Vince Clark is an expert in transcranial direct current 
stimulation, its mechanisms of action, and its use to enhance cognition, and will provide key guidance 
regarding the application of this neurostimulatory technology. Dr. Ronald Yeo is a prolific researcher 
in the neuropsychology and neuroimaging of TBI, and will provide methodological and research 
design expertise.  Additional guidance will be provided by Dr. Richard Campbell, who as part of the 
Clinical Core will be a resource for pragmatics of neuropsychological assessment, and Dr. Andrew 
Mayer, who is also expert in neuroimaging of TBI and methodological issues.  
Facilities/Resources of the UNM Center for Brain Recovery and Repair
Traumatic brain injuries are a common clinical disorder treated at UNM. Approximately 10,000 New 
Mexicans seek treatment for a TBI each year.  As UNM is the only Level 1 trauma center in the region 
and is situated in the largest city in the state with a metropolitan catchment area population of 1 
million, a large percentage of the TBIs sustained in New Mexico are treated at UNM.  The majority of 
TBIs are mTBI, with approximately 1000 New Mexicans each year hospitalized with TBI and 9000 
mild enough to be treated in the outpatient setting.  Therefore, we expect that if 1/10 of New 
Mexicans with mTBIs present to UNM each year, that equates to 900 mTBIs eligible for screening.  
We plan to screen these patients and recruit approximately 25-30 annually for the study, meaning 
that we are aiming to enroll 3% of eligible patients, which we believe is feasible.
Clinical Study Coordinator—In Year 1, a clinical study coordinator will be hired to support junior 
principal investigators’ research projects. The study coordinator will be responsible for the 
coordination and administration of clinical studies under the direction of the Core co-directors. The 
clinical study coordinator will help develop, implement, and coordinate research and administrative 
procedures for the successful management of clinical studies; be responsible for scheduling 
neuropsychological assessments, neuroimaging appointments, and treatment appointments; and will 
also be responsible for scheduling regular Core group meetings. 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 13 of 49
Version Date: January 29, 2019
Research Technician—In year 1, two technicians will be hired to assist in the junior PI’s projects. 
We will assign one research technician to each of the initial junior PI projects. Their effort will be 
dedicated to assist in recruitment/screening, neuropsychological assessment administration, scoring 
and summary report preparation, scheduling of treatments and neuroimaging procedures, as well as 
data entry of collected data. Research technicians will be made available to assist with other future 
junior PI projects and pilot projects.  
Technicians, research coordinators, and the investigators will undergo standard training in human 
research standards, ethics, conflict of interest, and also participate in weekly research group 
meetings regarding the specific protocol being studied, methodological and analytical issues, and 
subject recruitment, participation, and safety.
Transcranial Direct Current Stimulation (tDCS)—A tDCS system (neuroConn: DC-Stimulator PLUS) 
will be purchased in Year 1, with a second added in Year 2.  These are CE-certified medical devices 
for conducting non-invasive transcranial direct current stimulation (tDCS), alternating (tACS) or 
random noise (tRNS) current stimulation on subjects. Transcranial stimulation using weak electric 
currents over a period of several minutes is demonstrated to modify neuronal excitability and circuit 
function and can serve to provide long-lasting promotion of brain recovery and repair. 
Neuropsychological Assessment Measures. The Core will establish a library of advanced 
neuropsychological tools, applicable to assessment of different aspects of recovery and repair 
following stroke or TBI.  The library will be useful for subjects of different ages and severity of injury.  
This library will include novel, computer-based neuropsychological measures as well as traditional 
neuropsychological measures long utilized in neuropsychological research projects and 
recommended for specific clinical populations (e.g., TBI NINDS Common Data Elements). The Core 
will also develop and maintain an instrument bank of health-outcome measures, including state-of-
the-art, computer-administered measures. 
1) National Institutes of Health Executive Abilities: Measures and Instruments for Neurobehavioral 
Evaluation and Research (EXAMINER). EXAMINER is battery of reliable and valid tests of executive 
function developed under the auspices of the NINDS for clinical investigations and is adaptable 
across a wide range of ages and disorders (www.examiner.ucsf.edu). 
2) NIH Toolbox: Assessment of Neurological and Behavioral Function.  The NIH Toolbox is a state-of-
the-art set of standardized instruments developed by NIH to enhance data collection and advance 
and accelerate the pace of discovery in neuroscience research. The NIH Toolbox is a recently 
developed set of brief, computerized measures of key neuropsychological functions appropriate for 
use throughout the lifespan (i.e., 3+ years old) and across diverse study designs and settings. 
3) Patient Reported Outcomes Measurement Information System (PROMIS®).  The PROMIS®, is a 
system of highly reliable, precise measures of patient–reported (both child and adult) health status 
for physical, mental, and social well–being and can be useful in measuring effectiveness of treatment 
in clinical intervention studies. 
Data 
and 
sample 
collection. 
The 
Core 
will 
provide 
expert 
neuropsychological 
and 
electrophysiological assessment technical support. This will include providing testing rooms, 
neuropsychological 
tests 
and 
supplies, 
laptop 
computers, 
electroencephalography, 
and 
neuropsychology technicians/ psychometricians, as well as data entry and storage.  Core staff will 
assist investigators with scheduling of assessments, neuroimaging, and treatment appointments. The 
Core will provide space for interventions being studied as part of research projects. 
Neuropsychological assessment batteries will be administered by Core psychometricians under the 
supervision of the Core co-directors. Neuropsychological test data will be scored by the 
psychometricians, with scoring reviewed for accuracy by the supervisors. A neuropsychological test 
summary prepared by technicians and reviewed by the supervisors will be provided to investigators, 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 14 of 49
Version Date: January 29, 2019
participants, and referral sources if indicated. If requested, Core co-directors will also provide 
feedback to participants regarding neuropsychological assessment results. Participant hardcopy data 
will be stored in locked file cabinets in locked rooms within a locked, security-patrolled building. For 
analysis, participant data will be entered and stored in REDCap, a web-based electronic data capture 
program that is secure and HIPAA compliant available through the UNM CTSC Biomedical 
Informatics (http://hsc.unm.edu/research/ctsc/BMI/REDCap.shtml). Neuropsychological data will 
be entered by psychometrists into study databases with accuracy verified by double using UNM 
Health Sciences Center Library Services to create a data management plan to manage and provide 
access of research data collected in line with current NIH policies.  
3T MRI is housed immediately proximal to the neuropsychological testing rooms, as part of the 
MIND Research Network (MRN) advanced biomedical imaging core.  The imaging facilities 
have private changing rooms with lockers for personal items.
Should patients require any medical or psychological care as a consequence of participation in 
research, UNM Health Sciences Center is located immediately proximal to the MIND Research 
Network and can provide basic to advanced care 24 hours a day, 7 days a week.
8. Prior Approvals
Departmental Approval form included.
9. Multi-Site Research   NA
10.Study Procedures 
Specific Aim 1.1: Acute effectiveness of tDCS in mmTBI
Experimental Design and Methods
     Participants:  Eighty TBI subjects will be recruited for this study, all having suffered mild or 
moderate TBI (mmTBI, as defined before) at least 3 months prior to study enrollment, but not more 
than 15 years prior to enrollment. 80 age- and sex-matched healthy controls will be recruited. All 
participants will be 18-55 years of age.  We will expect to screen approximately 120 patients with 
mmTBI in order to reach our goal of 80 TBI subjects. The experimental pre-post, double-blind design 
is graphically displayed. It includes randomization of TBI patients to either a left-sided active 
transcranial direct current stimulation (tDCS) protocol, or sham treatment group to foster isolation 
and identification of any tDCS treatment effects.  To enhance our statistical power to identify 
predictors of treatment response in mmTBI patients, 40 TBI subjects and 40 controls will be assigned 
to each group: left-sham and left-active.  
Recruitment:   Recruitment primarily will be through the UNM Hospital Emergency Department (ED) 
(the only Level 1 trauma center in New Mexico). The UNM Health Sciences Center (HSC) Clinical and 
Translational Science Center (CTSC) Participant Recruitment Service (PRS) for Clinical Research will 
monitor ED intake records for patients who meet criteria once released from the hospital, then notify 
the study team of these cases. A second means of recruitment will involve direct referrals from UNM 
and non-UNM ED physicians and/or referrals from any clinic in the Albuquerque metropolitan area, 
via the distribution of flyers and calls to clinical directors to publicize the study. A third means of 
recruitment will involve information listed on the UNM CBRR and MRN websites, and posted flyers.

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 15 of 49
Version Date: January 29, 2019
Subjects who meet initial criteria for inclusion will be contacted by a member of the research team 
and invited to enroll in the study. Interested patients will be invited to the offices of the Center for 
Brain Recovery and Repair clinical core for formal screening procedures. A brief structured interview 
will be administered along with the NSI. If potential participants do not meet study criteria, they will 
be thanked for their time and identifying information recorded for future reference. Subjects with a 
legally authorized representative (LAR) will be excluded from the study, and all participants will be 
screened for LAR. All participants will be adults (ages 18-55), and all participants will consent for 
themselves. Although participants will be recruited from referral or from emergency department (or 
other) records, no participant will be enrolled in the study without being given sufficient opportunity 
to consider whether or not to participate. In most cases, they will undergo multiple interactions with 
study personnel over the course of days, and during each they will have the opportunity to ask 
questions and discuss their decision to participate. They will have multiple opportunities to 
reconsider any decisions during the screening and consent process, minimizing the possibility of 
coercion or undue influence by the researchers. If potential participants successfully meet basic 
study criteria, they will be invited to undergo consent procedures and enrolled in the study. All 
participants will be fluent in English, and the information contained in the consent form will be 
discussed with them in addition to their having a written description of the study in the form, to 
assure that they truly understand the study procedures. 
Randomization will occur at time of consenting.  The study coordinator who consented the patient 
will use a coin-tossing procedure to determine whether the subject is assigned to the active group 
(group 1) or control group (group 2).  Modifications will be made as necessary toward the end of 
enrollment to ensure equal group size and balanced distribution of demographic variables such as 
age and gender.  The study coordinator will not be blinded to group assignment, and with the 
assistance of the Clinical Core, will program the TDCS devices to deliver active or sham stimulation 
depending on which group the subject has been assigned.  However, the coordinator will not be 
involved in performing any stimulation procedures.  The study technician and principle investigator, 
who will be responsible for administering the stimulation, will not be aware of which group receives 
active versus control, and will thus be blinded, as the TDCS device will only display the group number 
(1 or 2). 
Once group membership is determined, individual participants may undergo demographic data 
collection, neuropsychological assessments and tDCS treatment sessions. They may also undergo 
EEG and/or MRI. Direct identifiers of participants will be maintained on a separate database that will 
be stored behind locked doors, in a locked filing cabinet in a secure area of the Clinical Core.     
     Demographic Data: As part of the initial assessment, basic demographic data regarding the subject 
may be noted down, including age, gender, socioeconomic status, educational attainment, 
handedness, use of common stimulants such as caffeine, and brain injury severity. They may also be 
asked if they are willing to allow their medical record to be accessed, for the purposes of confirming 
details about any TBI as well as obtaining results of neuroimaging studies done at the time of injury 
or afterward.   This will include medical, surgical, neurological and psychiatric history, results of lab 
tests, brain scans, electroencephalography tests, medication lists, information from doctor’s visits 
and hospital visits.  
     Neuropsychological testing procedures: All 
neuropsychological 
testing 
will 
be 
administered in the Center for Brain 
Recovery and Repair Core by trained study 
personnel under direct supervision of core 
directors, clinical neuropsychologists Drs. 
Yeo, Campbell, or the PI. The primary 
dependent outcome variables to be studied 
are the three composite scores generated by 
!5
0
5
10
15
20
25
30
35
40
Time,(in,min),

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 16 of 49
Version Date: January 29, 2019
the Examiner battery (e.g. Cognitive Control, Fluency, and Working Memory). The following domains 
and tests will be administered:  Executive Abilities: Measures and Instruments for Neurobehavioral 
Evaluation and Research (Examiner); Digit Span; Delis-Kaplan Executive Function Systems (DKEFS) 
Trailmaking Test Conditions 2 and 4; Hopkins Verbal Learning Test (HVLT); Frontal Systems 
Behavior Scale (FrSBe); Test of Memory Malingering (TOMM); Wechsler Test of Adult Reading 
(WTAR); Digit Symbol Coding; Handedness; Socioeconomic Status (SES); Neurobehavioral Symptom 
Inventory (NSI); PROMIS-29 profile; Glasgow Outcome Scale-Extended (GOSE).
     Resting and task-related electroencephalography: Electroencephalograph (EEG) may be done after 
neuropsychological testing in a subset of subjects. The participant will wear a cap during the EEG to 
record brain waves. EEG setup takes between 10 and 30 minutes, and subsequent recording takes 
one to two hours.  During EEG assessments participants will complete numerous active tasks.   Each 
task is designed to parse different cognitive mechanisms that contribute to adaptive performance.  In 
perceptual tasks, participants will discriminate tone pitches amongst novel distracting tones.  In 
decision making tasks, participants are required to classify stimuli based on pre-determined types of 
rules.  For learning tasks, participants are asked to select among two or more pictures on the screen 
by pressing a button on the keyboard or gamepad, they are then presented with a reward (‘+1’) or 
not (‘0) following their choice.  For memory tasks, participants will view stimuli one at a time on the 
computer screen, and will be probed on their memory of these stimuli after a short delay. Some tasks 
alter the fidelity of the stimuli to make decisions more difficult, others alter the perceptual-motor 
mappings to make response selection more difficult, and others simply probe risk and reward 
preferences.
Magnetic resonance imaging:  MRI scan(s) will involve simultaneous functional or cognitive 
tasks, including sequences assessing diffusion tensor imaging (DTI), magnetic resonance 
spectroscopy (MRS), functional MRI (fMRI), and structural sequences. Total scan time, 
including participant setup and removal, is expected to take 1.5 hours. Based on the study by 
Gasparovic et al in 2009 examining MR spectroscopy in mild TBI, utilizing an effect size of 1.27, a 
planned sample size of 30 subjects receiving MRI will achieve 80% power to detect a difference 
between groups. Participants may lie down on a table and be placed into a long donut-shaped 
magnet. During the scan, participants will be shown pictures and/or words and will be asked to 
make decisions about the information presented in them. No contrast will be used. Any female 
over 18 who thinks she may be pregnant will complete a urine pregnancy screen before the MRI 
scan. Results of pregnancy screens will be kept strictly confidential as per MRN policy. Urine 
samples will be disposed of immediately after testing. 
     Left DLPFC anodal tDCS Intervention: On the same day as assessment or the next day, participants 
will receive either active left anodal tDCS for a total of 30 minutes or sham for an equivalent duration, 
each day for up to ten consecutive weekdays.  Current will be ramped up over 1 minute at initiation 
and ramped down over 1 minute with termination. 
      A NeuroConn tDCS (investigational) machine will be used to administer tDCS current. Targeting of 
the left DLPFC (F3 position, International 10-20 system of EEG coordinates) may be done by (1) 
locating the vertex (Cz) at the midpoint of the nasion-inion line and the midpoint of the preauricular-
preauricular line; (2) locating M1 at 20% of the Cz-preauricular distance, measured from Cz; (3) 
locating F3 5 centimeters anterior to M1 in the horizontal plane. This method has been shown to be 
suitable for tDCS electrode targeting of left DLPFC.59 The Beam F3 method may also be used, which 
yields equivalent or better accuracy. Square-shaped solution-soaked or gel-soaked sponge 
electrodes, held by a rubber casing, are applied to the scalp using elastic bandage material. The anode 
will be placed on the scalp over the F3 target location and the cathode placed on the right upper arm 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 17 of 49
Version Date: January 29, 2019
below the deltoid. Current for the treatment condition will be applied at 2.0 mA for a total delivered 
charge of 60 mA-min.
     Safety of stimulation. During tDCS application, subjects will describe physical sensations such as 
tingling or itching using a 10-point anchored Likert scale.  Administration of tDCS will be stopped 
immediately if subjects report a 7 or above for discomfort, or if subjects wish to stop at any time. 
Subjects will also have their mood, energy, pain, and arousal levels assessed using visual analog 10-
point scales. These checks will occur every ten minutes during the stimulation session. 
     Double blind design and sham treatment: The sham stimulation (control) group will receive up to 
0.2 mA current for 30 minutes each session, with an initial ramping up and down of stimulation to 
mimic active stimulation.  The sham current is used as a control condition, rather than the absence of 
stimulation, to equate aspects of the procedure (preparation and application of electrodes, 
attachment with adhesive strips, etc.), and to give the participant a degree of physical sensation that 
is somewhat similar to that of the 2.0 mA stimulation group while remaining well below the level 
sufficient to affect brain function and behavior.60 To accomplish a double blind, the tDCS machine is 
programmed to randomize sham versus active stimulation and keeps track of the stimulation 
protocol for later downloading. 
     Cognitive control Tasks: Participants may be administered the cognitive training battery for 30 
minutes, during treatment and sham. Session procedures will begin with tDCS electrode placement 
while seated in a comfortable chair. After initiation of tDCS, the cognitive training will be 
administered on a laboratory computer. The two tasks will be presented for 15 minutes each, in 
counterbalanced alternating order over the ten sessions. The tasks to be coupled with tDCS are the 
AX-CPT (set shifting/response inhibition) and a dual auditory/visual N-back task (working memory), 
and were selected based on their activation of the critical neural networks associated with the three 
executive functions of interest.61–64 AX-CPT is a continuous performance task in which subjects must 
respond to specific paired letter combinations (A followed by X) with a button press while inhibiting 
response to non-target combinations (AY, BY, BX) (Figure 8).  The dual N-back task is a continuous 
performance test in which subjects respond to simultaneous sequences of visuospatial and auditory 
stimuli being presented that match preceding stimuli n-steps earlier in the sequence.65 
Specific Aim 1.2:  Persistence of tDCS effects and quality of life
Experimental Design and Methods
     Participants:  TBI subjects enrolled in Aim 1.1 will be entered into a data registry with 
comprehensive contact information, including contact information (phone, email, fax, mail address) 
not just on participants, but also on multiple collaterals we can contact for 6 month and 1 year 
assessments. 
     Assessments: Initial screening will be done prior to tDCS intervention, and will be performed 
verbally to resemble subsequent phone interviews.  
These assessments will include the 
Neurobehavioral Symptom Inventory (NSI), and the PROMIS-29 quality of life profile.  Dimensions 
queried by the PROMIS-29 survey will include physical function, anxiety, depression, fatigue, pain, 
sleep, and social roles.  At 6 months and 1 year after the end of stimulation, subjects will be contacted 
by phone by the research team for a brief assessment of their post-traumatic symptoms and quality 
of life. Subjects not able to be contacted by phone will be sent a letter with the surveys in paper form 
to be returned via mail, fax, or email.
Specific Aim 1.3:  Clinical predictors of tDCS response
Experimental Design and Methods
     Participants:  TBI subjects from Aim 1.1 will be carried forward for study in Aim 1.3. Key clinical 
variables in the study group will be analyzed for association with tDCS effect, namely, lesser post-
traumatic symptom burden as measured by the NSI, mild versus moderate severity of TBI, lack of 
neuroimaging abnormalities on MRI, and higher premorbid level of intelligence as measured by the 
WTAR, as these are factors shown to predict better recovery from TBI.44,66,67
Specific Aim 2.1:  Effectiveness of tDCS for depression after mmTBI

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 18 of 49
Version Date: January 29, 2019
We will undertake an investigation of tDCS for depressed mood after mmTBI.  The same protocol as 
for Aim 1 will be employed to investigate Aim 2, with a focus on depressive symptoms.  The 
stimulation paradigm is similar to the regimen used by Brunoni et al. in their study comparing tDCS 
to sertraline for depression (10 sessions, 30 minutes/session).  However, their paradigm is limited in 
its power to identify the therapeutic element of tDCS for depression, because it does not separate the 
effects of simultaneous anodal/cathodal influences.  Our configuration with the cathode placed on 
the contralateral arm, developed and tested in our lab,68 thereby ensures that only one type of 
neuromodulation is delivered to the brain, rather than two. Subjects receiving active anodal left 
prefrontal tDCS for ten days will experience significantly greater improvement in depressive 
symptoms compared to sham stimulation, as assessed with NIH Common Data Elements depression 
instruments, that will be detectable immediately after stimulation and at 1 month post-stimulation.  
Experimental Design and Methods
     Recruitment:   Recruitment, enrollment, and data collection for Aim 2 will be identical to the 
experimental design of Aim 1.  Subjects will be randomly assigned to active stimulation or sham 
stimulation groups.
     Depression Assessments:  As part of the neuropsychological test battery administered to the 
participants before, immediately after, and at 1 month after tDCS, subjects will be assessed for 
depressive symptoms using NIH Common Data Elements instruments as well as reliable and valid 
instruments for detecting mood disturbances in TBI populations.  These tests are the Beck 
Depression Inventory (BDI-II),69  and the Hamilton Rating Scale for Depression (HAM-D).70 Post-
traumatic stress disorder (PTSD) symptoms, which often predispose to depression after TBI, will be 
assessed using the PTSD Checklist (PCL).71 These will be conducted verbally, so as to ensure 
similarity of delivery with the long-term assessments.  Any patient who reports thoughts of death or 
suicidal ideation at any point during the stimulation protocol or assessments will be immediately 
evaluated by the PI and given appropriate emergency medical care at the UNM Psychiatric 
Emergency Service.  
     Stimulation Protocol:  The protocol will be identical to the stimulation regimen described in Aim 1.  
During the procedure for each stimulation session, participants will be asked to rate their mood 
according to a 10-point visual analog scale before and after each stimulation session (10 sessions 
total).  This will monitor for daily fluctuations in mood as well as any rare stimulation-related severe 
mood changes.  
Specific Aim 2.2: 
The subjects from Aim 2.1 will be automatically included.  At 6 months and 1 year after stimulation, 
subjects will be contacted via telephone and administered the depression assessment tools utilized 
before, immediately after, and 1 month after stimulation.  
Specific Aim 2.3:  Subjects from Aim 2.1 will be carried forward for study in Aim 2.3. Patient and 
injury characteristics will predict positive response to tDCS, namely, higher premorbid intellectual 
function (WTAR), lesser severity of injury (mild versus moderate), lack of neuroimaging 
abnormalities on MRI, and more severe pre-stimulation depressive symptoms (BDI, HAM-D).  
Understanding which of the clinical variables described above moderate the efficacy of tDCS in 
mmTBI will allow for more precise patient selection and better overall efficacy in future applications.
Each of the 80 participants will receive $20/hr in the form of cash cards for taking part in the 
study..  This is felt to be a fair amount that is not coercive and will help decrease attrition for 
this study which involves many visits.
11.Data Analysis
All data will undergo standard preprocessing (e.g. motion correction, spatial normalization) and 
quality control prior to statistical modeling. Depending on the specific question of the study, data 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 19 of 49
Version Date: January 29, 2019
may be analyzed using the general linear model, independent components analysis, machine 
learning techniques, or a variety of other standard approaches for neuroimaging data. Drs. Yeo, 
and Hunter are skilled in analysis of the various MRI sequences and will assist the PI in analysis 
of the neuroimaging data.
Statistical analyses will utilize the CTSC Biostatistics core.  Power analyses and statistical analysis 
strategy were determined with our statistician Dr. Ronald Schrader, who will continue to provide 
recommendations and support throughout the project.  Sufficient group sizes were determined on 
the basis of data derived from preliminary studies. Clark and colleagues found an effect size of 
Cohen’s d = 1.2 for tDCS to induce improvements in cognition.21 For our power calculations we will 
assume a more conservative effect size of d = 0.7 which is consistent with a recent meta-analysis of 
tDCS effect sizes.22 With 40 tDCS treatment patients compared to 40 sham patients and an effect size 
of 0.7, we have 80% power to detect effects of active versus sham treatment in a two-sample t-test. 
Power in the linear mixed model analysis should be superior that that of the t-test. For Aim 1.1, the 
central analyses evaluate group (active vs. sham) differences in the EEG data and on the three 
Examiner composite variables across the three initial time points (before, immediately after, and 1 
month after tDCS stimulation protocol). To test this hypothesis, three separate linear mixed models 
analyses will be performed using the three Examiner composite scores (Fluency, Cognitive Control, 
Working Memory) as dependent variables. In each analysis, we will incorporate three covariates that 
may predict variation in learning (severity: mild vs. moderate, premorbid intelligence: WTAR score, 
and symptom burden: NSI). This will allow us to determine predictors of treatment response 
(Specific Aim 1.3). Sex, ethnicity, and age will also be entered into the statistical model. The effects of 
these covariates will be estimated by constructing appropriate contrasts in model effects. A similar 
set of analyses will evaluate group differences on the variables assessed in our long-term oral/phone 
follow-up (five data points: (1) before tDCS, (2) immediately after tDCS, (3) 1 month post-tDCS, (4) 6 
months, and (5) 1 year) for Aim 1.2. For these analyses dependent variables will be the total 
cognitive items score of the NSI and the PROMIS-29 profile total score). Significant effects will be 
followed up with more fine-grained analysis of the components of composite scores. The use of linear 
mixed-models minimizes the adverse impact of a missing data point, which may well occur in a 
longitudinal clinical study such as this.  Expected attrition will be taken into account with an 
intention-to-treat analysis.  Missing data patterns will be analyzed to assess the extent to which they 
are informative (in contrast to missing at random), and analyses adjusted accordingly.  All EEG data 
will undergo standard preprocessing (e.g. motion correction, spatial normalization) and quality 
control prior to statistical modeling. Depending on the specific question of the study, data may be 
analyzed using the general linear model, independent components analysis, machine learning 
techniques, or a variety of other standard approaches for neuroimaging data. 
12.Provisions to Monitor the Data to Ensure the Safety of Subjects
Data safety and monitoring will be carried out to ensure and maintain the scientific integrity of this 
project and to protect the safety of our participants.  Safety monitoring is the process during the 
study that involves review of accumulated outcome data for groups of subjects to determine if any of 
the procedures practiced should be altered or stopped.  Ultimately, the PI (Quinn) will be responsible 
for monitoring the safety of the study and complying with the reporting requirements.  An 
independent Data Safety and Monitoring Board (DSMB) will review the study data on a quarterly 
basis with the PI to ensure participant safety. The DSMB for this study will be composed of Dr. 
Christopher Abbott, the medical director of the Electroconvulsive Therapy Service at UNM, and Dr. 
Jose Padin-Rosado, staff epileptologist of the Epilepsy Monitoring Unit at UNM.  Their experience in 
assuring safety of brain stimulation therapies and seizure monitoring protocols make them ideally 
suited to serving on this project’s DSMB.  Continuous, close monitoring of participant safety will 
include prompt and frequent reporting of safety data (i.e., adverse/serious adverse events) to the 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 20 of 49
Version Date: January 29, 2019
DMSB, the University of New Mexico Health Sciences Center Institutional Review Board (UNMHSC 
IRB) and/or appropriate NIH staff with oversight responsibility.  The PI will provide a summary of 
the safe conduct of the study to NIH on an annual basis as part of the progress report.  All AEs 
occurring during the course of the study will be collected, documented, and reported to the UNMHSC 
IRB.
    
The review of data may result in early termination of the study, amendment to the protocol, or 
changes to the data collection plan or study forms if it appears that there are adverse events 
occurring at a rate significantly greater than that found in similar tDCS studies involving subjects 
with neurological disorders (ie. stroke).  Should the protocol or data collection plans or study forms 
be amended as a result of data review, the IRB will be notified and the amendment approved prior to 
study amendment implementation.  In addition, the participants will be notified of any significant 
new findings that develop during the course of research that may affect their wish to continue 
participation in the study. 
13.Withdrawal of Subjects
During tDCS application, subjects will describe physical sensations such as tingling or itching 
using a 10-point anchored Likert scale. Administration of tDCS will be stopped immediately 
if subjects report a 7 or above for discomfort, or if subjects wish to stop at any time.  Subjects 
will also have their mood, energy, pain, and arousal levels assessed using visual analog 10-
point scales. These checks will occur every ten minutes during the stimulation session.  Any 
report of pain or decreased level of arousal by the patient will result in stopping of 
stimulation.
If at any time a participant wishes to withdraw from the study, they will be debriefed by the 
study coordinator or principal investigator as to the reason for their withdrawal. They will 
be offered the chance to partially withdraw from the stimulation protocol and continue in 
the data collection aspect if they so wish.  Otherwise the participant will then be thanked for 
their time, and they will be compensated for the extent of their participation.  
If the participant wishes to withdraw, they will be asked if they will allow data already 
collected on them to be used in the study analysis.  If not, the data associated to their 
identifying code will be purged from the study database.
14.Data Management/Confidentiality
Neuropsychological testing and questions regarding depression, post-concussive symptoms, and 
quality of life will be collected from all participants. All forms of data described above will be 
recorded on to paper and pencil or computerized data forms that do not contain identifying 
information. A separate file contains contact information for the purpose of mailing the radiology 
review letter and future contact, in needed, but has no personal data or protected health information 
that is collected as part of the study.
No personally identifying information will be coded on the questionnaires, neuropsychological 
measures, brain imaging data, or any other data recording instruments, assuring confidentiality to 
the best of our ability. Subject identification numbers are assigned to each participant.  Only the PI 
and HIPAA-trained project coordinator have access to the file that links names with subject numbers.  
All data are stored in locked file cabinets in a locked office, on password-protected computers located 
behind a secure and maintained firewall. Data will also be collected and stored on a drive only 
accessible by the research team on a secure MRN server, and/or in the COINS database on an Amazon 
Web Services (AWS) HIPAA compliant cloud server. The cloud based server and any other electronic 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 21 of 49
Version Date: January 29, 2019
storage is accessible only by the research team, and data is coded with the unique subject 
identification numbers.
All data are collected by the PI, or trained research assistants who have completed on-line training in 
human subjects’ research, HIPAA and research integrity; who are trained in our lab on research data 
management and confidentiality; and who are trained to criterion on project protocol. Data will be 
collected specifically for this proposed research project.
Participants will be assured that all records will be kept confidential in research files located in a 
locked office and entered into a password-protected computer located behind a secure and 
maintained firewall. Breach of confidentiality is highly unlikely because all personally identifying 
information will be kept separate from data collected, and will be linked only by a master subject 
identification list maintained by the project coordinator and PI.  MRN retains the link between 
identifiers and URSI indefinitely for the potential future benefit to the research participant. 
Specifically, it may become medically advantageous in the future for a former participant to have 
access to the clinical information that is present in most radiological scans. For example, if a 
participant is diagnosed with a neurological condition (e.g. multiple sclerosis, glioblastoma, TBI, 
etc.) it may be clinically beneficial for the participant’s physician to have access to a research 
scan that was performed at an earlier time-point to determine disease course and severity.
In order to address any concerns regarding coercion, participants will be informed that they are free 
to choose not to participate and may withdraw at any time (this is included in the consent form). 
Finally, because any information gathered as part of this study is confidential, we cannot intervene 
on an individual level unless it is discovered that there is imminent threat to the life of the 
participant, to others, or if there is any indication of child or elder abuse.  In these rare cases, we 
would consider the risk to self and others and intervene as we would if the individual endorsed other 
intent to harm themselves (i.e., talk with the participant and express concern, present the participant 
with local options for treatment, encourage him/her to disclose the issue to authorities, and if 
unwilling, inform them that we must disclose the information to authorities for their (or others’) 
safety.
We will also provide all participants and their families with a referral list of community support, 
treatment, and educational resources about TBI.  This information will also be explained during the 
consent process. In addition, if a participant’s status with respect to any of the study criteria change 
during the experiment (i.e., initiation of substance abuse), the participant’s participation in the study 
may be terminated without their consent.  Our consent form will include a statement regarding 
anticipated circumstances under which the subject’s participation may be terminated by the 
investigator without regard to the subject’s consent and a statement indicating that significant new 
findings developed during the course of the research which may relate to the subject’s willingness to 
continue participation will be provided.
Statistical analyses will utilize the CTSC Biostatistics core.  Power analyses and statistical analysis 
strategy were determined with our statistician Dr. Ronald Schrader, who will continue to provide 
recommendations and support throughout the project.  For Aim 1.1, the central analyses evaluate 
group (active vs. sham) differences on the three Examiner composite variables across the three initial 
time points (before, immediately after, and 1 month after tDCS stimulation protocol). To test this 
hypothesis, three separate linear mixed models analyses will be performed using the three Examiner 
composite scores (Fluency, Cognitive Control, Working Memory) as dependent variables. In each 
analysis, we will incorporate three covariates that may predict variation in learning (severity: mild 
vs. moderate, premorbid intelligence: WTAR score, and symptom burden: NSI). This will allow us to 
determine predictors of treatment response (Specific Aim 1.3). Sex, ethnicity, and age will also be 
entered into the statistical model. The effects of these covariates will be estimated by constructing 
appropriate contrasts in model effects. A similar set of analyses will evaluate group differences on 
the variables assessed in our long-term oral/phone follow-up (five data points: (1) before tDCS, (2) 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 22 of 49
Version Date: January 29, 2019
immediately after tDCS, (3) 1 month post-tDCS, (4) 6 months, and (5) 1 year) for Aim 1.2. For these 
analyses dependent variables will be the total cognitive items score of the NSI and the PROMIS-29 
profile total score). Significant effects will be followed up with more fine-grained analysis of the 
components of composite scores. The use of linear mixed-models minimizes the adverse impact of a 
missing data point, which may well occur in a longitudinal clinical study such as this.  Expected 
attrition will be taken into account with an intention-to-treat analysis.  Missing data patterns will be 
analyzed to assess the extent to which they are informative (in contrast to missing at random), and 
analyses adjusted accordingly. Data will be stored in Excel spreadsheet form as well as on hard 
copies.  
Digital data will be stored on secure encrypted drives located behind a secure firewall.  Data 
will be reviewed by the PI for quality control.
Human subjects in the proposed protocol may receive screening and diagnostic interviews, 
phenotypic assessment (including emotional, cognitive and behavioral functioning), 
including interview and questionnaire queries regarding their mental health history, 
substance use history, and history of prior brain injuries and other neurological disease or 
injury. A link between identifiers and data be created; It will be stored separately in a locked 
file cabinet behind locked doors in a secure area of the Clinical Core for the duration of the 
study (5 years). It will be disposed of and shredded after the conclusion of the final data 
analysis.  Only the PI and trained research personnel will have access to the data, and will be 
solely responsible for receipt or transmission of the data. No data will be collected, 
transmitted, and/or stored via the internet. No data will be collected via audio/digital 
recordings. No data will be collected on video recordings or via photographs. Data will be 
stored for the duration of the study and will be destroyed after the final data analysis is 
complete.  It will be stored at the Clinical Core on secured encrypted drives (digital) and in 
locked file cabinets behind locked doors in a secure area of the Clinical Core.
 A Certificate of Confidentiality (CoC) has been received from the NIH once IRB approval is in 
place.  The CoC helps the researchers to protect the privacy of the subjects enrolled in the 
study from compulsory legal demands, such as court orders and subpoenas, for identifying 
information or identifying characteristics of a subject.  This study is eligible for a CoC 
because it will collect personally identifiable, sensitive information about subjects, and will 
be federally funded.  Sensitive information in this study includes information about a 
subject’s neuropsychological performance and emotional states.  This is information that if 
released could be damaging to a subject’s financial standing, employability, or reputation 
within the community; pertains to a subject’s psychological well-being or mental health; and 
might lead to social stigmatization or discrimination if it were disclosed.   
15.Data and Specimen Banking  (see section on Data Management)
16.Risks to Subjects 
Participation in this study for both healthy controls and mmTBI subjects may involve minor risks 
and/or discomforts associated with possible breach of confidentiality risk, neuropsychological 
testing, MRI, EEG, and tDCS.  
MRI: Radio and magnetic waves associated with MRI scans are not associated with any known 
adverse effects. MRI is non-invasive and considered minimal risk by the FDA and OHRP. 
However, the scanner is a large magnet, so it could move objects containing ferrous metal in the 
room during the scan.  All control and mmTBI participants are screened using the MRI safety 
screening form prior to be being scanned.  Participants with any MRI scanning contraindications 
will be excluded from study participation.  Participants may be bothered by feelings of 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 23 of 49
Version Date: January 29, 2019
claustrophobia (uncommon). The MRI also makes loud ‘drum’ beating noises during the study.  
Headphones are provided for protection. Rarely, large or recent tattoos can heat up during an 
MRI scan and cause skin irritation like a sunburn (uncommon). No long-term harmful effects 
from MRI are known. However, since the effect of MRI on early development of the fetus is 
unknown, participants who are pregnant will not be allowed to go in the MRI. Females 18 years 
of age or older who suspect they may be pregnant will be asked to take a urine pregnancy test 
before being allowed to participate in the study. The test results will only be shared with 
participant. 
Neuropsychological tests.  The neuropsychological tasks involved in the protocol entail no foreseeable 
risk, besides perhaps fatigue or mild to moderate demands on attention and cognition. These are 
typically very marginally significant risks, mitigated by the fact that if a patient fatigues during 
testing they are given a rest break or are rescheduled.  There is also mild psychological risk inherent 
in testing participants for cognitive abilities.
One potential risk is breach of confidentiality related to collection of sensitive information.  
Confidentiality issues are significant since this study collects a variety of sensitive data, in particular 
with respect to substance use. Because personal information is gathered, there exists the risk of 
possible invasion of privacy. However, our hard copy data is stored in locked cabinets in locked 
rooms within a locked, security-patrolled building; and there has never been a breach of 
confidentiality in our lab. Hence we believe that the likelihood of invasion of privacy is minimal. 
EEG: There is a very small possibility that participants with sensitive skin (e.g., contact dermatitis) 
may experience some skin irritation from the EEG gel or metal sensor (uncommon). 
tDCS.  There are several risks associated with tDCS treatment and sham procedures, however, based 
on our experience with this technology (>500 research subjects run to date), we believe that these 
risks are minimal. Common expectable side effects during tDCS include skin redness, itching 
sensation, mild fatigue or drowsiness, nausea, and headache.72  All patients undergoing stimulation 
with tDCS will be asked to rate their discomfort with these symptoms every ten minutes, and the 
treatment will be terminated if discomfort rises above 7 on a 10-point anchored Likert scale, or at 
any time the patient wishes to stop. All efforts will be made to reduce subject discomfort and avoid 
the rare occurrence of skin burns, including evidence-based techniques such as using saline-soaked 
sponges with lower concentrations (~15mM) of solution; offering emollient cream for reddened 
areas following stimulation; preventing electrodes from drying out during stimulation; disinfecting 
all treatment sponges regularly; not stimulating over skin with lesions or dermatologic conditions; 
checking skin impedance before stimulation.59,7374 When these precautions are followed with 
conventional tDCS protocols (i.e., 1-2 mA stimulation for up to 30 minutes), using optimized safety 
protocols, significant adverse effects, such as burns on the skin near electrode affixation or heating of 
the electrodes affecting nearby scalp surface have not been reported.75 
Rare mood changes with tDCS have been observed in studies of depressed patients, resulting in 
several cases of hypomania.76,77 Most of these patients were taking concurrent antidepressants.  
Precautions taken in this study include excluding patients on psychotropic medications, and 
monitoring mood with visual analog scales during stimulation, and pre/post-treatment depressive 
symptom questionnaires.  There has not been a reported instance of suicidality caused by tDCS.  
In healthy controls there have been no reported adverse events of TDCS, other than the physical 
sensations and skin irritation above. Of critical importance is the safety of tDCS in patients with 
neurological illnesses that may carry some increased vulnerability to either brain damage or 
seizures.  The experimental threshold at which tDCS causes brain injury was found to be two orders 
of magnitude above the current densities used in humans, making stimulation at the scalp with 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 24 of 49
Version Date: January 29, 2019
contemporary protocols causing brain damage extremely unlikely.78 tDCS is widely used in post-
stroke patients in protocols that place the stimulating electrodes ipsilateral to the lesion and very 
often close to perilesional areas, without any increased side effects or adverse consequences.2040 
Even more reassuring, tDCS at 1.0-2.0 mA has been performed over damaged left frontal cortex in 37 
patients with moderate to severe TBIs, who are at the highest risk of post-traumatic seizures and 
demonstrate the greatest levels of structural damage, without adverse events, seizures, or 
decrements in neurologic status.43,44,79  A review of and contact with studies registered in 
clinicaltrials.gov for tDCS in TBI (Spaulding, NYU, U. Leige) did not discover any occurrence of 
seizures or adverse events.
Safeguard exclusions that the study will have in place are enumerated above, and will ensure that 
neurologically unstable patients are screened out of the study, or those who might be at higher risk 
from cranial electrical stimulation.  A Data Safety and Monitoring Board composed of Dr. Christopher 
Abbott and Dr. Jose Padin-Rosado, specialists in neurostimulation and seizures respectively, will be 
meeting with the PI quarterly to review outcome data to ensure rigorous protection of patients, as 
described below. 
17.Potential Benefits to Subjects
This study has the potential for providing mild transient benefits in cognition and mood for 
individual subjects.  The probability for these improvements is moderate, given that multiple 
prospective blinded controlled studies have demonstrated transient improvements in cognition and 
mood for patients with strokes, neurodegenerative diseases, and in healthy controls. This study has 
the potential to increase scientific understanding of the extent to which TBI-related cognitive deficits 
can be remediated with tDCS using a longitudinal design. Participants will receive a radiology 
review and report of their MRI scan and will be compensated for their time and inconvenience. 
No other direct benefit to participants is anticipated.
18.Recruitment Methods
Recruitment primarily will be through the UNM Hospital Emergency Department (ED) (the only 
Level 1 trauma center in New Mexico). The UNM Health Sciences Center (HSC) Clinical and 
Translational Science Center (CTSC) Participant Recruitment Service (PRS) for Clinical Research will 
monitor ED intake records for patients who meet criteria once released from the hospital, then notify 
the study team of these cases. A second means of recruitment will involve direct referrals from UNM 
and non-UNM ED physicians and/or referrals from any clinic in the Albuquerque metropolitan area, 
via the distribution of flyers and calls to clinical directors to publicize the study.   This will include 
referrals from the New Mexico VA Health Care System. Flyers for VA clinics will include disclaimer 
language required by the Veterans Administration and we will obtain a facility approval letter from 
the New Mexico VA. A third means of recruitment will involve information listed on the UNM CBRR 
and MRN websites. Patients who meet initial criteria for inclusion will be contacted by a member of 
the research team and invited to enroll in the study. Interested patients will be invited to the offices 
of the Center for Brain Recovery and Repair clinical core for formal screening procedures. A brief 
structured interview will be administered along with the NSI. If potential participants do not meet 
study criteria, they will be thanked for their time and identifying information recorded for future 
reference. Subjects with a legally authorized representative (LAR) will be excluded from the study, 
and all participants will be screened for LAR. All participants will be adults (ages 18-55), and all 
participants will consent for themselves. Although participants will be recruited from referral or 
from emergency department (or other) records, no participant will be enrolled in the study without 
being given sufficient opportunity to consider whether or not to participate. In most cases, they will 
undergo multiple interactions with study personnel over the course of days, and during each they 
will have the opportunity to ask questions and discuss their decision to participate. They will have 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 25 of 49
Version Date: January 29, 2019
multiple opportunities to reconsider any decisions during the screening and consent process, 
minimizing the possibility of coercion or undue influence by the researchers. If potential participants 
successfully meet basic study criteria, they will be invited to undergo consent procedures and 
enrolled in the study. All participants will be fluent in English, and the information contained in the 
consent form will be discussed with them in addition to their having a written description of the 
study in the form, to assure that they truly understand the study procedures. 
A modified repeated fair coin-tossing randomization procedure will determine group assignment, 
and modifications will be made as necessary toward the end of enrollment to ensure equal group 
size. Randomization will occur at time of consenting.  The study coordinator who consented the 
patient will use a coin-tossing procedure to determine whether the subject is assigned to the active 
group (group 1) or control group (group 2).  Modifications will be made as necessary toward the end 
of enrollment to ensure equal group size and balanced distribution of demographic variables such as 
age and gender.  The study coordinator will not be blinded to group assignment, and with the 
assistance of the Clinical Core, will program the TDCS devices to deliver active or sham stimulation 
depending on which group the subject has been assigned.  However, the coordinator will not be 
involved in performing any stimulation procedures.  The study technician and principle investigator, 
who will be responsible for administering the stimulation, will not be aware of which group receives 
active versus control, and will thus be blinded, as the TDCS device will only display the group number 
(1 or 2).  
Once group membership is determined, individual participants will be scheduled for demographic 
data collection, neuropsychological assessments, EEG, and tDCS treatment sessions. Direct identifiers 
of participants will be maintained on a separate database that will be stored behind locked doors, in 
a locked filing cabinet in a secure area of the Clinical Core.
19.Provisions to Protect the Privacy Interests of Subjects

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 26 of 49
Version Date: January 29, 2019
Neuropsychological testing and questions regarding depression, post-concussive symptoms, and 
quality of life will be collected from all participants. All forms of data described above will be 
recorded on to paper and pencil or computerized data forms that do not contain identifying 
information. A separate file contains contact information but has no personal data or protected 
health information that is collected as part of the study.
   
No personally identifying information will be coded on the questionnaires, neuropsychological 
measures, brain imaging data, or any other data recording instruments, assuring confidentiality to 
the best of our ability. Subject identification numbers are assigned to each participant.  Only the PI 
and HIPAA-trained project coordinator have access to the file that links names with subject numbers.  
All data are stored in locked file cabinets in a locked office, and on password-protected computers 
located behind a secure and maintained firewall until the time of study completion, or as long as the 
participant has agreed to have identifying information held for the purposes of future studies.
    
All data are collected by the PI, or trained research assistants who have completed on-line training in 
human subjects’ research, HIPAA and research integrity; who are trained in our lab on research data 
management and confidentiality; and who are trained to criteria on project protocol. Data will be 
collected specifically for this proposed research project.
Specially designated interview rooms will be used for the purposes of obtaining consent, conducting 
research, and debriefing subjects.  These rooms will be behind locked facility doors to which only the 
PI and trained research assistants will have access, ensuring privacy of the study participants.   
20.Economic Burden to Subjects
Responsible Party
Research Procedures
Number of 
Samples/Procedures
Study
3rd Party Payer 
or Participant
tDCS
1-10
x
Neuropsychological Testing
3
x
Telephone Interviews
2
x
EEG testing
2
x
MRI
2
     
     
     
     
     
     
Responsible Party
Standard of Care Procedures
Number of 
Samples/Procedures
Study
3rd Party Payer 
or Participant
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
Participants will be responsible for travel to and from the testing site. Participants will not 
be charged for the costs of an investigational drug or device or intervention.  Participants 
will be responsible for paying for treatment of adverse events.  As tDCS employs extremely 
low currents and numerous studies have documented minimal risk of adverse events, any 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 27 of 49
Version Date: January 29, 2019
adverse events requiring medical care will be extremely unlikely.  Participants will not be 
charged for any of the experimental study procedures, including MRI scans. If incidental 
findings from the study result in the need for further evaluation/treatment, the participant 
or their insurance company will be responsible for additional clinical evaluation/treatment 
that may be needed. Also, incidental finding information is disclosed only to the individual 
participant. However, if a participant chooses to disclose such information also to their 
personal physician, this may become part of their medical record which may or may not 
have an effect in the future on getting health or life insurance.
21. Compensation
Each of the 80 participants will receive$20/hr in the form of cash cards for taking part in the 
study.  This is felt to be a fair amount that is not coercive and will help decrease attrition for 
this study which involves many visits.
22.Compensation for Research-Related Injury
Any medical care required by participants for injuries incurred during the research study will be 
performed at cost to the participant.  All participants will be given information during the consent 
interview and provided at any time during the study regarding how to access urgent and emergency 
care at UNM, including emergency psychiatric care at UNM PES. These facilities are within 5-10 
minute walk to the MIND Research Network Domenici Hall where the study facilities are located, and 
may also be accessed easily via emergency medical rescue (ie. 911 EMS).  
23.Consent Process
Consent will be obtained by the PI, the research coordinator, or a research assistant.  All persons 
obtaining consent will be trained and certified in the ethical treatment of human participants in 
research studies as taught in IRB-required courses.  
Human participants who have suffered mmTBI (ages 18-55) will be recruited from the UNM Hospital 
ED and from other local Emergency Departments via phone call.  If a patient shows interest in 
participating in our study, a brief prescreening will be done prior to initiating informed consent 
procedures.  The prescreening procedures will assure that each potential participant meets study 
inclusion and exclusion criteria.  
In regards to screening for pregnancy, female subjects will be asked if they are pregnant, not 
pregnant, or not sure.  If a subject answers she is pregnant, she will be excluded from the study.  If 
she answers not pregnant, she will be enrolled and advised to use two forms of birth control during 
the time of the stimulation phase of the study.  If she answers that she is unsure, she will be offered a 
screening urine pregnancy test.  If she is not able or willing to take the pregnancy test, she will be 
excluded from the study.  
If, after prescreening, the patient remains interested and eligible, the project will be described in 
great details and the potential participant and their caregivers will be invited to ask questions prior 
to providing consent.  If the participant is willing, they will be invited to schedule an appointment to 
undergo informed consent prior to study initiation.  Appointments will be held at the Clinical Core in 
designed interview rooms behind secure facility doors so as to ensure privacy. Consent forms will be 
provided, as well as forms that again describe the study procedures and potential risks in detail.  If 
potential participants are unsure about participation, they will be given a copy of the consent form 
with our contact information and be invited to call if they decide to participate.  Once informed 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 28 of 49
Version Date: January 29, 2019
consent is obtained and the appropriate forms signed, the complete procedures of the study, as 
described in the consent forms, are provided to prospective subjects.  We review the forms, and file 
them away in a locked file cabinet in a locked office, away from any material with personal or 
sensitive study data.  Participants may withdraw their consent at any time during the study.  At each 
study encounter participants are reminded that they have the ability to withdraw consent at any 
time.  
All subjects will be asked whether they have the ability to consent themselves, or whether 
they have a legally authorized representative (LAR) available to make decisions with regard 
to informed consent for them.  In such cases, patients with a LAR will be excluded from 
participation.
The process of determining whether an individual is capable of consent will take place after the study 
has been explained, but before the subject is asked to sign the consent form.  A short list of questions 
regarding the purpose of the research, the research intervention, the clinical trial structure, the risks 
and benefits of the study, and the voluntary nature of it will be given to the subject before signing the 
consent form, to ensure capacity to understand and comprehend the study.  Each subject must 
answer 100% of the questions correctly; if answers are ambiguous or unclear the research team 
member will prompt the subject to clarify their meaning.  If any questions are not answered 
correctly, the research team member will remind the subject of the pertinent information, and then 
ask the question(s) again.  This will be repeated up to 2 times.  If the subject still fails to answer the 
questions 100% appropriately after the third attempt, they may be invited back to undergo the 
consent process again on a different day.  If after a second consent process the subject still cannot 
answer the questions 100% correctly, that subject will be excluded from the study.
The participants will be reminded at each study encounter that they have the ability to withdraw 
consent at any time to protect against loss of capacity to consent. Given the safety of tDCS to 
dorsolateral prefrontal cortex has been shown in numerous large controlled studies, it is highly 
unlikely that there to be any deterioration in decisional capacity as a result of the tDCS itself.  
24.Documentation of Consent  (see attached forms)
25.Study Test Results/Incidental Findings  (see next section)
26.Sharing Study Progress or Results with Subjects
As the neuropsychological and EEG tests employed in the study are for research purposes 
and not diagnostic purposes, these results will not be shared with the participants, unless 
their physician requests to see a report. In this instance the Clinical Core will obtain the 
participant’s permission to generate a summary report of the neuropsychological test results 
and send this to the participant’s primary care physician. Subjects will not be provided with 
summaries of trial progress, or summaries of study results.
All research MRI scans are read for incidental findings by a radiologist.  An e-mail 
notification is sent to the participant letting them know new results are available. The 
participant can securely log in to the COINS Homepage to access their MRI radiology 
report. No sensitive or identifying information is sent via e-mail. If an abnormality that 
requires follow-up is identified, such as a Doctor Referral recommendation, a hard copy 
of the report may be mailed to the participant in addition to the e-mail notification. In 
these cases, the MRN Medical Director may also attempt to contact the participant by 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 29 of 49
Version Date: January 29, 2019
phone to explain the information and help answer questions. If the participant does not 
need an email and/or does not have an email address and does not want an email account, 
the email info@mrn.org will be added as the study record email. This will notify the RO 
team when the participant’s scan has been read, and that a letter will need to be mailed to 
the participant’s address on file.
  
27.Inclusion of Vulnerable Populations
There will be no gender restrictions with regard to sample inclusion.  It is expected that our sample 
will reflect national sample characteristics of TBI populations; approximately 59% male and 41% 
female (CDC 2006).  It is expected that our unselected sample, drawn from the ED at a large state-
funded hospital, will result in TBI-group gender rations reflecting those of the CDC epidemiological 
sample.  The age range of 18-55 years was selected because we did not want to include 
developmental processes in our analyses and by 18 years old, many major neurodevelopmental 
changes in the brain will have taken place.  Using similar logic, we chose to include participants up to 
the age of 55 because we do not want to include advancing age-related changes in our analyses.  It is 
expected that the sample included in this study will reflect the demographics of the greater 
Albuquerque metropolitan community. The racial composition of the community is 69.7% White, 
2.47% African American, 5.53% Native American, 1.64% Asian, 0.10% Pacific Islander, 16.37% from 
other races, and 4.15% from two or more races.  Hispanic or Latino people of any race were 41.48% 
of the population.  Through randomization, we will ensure that the sample obtained represents the 
study population.  Adults unable to consent, individuals who are not yet adults (infants, children, 
teenagers), pregnant women, and prisoners will be excluded from the study.
The compensation for participation in the study is calibrated so as not to exert undue influence on 
economically disadvantaged participants.  The materials, instructions, consents, and scripts involved 
in the study will be geared toward a low-enough educational level that the majority of educationally 
disadvantaged participants will be able to understand them.
    
Recruitment will be unrestricted with regard to minorities, with the exception that non-English 
reading/speaking-only individuals will not be eligible.  Albuquerque’s population is multicultural, 
with a particularly large representation of Hispanic (mostly Mexican American) people.  Ethnicity, 
Hispanic or other, will be determined through self-identification.  In compliance with NIH policy 
participants will be asked to self identify as to Hispanic or Non-Hispanic as well as American Indian 
or Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, and 
White.  All possible combinations of the multiple responses will be reported.
28.Community-Based Participatory Research  NA
29.Research Involving American Indian/Native Populations  NA
30.Transnational Research  NA
31.Drugs or Devices
A NeuroConn (www.neuroconn.de) tDCS machine will be used to administer tDCS current. Square-
shaped, 11 cm2 saline water (15mM) solution-soaked sponge electrodes, held by a rubber casing, are 
applied to the scalp using elastic bandage material. The anode will be placed on the scalp over the F3 
target location and the cathode placed on the right upper arm below the deltoid. Current for the 
treatment condition will be applied at 2.0 mA for a total delivered charge of 60 mA-min.

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 30 of 49
Version Date: January 29, 2019
Dr. Quinn as well as the research coordinator and technician who will be applying tDCS will undergo 
training with Dr. Vincent Clark, who is a national expert in tDCS and has published extensively on the 
safe and efficacious use of tDCS for cognitive enhancement.  Dr. Quinn will also undergo training with 
his external mentor Dr. Marom Bikson, who is also a national expert on tDCS safety and mechanisms 
of action.  
We have extensive experience using 11 cm2 sponges with 2.0 mA for 30 minute sessions, with 
excellent tolerability of skin sensation, and effective blinding of stimulation.23 The use of 35 cm2 
sponges spreads stimulation over a significantly larger area and reduces efficacy to achieve cortical 
excitability.80,81 Given that our patient population is an outpatient, ambulatory, mild to moderate TBI 
population and that these current strengths and amounts have already been administered safely to 
patients with stroke and TBI lesions ipsilateral and proximal to the site of stimulation, we feel these 
parameters are extremely safe.  Our group is currently studying tDCS in subjects with tobacco use 
disorder, alcohol use disorder, and schizophrenia and are finding the stimulation to be very safe and 
well tolerated. To date, 138 subjects have undergone published tDCS protocols with our group and 
only two subjects withdrew because of intolerable sensations.  We find that about 1% of subjects on 
the average can't tolerate the skin stimulation caused by tDCS (heat, itching or burning sensations) 
and so we stop for them.  The other 99% tolerate it well.  We had one case of a system with a small 
piece of bare wire that touched the skin and caused a skin burn, which was small but needed 
attention.  This can be avoided by having a tDCS setup with fully insulated wiring.
A Data Safety and Monitoring Board will review study data with the PI quarterly for any side effects 
or adverse events. The device will be kept behind locked doors at all times at the Clinical Core of the 
Center when not being used expressly for the current study.  The principal investigator and trained 
research personnel will be the only persons with access to the device. 
There are no long term neuropsychiatric effects from tDCS.  With repeated stimulation, some subjects 
get dry skin.  Applying lotion helps to ameliorate this.  Using EEG gel rather than saline for the 
electrode conductor helps reduce this occurrence as well.
The TDCS device is determined to be a Non-Significant Risk device by the sponsor-investigator 
(Davin Quinn, MD) for the following reasons:
1)
It is not intended as an implant
2)
It does not present a potential for serious risk to the health, safety, or welfare of the subjects
3)
It is not proposed to be for a use in supporting or sustaining human life
4)
It is not for a use of substantial importance in diagnosing, curing, mitigating, or treating 
disease, or preventing impairment of human health
According to the FDA, serious adverse events are those in which the outcome is death, life-
threatening, hospitalization, disability/permanent damage, congenital anomaly, requiring 
intervention to prevent permanent impairment, or other serious events such as refractory seizures, 
cardiorespiratory arrest, or anaphylactic reaction.  No serious adverse events attributable to TDCS 
have been reported in the more than 10,000 subjects investigated in the contemporary TDCS 
literature since 1998.  This literature includes studies in patients with severe brain injury, stroke, 
epilepsy, and neurodegenerative disorders, none of whom have been reported to experience serious 
adverse events.  Specifically, there have been no reports or evidence presented of damage to the 
brain, seizures, or cardiorespiratory arrest.  Animal studies of charge densities necessary to induce 
brain damage in rats were found to be 100 times higher than the charge density used in TDCS trials 
with standard parameters (< 2.5 mA, no more than 2 sessions daily, < 60 min per session, use of 
electrodes that minimize skin burns) as determined by world-wide expert consensus.  The commonly 
reported side effects of TDCS are itching, burning, tingling, headache, and discomfort (10-40%), all of 
which are mild and transient.  As this trial will be operating within standard parameters as defined 

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 31 of 49
Version Date: January 29, 2019
above, we believe our use of TDCS in subjects with mild-moderate traumatic brain injury represent a 
Non-Significant Risk.

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 32 of 49
Version Date: January 29, 2019
Checklist Section
This section contains checklists to provide information on a variety of topics that require special 
determinations by the IRB.  Please complete all checklists relevant to your research.
I.
Waivers or Alterations of Consent, Assent, and HIPAA Authorization
A. Partial Waiver of Consent for Screening/Recruitment
Complete this checklist if you are requesting a partial waiver of consent so that you 
can review private information to identify potential subjects and/or determine 
eligibility prior to approaching potential subjects for consent or parental permission.
1. Describe the data source that you need to review (e.g., medical records):
Medical records
2. Describe the purpose for the review (e.g., screening):
Screening
3. Describe who will conducting the reviews (e.g., investigators, research staff):
Research staff
4. Do all persons who will be conducting the reviews already have permitted 
access to the data source?
x
 Yes
 No. Explain: 
5. Verify that each of the following are true or provide an alternate justification 
for the underlined regulatory criteria:
a) The activity involves no more than minimal risk to the subjects 
because the records review itself is non-invasive and the results of the 
records review will not be used for any purposes other than those 
described above.
x
 True
 Other justification:      
b) The waiver or alteration will not adversely affect the rights and 
welfare of the subjects because eligible subjects will be approached for 
consent to participate in the research and are free to decline.  Further, 
the information accessed during the records review will not be 
disclosed to anyone without a legitimate purpose (e.g., verification of 
eligibility).
x
 True

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 33 of 49
Version Date: January 29, 2019
 Other justification:      
c) The research could not practicably be carried out without the waiver or 
alteration because there is no other reasonably efficient and effective 
way to identify who to approach for possible participation in the 
research.  
x
 True
 Other justification:      
d) Whenever appropriate, potentially eligible subjects will be presented 
with information about the research and asked to consider 
participation.  (Regulatory criteria: Whenever appropriate, the 
subjects will be provided with additional pertinent information after 
participation.)
x
 True
 Other justification:      
Partial Waiver of HIPAA Authorization for Screening/Recruitment
Complete the following additional questions/attestations if the records you will 
review to identify potential subjects and/or determine eligibility include Protected 
Health Information (PHI).
6. Will you be recording any PHI when conducting the records review to identify 
potential subjects and/or determine eligibility?
 Yes. Describe:      
x
 No
7. If you answered “Yes” to question 6 above, please describe when you will 
destroy identifiers (must be the earliest opportunity consistent with the 
conduct of the research) or provide justification for why they must be 
retained:
     
8. The PHI accessed or recorded for identification/screening purposes will not be 
reused or disclosed to (shared with) any other person or entity, except as 
required by law, for authorized oversight of the research study, or for other 
research for which the use or disclosure of the PHI would be permitted under 
the Privacy Rule.
x
 True
 False

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 34 of 49
Version Date: January 29, 2019
B. Waiver of Documentation of Consent
Complete this checklist if you intend to obtain consent verbally but will not be 
obtaining signatures from subjects on a consent form to document consent.  Waivers 
of documentation of consent are commonly requested when using scripts, information 
sheets, or email or survey introductions to present the elements of consent instead of 
using a traditional consent form.
1. Are you requesting a waiver of documentation of consent for some or all 
subjects?
 All
 Some. Explain:      
2. Provide justification for one of the following:
a) That the only record linking the subject and the research would be the 
consent document and the principal risk would be potential harm 
resulting from a breach of confidentiality. Each subject will be asked 
whether the subject wants documentation linking the subject with the 
research, and the subject's wishes will govern.
     
b) That the research presents no more than minimal risk of harm to 
subjects and involves no procedures for which written consent is 
normally required outside of the research context.
     
3. Do you intend to provide subjects with a written statement regarding the 
research in lieu of a traditional consent form?
 Yes. Please attach a copy to your submission in Click.
x
 No
C. Alteration of Consent
Complete this checklist if you intend to obtain consent but will be eliminating or 
altering one or more of the required elements of consent. Alterations of consent are 
commonly requested for research involving deception or for minimal risk research 
when an abbreviated consent is desired and one or more of the required element are 
not relevant to the research.
Note: FDA-regulated research is not eligible for an alteration of consent.
1. Which element(s) of consent do you wish to eliminate and why?
     

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 35 of 49
Version Date: January 29, 2019
2. Which element(s) of consent do you wish to alter and why?
     
3. Provide justification for each of the following regulatory criteria:
a) The research involves no more than minimal risk to the subjects:
     
b) The waiver or alteration will not adversely affect the rights and 
welfare of the subjects:
     
c) The research could not practicably be carried out without the waiver or 
alteration:
     
d) Whenever appropriate, the subjects will be provided with additional 
pertinent information after participation:
     
D. Full Waiver of Consent/Parental Permission
Complete this checklist if you are requesting a full waiver of consent for all subjects 
or certain subject groups (e.g., retrospective cohort).  Full waivers of consent are 
commonly requested when the research does not include any opportunity for 
interaction with subjects (e.g., chart review).
Note: FDA-regulated research is not eligible for a full waiver of consent using these 
criteria.  If you believe that your FDA-regulated research may be eligible for a waiver 
under another mechanism, such as planned emergency research, contact the HRPO 
for assistance in determining what information to provide to the HRRC.
1. Are you requesting a waiver for some or all subjects?
 All
 Some. Explain:      
2. Provide justification for each of the following regulatory criteria:
a) The research involves no more than minimal risk to the subjects:
     
b) The waiver or alteration will not adversely affect the rights and 
welfare of the subjects:
     

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 36 of 49
Version Date: January 29, 2019
c) The research could not practicably be carried out without the waiver or 
alteration:
     
d) Whenever appropriate, the subjects will be provided with additional 
pertinent information after participation:
     
E. Full Waiver of Consent/Parental Permission (Public Benefit or Service 
Programs)
Complete this checklist if you are requesting a full waiver of consent for all subjects 
or certain subject groups (e.g., retrospective cohort) and the research involves the 
evaluation of a public benefit or service program.  
1. Are you requesting a waiver for some or all subjects?
 All
 Some. Explain:      
2. Provide justification for each of the following regulatory criteria:
a) The research or demonstration project is to be conducted by or subject 
to the approval of state or local government officials and is designed to 
study, evaluate, or otherwise examine: (i) public benefit or service 
programs; (ii) procedures for obtaining benefits or services under those 
programs; (iii) possible changes in or alternatives to those programs or 
procedures; or (iv) possible changes in methods or levels of payment 
for benefits or services under those programs:
     
b) The research could not practicably be carried out without the waiver or 
alteration.
     
F. Full Waiver of HIPAA Authorization
Complete this checklist if you are requesting a full waiver of the requirement to 
obtain HIPAA authorization for all subjects or certain subject groups (e.g., 
retrospective cohort).  Full waivers of HIPAA authorization are commonly requested 
when the research does not include any opportunity for interaction with subjects 
(e.g., chart review).
1. Are you requesting a waiver of authorization for some or all subjects?
 All
 Some. Explain:      

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 37 of 49
Version Date: January 29, 2019
2. Describe your plan to protect health information identifiers from improper use 
and disclosure:
     
3. Describe your plan to destroy identifiers at the earliest opportunity consistent 
with conduct of the research (absent a health or research justification for 
retaining them or a legal requirement to do so):
     
4. Describe why the research could not practicably be conducted without the 
waiver or alteration:
     
5. The PHI accessed or recorded for identification/screening purposes will not be 
reused or disclosed to (shared with) any other person or entity, except as 
required by law, for authorized oversight of the research study, or for other 
research for which the use or disclosure of the PHI would be permitted under 
the Privacy Rule.
 True
 False
G. Other Waiver Types
If you are seeking another waiver type (e.g., Planned Emergency Research, Waiver of 
Parental Permission to Protect Child Participants, Enforcement Discretion for In 
Vitro Diagnostics, etc. contact the HRPO office for assistance in determining what 
information to submit for the HRRC’s consideration.
II. Vulnerable Populations
A. Adults with Cognitive Impairments
Complete this checklist if the subject population will include adults with cognitive 
impairments.  
This checklist does not need to be completed if the research doesn’t involve 
interactions or interventions with subjects and will be conducted under a waiver of 
consent.
1. Describe why the objectives of the study cannot be met without inclusion of 
adults with cognitive impairments.
.  
2. Describe how capacity to consent will be evaluated.

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 38 of 49
Version Date: January 29, 2019
     
3. If subjects may regain capacity to consent, or if subjects may have fluctuating 
capacity to consent, describe your plans to evaluate capacity to consent 
throughout the research and to obtain consent to continue participation if 
capacity is regained.
     
4. Describe your plans, if any, to provide information about the research to 
subjects and the steps you will take to assess understanding.
     
5. Describe your plans to obtain assent, including whether assent will be 
obtained from none, some, or all subjects.
     
6. Describe why risks to subjects are reasonable in relation to anticipated 
benefits to the subjects.
     
7. If this study involves a health or behavioral intervention, describe why the 
relation of the anticipated benefit to the risk of the research is at least as 
favorable to the subjects as that presented by alternative procedures.
     
8. Describe your plans for monitoring the well-being of subjects including any 
plans to withdraw subjects from the research if they appear to be unduly 
distressed.
     
B. Children
Complete this checklist if the subject population will include children.
1. Select the category of research that you believe this research falls within and 
provide justification for any associated criteria.  If there are different 
assessments for different groups of children or arms (e.g., placebo vs. drug), 
include a memo to provide an assessment for each group.  
 Research not involving greater than minimal risk. (Minimal risk means 
that the probability and magnitude of harm or discomfort anticipated 
in the research are not greater in and of themselves than those 
ordinarily encountered in daily life or during the performance of 
routine physical or psychological examinations or tests.)

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 39 of 49
Version Date: January 29, 2019
 Research involving greater than minimal risk but presenting the 
prospect of direct benefit to the individual subjects.
Provide justification for each of the following criteria:
(1) The risk is justified by the anticipated benefit to the subjects:
     
(2) The relation of the anticipated benefit to the risk is at least as 
favorable to the subjects as that presented by available 
alternative approaches:
     
 Research involving greater than minimal risk and no prospect of direct 
benefit to individual subjects, but likely to yield generalizable 
knowledge about the subject's disorder or condition.
Provide justification for each of the following criteria:
(1) The risk represents a minor increase over minimal risk:
     
(2) The intervention or procedure presents experiences to subjects 
that are reasonably commensurate with those inherent in their 
actual or expected medical, dental, psychological, social, or 
educational situations:
     
(3) The intervention or procedure is likely to yield generalizable 
knowledge about the subjects' disorder or condition which is of 
vital importance for the understanding or amelioration of the 
subjects' disorder or condition
     
C. Pregnant Women and Fetuses
Complete this checklist if the subject population will include pregnant women and 
fetuses.
This checklist does not need to be completed if the research is both minimal risk and 
is not conducted, funded, or otherwise subject to regulation by DHHS, DOD, EPA, or 
VA.
Provide justification for each of the following:
1. Where scientifically appropriate, preclinical studies, including studies on 
pregnant animals, and clinical studies, including studies on non-pregnant 
women, have been conducted and provide data for assessing potential risks to 
pregnant women and fetuses.

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 40 of 49
Version Date: January 29, 2019
     
2. The risk to the fetus is caused solely by interventions or procedures that hold 
out the prospect of direct benefit for the woman or the fetus; or, if there is no 
such prospect of benefit, the risk to the fetus is not greater than minimal and 
the purpose of the research is the development of important biomedical 
knowledge which cannot be obtained by any other means.
     
3. Any risk is the least possible for achieving the objectives of the research.
     
D. Neonates of Uncertain Viability or Nonviable Neonates
Complete this checklist if the subject population will include neonates of uncertain 
viability.
Provide justification for each of the following:
1. Where scientifically appropriate, preclinical and clinical studies have been 
conducted and provide data for assessing potential risks to neonates.
     
2. Each individual providing consent is fully informed regarding the reasonably 
foreseeable impact of the research on the neonate.
     
3. Individuals engaged in the research will have no part in determining the 
viability of a neonate.
     
4. The research holds out the prospect of enhancing the probability of survival of 
the neonate to the point of viability, and any risk is the least possible for 
achieving that objective, or, the purpose of the research is the development of 
important biomedical knowledge which cannot be obtained by other means 
and there will be no added risk to the neonate resulting from the research
     
E. Nonviable Neonates
Complete this checklist if the subject population will include nonviable neonates.
Provide justification for each of the following:
1. Where scientifically appropriate, preclinical and clinical studies have been 
conducted and provide data for assessing potential risks to neonates.

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 41 of 49
Version Date: January 29, 2019
     
2. Each individual providing consent is fully informed regarding the reasonably 
foreseeable impact of the research on the neonate.
     
3. Individuals engaged in the research will have no part in determining the 
viability of a neonate.
     
4. The purpose of the research is the development of important biomedical 
knowledge that cannot be obtained by other means.
     
Verify each of the following:
5. Vital functions of the neonate will not be artificially maintained
 True
 False
6. The research will not terminate the heartbeat or respiration of the neonate
 True
 False
7. There will be no added risk to the neonate resulting from the research
 True
 False
F. Biomedical and Behavioral Research Involving Prisoners
Complete this checklist if the subject population will include prisoners.
Note: Minimal risk for research involving prisoners is the probability and magnitude 
of physical or psychological harm that is normally encountered in the daily lives, or 
in the routine medical, dental, or psychological examination of healthy persons.
1. Select and justify which allowable category of research involving prisoners 
this research falls within:
 Study of the possible causes, effects, and processes of incarceration, and of 
criminal behavior, provided that the study presents no more than minimal 
risk and no more than inconvenience to the subjects
     

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 42 of 49
Version Date: January 29, 2019
 Study of prisons as institutional structures or of prisoners as incarcerated 
persons, provided that the study presents no more than minimal risk and 
no more than inconvenience to the subjects
     
 Research on conditions particularly affecting prisoners as a class (for 
example, vaccine trials and other research on hepatitis which is much 
more prevalent in prisons than elsewhere; and research on social and 
psychological problems such as alcoholism, drug addiction, and sexual 
assaults)
     
 Research on practices, both innovative and accepted, which have the intent 
and reasonable probability of improving the health or well-being of the 
subject
     
 Epidemiologic studies in which the sole purpose is to describe the 
prevalence or incidence of a disease by identifying all cases or to study 
potential risk factor associations for a disease, the research presents no 
more than Minimal Risk and no more than inconvenience to the subjects, 
and Prisoners are not a particular focus of the research.
     
2. Provide justification for each of the following regulatory criteria:
a) Any possible advantages accruing to the prisoner through his or her 
participation in the research, when compared to the general living 
conditions, medical care, quality of food, amenities and opportunity 
for earnings in the prison, are not of such a magnitude that his or her 
ability to weigh the risks of the research against the value of such 
advantages in the limited choice environment of the prison is impaired
     
b) The risks involved in the research are commensurate with risks that 
would be accepted by nonprisoner volunteers
     
c) Procedures for the selection of subjects within the prison are fair to all 
prisoners and immune from arbitrary intervention by prison authorities 
or prisoners. Unless justification is provided, control subjects must be 
selected randomly from the group of available prisoners who meet the 
characteristics needed for that particular research project
     

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 43 of 49
Version Date: January 29, 2019
d) The information is presented in language which is understandable to 
the subject population
     
e) Adequate assurance exists that parole boards will not take into account 
a prisoner's participation in the research in making decisions regarding 
parole, and each prisoner is clearly informed in advance that 
participation in the research will have no effect on his or her parole
     
f)
When appropriate, adequate provision has been made for follow up 
examination or care after research participation, taking into account 
the varying lengths of individual prisoners' sentences, and for 
informing participants of this fact
     
III.Medical Devices
Complete this checklist if the research evaluates the safety or effectiveness of a medical device.  
If more than one medical device is being evaluated, provide the requested information for each.
A. Device Name: Transcranial Direct Current Stimulator
B. Manufacturer: NeuroConn
C. Does the research involve a Significant Risk Device under an IDE?
 Yes. Include documentation of the FDA approval of the IDE with your submission.  
Acceptable methods of documentation include: (1) FDA letter noting IDE number 
and approval status; (2) Industry sponsor letter noting IDE number and FDA 
approval status; or (3) FDA-approved industry sponsor protocol with IDE number 
noted 
x
 No
D. Is the research IDE-exempt?
x
 Yes. Include a FDA letter with your submission noting the determination that the 
research is IDE-exempt or a letter from the sponsor (or sponsor-investigator) 
justifying why they believe the research is IDE-exempt*.  
 No
E. Does the research involve a Non-Significant Risk (NSR) Device?

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 44 of 49
Version Date: January 29, 2019
x
 Yes. Include a FDA letter with your submission noting the determination that the 
research is NSR or a letter from the sponsor (or sponsor-investigator) justifying why 
they believe the research is NSR**.  
 No
* This FDA guidance includes a description for when a device study is exempt from the 
IDE requirements: 
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf 
**This FDA guidance includes information on how to differentiate between Significant 
Risk and Non-Significant Risk device studies: 
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126418.pdf 
References
1. 
Faul M, Xu L, Wald MM, Coronado VG. Traumatic Brain Injury in the United States: Emergency 
Department Visits, Hospitalizations and Deaths 2002-2006. Atlanta, GA; 2010.
2. 
Coronado VG, McGuire LC, Sarmiento K, et al. Trends in Traumatic Brain Injury in the U.S. and the public 
health response: 1995-2009. J Safety Res. 2012;43(4):299–307. doi:10.1016/j.jsr.2012.08.011.
3. 
Overpeck M, Hubbard G, Cotner J. Traumatic and Acquired Brain Injury in New Mexico.; 2010.
4. 
McMahon P, Hricik A, Yue JK, et al. Symptomatology and Functional Outcome in Mild Traumatic Brain 
Injury: Results from the Prospective TRACK-TBI Study. J Neurotrauma. 2013;8:1–8. 
doi:10.1089/neu.2013.2984.
5. 
Stuss DT. Traumatic brain injury: relation to executive dysfunction and the frontal lobes. Curr Opin Neurol. 
2011;24(6):584–9. doi:10.1097/WCO.0b013e32834c7eb9.
6. 
Mayberg HS. Modulating dysfunctional limbic-cortical circuits in depression. Br Med Bull. 2003;65:193–
207. doi:10.1093/bmb/ldg65.193.
7. 
Dimoska-Di Marco A, McDonald S, Kelly M, Tate R, Johnstone S. A meta-analysis of response inhibition 
and Stroop interference control deficits in adults with traumatic brain injury (TBI). J Clin Exp 
Neuropsychol. 2011;33(4):471–85. doi:10.1080/13803395.2010.533158.
8. 
Homaifar BY, Brenner LA, Forster JE, Nagamoto H. Traumatic Brain Injury , Executive Functioning , and 
Suicidal Behavior: A Brief Report. Rehabil Psychol. 2012;57(4):337–341. doi:10.1037/a0030480.
9. 
Schiehser D, Delis D, Filoteo JV, et al. Are self-reported symptoms of executive dysfunction associated with 
objective executive function performance following mild to moderate traumatic brain injury? J Clin Exp 
Neuropsychol. 2011;33(6):704–714. doi:10.1080/13803395.2011.553587.Are.
10. 
Jorge RE, Robinson RG, Moser D, Tateno A, Crespo-Facorro B, Arndt S. Major depression following 
traumatic brain injury. Arch Gen Psychiatry. 2004;61(1):42–50. doi:10.1001/archpsyc.61.1.42.

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 45 of 49
Version Date: January 29, 2019
11. 
Larson MJ, Farrer TJ, Clayson PE. Cognitive control in mild traumatic brain injury: conflict monitoring and 
conflict adaptation. Int J Psychophysiol. 2011;82(1):69–78. doi:10.1016/j.ijpsycho.2011.02.018.
12. 
Cicerone KD, Langenbahn DM, Braden C, et al. Evidence-based cognitive rehabilitation: updated review of 
the literature from 2003 through 2008. Arch Phys Med Rehabil. 2011;92(4):519–30. 
doi:10.1016/j.apmr.2010.11.015.
13. 
Willmott C, Ponsford J, Olver J, Ponsford M. Safety of methylphenidate following traumatic brain injury: 
impact on vital signs and side-effects during inpatient rehabilitation. J Rehabil Med. 2009;41(7):585–7. 
doi:10.2340/16501977-0369.
14. 
Giacino JT, Whyte J, Bagiella E, et al. Placebo-controlled trial of amantadine for severe traumatic brain 
injury. N Engl J Med. 2012;366(9):819–26. doi:10.1056/NEJMoa1102609.
15. 
McAllister TW, Flashman L a, McDonald BC, et al. Dopaminergic challenge with bromocriptine one month 
after mild traumatic brain injury: altered working memory and BOLD response. J Neuropsychiatry Clin 
Neurosci. 2011;23(3):277–86. doi:10.1176/appi.neuropsych.23.3.277.
16. 
Diaz-Arrastia R, Kochanek PM, Bergold P, et al. Pharmacotherapy of Traumatic Brain Injury: State of the 
Science and the Road Forward. J Neurotrauma. 2014;31(2):135–158.
17. 
Fann JR, Hart T, Schomer KG. Treatment for Depression after Traumatic Brain Injury: A systematic review. 
J Neurotrauma. 2009;2402(December):2383–2402.
18. 
Wheaton P, Mathias JL, Vink R. Impact of pharmacological treatments on cognitive and behavioral outcome 
in the postacute stages of adult traumatic brain injury: a meta-analysis. J Clin Psychopharmacol. 
2011;31(6):745–57. doi:10.1097/JCP.0b013e318235f4ac.
19. 
Kalu UG, Sexton CE, Loo CK, Ebmeier KP. Transcranial direct current stimulation in the treatment of 
major depression: a meta-analysis. Psychol Med. 2012;42(9):1791–800. doi:10.1017/S0033291711003059.
20. 
Baker JM, Rorden C, Fridriksson J. Using transcranial direct-current stimulation to treat stroke patients with 
aphasia. Stroke. 2010;41(6):1229–36. doi:10.1161/STROKEAHA.109.576785.
21. 
Reis J, Schambra HM, Cohen LG, et al. Noninvasive cortical stimulation enhances motor skill acquisition 
over multiple days through an effect on consolidation. PNAS. 2009;106(5):1590–1595.
22. 
Freitas C, Mondragón-Llorca H, Pascual-Leone A. Noninvasive brain stimulation in Alzheimer’s disease: 
systematic review and perspectives for the future. Exp Gerontol. 2011;46(8):611–27. 
doi:10.1016/j.exger.2011.04.001.
23. 
Clark VP, Coffman B a, Mayer AR, et al. TDCS guided using fMRI significantly accelerates learning to 
identify concealed objects. Neuroimage. 2012;59(1):117–28. doi:10.1016/j.neuroimage.2010.11.036.
24. 
Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct 
current stimulation. 2000:633–639.
25. 
Olma MC, Dargie R a, Behrens JR, et al. Long-Term Effects of Serial Anodal tDCS on Motion Perception 
in Subjects with Occipital Stroke Measured in the Unaffected Visual Hemifield. Front Hum Neurosci. 
2013;7(June):314. doi:10.3389/fnhum.2013.00314.

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 46 of 49
Version Date: January 29, 2019
26. 
Monte-Silva K, Kuo M-F, Hessenthaler S, et al. Induction of late LTP-like plasticity in the human motor 
cortex by repeated non-invasive brain stimulation. Brain Stimul. 2013;6(3):424–32. 
doi:10.1016/j.brs.2012.04.011.
27. 
Boggio PS, Nunes A, Rigonatti SP, Nitsche M a, Pascual-Leone A, Fregni F. Repeated sessions of 
noninvasive brain DC stimulation is associated with motor function improvement in stroke patients. Restor 
Neurol Neurosci. 2007;25(2):123–9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17726271.
28. 
Ko M, Han S, Park S, Seo J, Kim Y. Neuroscience Letters Improvement of visual scanning after DC brain 
polarization of parietal cortex in stroke patients with spatial neglect. 2008;448:171–174. 
doi:10.1016/j.neulet.2008.10.050.
29. 
Hummel F, Celnik P, Giraux P, et al. Effects of non-invasive cortical stimulation on skilled motor function 
in chronic stroke. Brain. 2005;128(Pt 3):490–499. doi:10.1093/brain/awh369.
30. 
Monti A, Cogiamanian F, Marceglia S, et al. Improved naming after transcranial direct current stimulation 
in aphasia. J Neurol Neurosurg Psychiatry. 2008;79:451–453. doi:10.1136/jnnp.2007.135277.
31. 
Dockery CA, Hueckel-weng R, Birbaumer N, Plewnia C. Enhancement of Planning Ability by Transcranial 
Direct Current Stimulation. J Neurosci. 2009;29(22):7271–7277. doi:10.1523/JNEUROSCI.0065-09.2009.
32. 
Fregni F, Boggio PS, Nitsche M, et al. Anodal transcranial direct current stimulation of prefrontal cortex 
enhances working memory. Exp Brain Res. 2005;166:23–30. doi:10.1007/s00221-005-2334-6.
33. 
Boggio PS, Bermpohl F, Vergara AO, et al. Go-no-go task performance improvement after anodal 
transcranial DC stimulation of the left dorsolateral prefrontal cortex in major depression. J Affect Disord. 
2007;101(1-3):91–98. doi:10.1016/j.jad.2006.10.026.
34. 
Metuki N, Sela T, Lavidor M. Enhancing cognitive control components of insight problems solving by 
anodal tDCS of the left dorsolateral prefrontal cortex. Brain Stimul. 2012;5(2):110–5. 
doi:10.1016/j.brs.2012.03.002.
35. 
Falcone B, Coffman BA, Clark VP, Parasuraman R. Transcranial Direct Current Stimulation Augments 
Perceptual Sensitivity and 24-Hour Retention in a Complex Threat Detection Task. PLoS One. 2012;7(4):1–
10. doi:10.1371/journal.pone.0034993.
36. 
Boggio PS, Zaghi S, Beatriz A, Fecteau S, Pascual-leone A, Fregni F. Modulation of risk-taking in 
marijuana users by transcranial direct current stimulation ( tDCS ) of the dorsolateral prefrontal cortex ( 
DLPFC ). Drug Alcohol Depend. 2010;112(3):220–225. doi:10.1016/j.drugalcdep.2010.06.019.
37. 
Floel a, Cohen LG. Contribution of noninvasive cortical stimulation to the study of memory functions. Brain 
Res Rev. 2007;53(2):250–9. doi:10.1016/j.brainresrev.2006.08.006.
38. 
Beeli G, Casutt G, Baumgartner T, Jäncke L. Behavioral and Brain Functions Modulating presence and 
impulsiveness by external stimulation of the brain. Behav brain Funct. 2008;7:1–7. doi:10.1186/1744-9081-
4-33.
39. 
Fecteau S, Knoch D, Fregni F, Sultani N, Boggio P, Pascual-leone A. Diminishing Risk-Taking Behavior by 
Modulating Activity in the Prefrontal Cortex : A Direct Current Stimulation Study. J Neurosci. 
2007;27(46):12500–12505. doi:10.1523/JNEUROSCI.3283-07.2007.

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 47 of 49
Version Date: January 29, 2019
40. 
Flöel A. tDCS-enhanced motor and cognitive function in neurological diseases. Neuroimage. 2014;85 Pt 
3:934–47. doi:10.1016/j.neuroimage.2013.05.098.
41. 
Kim SJ, Kim BK, Ko YJ, Bang MS, Kim MH, Han TR. Functional and histologic changes after repeated 
transcranial direct current stimulation in rat stroke model. J Korean Med Sci. 2010;25(10):1499–505. 
doi:10.3346/jkms.2010.25.10.1499.
42. 
Yoon KJ, Oh B-M, Kim D-Y. Functional improvement and neuroplastic effects of anodal transcranial direct 
current stimulation (tDCS) delivered 1 day vs. 1 week after cerebral ischemia in rats. Brain Res. 
2012;1452:61–72. doi:10.1016/j.brainres.2012.02.062.
43. 
Kang E, Kim D, Paik N. Transcranial Direct Current Stimulation of the Left Prefrontal Cortex Improves 
Attention in Patients with Traumatic Brain Injury : A Pilot Study. J Rehabil Med. 2012;44:346–350. 
doi:10.2340/16501977-0947.
44. 
Leśniak M, Polanowska K, Seniów J, Członkowska A. Effects of Repeated Anodal tDCS Coupled With 
Cognitive Training for Patients With Severe Traumatic Brain Injury: A Pilot Randomized Controlled Trial. J 
Head Trauma Rehabil. 2013. doi:10.1097/HTR.0b013e318292a4c2.
45. 
Coffman B a, Trumbo MC, Clark VP. Enhancement of object detection with transcranial direct current 
stimulation is associated with increased attention. BMC Neurosci. 2012;13:108. doi:10.1186/1471-2202-13-
108.
46. 
Quinn DK, Rees C, Brodsky A, et al. Catatonia After Deep Brain Stimulation Successfully Treated With 
Lorazepam and Right Unilateral Electroconvulsive Therapy: A Case Report. J ECT. 2013;00(00):1–3. 
doi:10.1097/YCT.0b013e31829e0afa.
47. 
Quinn DK, Deligtisch A, Rees C, et al. Differential Diagnosis of Psychiatric Symptoms After Deep Brain 
Stimulation for Movement Disorders. Neuromodulation. 2014;2013. doi:10.1111/ner.12153.
48. 
Ling JM, Peña A, Yeo R a, et al. Biomarkers of increased diffusion anisotropy in semi-acute mild traumatic 
brain injury: a longitudinal perspective. Brain. 2012;135(Pt 4):1281–92. doi:10.1093/brain/aws073.
49. 
Yeo R a, Gasparovic C, Merideth F, Ruhl D, Doezema D, Mayer AR. A longitudinal proton magnetic 
resonance spectroscopy study of mild traumatic brain injury. J Neurotrauma. 2011;28(1):1–11. 
doi:10.1089/neu.2010.1578.
50. 
Mayer AR, Ling JM, Yang Z, Pena A, Yeo R a, Klimaj S. Diffusion abnormalities in pediatric mild 
traumatic brain injury. J Neurosci. 2012;32(50):17961–9. doi:10.1523/JNEUROSCI.3379-12.2012.
51. 
Mayer a R, Ling J, Mannell M V, et al. A prospective diffusion tensor imaging study in mild traumatic brain 
injury. Neurology. 2010;74(8):643–50. doi:10.1212/WNL.0b013e3181d0ccdd.
52. 
Mayer AR, Yang Z, Yeo R a, et al. A functional MRI study of multimodal selective attention following mild 
traumatic brain injury. Brain Imaging Behav. 2012;6(2):343–54. doi:10.1007/s11682-012-9178-z.
53. 
Quinn DK, Flaherty AW, Herman JB, Kleinschmidt TL. Over the rainbow: a case of traumatic brain injury. 
Harv Rev Psychiatry. 18(1):56–66. doi:10.3109/10673220903523953.
54. 
Yarns BC, Quinn DK. Telephone effect in akinetic mutism from traumatic brain injury. Psychosomatics. 
2013;54(6):609–10. doi:10.1016/j.psym.2013.06.006.

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 48 of 49
Version Date: January 29, 2019
55. 
Cavanagh JF, Shackman AJ. Frontal midline theta reflects anxiety and cognitive control: Meta-analytic 
evidence. J Physiol. 2015;109(1-3):3–15. doi:10.1016/j.jphysparis.2014.04.003.
56. 
Cavanagh JF, Frank MJ. Frontal theta as a mechanism for cognitive control. Trends Cogn Sci. 
2014;18(8):414–421. doi:10.1016/j.tics.2014.04.012.
57. 
Larson MJ, Perlstein WM, Demery J a, Stigge-Kaufman D a. Cognitive control impairments in traumatic 
brain injury. J Clin Exp Neuropsychol. 2006;28(6):968–86. doi:10.1080/13803390600646860.
58. 
Larson MJ, Fair JE, Farrer TJ, Perlstein WM. Predictors of performance monitoring abilities following 
traumatic brain injury: the influence of negative affect and cognitive sequelae. Int J Psychophysiol. 
2011;82(1):61–8. doi:10.1016/j.ijpsycho.2011.02.001.
59. 
DaSilva AF, Volz MS, Bikson M, Fregni F. Electrode positioning and montage in transcranial direct current 
stimulation. J Vis Exp. 2011;(51):e2744, doi:10.3791/2744. doi:10.3791/2744.
60. 
Miranda PC, Lomarev M, Hallett M. Modeling the current distribution during transcranial direct current 
stimulation. Clin Neurophysiol. 2006;117(7):1623–1629. doi:10.1016/j.clinph.2006.04.009.
61. 
Seignourel PJ, Robins DL, Larson MJ, Demery J a, Cole M, Perlstein WM. Cognitive control in closed head 
injury: context maintenance dysfunction or prepotent response inhibition deficit? Neuropsychology. 
2005;19(5):578–90. doi:10.1037/0894-4105.19.5.578.
62. 
Munakata Y, Herd S a, Chatham CH, Depue BE, Banich MT, O’Reilly RC. A unified framework for 
inhibitory control. Trends Cogn Sci. 2011;15(10):453–9. doi:10.1016/j.tics.2011.07.011.
63. 
Braver TS, Cohen JD. Working Memory , Cognitive Control , and the Prefrontal Cortex : Computational 
and Empirical Studies.
64. 
Pontifex MB, O’Connor PM, Broglio SP, Hillman CH. The association between mild traumatic brain injury 
history and cognitive control. Neuropsychologia. 2009;47(14):3210–6. 
doi:10.1016/j.neuropsychologia.2009.07.021.
65. 
Jaeggi SM, Seewer R, Nirkko AC, et al. Does excessive memory load attenuate activation in the prefrontal 
cortex? Load-dependent processing in single and dual tasks: functional magnetic resonance imaging study. 
Neuroimage. 2003;19(2):210–225. doi:10.1016/S1053-8119(03)00098-3.
66. 
Sterr A, Herron K a, Hayward C, Montaldi D. Are mild head injuries as mild as we think? Neurobehavioral 
concomitants of chronic post-concussion syndrome. BMC Neurol. 2006;6:7. doi:10.1186/1471-2377-6-7.
67. 
Harman-Smith YE, Mathias JL, Bowden SC, Rosenfeld J V, Bigler ED. Wechsler Adult Intelligence Scale-
Third Edition profiles and their relationship to self-reported outcome following traumatic brain injury. J Clin 
Exp Neuropsychol. 2013;35(8):785–98. doi:10.1080/13803395.2013.824554.
68. 
Clark VP, Coffman B a, Trumbo MC, Gasparovic C. Transcranial direct current stimulation (tDCS) 
produces localized and specific alterations in neurochemistry: a 1H magnetic resonance spectroscopy study. 
Neurosci Lett. 2011;500(1):67–71. doi:10.1016/j.neulet.2011.05.244.
69. 
McCauley SR, Pedroza C, Brown S a, et al. Confirmatory factor structure of the Center for Epidemiologic 
Studies-Depression scale (CES-D) in mild-to-moderate traumatic brain injury. Brain Inj. 2006;20(5):519–
27. doi:10.1080/02699050600676651.

PROTOCOL TITLE: Transcranial direct current stimulation for treatment of deficits after 
traumatic brain injury. 
Page 49 of 49
Version Date: January 29, 2019
70. 
Ashman T a, Cantor JB, Gordon W a, et al. A randomized controlled trial of sertraline for the treatment of 
depression in persons with traumatic brain injury. Arch Phys Med Rehabil. 2009;90(5):733–40. 
doi:10.1016/j.apmr.2008.11.005.
71. 
Vasterling JJ, Brailey K, Proctor SP, Kane R, Heeren T, Franz M. Neuropsychological outcomes of mild 
traumatic brain injury, post-traumatic stress disorder and depression in Iraq-deployed US Army soldiers. Br 
J Psychiatry. 2012;201(3):186–92. doi:10.1192/bjp.bp.111.096461.
72. 
Poreisz C, Antal A, Paulus W. Safety aspects of transcranial direct current stimulation concerning healthy 
subjects and patients. Brain Res Bull. 2007;72:208–214. doi:10.1016/j.brainresbull.2007.01.004.
73. 
Schiller C, Reisinger E, Nitsche M. Skin lesions after treatment with transcranial direct current stimulation 
(tDCS). Brain Stimul. 2008;1(4):386–387. doi:10.1016/j.brs.2008.04.003.
74. 
Dundas JE, Thickbroom GW, Mastaglia FL. Perception of comfort during transcranial DC stimulation : 
Effect of NaCl solution concentration applied to sponge electrodes. Clin Neurophys. 2007;118:1166–1170. 
doi:10.1016/j.clinph.2007.01.010.
75. 
Bikson M, Datta A, Elwassif M. Establishing safety limits for transcranial direct current stimulation. Clin 
Neurophysiol. 2009;120(6):1033–1034. doi:10.1016/j.clinph.2009.03.018.
76. 
Gálvez V, Alonzo A, Martin D, Mitchell PB, Sachdev P, Loo CK. Hypomania induction in a patient with 
bipolar II disorder by transcranial direct current stimulation (tDCS). J ECT. 2011;27(3):256–8. 
doi:10.1097/YCT.0b013e3182012b89.
77. 
Brunoni AR, Valiengo L, Baccaro A, et al. The sertraline vs. electrical current therapy for treating 
depression clinical study: results from a factorial, randomized, controlled trial. JAMA psychiatry. 
2013;70(4):383–91. doi:10.1001/2013.jamapsychiatry.32.
78. 
Liebetanz D, Koch R, Mayenfels S, König F, Paulus W, Nitsche M a. Safety limits of cathodal transcranial 
direct current stimulation in rats. Clin Neurophysiol. 2009;120(6):1161–7. doi:10.1016/j.clinph.2009.01.022.
79. 
Angelakis E, Liouta E, Andreadis N, et al. Transcranial Direct Current Stimulation Effects in Disorders of 
Consciousness. Arch Phys Med Rehabil. 2013. doi:10.1016/j.apmr.2013.09.002.
80. 
Bastani a., Jaberzadeh S. a-tDCS Differential Modulation of Corticospinal Excitability: The Effects of 
Electrode Size. Brain Stimul. 2013;6(6):932–937. doi:10.1016/j.brs.2013.04.005.
81. 
Faria P, Hallett M, Miranda PC. A finite element analysis of the effect of electrode area and inter-electrode 
distance on the spatial distribution of the current density in tDCS. J Neural Eng. 2011;8(6):066017. 
doi:10.1088/1741-2560/8/6/066017.