Remotely Supervised Transcranial Direct Current Stimulation for Persistent Post-traumatic Headache: A Pilot Study
Phase: NA
Conditions: Persistent Post Traumatic Headache, Mild Traumatic Brain Injury
Sponsor: VA Office of Research and Development

 
 
 
 
 
 
 
 
 
Remotely supervised tDCS for persistent post traumatic headache in Veterans 
(ReStore) 
Funding Agency: RX-003194-01A1 
 
Principal Investigator/Study Chair: Dr. X. Michelle Androulakis 
November 12, 2019 
 
 

 
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Abstract 
 
Objectives: To evaluate the feasibility and efficacy of transcranial Direct Current 
Stimulation (tDCS) administered at home with real-time monitoring via VA Telehealth 
remote supervision for persistent post traumatic headache (PTH) associated with mTBI, 
and the impact of this treatment on functional recovery in Operation Enduring 
Freedom/Operation Iraqi Freedom veterans.  
Methods: We will enroll 24 participants age 20-60 years old who meet the diagnostic 
criteria for persistent PTH associated with mild TBI. tDCS will be remotely administrated 
for a total of 20 sessions over a four-week period.  
Primary endpoint: To evaluate the changes in numbers of moderate to severe 
headache days per month from baseline period to the end of treatment phase, and to 
the end of follow-up phase. 
Secondary endpoints:  
1. To evaluate the changes of total number of headache days per month, acute 
pain medication used based on number of doses of medication taken from 
baseline period to end of treatment phase, and to end of follow-up phase in the 
same cohort. 
2. To evaluate the impact of headaches on the quality of life measures (pain and 
disability) based on change in Headache impact test-6 (HIT-6),  Rivermead Post-
Concussion Symptoms (PCS) questionnaire, depression severity as measured 
by PHQ-9, PTSD severity as measured by PCL-5, insomnia as measure by 
Insomnia Severity Index (ISI), and anxiety as measured by Beck Anxiety 
Inventory (BAI) from baseline period to end of treatment phase, and to end of 
follow-up phase in persistent PTH.  
3. To evaluate the changes in modulatory capacity of patients’ cardio-autonomic 
function as a measure of heart rate variability (HRV) from baseline period to end 
of treatment phase.  
 
 
 

 
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List of Abbreviations 
 
 Abbreviations used: 
 
PTH - Post Traumatic Headache  
mTBI – Mild Traumatic Brain Injury  
OEF – Operation Enduring Freedom  
OIF – Operation Iraqi Freedom  
SN – Salience Network  
CEN – Central Executive Network  
ICHD – International classification of headache disorders 
MOH – Medication Overuse Headache  
HIT-6 – Headache Impact Test 6  
PROMIS – Patient-Reported Outcomes Measurement Information System  
PHQ-9 – Patient Health Questionnaire  
BAI – Beck Anxiety Inventory  
dlPFC – Dorsolateral Prefrontal Cortex  
tDCS – Transcranial direct current stimulation  
TMS – Transcranial magnetic stimulation  
CGRP – calcitonin gene related peptide  
CT – Clinical trial 
PCL-5 – PTSD checklist for DSM-5 
PCS – Rivermead Post-Concussion Symptoms 
UI – User Interface 
SMI – Soterix Medical Inc. 
 
 
 
 
 
 
 
 
 
 

 
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Contents 
Protocol Title: ...................................................................................................................... 5 
1.0 
Study Personnel ....................................................................................................... 5 
2.0 
Introduction ............................................................................................................... 6 
3.0 
Objectives ................................................................................................................. 9 
4.0 
Resources and Personnel ...................................................................................... 10 
5.0 
Study Procedures ................................................................................................... 10 
5.1 Study Design ........................................................................................................... 10 
5.2 Recruitment Methods .............................................................................................. 10 
5.3 Informed Consent Procedures ................................................................................ 13 
5.4 Inclusion/Exclusion Criteria..................................................................................... 13 
5.5 Study Evaluations ................................................................................................... 14 
5.6 Data Analysis .......................................................................................................... 17 
5.7 Withdrawal of Subjects ........................................................................................... 17 
6.0 
Reporting ................................................................................................................ 18 
7.0 
Privacy and Confidentiality ..................................................................................... 18 
8.0 
Communication Plan ................................................................................................ 8 
9.0 
References ............................................................................................................. 19 
 

 
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1.0 
Study Personnel (PI) 
 
Principal Investigator/Study Chair:  
X. Michelle Androulakis, MD, MS, FAHS 
Chief of Neurology Division 
R223D, B106 
WJB Dorn VA Medical Center 
6439 Garners Ferry Road,  
Columbia, SC 29209 
803-776-4000,x 4077 

 
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2.0 
Introduction 
Background for Persistent PTH: Prevalence and incidence of mTBI and persistent 
post traumatic headache (PTH) are increasing among Veterans of Operation Enduring 
Freedom (OEF) and Operation Iraqi Freedom (OIF) (McKenzie-Hartman 2017). 
Persistent PTH and associated physical, functional disability as well as decreased 
quality of life significantly impact OEF/OIF veterans. The recent opioid crisis raises 
concerns about medication overuse headaches in this population. Many OEF/OIF 
veterans are in the prime of their lives and are desperately in need of non-
pharmacological treatment for this chronic debilitating neurological disorder, to lead a 
more productive life at work and home. Persistent PTH likely has multidimensionality: 
When headaches become persistent over years after mTBI, biopsychosocial and 
behavioral factors modulate the brain circuits beyond those involved in pain perception, 
resulting in dys-synchronization of intrinsic functional brain networks responsible for 
saliency modulation (salience network), goal directed behavior (executive network) and 
sense of self (default mode network). This process is likely similar to that of chronic 
migraine, as we have elucidated in a recent study (Androulakis et al. 2017, 2018). 
Potential of remote tDCS for persistent PTH: The Veterans Health administration, US 
Department of Health and Human Services and Centers for Disease Control all support 
use of evidence based non-pharmacological treatment for chronic pain. tDCS 
(transcranial direct current stimulation) has gained attention as a noninvasive 
neuromodulatory approach for depression, chronic migraine, cognitive impairment 
involving attention, working memory and executive function, loss of inhibitory control, 
sleep disturbance and aphasia. (Kang, Kim, and Paik 2012; Demirtas-Tatlidede et al. 
2012; Baker, Rorden, and Fridriksson 2010; Angelakis et al. 2014; Andrade et al. 2017). 
A systematic review and meta-analysis from 2016 suggest that tDCS could be a 
promising non-pharmacological alternative treatment for migraine pain. It may be 
particularly useful for individuals seeking to reduce the use of acute pain medications 
(Shirahige et al. 2016; Stagg and Nitsche 2011).  
tDCS mechanism: The exact mechanisms underlying the effectiveness of tDCS in pain 
modulation are yet to be elucidated. Mounting evidence in pre-clinical and clinical 
studies suggests that tDCS can modify the neuronal excitability (Stagg and Nitsche 
2011; Jackson M et al. 2016; Brunoni AR 2012) and is capable of improving connectivity 
of large-scale brain networks via improved synchronization (Peña-Gómez et al. 2012). 

 
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tDCS may modulate mu-opioid and GABA levels, interfere with excitatory and inhibitory 
balance by oscillating with intrinsic neural networks, as well as influence the cortical 
thalamic network in pain control (Jackson et al. 2016; Dasilva et al. 2012; DosSantos et 
al. 2014; DosSantos et al. 2012; Foerster et al. 2015). Clinical trials using remotely 
administered tDCS for Multiple Sclerosis (MS) and Parkinson’s disease validated 
cumulative benefit of remote tDCS administration (Charvet et al. 2018; Dobbs et al. 
2018). However, the effects of tDCS on persistent PTH have yet to be evaluated in 
remotely administered, at-home setting.  
tDCS Stimulation Sites for persistent PTH: Analysis of one of our recent fMRI studies 
revealed that node to node functional connectivity of the bilateral dorsolateral prefrontal 
cortex (dlPFC) within the salience network (SN) and central executive network (CEN), 
important in top down cognitive control of pain (Androulakis et al. 2017, 2018), is 
abnormal in chronic migraine. Migraine and chronic migraine are the common 
phenotypes in persistent PTH. Earlier tDCS studies (outpatient clinic settings) in 
migraine used tDCS to: 1. Increase resting membrane potential in M1 via anodal 
stimulation, with the reference electrode placed over the contralateral supraorbital (SO) 
cortex, 2. Decrease resting membrane potential over Oz via cathodal stimulation with 
the reference electrode placed over Cz, and 3. Increase resting state membrane 
potential in the left dlPFC (dorsolateral prefrontal cortex) via anodal stimulation, with the 
reference electrode placed over SO (Andrade et al. 2017; Shirahige et al. 2016). 
Among these different electrode configurations, left dlPFC was found to be more 
effective than left M1 for pain control. We plan to place Cathodal electrode over Oz 
instead of contralateral OS because we want to avoid the possibility of inhibiting the 
contralateral PFC or interior frontal gyrus near the traditional cathodal site supraorbital 
(SO). Mood irritability and disinhibition are frequent symptoms associated with 
mTBI and persistent PTH. Inadvertently inhibiting brain regions near SO such as 
contralateral PFC or inferior frontal gyrus, which is important in behavior disinhibition, 
depression, and other neuropsychological symptoms prevalent in mTBI, may cause 
unwanted side effects. Given the lower threshold of neuronal excitability in occipital 
cortex of migraine patients (Aurora et al. 1998), we suspect that similar underpinnings 
may exist in persistent PTH. Interestingly, targeting cathodal stimulation site over Oz 
effectively reduced pain intensity in migraine patients (Antal et al. 2011). Furthermore, 
cathodal stimulation over Oz will effectively decrease cortical hyperexcitability in visual 
cortex without interfering the cortical descending inhibitory pathways on the 
contralateral side. In this pilot study, we propose a novel electrode placement 
montage in which the stimulating (anodal) electrode is placed over the left dlPFC 
(F3) and a single reference (cathodal) electrode is placed over the lower occipital 
pole (Oz).  Our computational model demonstrates the current flow for this 
configuration(Figure 1). 
 

 
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Figure 1: A computational model demonstrates the electrical field intensity using the 
tDCS mini Clinical Trial device: Anodal electrode placed over F3 (left dorsolateral 
prefrontal cortex), cathodal electrode placed over Oz.  
Advantage of remote administration monitored by VA Telehealth: Remotely 
administrated tDCS with real-time video monitoring, delivered to veterans at home, 
offers unique advantages in terms of travel arrangement, healthcare utilization, 
increased treatment sessions, recruitment for future clinical trials with larger sample 
size, and preventing high dropout rates associated with tDCS administered in an 
outpatient setting. Furthermore, combining remote tDCS technology with mindfulness 
meditation via VA health system supported Mindfulness Coach program, and other 
cognitive/physical/occupational rehabilitation therapy may provide synergistic effects. 

 
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Multiple tDCS treatments are necessary for optimal and sustained benefit, especially 
when combined with cognitive training to enhance overall outcome (Kasschau et al.; 
Martin et al. 2014; Elmasry et al. 2015; Brunoni et al. 2014). We propose a new 
clinical tDCS paradigm which will enable safe, longer, repetitive tDCS treatment 
combined with mindfulness meditation, while maintaining the treatment fidelity 
through video monitoring. Based on the data generated from this pilot study, we plan 
to submit a larger scale, randomized clinical trial to investigate the efficacy of remotely 
administered tDCS with real-time monitoring for PTH in a phase II study. Ultimately, we 
hope that clinical application of this new delivery method of tDCS will facilitate outreach 
to rural communities, where Veterans have limited access to care related to persistent 
PTH.  
3.0 
Objectives 
We propose to evaluate the feasibility and efficacy of transcranial Direct Current 
Stimulation (tDCS) (manufactured by Soterix Medical) administered at home with real-
time monitoring via VA Telehealth for persistent post traumatic headache (PTH) 
associated with mTBI, and the impact of this treatment on persistent PTH associated 
functional recovery. This pilot study will also evaluate recruitment strategies and 
participants clinical characteristics. We seek preliminary evidence for a merit review 
grant of a larger scale, randomized and sham controlled phase IIb clinical trial to 
evaluate efficacy of remotely administered tDCS for persistent PTH in veterans.  
 
Specific Aim 1: 
To evaluate feasibility and improvement in numbers of moderate to severe headache 
days per month from baseline period to end of treatment phase, and to the end of 
follow-up phase. 
 
Specific Aim2:  
1. To evaluate improvement in total number of headache days per month and acute 
pain medication used based on number of doses of medication taken from 
baseline period to end of treatment phase, and to end of follow-up phase in the 
same cohort. 
2. To evaluate the impact of headaches on the quality of life measures (pain and 
disability) based on change in Headache impact test-6 (HIT-6), Rivermead Post-
Concussion Symptoms (PCS) questionnaire, depression as measured by PHQ-9, 
PTSD severity as measured by PCL-5, insomnia as measure by Insomnia 
Severity Index (ISI), and anxiety as measured by Beck Anxiety Inventory (BAI) 
from baseline period to end of treatment phase, and to end of follow-up phase in 
persistent PTH.  

 
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3. To evaluate the changes in modulatory capacity of patients’ cardio-autonomic 
function as a measure of heart rate variability (HRV) from baseline period to end 
of treatment phase.  
4.0 
Resources and Personnel 
The proposed research will be conducted at Dorn VA medical center, B106, Neurology 
Dept. . The PI will be responsible for overseeing all aspects of this project, including 
recruitment, screening, data collection, data analysis and preparation of manuscripts. 
5.0 
Study Procedures 
5.1 Study Design 
 
Participants will receive a total of 20 sessions with 20 minutes of tDCS stimulation 
administered during each weekday (see flow chart for details). The anode will be placed 
over the left dlPFC (F3) according to international 10-20 EEG system, and the cathode 
will be placed at Oz. Using this montage, computational modelling demonstrates the 
flow of current from left PFC region to the occipital pole, with no current flow over right 
PFC or inferior frontal cortex (Figure 1). Sham stimulation will be delivered using the 
conventional method of ramping the current up to 2.0 mA and the down over the first 
minute of the session and then repeated during the last minute of the session, no 
current are delivered in between. During the 20-minute treatment session, both 
treatment and sham groups will complete mindfulness meditation via VA health system 
approved program (Mindfulness Coach).  
This will be a randomized, double-blind study of 20 tDCS treatment sessions. To ensure 
double-blinding of the study, the PI with designate a separate clinic nurse who is not 
part of the study team and is blind to group membership to be in charge of programming 
the tDCS device according to the device manual. The device will be programmed to 
subject’s correct randomized treatment group. Patients will be randomized equally to 
stimulation group versus sham groups using randomization function with a statistical 
software (R). This person (nurse) will keep a secure randomization log and will not be 
involved in the screening, baseline, treatment sessions or follow-up visits. The blind 
may be broken if it becomes medically necessary to reveal which treatment a patient 
received. The investigator may contact any personnel within the randomizing group to 
request unmasking a subject’s treatment. 
All participants will undergo vital sign and BMI evaluation, a neurological examination 
and complete a medical questionnaire and to ascertain demographics including age, 
sex, race, marital status, educational level, and clinical characteristics to include: the 
headache features, medications, medical/surgical history, family history, HIT-6, 
Rivermead Post-Concussion Symptoms (PCS) questionnaire, depression severity as 

 
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measured by PHQ-9, ISI, PTSD severity as measured by PCL-5, insomnia as measured 
by Insomnia Severity Index (ISI), and anxiety as measured by Beck Anxiety Inventory 
(BAI). Detailed descriptions for each questionnaire above are included in 
appendix. A tolerability test using the tDCS device will be done at first clinic visit for 
each patient to confirm each subject can tolerate current stimulation. Patient that fail the 
tolerability task will be considered a screen-fail and will be discontinued from the study. 
Before the first and after the last tDCS session, participant’s heart rate will be monitored 
via electrocardiogram (EKG or ECG) while completing a physical and cognitive stress 
test. This will enable us to determine changes in heart rate variability at the start of 
treatment to the end of treatment phases. A more detailed description for the EKG 
tasks is included in Study Evaluations. We will use the daily headache diary to 
record changes in headache symptoms throughout the study.  
Due to the differences in how individuals describe pain, we will adopt the following 
definition for headache severity:  
• Mild headache is defined as a nagging, annoying headache with little to no 
interference with daily activity.  
• Moderate headache is defined as headache that is bothersome, interferes 
significantly with daily activity, and usually requires medication.  
• Severe headache is defined as a disabling or intolerable pain that causes 
inability to perform routine daily activity (details are described in our patient 
questionnaires). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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5.2 Recruitment Methods 
We anticipate enrolling at least 4 participants quarterly, with a total enrollment period of 
12-15 months. Veterans will be recruited from the Dorn VA neurology headache clinic or 
interdisciplinary outpatient pain clinic. Dr. Reyes, the Co-I of this project is the director of 
our OIPP pain clinic who sees about 80 PTH patients annually. Additional participants 
may be recruited from TBI clinic or TBI registry if necessary. A Real SSN Access 
Request has been submitted through DART for access to the TBI registry for pre-
screening purposes. Potential subjects will be approached in clinics (neurology and 
rehab) by a member of the health care team or study personnel to assess interest in 
participating in the tDCS study. Recruitment flyers will be utilized in Neurology and 
rehab clinics. In addition, potential subjects identified through electronic medical records 
or clinic lists may be mailed a letter providing an overview of the tDCS study.  An initial 
eligibility screen may be done via phone and will contain general information such as 
social demographics (i.e. age, sex, race), medical history and headache characteristics 
(appendix for PTH questionnaire). If the phone interview determines that the subject is 
potentially eligible, an appointment will be made for an in-person screening visit. Every 
effort will be made to include minority and women in this study. 
 
Potential Benefits of the Proposed Research to Human Subjects & Others 
Study participants may or may not benefit from their participation.  All participants will 
receive tDCS (treatment vs sham) and mindfulness meditation. Self-efficacy may be 
greatly improved by providing encouragement to participants to take an active, 
autonomous role in their health.  There is also monetary compensation for completing 
the tDCS sessions. There are potential benefits to other chronic post traumatic 
headache sufferers and to the scientific community, as we will develop a better 
understanding of the benefit and risk associated with at home tDCS administration. 
Given the paucity of risks, and the precautions and procedures to minimize those that 
do exist (as described in the previous section), this study is reasonable in relation to its 
anticipated benefits. 
 
Importance of the knowledge to be gained 
Results of the proposed research will make a significant contribution to the scientific 
knowledge regarding the feasibility and safety of remotely administrated tDCS for 
persistent PTH. The proposed clinical studies may lead towards identification of novel 
tDCS stimulation targets, utilization of telehealth for PTH, which help improve the 
management of persistent PTH. 
 
Protection Against Risks  

 
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Notification of Screening Results: Participants will be notified that they have passed 
or failed the screening directly in person. This notification will occur as soon as 
information regarding eligibility becomes available. For example, if a screening failure 
occurs during an interview, the participant will be told that they do not meet study 
criteria and will be sent home without completing additional screening procedures. In 
the case of a screening failure, all documents containing a participant’s personal health 
information will be destroyed. 
 
Confidentiality: Every effort will be made to keep the information in the study 
confidential, as described in “Sources of Materials”. In the case of screen failures, all 
documents containing the participant’s health information will be destroyed. All data files 
and analyses will be performed on VA research computers using only code numbers to 
identify participants. Only summaries of group data will be reported in any publications 
or presentations, with no identification of individuals. Adverse Events: All adverse 
events will be reported to the IRB immediately by PI, Co-I or research assistant. 
 
5.3 Informed Consent Procedures 
 
Recruitment: All participants will be recruited from Dorn VA medical center neurology 
clinic. Additional participants may be recruited from TBI clinic and TBI registry if 
necessary. A HIPAA waiver will be applied for to permit use of the phone screen. If the 
phone pre-screening interview determines that the subject is potentially eligible, an 
appointment will be made for an in-person screening visit. Every effort will be made to 
include minority and women in this study. 
 
Informed Consent: Written informed consent will be obtained by PI, Co-I, or research 
assistant/coordinators. The person obtaining informed consent will review the consent 
form in detail with the participants. The subjects will be encouraged to ask any 
questions they may have regarding the study and consent procedures. Once the 
subjects demonstrated an acceptable level of comprehension, consent will be obtained. 
 
 
5.4 Inclusion/Exclusion Criteria 
 
Inclusion criteria:  
1. Verified history of mTBI using VA TBI identification clinical interview screening 
criteria (Vanderploeg et al. 2012),  

 
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2. Persistent PTH as defined by ICHD III diagnostic criteria (Headache 
Classification Committee of the International Headache Society (IHS) The 
International Classification of Headache Disorders, 3rd Edition 2018).  
3. Verification of headache frequency through prospectively collected baseline 
information during the 28-day screening/baseline phase. 
4. Not currently taking a migraine or headache preventive medication OR has been 
taking a stable dose of a preventive for at least 60 days prior to screening and 
agrees to not start, stop, or change medication and/or dosage during the study 
period.  
5. We will include medication overuse headache as defined by ICHD III diagnostic 
criteria.  
6. Participant is either not of childbearing potential, or if they are of childbearing 
potential, they agree either to remain abstinent or use (or have their partner use) 
an acceptable method of birth control for the duration of the study.  
7. Male or female, age between 20-60 who demonstrates compliance with the Daily 
Headache Diary during the 28-day baseline phase as defined by entry of 
headache data on a minimum of 22 to 28 days (80% diary compliance).  
Exclusion criteria:  
1. Unable to complete headache diary as required by protocol. 
2. Any psychiatric condition with psychotic features, and/or any other psychiatric 
disorder not stable or well controlled, that would interfere in the ability to 
complete study activities  
3. Received onabotulinumtoxinA, cognitive behavior therapy, physical therapy or 
any other form of non-pharmacological therapy for headaches during the 3 
months before baseline and 4 months before the first treatment.  
4. Has a planned military deployment within the 6 months post screening.  
5. Active substance abuse within last 4 months.  
6. History of seizure, stroke, multiple sclerosis or other unstable neurological 
condition or a significant abnormal neurological examination.  
7. Unable to tolerate 2mA tDCS stimulation.  
8. Have any other conditions that in the judgment of the Investigator would make 
the participants unsuitable for inclusion or interfere with participating or 
completing the study. 
9. Does not have a valid email address and/or access to internet 
 
5.5 Study Evaluations 
 
tDCS Protocol: The first tDCS session combined with mindfulness meditation will be 
completed in the clinic after training on how to operate the device and a brief (60 

 
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second) tolerability test in clinic (some participants with sensitive scalps may be too 
uncomfortable to participate). Before the first tDCS session in the clinic we will utilize a 
standard 3-lead electrocardiogram (EKG) to measure participant’s heart rate 
sequentially during a motor and cognitive task and at rest in order to assess heart rate 
variability (HRV) following tDCS treatment. This assessment, including set-up and 
transition between tasks, is expected to last approximately 30-35 minutes. The order of 
EKG measures will be as follows: 6-minute resting baseline, 6-minute physical stressor, 
6-minute resting recovery, 6-minute cognitive stressor, and 6-minute resting recovery. 
During the resting assessments, participants will be seated comfortably at a 45-dregree 
angle while their heart rate is monitored. For the physical stress assessment, 
participants will squeeze a hand dynamometer (Baseline Pneumatic Squeeze Bulb 
Dynamometer, Baseline Products, Ventura CA) at approximately 30% of their maximum 
hand-grip contraction while seated in the same manner. During the cognitive stress 
assessment, participants will complete an executive function task (2-back task) while 
seated in the same manner. The 2-back task is a visual n-back test similar to the classic 
memory game. 2 back, n=2, has the person remember the item from two turns back. 
This task will be administered to the patient electronically via pc. Once the first in-clinic 
session is complete, participants will be discharged with a tDCS study kit (tDCS device, 
headset, sponges, saline solution, extra batteries). Participants will be given instructions 
on completing treatment sessions at home using the secure VA Telehealth platform and 
the VA mindfulness coach application. If participants don’t have access to a tablet or 
computer at home they will be provided with a VA approved tablet with wireless 
connection during their participation in the study. Subsequent visits will be completed 
via the VA Telehealth platform with real-time supervision by a study coordinator or 
investigator. Participants will be supervised throughout the entire treatment session to 
ensure strict adherence to the device safety measures and study stop criteria (Charvet 
et al. 2017).  Side effects and tolerability will be monitored at each visit by evaluating 
any adverse events such as pain, paresthesia, any other discomfort or any unexpected 
events. Headache severity ratings of mild, moderate or severe will be recorded before, 
during and after each tDCS session. Participants will return to the clinic to complete the 
last treatment session. During this last session, participant’s heart rate will be monitored 
via EKG following the same procedures and tasks as stated above for the first in-clinic 
tDCS session. The table below summarizes the procedures that will be done 
during each session throughout the study. 
 
 
 
 
 
 
 

 
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Procedures 
Baseline 
Visit 
Treatment Phase 
Post Treatment Follow-Up 
Phase 
Visit 
2/First 
tDCS 
Session 
Remote 
tDCS 
Sessions 
2-19 
Last 
tDCS 
Session 
20 
Daily Phone Calls (12 weeks) 
Study Day 
0 
28 days 
 
56 (+/-3) 
57–140 (+/-3) 
Informed Consent 
X 
 
 
 
 
Neurological Exam 
X 
X 
 
X 
 
Physical Exam 
X 
X 
 
X 
 
Vital Signs 
X 
X 
 
X 
 
EKG 
 
X 
 
X 
 
Verify 
Inclusion/Exclusion 
X 
X 
 
X 
 
Medical History 
X 
X 
 
X 
 
Diary Instruction 
X 
 
 
 
 
Review Diary 
 
X 
X 
X 
X 
Give/collect 
Telehealth tablet 
X 
 
 
 
*Participant will mail back 
tablet after last follow up 
Train/Administer 
tDCS 
 
X 
X 
X 
 
Collect Adverse 
Events 
 
X 
X 
X 
X 
Demographics and 
Headache Surveys 
X 
 
 
 
 
HIT-6 
 
X 
 
X 
X (only weeks 4, 8, and 12) 
PHQ-9 and BAI 
 
X 
 
X 
X (only weeks 4, 8, and 12) 
PLC-5 and PCS 
 
X 
 
X 
X (only weeks 4, 8, and 12) 
Insomnia survey 
 
X 
 
X 
X (only weeks 4, 8, and 12) 
Rivermead post-
concussion 
symptoms (PCS) 
 
X 
 
X 
X (only weeks 4, 8, and 12) 
 
 
Mindfulness Coach: Both the stimulation group and sham group will receive 
mindfulness meditation using mindfulness Coach app during each tDCS session. 
Mindfulness Coach is designed for Veterans and Service Members and can be used 
alone or in combination with a trained health professional (App Version: 2.0). 
 
Remote tDCS device and Safety: The Soterix Medical mini Clinical Trial (CT) device 
will to be used by patients at home in conjunction with constant real-time monitoring by 
clinical staff via VA Telehealth using well defined stop criteria (Charvet et al. 2018). 
Treatment parameters are pre-programed by accessing the ‘administrator mode’ to 
deliver 20 mins of 2mA stimulation during each session through sponge electrodes 

 
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(5cmx5cm). The administrator enters an access code and selects the tDCS dose: 
number of treatment sessions, intensity, and duration (10 participants will receive active 
stimulation applied to left dlPFC, 10 will receive sham treatment applied to left dlPFC, 
both groups will receive the same mindfulness meditation during the tDCS session). 
The administrator is then presented with a unique one-time activation code generated 
for each stimulation session. These codes will be stored at a secure location in our VA 
medical center. These parameters cannot be altered without the access code of the 
administrator, any attempts to deliver un-authorized sessions (such as prolonged 
treatment session, atypical electrode impedance or any other administration of 
tDCS not specified by the study team) will results in device shutdown. Electrodes 
impedance will be measured in real-time and displayed on the device screen and 
viewed by administrator during each session. Mini-CT tDCS can be remotely 
discontinued through its portal (ElectraRX program) if non-compliance is found during 
the treatment sessions. Patients will be given a package consisting customized 
headgear with electrodes (Anode on F3 and cathode on Oz), stimulation unit, sponges, 
and batteries. The unique electrodes (SNAP pad) allow loading onto headgear (SNAP 
strap) at fixed locations preventing incorrect electrode placement and a picture 
will be taken at each session to confirm the stimulation sites. The SNAP electrodes 
are pre-saturated with saline and carbon electrodes are pre-inserted to prevent 
potential electrode preparation errors (saline saturation level, direct contact of rubber 
electrode leading to skin burn, etc.). The mini-CT device has extensive regulatory 
approvals worldwide (EU-CE, Canada- Health Canada, Australia, etc.) and is 
approved for investigational use in the USA.  
 
5.6 Data Analysis 
Sample size and statistical analysis: A total of 24 veterans will be included in this 
pilot study. Descriptive statistics will establish baseline demographics, clinical 
characteristics, study completion rate (session discontinuation rate, and adverse event 
frequency. Comparison between treatment and sham control groups will be performed 
using two-tailed independent sample t-tests, and liner regression. Comparison of 
pretreatment and post-treatment scores in both groups will be calculated using paired-
samples two-tailed t-tests. Statistical analysis will be performed using IBM SPSS 
Statistic 23. Reduction and extraction of HRV indexes from EKG assessments will be 
performed with Kubios HRV, version 2.0 (Biosignal Analysis and Medical Imaging 
Group, Kuopio, Finland). 
 
5.7 Withdrawal of Subjects 
As part of the consent process, subjects are advised that their participation to this study 
is voluntary and that they are free to withdraw their consent and discontinue 
participation in the study at any time throughout the study, without negative 
consequences to their relationship with their care at VAMC. 

 
Protocol – Version 11/12/2019 
Page 18 of 21 
 
 
6.0 
Reporting 
Any unanticipated problems, serious adverse events, and protocol deviations will 
be reported to IRB within 24 hours of working day.  
 
7.0 
Privacy and Confidentiality 
Every effort will be made to keep the information in the study confidential, as described 
in “Sources of Materials”. In the case of screen failures, all documents containing the 
participant’s health information will be destroyed. All data files and analyses will be 
performed on VA research computers with password protection using only code 
numbers to identify participants. Only summaries of deidentified group data will be 
reported in any publications or presentations following VA data management and 
access policy.  
Adverse Events: All adverse events will be reported to the IRB immediately by PI, Co-I 
or research assistant. 

 
Protocol – Version 11/12/2019 
Page 19 of 21 
 
 
8.0 
References 
1. Andrade, Suellen Marinho, Renata Emanuela Lyra de Brito Aranha, Eliane 
Araújo de Oliveira, Camila Teresa Ponce Leon de Mendonça, Wanessa Kallyne 
Nascimento Martins, Nelson Torro Alves, and Bernardino Fernández-Calvo. 
2017. “Transcranial Direct Current Stimulation over the Primary Motor vs 
Prefrontal Cortex in Refractory Chronic Migraine: A Pilot Randomized Controlled 
Trial.” Journal of the Neurological Sciences 378 (July): 225–32. 
2. Androulakis, X. Michelle, Kaitlin Krebs, B. Lee Peterlin, Tianming Zhang, Nasim 
Maleki, Souvik Sen, Chris Rorden, and Priyantha Herath. 2017. “Modulation of 
Intrinsic Resting-State fMRI Networks in Women with Chronic Migraine.” 
Neurology 89 (2): 163–69. 
3. Androulakis, X. Michelle, Chris Rorden, B. Lee Peterlin, and Kaitlin Krebs. 2017. 
“Modulation of Salience Network Intranetwork Resting State Functional 
Connectivity in Women with Chronic Migraine.” Cephalalgia: An International 
Journal of Headache, January, 333102417748570. 
4. Androulakis, X. Michelle, Kaitlin A. Krebs, Charmaine Jenkins, Nasim Maleki, 
Alan G. Finkel, Chris Rorden, and Roger Newman. 2018. “Central Executive and 
Default Mode Network Intranet Work Functional Connectivity Patterns in Chronic 
Migraine.” Journal of Neurological Disorders 6 (5). https://doi.org/10.4172/2329-
6895.1000393. 
5. Angelakis, Efthymios, Evangelia Liouta, Nikos Andreadis, Stephanos Korfias, 
Periklis Ktonas, George Stranjalis, and Damianos E. Sakas. 2014. “Transcranial 
Direct Current Stimulation Effects in Disorders of Consciousness.” Archives of 
Physical Medicine and Rehabilitation 95 (2): 283–89. 
6. Antal, Andrea, Naomi Kriener, Nicolas Lang, Klara Boros, and Walter Paulus. 
2011. “Cathodal Transcranial Direct Current Stimulation of the Visual Cortex in 
the Prophylactic Treatment of Migraine.” Cephalalgia: An International Journal of 
Headache 31 (7): 820–28. 
7. Aurora, S. K., B. K. Ahmad, K. M. Welch, P. Bhardhwaj, and N. M. Ramadan. 
1998. “Transcranial Magnetic Stimulation Confirms Hyperexcitability of Occipital 
Cortex in Migraine.” Neurology 50 (4): 1111–14. 
8. Baker, Julie M., Chris Rorden, and Julius Fridriksson. 2010. “Using Transcranial 
Direct-Current Stimulation to Treat Stroke Patients with Aphasia.” Stroke; a 
Journal of Cerebral Circulation 41 (6): 1229–36. 
9. Brunoni, Andre Russowsky, Michael A. Nitsche, Nadia Bolognini, Marom Bikson, 
Tim Wagner, Lotfi Merabet, Dylan J. Edwards, et al. 2012. “Clinical Research 
with Transcranial Direct Current Stimulation (tDCS): Challenges and Future 
Directions.” Brain Stimulation 5 (3): 175–95. 
10. Brunoni, A. R., P. S. Boggio, R. De Raedt, I. M. Benseñor, P. A. Lotufo, V. 
Namur, L. C. L. Valiengo, and M. A. Vanderhasselt. 2014. “Cognitive Control 
Therapy and Transcranial Direct Current Stimulation for Depression: A 
Randomized, Double-Blinded, Controlled Trial.” Journal of Affective Disorders 
162 (June): 43–49. 

 
Protocol – Version 11/12/2019 
Page 20 of 21 
 
11. Charvet, Leigh E., Bryan Dobbs, Michael T. Shaw, Marom Bikson, Abhishek 
Datta, and Lauren B. Krupp. 2018. “Remotely Supervised Transcranial Direct 
Current Stimulation for the Treatment of Fatigue in Multiple Sclerosis: Results 
from a Randomized, Sham-Controlled Trial.” Multiple Sclerosis  24 (13): 1760–69. 
12. Dasilva, Alexandre F., Mariana E. Mendonca, Soroush Zaghi, Mariana Lopes, 
Marcos Fabio Dossantos, Egilius L. Spierings, Zahid Bajwa, Abhishek Datta, 
Marom Bikson, and Felipe Fregni. 2012. “tDCS-Induced Analgesia and Electrical 
Fields in Pain-Related Neural Networks in Chronic Migraine.” Headache 52 (8): 
1283–95. 
13. Demirtas-Tatlidede, Asli, Andrew M. Vahabzadeh-Hagh, Montserrat Bernabeu, 
Jose M. Tormos, and Alvaro Pascual-Leone. 2012. “Noninvasive Brain 
Stimulation in Traumatic Brain Injury.” The Journal of Head Trauma 
Rehabilitation 27 (4): 274–92. 
14. Dobbs, Bryan, Natalie Pawlak, Milton Biagioni, Shashank Agarwal, Michael Shaw, 
Giuseppina Pilloni, Marom Bikson, Abhishek Datta, and Leigh Charvet. 2018. 
“Generalizing Remotely Supervised Transcranial Direct Current Stimulation 
(tDCS): 
Feasibility 
and 
Benefit 
in 
Parkinson’s 
Disease. 
Journal 
of 
Neuroengineering and Rehabilitation 15 (1): 114. 
15. DosSantos, Marcos Fabio, Tiffany M. Love, Ilkka Kristian Martikainen, Thiago 
Dias Nascimento, Felipe Fregni, Chelsea Cummiford, Misty Dawn Deboer, Jon-
Kar Zubieta, and Alexandre F. M. Dasilva. 2012. “Immediate Effects of tDCS on 
the μ-Opioid System of a Chronic Pain Patient.” Frontiers in Psychiatry / Frontiers 
Research Foundation 3 (November): 93. 
16. DosSantos, Marcos F., Ilkka K. Martikainen, Thiago D. Nascimento, Tiffany M. 
Love, Misty D. DeBoer, Heidi M. Schambra, Marom Bikson, Jon-Kar Zubieta, and 
Alexandre F. DaSilva. 2014. “Building up Analgesia in Humans via the 
Endogenous μ-Opioid System by Combining Placebo and Active tDCS: A 
Preliminary Report.” PloS One 9 (7): e102350. 
17. Elmasry, Jessica, Colleen Loo, and Donel Martin. 2015. “A Systematic Review of 
Transcranial 
Electrical 
Stimulation 
Combined 
with 
Cognitive 
Training.” 
Restorative Neurology and Neuroscience 33 (3): 263–78. 
18. Foerster, Bradley R., Thiago D. Nascimento, Misty DeBoer, Marycatherine A. 
Bender, Indie C. Rice, Dennis Q. Truong, Marom Bikson, et al. 2015. “Excitatory 
and Inhibitory Brain Metabolites as Targets of Motor Cortex Transcranial Direct 
Current Stimulation Therapy and Predictors of Its Efficacy in Fibromyalgia.” 
Arthritis & Rheumatology (Hoboken, N.J.) 67 (2): 576–81. 
19. “Headache Classification Committee of the International Headache Society (IHS) 
The International Classification of Headache Disorders, 3rd Edition.” 2018. 
Cephalalgia: An International Journal of Headache 38 (1): 1–211. 
20. Jackson, Mark P., Asif Rahman, Belen Lafon, Gregory Kronberg, Doris Ling, 
Lucas C. Parra, and Marom Bikson. 2016. “Animal Models of Transcranial Direct 
Current Stimulation: Methods and Mechanisms.” Clinical Neurophysiology: 
Official Journal of the International Federation of Clinical Neurophysiology 127 
(11): 3425–54. 
21. Kang, Eun-Kyoung, Dae-Yul Kim, and Nam-Jong Paik. 2012. “Transcranial Direct 
Current Stimulation of the Left Prefrontal Cortex Improves Attention in Patients 
with Traumatic Brain Injury: A Pilot Study.” Journal of Rehabilitation Medicine: 

 
Protocol – Version 11/12/2019 
Page 21 of 21 
 
Official Journal of the UEMS European Board of Physical and Rehabilitation 
Medicine 44 (4): 346–50. 
22. Kasschau, M., K. Sherman, L. Haider, A. Frontario, M. Shaw, A. Datta, M. 
Bikson, and L. Charvet. n.d. “A Protocol for the Use of Remotely-Supervised 
Transcranial Direct Current Stimulation (tDCS) in Multiple Sclerosis (MS) J Vis 
Exp. 2015 Dec 26;(106): e53542. Doi: 10.3791/53542.” 
23. Martin, Donel M., Rose Liu, Angelo Alonzo, Melissa Green, and Colleen K. Loo. 
2014. “Use of Transcranial Direct Current Stimulation (tDCS) to Enhance 
Cognitive Training: Effect of Timing of Stimulation.” Experimental Brain 
Research. Experimentelle Hirnforschung. Experimentation Cerebrale 232 (10): 
3345–51. 
24. McKenzie-Hartman, Tamara. 2017. “Defense and Veterans Brain Injury Center.” 
In Encyclopedia of Clinical Neuropsychology, edited by Jeffrey Kreutzer, John 
DeLuca, and Bruce Caplan, 1–5. Cham: Springer International Publishing. 
25. Peña-Gómez, Cleofé, Roser Sala-Lonch, Carme Junqué, Immaculada C. 
Clemente, Dídac Vidal, Núria Bargalló, Carles Falcón, Josep Valls-Solé, Álvaro 
Pascual-Leone, and David Bartrés-Faz. 2012. “Modulation of Large-Scale Brain 
Networks by Transcranial Direct Current Stimulation Evidenced by Resting-State 
Functional MRI.” Brain Stimulation 5 (3): 252–63. 
26. Shirahige, Lívia, Lorena Melo, Fernanda Nogueira, Sérgio Rocha, and Kátia 
Monte-Silva. 2016. “Efficacy of Noninvasive Brain Stimulation on Pain Control in 
Migraine Patients: A Systematic Review and Meta-Analysis.” Headache: The 
Journal of Head and Face Pain 56 (10): 1565–96. 
27. Stagg, Charlotte J., and Michael A. Nitsche. 2011. “Physiological Basis of 
Transcranial Direct Current Stimulation.” The Neuroscientist: A Review Journal 
Bringing Neurobiology, Neurology and Psychiatry 17 (1): 37–53. 
 
 
 

Amendment made to the original protocol 
1. Due to COVID pandemic in 2020, all clinical trial activities in our facility was 
shut down for 6 months, subsequently our study was allowed to resume after 
changing the study protocol to minimize in-person clinic visit. As such, one of 
the secondary outcomes as removed from our Aims : evaluate the changes in 
modulatory capacity of patients’ cardio-autonomic function as a measure of 
heart rate variability (HRV) from baseline period to end of treatment phase.  
2. Additionally, we also changed last tDCS in-clinic visit to telehealth visit. 
Participants were provided prepaid labels to send the device / tablets back to 
research office after completion of all RS-tDCS sessions.  
3. Lastly, we have changed post-tDCS follow up period to 4 weeks. In the original 
protocol, participants were followed up at 4 weeks, 8 weeks, and 12 weeks after 
tDCS/sham treatment. Due to significant burden of post traumatic headache on 
veterans with TBI, we have observed that many participants had difficulty to 
continue follow up after 4 weeks due to headache burden and desire to start 
new medication or non-pharmacological intervention for headache. Several 
participants even inquired about continuation of tDCS treatment. As such, we 
think withholding additional treatment 4 weeks after tDCS may negatively 
impact veterans' quality of life. 
 

 
 
 
Patient Health Questionnaire (PHQ-9) 
During the last 2 weeks, how often have you been bothered by any of the following problems? 
 
Not At All 
Several Days 
More Than 
Half The Days 
Nearly Every 
Day 
Little interest or pleasure in doing things 
0 
1 
2 
3 
Feeling down, depressed, or hopeless 
0 
1 
2 
3 
Trouble falling or staying asleep, or sleeping 
too much 
0 
1 
2 
3 
Feeling tired or having little energy 
0 
1 
2 
3 
Poor appetite or overeating 
0 
1 
2 
3 
Feeling bad about yourself - or that you are a 
failure or have let yourself or your family down 
0 
1 
2 
3 
Trouble concentrating on things, such as 
reading the newspaper or watching television 
0 
1 
2 
3 
Moving or speaking so slowly that other people 
could have noticed? Or the opposite - being so 
fidgety or restless that you have been moving 
around a lot more than usual 
0 
1 
2 
3 
Thoughts that you would be better off dead or 
of hurting yourself 
0 
1 
2 
3 
 
 
For study coordinator:  
0 
+  
+  
+ 
= Total score: 
 
If you checked off any problems, how difficult have these problems made it for you to do you work, take 
care of things at home, or get along with other people? 
 
Not difficult at all 
Somewhat difficult 
Very difficult 
Extremely difficult 
☐ 
☐ 
☐ 
☐ 

 
 
 
 
 
 
HIT-6 Questionnaire 
This questionnaire asks about the effects your headaches are having on your life. 
Please circle only one answer per question. The coordinator will score the questionnaire. 
 
1. When you have headaches, how often is the pain severe? 
Never 
Rarely 
Sometimes 
Very Often 
Always 
2. How often do headaches limit your ability to do usual activities including housework, work, 
school or social activities? 
Never 
Rarely 
Sometimes 
Very Often 
Always 
3. When you have a headache, how often do you wish you could lie down? 
Never 
Rarely 
Sometimes 
Very Often 
Always 
4. In the past 4 weeks, how often have you felt too tired to do work or daily activities because 
of your headaches? 
Never 
Rarely 
Sometimes 
Very Often 
Always 
5. In the past 4 weeks, how often have you felt fed up or irritated because of yourheadaches? 
Never 
Rarely 
Sometimes 
Very Often 
Always 
6.  In the past 4 weeks, how often did headaches limit your ability to concentrate on work or 
daily activities? 
Never 
Rarely 
Sometimes 
Very Often 
Always 
 
 
 
 
Column 1 
6 points ea. 
 
Column 2 
8 points ea. 
 
Column 3 
10 points ea. 
 
Column 4 
11 points ea. 
 
Column 5 
13 points ea. 
TOTALSCORE 
Scoring 48 or less = little or no impact 
50-54 
= some impact 
56-58 
= substantial impact 
60+ 
= very severe impact 

 
 
 
Beck Anxiety Inventory (BAI) 
Below is a list of common symptoms of anxiety. Please carefully read each item on the list. During the last 
month (including today), how much have you been bothered by any of the following problems? Please circle the 
corresponding number. 
 
Not At All 
Mildly, but it didn’t bother 
me much 
Moderately – it wasn’t 
pleasant at times 
Severely - it bothered 
me a lot 
Numbness or tingling 
0 
1 
2 
3 
Feeling hot 
0 
1 
2 
3 
Wobbliness in legs 
0 
1 
2 
3 
Unable to relax 
0 
1 
2 
3 
Fear of worst happening 
0 
1 
2 
3 
Dizzy or lightheaded 
0 
1 
2 
3 
Heart pounding / racing 
0 
1 
2 
3 
Unsteady 
0 
1 
2 
3 
Terrified or afraid 
0 
1 
2 
3 
Nervous 
0 
1 
2 
3 
Feeling of choking 
0 
1 
2 
3 
Hands trembling 
0 
1 
2 
3 
Shaky / unsteady 
0 
1 
2 
3 
Fear of losing control 
0 
1 
2 
3 
Difficulty in breathing 
0 
1 
2 
3 
Fear of dying 
0 
1 
2 
3 
Scared 
0 
1 
2 
3 
Indigestion 
0 
1 
2 
3 
Faint / lightheaded 
0 
1 
2 
3 
Face flushed 
0 
1 
2 
3 
Hot / cold sweats 
0 
1 
2 
3 
 
For study coordinator:  
0 
+  
+  
+  
= Total score: 

 
 
 
PLC-5 
Below is a list of problems that people sometimes have in response to a very stressful experience. Please read each problem 
carefully and then circle one of the numbers to the right to indicate how much you have been bothered by that problem in the past 
month. 
In the past month, how much were you bothered by: 
Not at 
all 
A little 
bit 
Moderately 
Quite 
a bit 
Extremely 
1. Repeated, disturbing, and unwanted memories of the 
stressful experience? 
0 
1 
2 
3 
4 
2. Repeated, disturbing dreams of the stressful experience? 
0 
1 
2 
3 
4 
3. Suddenly feeling or acting as if the stressful experience were 
actually happening again (as if you were actually back there 
reliving it)? 
0 
1 
2 
3 
4 
4. Feeling very upset when something reminded you of the 
stressful experience? 
0 
1 
2 
3 
4 
5. Having strong physical reactions when something 
reminded you of the stressful experience (for example, 
heart pounding, trouble breathing, sweating)? 
0 
1 
2 
3 
4 
6. Avoiding memories, thoughts, or feelings related to the 
stressful experience? 
0 
1 
2 
3 
4 
7. Avoiding external reminders of the stressful experience(for 
example, people, places, conversations, activities, objects, or 
situations)? 
0 
1 
2 
3 
4 
8. Trouble remembering important parts of the stressful 
experience? 
0 
1 
2 
3 
4 
9. Having strong negative beliefs about yourself, other 
people, or the world (for example, having thoughts such 
as: I am bad, there is something seriously wrong with 
me, no one can be trusted, the world is completely 
dangerous)? 
0 
1 
2 
3 
4 
10. Blaming yourself or someone else for the stressful 
experience or what happened after it? 
0 
1 
2 
3 
4 
11. Having strong negative feelings such as fear, horror, anger, 
guilt, or shame? 
0 
1 
2 
3 
4 
12. Loss of interest in activities that you used to enjoy? 
0 
1 
2 
3 
4 
13. Feeling distant or cut off from other people? 
0 
1 
2 
3 
4 
14. Trouble experiencing positive feelings (for example, being 
unable to feel happiness or have loving feelings for people 
close to you)? 
0 
1 
2 
3 
4 
15. Irritable behavior, angry outbursts, or acting aggressively? 
0 
1 
2 
3 
4 
16. Taking too many risks or doing things that could cause 
you harm? 
0 
1 
2 
3 
4 
17. Being “super alert” or watchful or on guard? 
0 
1 
2 
3 
4 
18. Feeling jumpy or easily startled? 
0 
1 
2 
3 
4 
19. Having difficulty concentrating? 
0 
1 
2 
3 
4 
20. Trouble falling or staying asleep? 
0 
1 
2 
3 
4 
 
For study coordinator:  
0 
+  
+  
+  
+  
= Total score: 

 
 
 
Insomnia Severity Index 
 
The Insomnia Severity Index has seven questions. The seven answers are added up to get a total score. When you 
have your total score, look at the 'Guidelines for Scoring/Interpretation' below to see where your sleep difficulty fits. 
 
For each question, please CIRCLE the number that best describes your answer. 
Please rate the CURRENT (i.e. LAST 2 WEEKS) SEVERITY of your insomnia problem(s). 
 
Insomnia Problem 
None 
Mild 
Moderate 
Severe 
Very Severe 
1. Difficulty falling asleep 
0 
1 
2 
3 
4 
2. Difficulty staying asleep 
0 
1 
2 
3 
4 
3. Problems waking up too early 
0 
1 
2 
3 
4 
 
4. How SATISFIED/DISSATISFIED are you with your CURRENT sleep pattern? 
Very Satisfied 
Satisfied 
Moderately Satisfied 
Dissatisfied 
Very Dissatisfied 
0 
1 
2 
3 
4 
 
5. How NOTICEABLE to others do you think your sleep problem is in terms of impairing the quality of your life? 
Not at all 
Noticeable 
A Little 
Somewhat 
Much 
Very Much Noticeable 
0 
1 
2 
3 
4 
 
6. How WORRIED/DISTRESSED are you about your current sleep problem? 
Not at all 
Worried 
A Little 
Somewhat 
Much 
Very Much Worried 
0 
1 
2 
3 
4 
 
7. To what extent do you consider your sleep problem to INTERFERE with your daily functioning (e.g. daytime 
fatigue, mood, ability to function at work/daily chores, concentration, memory, mood, etc.) CURRENTLY? 
Not at all 
Interfering 
A Little 
Somewhat 
Much 
Very Much Interfering 
0 
1 
2 
3 
4 
 
 
For study coordinator: 
 
Guidelines for Scoring/Interpretation 
 
Add the scores for all seven items (questions 1 + 2 + 3 + 4 + 5 +6 + 7) =  
your total score 
 
Total score categories: 
0–7 = No clinically significant insomnia 
8–14 = Subthreshold insomnia 
15–21 = Clinical insomnia (moderate severity) 
22–28 = Clinical insomnia (severe) 
 
 
 
 
 
Used via courtesy of www.myhealth.va.gov with permission from Charles M. Morin, Ph.D., Université Lava 

 
The Rivermead Post-Concussion Symptoms Questionnaire* 
 
After a head injury or accident some people experience symptoms which can cause worry or nuisance. 
We would like to know if you now suffer from any of the symptoms given below.  As many of these 
symptoms occur normally, we would like you to compare yourself now with before the accident. For 
each one, please circle the number closest to your answer. 
 
0    =   Not experienced at all 
1    =   No more of a problem 
2 = A mild problem 
3 = A moderate problem 
4 = A severe problem 
 
 
Compared with before the accident, do you now (i.e., over the last 24 hours) suffer from: 
 
Headaches.................................................. 0 
1 
2 
3 
4 
Feelings of Dizziness ................................. 0 
1 
2 
3 
4 
Nausea and/or Vomiting ........................... 
0 
1 
2 
3 
4 
Noise Sensitivity, 
easily upset by loud noise ................ 0 
1 
2 
3 
4 
Sleep Disturbance...................................... 0 
1 
2 
3 
4 
Fatigue, tiring more easily ......................... 0 
1 
2 
3 
4 
Being Irritable, easily angered .................. 
0 
1 
2 
3 
4 
Feeling Depressed or Tearful .................... 0 
1 
2 
3 
4 
Feeling Frustrated or Impatient ................ 
0 
1 
2 
3 
4 
Forgetfulness, poor memory ..................... 0 
1 
2 
3 
4 
Poor Concentration .................................... 0 
1 
2 
3 
4 
Taking Longer to Think .............................. 0 
1 
2 
3 
4 
Blurred Vision ............................................. 0 
1 
2 
3 
4 
Light Sensitivity, 
Easily upset by bright light................ 0 
1 
2 
3 
4 
Double Vision ............................................. 0 
1 
2 
3 
4 
Restlessness .............................................. 0 
1 
2 
3 
4 
Are you experiencing any other difficulties?  
1.  
 
0 
1 
2 
3 
4 
2.  
 
0 
1 
2 
3 
4 
 
 
*King, N., Crawford, S., Wenden, F., Moss, N., and Wade, D. (1995) J. Neurology 242: 587-592