Modulating Impulsivity in Suicidal Adolescents With tDCS: A Proof of Concept Study
Phase: NA
Conditions: Impulsive Behavior
Sponsor: Lifespan

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 Title: Modulating Impulsivity in Suicidal Adolescents With Transcranial Direct Current Stimulation 
(tDCS)  
NCT03365102  
Latest approval date: 8/16/19  
 

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HUMAN RESEARCH PROTOCOL 
Suicide is one of the leading causes of death in adolescence. To advance prevention and 
treatment efforts, there is a need for research in this area to move beyond identifying correlates 
or markers of suicidal risk to determining causal risk factors. The adoption of new experimental 
paradigms providing experimental control over candidate causal risk factors has been 
recommended as a means of meaningfully advancing the field. Impulsivity is a risk factor 
particularly relevant to adolescent suicidality. Although most studies linking impulsivity to 
suicidality examined impulsivity at the trait level, neuropsychological indices of this construct 
are state-sensitive, and thus may be more clinically meaningful insofar as they reflect proximal 
and modifiable risk rather than general risk for suicidal behavior. 
One novel methodological paradigm that may hold promise in providing experimental 
control in the study of impulsivity is transcranial direct current stimulation (tDCS), a form of 
neurostimulation in which electrodes attached to the scalp deliver constant, low current 
stimulation to the brain. Although widely studied with adults, tDCS has rarely been applied in 
experiments with adolescents. Moreover, the mechanisms by which tDCS affects behavioral and 
cognitive impulsivity has not been adequately studied. One method to clarify the neural 
pathways underlying its effects is electroencephalography (EEG) and event-related potentials 
(ERPs).  
As a necessary first step in assessing state-sensitive impulsivity as a causal risk factor for 
suicidality, this study will assess the short-term effect of tDCS on impulsivity. That is, the 
researchers will evaluate the potential for tDCS to the right inferior frontal gyrus (rIFG) and left 
orbitofrontal cortex (lOFC) to modulate behavioral and cognitive impulsivity, respectively, in 
adolescent suicide attempters. Adolescents in a psychiatric hospital program will be enrolled if 
they attempted suicide prior to their admission and who had made an impulsive attempt as 
measured on the C-SSRS (attempt initiated within a day of thinking of it). Participants will be 
randomized to receive either anodal tDCS to the rIFG, anodal tDCS to the lOFC. Randomization 
will occur through a computer program (like flipping a coin with participants having an equal 
chance of being in each group). This will occur after we determine if the participant is eligible 
for the study. There will be 20 participants in each group. Participants will not be told which 
group they are randomized into. Baseline impulsivity measures will be re-given after tDCS or 
sham stimulation to assess changes in impulsivity. Additionally, EEG/ERP data will be collected 
during the impulsivity tasks, and resting-state EEG data will be collected pre- and post-tDCS. 
Participants Adolescents (N = 60) between the ages of 13 and 17 who have been admitted to an 
adolescent psychiatric hospital (inpatient or partial). Adolescents will be eligible to participate if 
they: (i) have attempted suicide prior to admission; (ii) had made an impulsive attempt as 
measured on the C-SSRS (attempt initiated within an hour of thinking of it); (iii) speak and read 
English fluently, (iv) have no significant cognitive disability based on a standard psychiatric 
exam, and (v) are not actively psychotic.  
Exclusion criteria are: (i) a significant general medical or neurological condition; (ii) history of 
seizure, head injury, brain surgery or tumor; (iii) intracranial metallic implants or implanted 
electrical devices; (iv) substance abuse or dependence in the past six months. 

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Sample Availability. Hospital admission data suggests more than 60 adolescents would meet 
these study criteria over the two year recruitment period. We have found in other studies 
recruiting from this site to allow for adequate time for in-depth assessment batteries larger than 
that of the proposed study. 
Consenting and Screening Evaluation. Parents and adolescent will be approached about 
participating in the study after review of their medical charts upon admission to the Bradley, 
Butler, or Hasbro. Study staff will obtain consent. All research staff will be trained in the steps 
necessary to obtain consent. All participants and their parents will be fully informed about the 
purpose and procedures of the study both verbally and through a written description contained in 
the assent/consent forms. All participants will be required to provide assent and their 
parents/guardians to sign an informed consent document in order to participate in the study. 
Once consented, participants will be assessed for a suicide attempt prior to index psychiatric 
admission using the C-SSRS. Next participants will be screened for current psychosis and 
cognitive disability using the K-SADS-PL and the WASI, respectively, and complete the 
screening form. Those meeting all eligibility criteria will complete the PROMIS and Connors-3, 
which will be included as covariates in analyses. Eligible participants will also be asked about 
their current medication use, and the information they provide will be confirmed with a parent. 
After completing these assessments, participants will be randomly assigned to receive either 
anodal tDCS to rIFG, anodal tDCS to lOFC, or sham stimulation. tDCS at a constant current of 
1.5 mA and sham stimulation will be applied for one 20-minute session. In the sham condition, 
the current will be ramped up to 1.5mA for 30 seconds and then ramped back down to 0. As this 
commonly used sham procedure produces a brief tingling sensation, participants are kept 
unaware of their experimental condition.  Prior to and  tDCS, participants will complete the SST 
and TCIP, while EEG is recorded to extract ERPs in a single-blind procedure. The participants 
and PI Liu will be blind to experimental condition, but Co-I Carpenter will not be blinded. 
Resting-state EEG, for 5 minutes, will be recorded before pre-stimulation tasks and after post-
stimulation tasks. These tasks were specifically chosen because they can be administered well 
within an hour, the approximate duration of effect from a single-session of tDCS. The side 
effects questionnaire will be administered following the tDCS session. Ordering of tasks will be 
counterbalanced.  These assessments will take about 3.5 hours total and they will be audio 
recorded for supervision and training purposes with participants’ permission. They will take 
place in an interview room in the hospital, outside of any clinical care. Adolescent participants 
and parents will be paid $100 and $25, respectively, upon completion of the study. 
Assessment Measures.  
i. 
Self-report measures  
Wechsler Abbreviated Scale of Intelligence (WASI; Wechsler, 1999): The WASI uses 
vocabulary, similarities, block design, and matrix reasoning subtests similar to those 
of the WAIS to provide an estimate of full scale IQ in approximately 30 minutes.   
 

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Depressive symptoms will be assessed using the pediatric version of the PROMIS 
depression scale. Higher scores reflect greater symptom severity. 
 
The Conners-3 Self-Report (Conners-3 SR; Kollins, Epstein, & Conners, 2004): 
Current ADHD symptoms will be assessed with the Connors-3, with higher scores 
reflecting greater severity. ADHD will be a covariate in all analyses, as impulsivity is 
a hallmark of this disorder. 
 
Suicidal ideation will be measured using the Passive and Active Suicidal Ideation 
Scale (PASIS). Higher scores reflect greater severity of ideation. 
 
Suicide Intent Scale (SIS): The SIS is an interviewer rating scale that assesses the 
degree of suicidal intent of a suicide attempt. Higher scores reflect greater suicidal 
intent. 
 
 Screening questionnaire: The screening questionnaire was adapted from those used 
in other tDCS studies conducted by Co-I Carpenter. This questionnaire is meant to 
check for potential head trauma and metallic implants. 
 
Side effects questionnaire: The side effects questionnaire was adapted from those 
used in other tDCS studies conducted by Co-I Carpenter This questionnaire is meant 
to check for any adverse events from the  tDCS stimulation. 
Lastly, participants will be asked to report their current medication use, and the 
information they provide will be confirmed with a parent.  
 
ii. 
Semi-structured interview assessments 
 
Schedule for Affective Disorders and Schizophrenia for School Aged Children - 
Present and Lifetime Versions (K-SADS-PL; Kaufman et al., 1997): The K-SADS-PL 
is a semi-structured diagnostic interview which provides a reliable and valid 
assessment of DSM-IV psychopathology in children and adolescents. Probes and 
objective criteria are provided to rate individual symptoms. Inter-rater agreement is 
high (range: 93% to 100%). Test-retest reliability and kappa coefficients are in the 
excellent range for present and lifetime diagnoses. Modules selected on the basis of 
relevance to suicide risk will be administered. These include depressive disorders, 
mania, psychosis, anxiety disorders, eating disorders, conduct disorder, alcohol and 
substance abuse, and post-traumatic stress disorder. 
 
Columbia-Suicide Severity Rating Scale (C-SSRS; Posner et al., 2011): The C-SSRS 
is an interviewer-rating scale, will be used to assess the occurrence of suicide 
attempts, and to differentiate suicide attempts from interrupted attempts and aborted 
attempts. To differentiate suicide attempts from nonsuicidal suicidal self-injury, the 

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former will be defined as any “self-destructive behavior with at least implied intent to 
die.”  
 
iii. 
Computerized neurological tasks – DDT (TCIP), SST  
 
Two Choice Impulsivity Paradigm (TCIP; Dougherty et al., 2003): The TCIP will be 
used as a delay discounting task (DDT) to assess impulsive choice, which requires 
participants to choose between immediate but small rewards and delayed but larger 
rewards over 50 trials. Delay discounting (or impulsive choice), is the tendency to 
undervalue an anticipated future reward as the time delay to obtaining the reward 
increases. A higher discounting rate (i.e., preference for smaller immediate rewards 
over larger delayed rewards) is viewed as reflecting greater cognitive impulsivity.  
 
Stop-Signal Task (SST; Hamilton et al., 2015): The SST will be used to assess 
behavioral impulsivity. The SST requires participants to respond to a target stimulus 
as quickly and accurately as possible by pressing a button, but also to withhold their 
response when they hear an auditory signal. Thus, this task involves a competition 
between activating and inhibiting processes.  
 
iv. 
tDCS and EEG. tDCS will be applied and EEG recordings made using a 
starstim/enobio device, with stimulation and recording electrodes located inside the 
cap. This device provides the user with up to 8 stimulating electrodes that can be 
programmed through software to be either anodal or cathodal in polarity and up to 32 
recording electrodes.  When not being used for stimulation, the 8 stimulating 
electrodes can also be used for recording, allowing for a total of 40 electrodes to be 
used for recording EEG pre- and post-stimulation. As in past studies, electrodes will 
be placed according to standard 10-10 coordinates corresponding to the rIFG (anode 
over F8 and cathode over FP1), which has been associated with behavioral 
impulsivity, and the lOFC (anode over FP1 and cathode over FP2), which has been 
linked with cognitive impulsivity.  
 
 
Data analysis 
Aim Hypothesis Dependent Independent  
Analysis 
MDE  
1 
H1 
SST 
tDCS/rIFG, time, 
tDCS/rIFG time 
GLM (repeated-measures 
ANOVA) 
d=0.35 
2 
H2 
SST 
As above, plus reduced 
theta power (EEG), 
increased P3 (ERP) 
As above with effects for 
EEG and ERP added; 
change in tDCS 
parameter estimate 
informs mediation 
r=0.35 
EA 
EH1 
DDT 
tDCS/IOFC, time, 
tDCS/IOFC time 
GLM (repeated-measures 
ANOVA) 
d=0.35 
EH2 
DDT 
As above, plus reduced 
VLFO (EEG), reduced 
SCPs (ERP) 
As above with effects for 
EEG and ERP added; 
change in tDCS 
r=0.35 

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parameter estimate 
informs mediation 
 All analyses will include PROMIS (depressive symptoms) and Connor‐3 (ADHD symptoms) 
as covariates 
 MDE minimal detectable effect, expressed as standardized mean difference (Cohen’s d) for 
aim 1 and minimal detectable correlation for aim 2 (n=60), assuming type‐I error level 5% and 
type‐II error level 20%. Repeated-measures ANOVA assumes correlation of 0.9 of repeated 
measures. 
Protection of Human Subjects 
Source of Research Material 
Adolescents will complete interviews, self-report measures, computer tasks, EEG testing, 
and tDCS. The data will be obtained for research purposes.  
Recruitment and Consent 
Parents and adolescents will be contacted about participating in the study after their 
medical records have been reviewed upon admission to Bradley, Butler or Hasbro. Medical 
charts will be reviewed by trained members of the research team familiar with the study criteria. 
These study staff will coordinate with treatment providers to arrange times to meet with 
potentially eligible patients and their parents in person. The staff will present and explain the 
study to the adolescent patient and his or her parent at Bradley, answer any questions they may 
have, and, if appropriate, present and explain the consent forms. All patients and parents will be 
fully informed of the purposes and procedures of the study. PI Liu will train the research staff in 
the steps necessary to obtain consent. All participants and parents will be fully informed about 
the purpose and procedures of the study both verbally and through a written description 
contained in the assent/consent forms. PI Liu and other study staff will be responsible for 
soliciting and obtaining informed consent/assent after any questions have been addressed. All 
participants will be required to provide assent and their parents or guardians to sign an informed 
consent document in order to participate in the study. Patients will be provided with a copy of the 
consent document, and the original will be placed in the PHI filing cabinet. 
Potential Risk 
This study does not pose greater than minimal risk. Risks associated with participating in this 
study include some emotional discomfort that may be elicited by discussing sensitive matters 
such as suicidal thoughts and instances in which the child has tried to harm him- or herself. The 
child may refuse to answer any questions that lead to too much discomfort. If he or she expresses 
suicidal thoughts, we will notify the child’s doctors so that they can take appropriate precautions. 
During the interviews and assessments, and when the child is completing the computer tasks he 
or she may become bored or tired. We will offer breaks frequently, and the child will be told that 
he or she can quit at any time if he or she gets tired.  
Additionally, there is minimal risk in participating in EEG testing or tDCS, as both of these 
procedures have been demonstrated to be safe for adolescents. tDCS has also been shown to be 
safe in adults. It has been studied less among children, but studies that have been done so far 
demonstrate it to be safe for this age group (Andrade et al., 2014; Kessler et al., 2013; Krishnan 

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et al., 2015; Moliadze et al., 2015). In particular, stimulations at 1.5mA (which will be used in 
the current study) have been found to be safe and well tolerated in pediatric samples (Kessler et 
al., 2013). In a recent safety study of tDCS conducted by Poreisz and colleagues (2007) the most 
common effects were mild tingling sensations (75%), light itching sensation (30%), moderate 
fatigue (35%), and transient mild headache (11.8%); and most of these effects did not differ from 
those of placebo stimulation.  For the current study, the participant will be asked to report any 
discomfort immediately.  If the participant reports discomfort, the stimulation can be turned off 
immediately. Participants’ parents will be encouraged to bring acetaminophen or ibuprofen in the 
case of a headache. These medications have promptly resolved discomfort in all prior cases of 
headaches or neck ache induced by tDCS. EEG is a safe and painless technique that is routinely 
used in clinical medicine. Lastly, all equipment has been tested by biomedical engineers at 
Neuroelectrics, who have certified their safety. 
Protection against Risk 
All study procedures will be explained to the participants with an emphasis on the 
voluntary nature of the study. Furthermore, staff members will be trained to respect participants’ 
wishes regarding their participation in the study or certain aspects of the study’s procedure (see 
Appendix).  
 
Potential risk from breach of confidentiality will be minimized by strictly adhering to the 
guidelines for research outlined by the Lifespan IRB, Rhode Island state law, the Federal Health 
Insurance Portability and Accountability Act of 1996 and its regulations (“HIPAA”), and the 
DHHS Federal Policy for the Protection of Human Subjects (45 CFR Part 46 Subpart D). This 
will include identifying participant research data by numeric ID only and maintaining any 
records containing potentially identifying information separate from any research data. Research 
data, as mentioned, will be accessible only to research staff and, and all electronic data will be 
password protected. Participant confidentiality will be breeched only to protect the safety and 
welfare of research participants and only in accordance with state and federal law. All records 
will be kept in a locked file and will be available only to research personnel who are 
knowledgeable of human subjects protection guidelines. A password will be necessary to access 
the computer data file. No names, only identification codes, will be used in presenting data in 
lectures, seminars, and papers. No names will be released without written consent of the parents 
or young adults who provided consent. Patients will be given full access to their data and 
professional interpretation if requested after completion of the study. 
 
Participant confidentiality will be breached only to protect the safety and welfare of 
research participants and only in accordance with state and federal law. It is possible that 
situations will arise in which children or parents provide the study staff with information that 
they are legally and ethically obligated to disclose (e.g., suicidal or homicidal intent, IV drug use, 
sexual abuse). All participants are informed in advance through the process of informed consent 
of the legal and ethical obligations of study staff should these issues arise. Whenever possible, 
study staff will handle these situations therapeutically. For example, if time limits and safety 
concerns allow, parents will be informed in advance and provided the opportunity to participate 
in the mandated report process. Research staff will contact PI Liu who will be responsible for 

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any on-site clinical decision-making. We have used these procedures in our other studies and 
they have been approved by our IRB.  
 
Research data (written records and tapes of interviews) will be kept in a locked file and 
electronic data will be password protected. All of these study related materials will only be 
accessible to research staff. To minimize the risk of distress stemming from assessment 
procedures, the interviewers will be trained on how to monitor participant response to answering 
questions about sensitive/stressful topics. Interviews will be scheduled at times most convenient 
for the families, and they will be compensated for time, travel, and any inconvenience entailed 
by completing the interview. 
 
All patients will be monitored with regard to suicidality and a safety plan will be 
implemented as needed. The safety plan will include: 1) the adolescent telling a designated adult 
if suicidal; 2) developing a coping plan; and 3) parents’ commitment to providing a safe 
environment. The participant’s psychiatrist or treatment provider will also be contacted with 
permission of the participant.  
 
A safety plan will also be implemented as needed with regard to tDCS. Participants will 
be monitored closely during the study period and any side effects will be documented.  All 
adverse events will be recorded and scored for severity and for relationship to the study as 
described, and all serious and unexpected adverse events will be reported to the IRB within 72 
hours. Dr. Felipe Fregni, Dr. Jorge Morales-Quezada, Dr. Noah Philip, Dr. Daniel Press, and Dr. 
Sarah Garnaat, and Dr. Brian Kavanaugh have agreed to be available to review and address any 
safety concerns and to review all study safety and efficacy data in a signed report twice a year. 
Their contact information is listed below:  
 
Felipe Fregni, MD, PhD, MPH 
Director, Laboratory of Neuromodulation, Spaulding Rehabilitation Hospital 
Associate Professor of Neurology, Harvard Medical School 
Associate Professor of Physical Medicine and Rehabilitation, Harvard Medical School 
1-617-952-6156 
fregni.felipe@mgh.harvard.edu 
  
Jorge Leon Morales-Quezada, MD 
Research Associate, Laboratory of Neuromodulation, Spaulding Rehabilitation Hospital 
Research Fellow, Department of Physical Medicine and Rehabilitation, Harvard Medical School 
1-617-573-2196 
jmorales@neuromodulationlab.org 
 
Noah Philip, MD 
Associate Professor 
Alpert Medical School of Brown University 
401-273-7100x2369 
Noah_Philip@Brown.edu 
 
Daniel Press, MD 

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Associate Professor 
Beth Israel Deaconess Medical Center 
617-667-0459 
dpress@bidmc.harvard.edu 
 
Sarah Garnaat, PhD 
Assistant Professor 
Alpert Medical School of Brown University 
 
Brian Kavanaugh, PsyD 
Assistant Professor 
Alpert Medical School of Brown University 
  
 
Although the physiological effects of tDCS at the intended dose wears off within an hour, 
we will follow-up with the parents, at the end of the study after the minor has received this 
stimulation to ensure the safety of the minor and ask that they monitor the minor. 
Potential Benefits of the Proposed Research 
 
There are no direct benefits from participating in the study. However, the information 
obtained from this study will further our understanding of impulsivity in suicidal adolescents and 
elucidate potential methods for modulating impulsivity among these adolescents. The potential 
benefits also include a more thorough understanding of impulsivity in suicidal adolescents will 
help inform future research and treatment of this population.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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