A Pilot Study of Transcranial Direct Current Stimulation (tDCS) in Children With Autism Spectrum Disorder
Phase: NA
Conditions: Autism Spectrum Disorder, Executive Dysfunction, Child Autism
Sponsor: Rutgers, The State University of New Jersey

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Protocol Title: A Pilot Study of Transcranial Direct Current Stimulation in Children with ASD
Protocol Version Date: V3 CLEAN 4 8 2021   
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INTERVENTIONAL RESEARCH PROTOCOL 
(HRP-503a)
STUDY INFORMATION

Title of Project: A Pilot Study of Transcranial Direct Current Stimulation in 
Children with ASD

Principal Investigator 
      Barbie Zimmerman-Bier M.D. 
      Clinical Associate Professor 

Principal Investigator Div. & Dept.
Department of Pediatrics, Division of Pediatric Neurology Robert Wood 
Johnson Medical School (RWJMS)

Principal Investigator Contact Info: 
Children's Health Institute 89 French Street, RM 1218 New Brunswick NJ 08901
Telephone Number 732-235-7083
           zimmerba@rwjms.rutgers.edu

Protocol Version and Date: v1 1/ 17/2021
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NCT 05105126

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Protocol Title: A Pilot Study of Transcranial Direct Current Stimulation in Children with ASD
Protocol Version Date: V3 CLEAN 4 8 2021   
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                TOPIC                                                                                                                PAGE
1.0
Research Design                                                                                                     3
1.1
Purpose/Specific Aims                                                                                           4
1.2
Research Significance                                                                                           4
  
Research Design and Methods___________________________________5-11                 
1.4
Preliminary Data______________________________________________11-12
1.5
Sample Size Justification________________________________________12
1.6
Study Variables_______________________________________________12-13
1.7
Drugs/Devices/Biologics________________________________________ 13
1.8
Specimen Collection____________________________________________13
1.9
Data Collection________________________________________________13-14
1.10
Timetable/Schedule of Events_____________________________________14-15
2.0
Project Management
2.1
Research Staff and Qualifications__________________________________14-15
2.2
Research Staff Training__________________________________________15
2.3
Resources Available____________________________________________  15-16
2.4
Research Sites_________________________________________________16-17
3.0
Multi-Center Research
4.0
Subject Considerations
4.1
Subject Selection and Enrollment Considerations _______________________18-19
4.2
Secondary Subjects_______________________________________________ 19
4.3
Number of Subjects________________________________________________19
4.4
Consent Procedures_________________________________________        __19-21
4.5
Special Consent Populations________________________________________21
4.6
Economic Burden and/or Compensation For Subjects____________________ 21
4.7
Risks of Harm/Potential for Benefits to Subjects to Subjects________________22-23
5.0
Special Considerations
5.1
Health Insurance Portability and Accountability Act (HIPAA)________________23
5.2
Family Educational Rights and Privacy Act (FERPA)______________________23
5.3
Code of Federal Regulations Title 45 Part 46 (Vulnerable Populations)_______ 23
5.4
General Data Protection Regulation (GDPR)____________________________23
5.5
 NJ Access to Medical Research Act (Surrogate Consent) _________________23
6.0
Data Management Plan
6.1
Data Analysis_________________________________________________       24-
6.2
Data Security__________________________________________________      25_
6.3
Data Safety And Monitoring_________________________________________26-27
6.4
Reporting Results_________________________________________________27-28
6.5
Secondary Use of the Data________________________________________    28 
7.0
Research Repositories  Specimens and/or Data________________________ 28
8.0
Approvals/Authorizations____________________________________________28
9.0
Bibliography______________________________________________________28-32
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Protocol Title: A Pilot Study of Transcranial Direct Current Stimulation in Children with ASD
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1.0 Research Design
1.1 Purpose/Specific Aims
A.  Objectives 
Although many children diagnosed with ASD make significant progress in learning and their cognitive 
skills improve with applied behavior analysis (ABA) and other teaching techniques, there are a significant 
number who show an absence or a plateau in various skills. Deficits in executive functioning are likely to 
be involved in many of these cognitive and learning disabilities due to poor functioning of the prefrontal 
cortex. Currently, the use of biological methods for improving learning and cognition is largely unexplored 
in research and practice.
Transcranial Direct Current Stimulation (tDCS) is a low-level electrical neurostimulation that has been 
used for various indications for decades and with no serious side effects. There is accumulating evidence 
that tDCS is effective in treating the comorbidities as well as the core symptoms of ASD. tDCS is most 
effective when used simultaneously with an active intervention. In this study, we will extract the effects of 
tDCS alone and in combination with ABA on the executive functioning skills and the core symptoms of 
ASD and monitor the results using an objective neurophysiological test (EEG).
The objective of this study is to pilot the use of transcranial direct current stimulation (tDCS) in 
combination with behavioral intervention to improve the acquisition of educational programs for students 
with ASD. 
We will be working with students in structured programs that provide comprehensive applied behavior 
analysis (ABA) with objective interventions and employ data-based evidence to guide the educational 
programs, either in-school or in-home. tDCS has been used for various indications over a couple of 
decades and has been shown to be very safe (30,000 treatment episodes yielded no serious side 
effects) and has been well-tolerated by children with ASD. The mechanism of tDCSs effectiveness is 
not clear, however animal studies show that tDCS can stimulate the flow of calcium ions through 
channels in the astrocytes, activating them, and facilitating their role in synapse formation and therefore 
learning.
B.  Hypotheses / Research Question(s)
Aim #1: To pilot the use of tDCS to children with ASD enrolled in ABA programs. We intend to provide 
the stimulation during the ABA therapy sessions focused on preselected cognitive programs and measure 
the outcome via a standardized instrument, and we will also use discrete acquisition data compiled as 
part of the students programming. 
There is accumulation evidence that  tDCS is effective in treating the core symptoms of ASD as well as 
co-morbidities, but there are still  gaps in our knowledge. Nearly all the existing studies were done on high 
functioning adults with ASD. The larger double-blind studies utilized general ASD outcome measures and 
specific comorbid symptoms were not examined, especially in combination with evidence-based 
intervention in a natural environment setting. This research study further our understanding of the benefits 
of tDCS in treating the comorbidities and core symptoms in children with ASD.  
Aim #2: To evaluate a biomarker of brain complexity at various points (before, during, and after the 
treatment) obtained through EEG measurements. We will use portable EEG devices which can be used 
in the therapy session. We hypothesize that through this treatment, circuits will be made more functional 
and this will be associated with increased complexity measured on the EEG, which has been shown to be 
associated with typical functioning when compared to ASD brainwaves.
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EEG data will be obtained and analyzed for complexity with a unique algorithm previously successful in 
separating ASD from controls and predicting outcome in children as young as 3 months old (Bosl, Tierney 
et al., 2011; Bosl, Tager-Flusberg et al., 2018).  The question of whether this will be predictive (at 
baseline) or associated with clinical improvement will be investigated. 
1.2 Research Significance
ASD is a highly heterogeneous disorder with numerous presentations, etiologies, and 
pathophysiology (London, 2014; Waterhouse, London et al., 2017). When devising treatments for 
ASD, the heterogeneity makes any unified biologic etiology or pathophysiology highly unlikely. 
Although many children diagnosed with ASD make significant progress in learning and their cognitive 
skills improve with ABA, there are many who show an absence or a plateau in various skills (Eaves & 
Ho 2008; Fein, Barton et al., 2013). It is more likely that the treatment for ASD will have to be a hybrid 
of the medical and behavioral models. There have been numerous calls for combining the two models 
of treatment, however for various reasons there is scant research on combined treatment (Yoo, 
Williams et al., 2003; Zarcone, Lindauer et al., 2004; Weeden, Ehrhardt et al., 2009). This proposal 
uses a novel biologic intervention that combines electrical brain stimulation with ABA 
treatment to target some of the cognitive deficits in ASD that until now have been relatively 
refractory to treatment.
There has been a growing enthusiasm for electrical stimulation techniques in all fields of treatment for 
brain disorders of various types. Noninvasive brain stimulation methods include transcranial magnetic 
stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current 
stimulation, high frequency random noise therapy, transcutaneous vagal stimulation, transcutaneous 
trigeminal stimulation and others (Paulus, 2011). The two most studied and promising for ASD are 
tDCS and TMS. Although TMS has shown success in ASD (Casanova, Hensley et al., 2014; 
Sokhadze, Casanova et al., 2017), a recent consensus statement emphasizes the need for better 
designed studies before this could be recommended as am indicated clinical treatment for autism 
(Cole, Enticott et al., 2019).
We have chosen to study tDCS for several reasons. 
1.
As explained above there is reason to believe that brain stimulation in combination with 
training or rehabilitation will yield maximal results (Page, Cunningham et al. 2015; 
Sathappan, Luber et al., 2019). 
2.
Both modalities can be combined with intervention, however tDCS is easily portable and so 
can be used in the locations in which teaching or training takes place, even at home.
3.
 It is also much less expensive and therefore could be widely used.
4.
It is remarkably safe
tDCS delivers exceedingly small amounts of energy to the brain compared to other forms of 
stimulation. Other forms of stimulation create an action potential and therefore drive the circuits which 
are being stimulated, and do not depend on the training component for their effect. tDCS works in 
conjunction with the training component of therapy. In theory, tDCS works by stimulating the circuits 
that are being used or exercised by the training component. Due to inadequate neuromodulation 
(London, 2018), the circuits are not firing efficiently. The small currents generated, rather than making 
the cells fire, create an improved neuromodulation, making the cells more amenable to firing. In this 
way, tDCS enhances the effectiveness of behavioral therapy and causes more efficient 
neuromodulation. 
Executive function deficits are common in children with ASD (Pennington & Ozonoff, 1996; Geurts et 
al., 2014). Given this deficit in executive functioning skills in people with ASD, several studies have 
examined the effects of tDCS on high functioning adults with ASD. Other studies have found 
reduction in the core symptoms of ASD in children See preliminary data 
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tDCS has used for a host of indications including pain management, ADHD, depression, cognitive 
improvement, language improvement, stroke rehabilitation, OCD and many more. The length of 
treatment is typically 20 minutes. There is still much debate, as to the frequency of treatment. Many 
studies have used single treatment episodes while others have treated for longer intervals such as a 
week or a month once or twice per day. We have chosen to treat for 20 sessions over 4 weeks which 
is the protocol used in one of the two controlled randomized crossover studies done in ASD on 24 
participants (the largest to date) (Gómez, Vidal et al., 2017). The safety of tDCS is remarkable, 
compared to nearly any other biologic treatments which have been used. In a review of over 
30,000 treatment episodes, there were no serious side effect noted (Bikson, Grossman et al., 
2016). Safety in children has also been addressed and similar to adults, the most common side effect 
is a tingling feeling under the electrode (which is short lived) in about 10% of children. About 5% of 
children report some temporary itching or reddening under the electrode and, again, no serious side 
effects (Krishnan, Santos et al., 2015).
In addition, we will be piloting the use of EEG prior to treatment as a digital biomarker which 
could predict response to the tDCS, and we will get EEGs before and after each arm of 
treatment/. We will be using an algorithm which measures EEG complexity and this method 
has been shown to be highly predictive of ASD from non-ASD in children as early as 3 months 
of age (Bosl, Tager-Flusberg et al., 2018).  See preliminary data.
1.3 Research Design and Methods
A.
Research Procedures
.

Study Subjects 
Participants will include school-aged children with ASD between the ages 5-12. We selected this 
age group because a diagnosis is typically made by the age of 5. This age group also allows us 
to profit from neuroplasticity while avoiding potential variables related to children undergoing 
puberty. This age group is also likely to be enrolled in intensive ABA programs aimed at executive 
functioning and social communication intervention. Based on the gender distribution of ASD in the 
population, we expect that our group will be approximately 75% male. Participants will be 
recruited from the local New Jersey community, from ABA schools and ABA agencies. 

Experimental Design
The study will use a randomized double-blind controlled placebo (sham tDCS) crossover design. 
The study will involve 5 total months of participation. Participants will be randomized into two 
groups using a random number generator. They will receive either: 
A) 20 active tDCS stimulation followed by 20 sham stimulation: or 
B) 20 sham stimulation followed by 20 active tDCS stimulation.

Randomization & Blinding
We anticipate recruiting 24 participants in anticipation of 4 subjects dropping out. We will use 
SAS programming to generate a randomization schedule with a block length of 6 and four blocks. 
Participants will enter the randomization schedule after consent is obtained and they are 
assigned a study ID. 
.  
Study ID
Randomization 
Schedule
ARM 1
ARM 2
001
1
tDCS
Sham
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Block 1 example- there will be four blocks = 24 participants recruited.
Subjects 21-24 (to account for drop outs) will receive randomization order of the subject they are replacing but will receive 
a new study ID. For example if the subject with study ID 004 drops out then subject with study ID0021 will receive 
randomization schedule 1.
Dr. Yoo will utilize the generated randomization schedule to provide  active tDCS and sham 
stimulation codes that will be entered into the tDCS device (by the parent)  prior to each session. 
These numeric codes will be random numbers and not distinct to the study group assignment, 
protecting the blind. Because of her role, Dr. Yoo will remain unblinded and will not be involved in 
any assessments. All other study staff, including Drs. Zimmerman-Bier, London, and Bosl, will 
remain blind. Parents, participants, and ABA providers will also remain blind. 
Both active and sham stimulations will be implemented once per weekday while children receive 
their regularly scheduled in-home or school-based ABA. Participants will be asked to continue 
their routine medication and behavioral regimen throughout the duration of the 5-month study. 
Participants parent or caregiver will be trained to use the tDCS device. They will be trained on 
how to turn on the device and enter the active or sham codes, as well as how to place the 
headgear in place. Our previous parent trainings typically took less than 30-mins and parents 
found them easy to use. If no parent or caregiver is available or willing during ABA therapy to 
apply the tDCS, a research assistant will travel to the participants ABA session to conduct the 
study sessions. 
●
Enrollment Baseline 1 (Assessment) Randomization and Desensitization = 4-week  
●
4 week/20 sessions of 1mA active or sham tDCS stimulation (depending on order 
assignment)  
●
4-week washout, then assessment 
●
4 week/ 20 sessions of 1mA active or sham tDCS stimulation (depending on order 
assignment)  
●
4-week washout, then assessment 
●
Discuss with study PI about open label  open label- up to 3 months
TABLE 1: Research Procedure
002
2
Sham
tDCS
003
2
Sham
tDCS
004
1
tDCS
Sham 
005
2
Sham 
tDCS
006
1
tDCS
Sham 
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
Device & Materials 
tDCS Device: 
The Soterix Medical 1x1 mini-CT Stimulator Model 1601 will be used. The constant current 
stimulator will have a maximum output of 1.0mA. 
Headgear: Each participants head will be measured and fitted with a custom headgear 
(Soterix Medical SNAP headgear) to position the electrodes at designated tDCS montage 
(F3-F4) as accurately as possible. 
Montage
The anodal electrode will be placed over F3 using the international 
1020 EEG electrode placement system to target the left 
dorsolateral prefrontal cortex (DLPFC) and the cathode electrode 
will be placed on the right dorsolateral prefrontal cortex. Forty 
stimulation sessions will be completed (20 active, 20 sham), each 
lasting 20 minutes per session at 1.0mA. 
Montage
Anode
Cathode
Total Number 
of tDCS Sessions
Duration of Each 
tDCS Session
Intensity of tDCS
F3
F4
40
20 mins
1.0 mA (milliamps)
Sponges: tDCS will be applied using a pair of disposables (i.e., onetime use) sponges 
pre-soaked with saline (Soterix Medical SNAP Pads). 
Once the participant is seated, the preparation time will take about 3 minutes to set up 
the tDCS device, snap the sponges onto the electrodes, and place the headgear on the 
participant. At the end of the 20-minute session, the device will turn itself off 
automatically. The device will also pause if the conductance is poor (e.g., when the 
participant removes the headgear) and resume once the conductance is adequate. 
Enrollment Baseline 1 
& Randomization
4 weeks
tDCS Active 
(n = 20 
sessions)
4 weeks
Withdrawl & 
Baseline 2
4 weeks
Sham 
(n = 20 
sessions)
4 weeks
Withdrawl & 
Baseline 3
4 weeks
Sham 
(n = 20 
sessions)
4 weeks
Withdrawl & 
Baseline2
4 weeks
tDCS Active 
(n = 20 
sessions)
4 weeks
Withdrawl & 
Baseline 3
4 weeks
F3
F4
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Each caregiver/parent will be trained on how to set up the device and place the headgear 
on their child. If no caregiver can be identified or a caregiver is unavailable, a research 
assistant set up and place the headgear on the subject.
. 
Difference between active vs. sham tDCS
Our tDCS device is designed to allow for sham (masked/placebo) stimulation. The active tDCS 
and sham are procedurally identical. Participants in both conditions will have the initial tingling 
sensation, except in sham stimulation, the current will be discontinued after 30 seconds while the 
power indicator remains. 
Study tDCS treatment
Once the participant is seated and engaged in ABA therapy, it will take approximately 3-minutes 
to enter the study code, snap the two sponges on the headgear, and place the headgear on the 
participant to begin the active or sham stimulation. At the end of the 20-minute session, the 
device will turn itself off automatically. The device will also pause if the conductance is poor (e.g., 
when the participant removes the headgear) and resume once the conductance is adequate. 
.
EEG 
Electroencephalogram (EEG):  The research assistant or study 
personnel will obtain a resting state EEG ( non- sleep ) at the subjects 
home ( or in ICD research room if preferred) . The Zeto portable eeg 
(https://zeto-inc.com/) is a wireless dry or semi dry electrode system 
that is FDA cleared for clinical use as well as research grade. It is 
designed for rapid application and adjusts to head sizes from 3 years to 
adults. It looks like a bicycle helmet, requires no goop, does not pull-on 
hair and can minimize motion artifacts.  It is a stand-alone unit that 
includes its own integrated amplifiers, digitizers, and 19 sensors on the 
head at the International 10/20 System locations. One to two minutes of 
awake, non-task-oriented EEG data will be recorded each EEG session
The Zeto system can be individualized to use high quality dry or semi- 
dry sensors depending on the sensory needs of the child. The semi dry system uses disposable 
sensors that are easily inserted into the headset. The headset can be wiped down with water and 
alcohol between users. It has been widely in the home for clinical monitoring during the CoVid19 
pandemic.  
Participating subjects will be seated with eyes open while a research assistant applies the EEG 
device. The procedure will attempt to limit the amount of head movement. Continuous EEG 
recordings will be taken with a standard 10-20 system of electrode placement using equipment 
from Zeto.inc  as described above. At least 2 minutes of baseline activity will be recorded after 
sensor impedances have been checked for acceptable contact. Electroencephalogram recording 
(EEG) will be collected at baseline, after the treatment period, and four weeks after the treatment 
during both phases.
Potential Problems
Effects from sham/placebo: Research-quality tDCS equipment has a built-in sham function. This 
produces a very small current for a few seconds at the beginning of the treatment. This is meant 
to simulate the active treatment which is a brief tingling of the skin under the electrodes which is 
rapidly accommodated to. In an evaluation of sham stimulation for placebo-controlled trials (Palm 
et al., 2013) it was found that participants were not able to distinguish between active tDCS and 
sham using the same prefrontal leads we are using in this study. In a recent review (Fonteneauet 
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al., 2019), there was an in depth questioning of the possibilities of the sham used in tDCS. They 
found that the blind could be compromised by the reddening under the electrodes which 
sometimes occurs. This is less of a problem in our study in that children have lower skin 
impedance and will have less reddening. In our preliminary work with children, we did not observe 
any reddening although this remains a possibility. A second issue is that in some studies, there 
has been a measurable effect even with this very small current for short durations however other 
studies have not found these effects. 
Desensitization to tDCS headband: Children with ASD may not tolerate wearing the tDCS 
headband for 20 minutes while engaged in ABA therapy. In order to facilitate tolerance and 
cooperation, we will provide 2-3 desensitization sessions per day during a week-long period. An 
eligible participant must be able to wear the headset for the full 20 minutes during the last two 
desensitization sessions in order to enroll in the study.  
Removal of tDCS headband: Despite these desensitization efforts, in a population of children with 
ASD, it is possible that participants may remove the tDCS headband during stimulation. This has 
occurred during our preliminary work, especially at 1.5mA (note that we are proposing to use 
1.0mA in this study). The tDCS device however can immediately sense the change in impedance 
and turn itself off automatically. We were able to reinstitute the treatment in a relatively short 
amount of time (<1 min) and the participant received the full length of treatment. It is unlikely that 
a short interruption would change the effects of the treatment. 
Non-consecutive sessions: We are proposing to stimulate participants during their weekday ABA 
sessions. It is possible that for a portion of the participants, completing 5-consecutive tDCS 
sessions during their ABA therapy may not be possible due to participant and/or therapist 
absence (holidays, illness, etc.). In such cases, we will make up those missed stimulation 
sessions in order to administer the total number of active and sham tDCS.   
Research Timeline  
Please note that the study participant will continue with ABA intervention throughout the entire 
study.   
Enrollment 
Week 1- 
Daily Living Skills: Each participant will be given the Vineland Adaptive Behavior Scale (VABS-
III). It assesses personal and social functioning for those up to 90 years of age, administered to a 
parent or caregiver using a semi-structured interview format.  The Medical History and 
Medication History will be obtained. 
Week2- 4  
Cognitive Profile: Results of cognitive testing (in IEP or psychological report provided by parent). 
A Leiter 3 cognitive assessment will be administered to study participant if the participant does 
not have a recent cognitive assessment (within past 3 years). .. 
Desensitization:  Participants will be introduced to the tDCS equipment. Most participants may 
require desensitization to the tDCS equipment (see Potential Problem section) to the tDCS. 
Desensitization to the tDCS equipment will be provided by Dr. Yoo.
Baseline Assessment 1
1.
Resting EEG
2.
Parent completed questionnaires 
a.
Behavior Rating Inventory of Executive Function (BRIEF)
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b.
 The Pervasive Developmental Disorder Behavior Inventory (PDDBI)
3.
ABA data for skills acquisition and target behavior for weeks 1-4 
4.
Randomizations to sham or tDCS 
*******************************************************************************************************************
Phase A or B- Weeks 5-8  

20 sessions of active or sham tDCS stimulation (depending on order assignment)  five 
sessions per week 
o
EEG  resting EEG after tDCS #20 
o
BRIEF, PDDBI,
o
 ABA data for skills acquisition and target behavior for weeks 5-8  
*******************************************************************************************************************
Baseline 2: Washout and Crossover  Weeks 9- 12(subject continues ABA therapy)  

EEG before tDCS session end of week 12

BRIEF, PDDBI end of week 12

 ABA data for skills acquisition and target behavior for weeks 9-12
*******************************************************************************************************************
Phase B or A  Weeks 13-16  

20 sessions of active or sham tDCS stimulation (depending on order assignment)  
o
Resting EEG after session #40 tDCS or sham
o
BRIEF, PDDBI end of week 16 
o
ABA data for skills acquisition and target behavior for weeks 13-16
Washout- Weeks 17-20 (subject continues ABA therapy) 
o
Resting EEG after week 20
o
BRIEF, PDDBI week 20 
o
ABA data for skills acquisition and target behavior for weeks 17-20
*******************************************************************************************************************
Schedule of Measurements per Study Phase TABLE 2
Weeks 5-8  
Weeks 9-12  
Weeks 13-16  
Weeks 17-20  
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PHASE 
 Enrollment
Baseline 1`
Phase A
(active or 
sham)
Crossover/ 
Baseline 2
Phase B
(active or 
sham)
Baseline 3
Time
Week 
1-3
Week 4 
Week 8
Week12 
Week 
16
Week 20
 Consent
X
 Medical History
X
 Leiter-3*
X
 Vineland-III
X
 Caregiver tDCS training
X
 Desensitization
X
 Randomization
X
 BRIEF
X
X
X
X
X
 PDDBI
X
X
X
X
X
 ABA program DTT data 
X
X
X
X
X
 EEG 2-5 min of continuous 
recording during rest.
X
X
X
X
X
*Completed for subjects that do not have a cognitive assessment within the past 3 years
B.
Study Duration
Subjects will participate in the study for 20 weeks.   
C.
Endpoints: 
20 sessions of active and sham tDCS stimulation
1.4 Preliminary Data
Research team: Case Reports
Case A is an 11-year-old nonverbal boy with ASD. He attends an after-school ABA program. He was 
referred by his mother for the absence of speech as well as difficulty with attention. Based on the referral 
concerns, we targeted cathode at F4 and anode at F3 for 20-mins at an intensity of 1mA for 20 minutes for 
9 sessions, followed by 5 additional sessions at 1.5mA during his ABA program. No side effect was 
observed. 
Our direct observations and parental and staff report indicate an increase in the accuracy of discrete trial 
performance in the areas of vocal imitation (echoics), oral-motor imitation, as well as an increase in 
spontaneous manding. Below are the data from his echoics program. This program was discontinued in 
2016 because of lack of progress despite several years of ABA therapy. The ABA provider re-introduced 
the echoics program and collected baseline data prior to tDCS. These data were shared at the end of the 
follow-up period (last data point) and analyzed post-hoc. Results show that on average, the accuracy was 
1% during baseline, 11% during tDCS stimulation, and 44% during follow-up trials. The cumulative percent 
accuracy shows the slope of each phase. Compared to the flatness of the baseline phase, tDCS phase 
shows relative increase accuracy, while during the follow-up, the slope of the cumulative is noticeably 
steeper, suggesting that tDCS may facilitate speech acquisition. 
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Case B is a 54-year-old woman with intellectual disability and obsessive-compulsive disorder (OCD) that 
began in her late teens. These behaviors included: emptying and restocking the refrigerator, emptying cans, 
jars, and containers, and sorting through trash. If denied access to the items, she made verbal threats and 
became aggressive. Because Bs mother was in search of a behavior therapist to treat her OCD and we 
wanted to wait until a therapist was identified in order to combine behavior therapy with tDCS, we used this 
waiting period to collect baseline RBS-R. When her mother was unable to identify a behavior therapist after 
two months, we agreed to move forward with tDCS alone. We administered the second RBS-R, which 
served as the second Baseline. We then trained her mother to apply tDCS at home, which took less than 
15 mins in our office. We then collected RBS-S after 10 tDCS sessions at 1.0mA. Because of lack of change 
in compulsive behaviors, we increased the intensity to 1.5mA for additional 10 tDCS sessions. 
We placed the cathode on the left supraorbital (FP1) and the anode at the center occipital (OZ). The results 
show that there was a decrease in compulsive behaviors between the first and second baseline. tDCS did 
not further reduce the compulsive behaviors. However, Ritualistic, Sameness, and Restricted subscales all 
showed a decrease following the tDCS sessions. The total RBS-R scores also show a difference between 
the two baseline and the post-tDCS phases, indicating that there was a reduction in repetitive behaviors. 
No side effect was reported.
1.5 Sample Size Justification
This is a pilot study.  Long-term objective for this proposal will be to accumulate treatment outcome data, 
EEG biomarker data and safety evidence, to warrant an adequately powered clinical trial
1.6 Study Variables
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A.   Independent Variables, Interventions, or Predictor Variables 
Subjects will continue to receive their ABA therapy provided by their regular therapist as standard 
of care. Subjects will be randomized to begin with either sham or tDCS treatment and then cross 
over to the other treatment arm. Each subject with receive tDCS or sham however the order will be 
different in the two groups. The active tDCS and sham are procedurally identical. 
B.  Dependent Variables or Outcome Measures: 
AIM 1: The following data will be used as outcome measures at the end of each phase of the study.
  
Primary The use of rating scales, completed by parents and teachers, measuring overt 
behavior is an often used and well-established method for assessing various domains of 
social, emotional, and behavioral functioning and treatment outcomes. As we are targeting 
the prefrontal areas, the primary outcome measure will be the Behavior Rating Inventory of 
Executive Function (BRIEF), a test that has normative data for children aged 2 to 90 years. 
It has parent versions containing 63 (preschool age) 86 (school age) items, taking 
approximately 10 to 15 minutes to complete. Each item score is converted within each scale 
for computation of T scores. The BRIEF contains eight subdomains of executive function: 1) 
Inhibit, 2) Shift, and 3) Emotional Control subdomains together result in an additional 
composite Behavioral Regulation Index (BRI). The subdomains 4) Initiate, 5) Working 
Memory, 6) Plan/Organize, 7) Organization of Materials, and 8) Monitor provide a composite 
Metacognition Index. The BRI and MI are also combined to obtain an overall Global 
Executive Composite (GEC).

Secondary 
Our secondary outcome measure will be the Pervasive Developmental Disorder Behavior 
Inventory (PDDBI) and the Discrete Trial Training (DTT) data from the participants ABA 
programs.  
The Pervasive Developmental Disorder Behavior Inventory (PDDBI) is an informant-
based assessment that was standardized on a large, well-diagnosed sample of children with 
ASD, ages 1.5 to 12.5 years. The PDDBI assesses the effectiveness of treatments in terms 
of Response to Interventions (RTI). It is also used to differentiate ASD from other conditions. 
Both teacher and parent rating forms are available consisting of 86 items, taking about 30 
minutes to complete. The PDDBI measures both adaptive and maladaptive behaviors related 
to ASD. It consists of the following Approach/Withdrawal Problems: 1) Sensory/Perceptual 
Approach, 2) Ritualisms/Resistance to Change, 3) Social Pragmatic Problems, 4) Semantic 
Pragmatic Problems, 5) Arousal Regulation Problems, 6) Specific Fears, 7) Aggressiveness. 
Under Receptive/Expressive Social Communication Abilities, there are 1) Social Approach 
Behaviors, 2) Expressive Language, and 3) Learning, Memory, and Receptive Language. 
Discrete trial training (DTT) is an evidence-based instructional method used to teach skills 
in a planned, controlled, and systematic manner (Smith, 2001). DTT is a widely used method 
within ABA, especially when teaching a behavior in small, teachable steps. DTT data will be 
collected from the participants ABA programs for the 5-month duration of the study. The data 
collected will be delineated by the study phases (i.e., dates). Cumulative skill acquisition 
during each phase will then be analyzed and graphed. We expect steeper slope of the graph 
with better skill acquisition, while lack of skill gain will show a flat slope. 
AIM 2: EEG data 
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EEG coherence measure is a useful indicator of cortical connectivity between functional areas in 
the brain. High coherence indicates a high level of synchronization between the two brain areas, 
whereas low coherence indicates a low level of synchronization. It has been shown that different 
EEG frequency bands correlate with different cognitive and emotional processes. EEG signals 
collected from the 19 standard 10-20 montage electrode positions will be used (Fp1, Fp2, F3, F7, 
Fz, F4, F8, T7, C3, Cz, C4, T8, P7, P3, Pz, P4, P8, O1, O2). Continuous sample segments of 30 
seconds will be selected from the processed resting state data and used to compute nonlinear 
digital biomarker values. Features will consist of the same NDI values and frequency bands as 
used in Bosl et al., (2018). All EEG data will be uploaded to Research Computing servers at 
Boston Childrens Hospital for analysis. The long-term objective for this proposal will be to 
accumulate treatment outcome data, EEG biomarker data and safety evidence, to warrant an 
adequately powered clinical trial.
1.7 Drugs/Devices/Biologics 
A.
Drug/Device Accountability and Storage Methods
There are 5 tDCS headsets available for use for the study.  Each subject will get a tDCS headset for 
use during the treatment/sham phases. The units will be cleaned with alcohol wipes in between use 
and stored in plastic bags in the research assistant office. 
The EEG systems will be kept in the storage case in the research assistant office. Prior to use for 
EEG recording the headset will be cleaned with a sanitizing wipe containing alcohol. The dry sensors 
will be cleaned individually with alcohol wipes.  Subjects using semi-dry sensors will have a new 
disposable sensor secured for use within one hour of recording.   
1.8 Specimen Collection N/A
1.9 Data Collection
A.
Primary Data Collection- all data will be entered into a RedCap database using the 
participant study ID. No personal identifiers will be entered into the RedCap database. 
 
AI: Descriptive Data

Vineland Adaptive Behavior Scales Third edition (https://www.pearsonassessments.com
(Sara S. Sparrow, PhD Domenic V. Cicchetti, PhD, Celine A. Saulnier, PhD).  is a well validated  
assessment of the childs daily living skills. Dr Yoo ( study psychologist) will use video-
conferencing,  using Q-Global On-Screen Administration (OSA) to guide the interview and score 
responses.as recommended by the American Psychological Association.  The VABS-III is 
organized around four Behavioral Domains: Communication, Daily Living Skills, Socialization, and 
Motor Skills. The VABS-III will take approximately 60 minutes to complete. It will be completed 
one time during the study in the baseline 1 phase. The results will be entered into a Redcap 
database using the childs personal study ID. No personal identifiers will be recorded or stored 

Leiter 3- (https://www.wpspublish.com) (for those subjects without cognitive assessment in the 
past 3 years) The Leiter 3 will be performed by the Dr Yoo. in the research rooms in the Child 
Health Institute. The Leiter-3 is a standardized nonverbal test of intelligence and cognitive abilities 
appropriate for individuals between the ages of 3-75 years. The Leiter-3 has been shown to be 
appropriate for individuals with autism and severe cognitive delays

     A2: Primary Outcome Date ( see section 1.6B for further information on these questionnaires) 

PDDBI- Ira L. Cohen, PhD, and Vicki Sudhalter, PhD (https://www.wpspublish.com) a link will be 
sent via email for the parent /caregiver to complete the PDDBI rating scale. The parent will complete 
the questionnaire 5 times during the study.  It takes 15 min to complete.
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
BRIEF -Gerard A. Gioia, PhD, Peter K. Isquith, PhD, Steven C. Guy, PhD, and Lauren Kenworthy, 
PhD- (https://www.parinc.com) a link will be sent via email for the parent /caregiver to complete the 
PDDBI rating scale. The parent will complete the questionnaire 5 times during the study. It takes 
30 minutes to complete.
B.
Secondary Data Collection 

Parents/ guardians will be asked to provide educational reports such as IEP or medical records 
(psychological testing) that indicates subject diagnosis of ASD as well as cognitive testing (within 
the last 3 years) for study participants. A Cognitive assessment such as WISC/ Stanford Binet will 
be reviewed at either via video conferencing during the Vineland assessment (shared screen) or 
during a study visit at the Childrens Health Institute. Data extraction onto de-identified data sheets 
with only participant study I.D. will be obtained by the study psychologist ( Dr. Yoo). See data sheet 
attachment.

Discrete Trial Data- ABA providers take data during therapy sessions either electronically or via 
paper/pen.  The study psychologist will discuss with the ABA therapist the participants current 
programs and select those programs that target executive functioning or attention. The ABA 
therapist will provide copies of the ABA data sheets for these specific therapy sessions.  The ABA 
data sheet will have only the participants study ID and will be emailed to the research assistant for 
further analysis by Dr. Yoo. 
1.10 Timetable/Schedule of Events
TABLE 1   see above   
TABLE 2                                                       
TABLE 2 
2.0 Project Management
2.1 Research Staff and Qualifications
. 
Drs London, Bosl ,Yoo and Zimmerman-Bier have a complementary and integrated expertise in all 
aspects of this research proposal and have worked together on research studies for 10 years. 
PHASE 
 Enrollment
Baseline 1`
Phase A
(active or 
sham)
Crossover/ 
Baseline 2
Phase B
(active or 
sham)
Baseline 3
Time
Week 1-
3
Week 4 
Week 8
Week12 
Week 16
Week 20
 Consent
X
 Medical History
X
 Leiter-3*
X
 Vineland-III
X
 Caregiver tDCS training
X
 Desensitization
X
 Randomization
X
 BRIEF
X
X
X
X
X
 PDDBI
X
X
X
X
X
 ABA program DTT data 
X
X
X
X
X
 EEG 2-5 min of continuous 
recording during rest.
X
X
X
X
X
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Dr. Zimmerman-Bier has extensive experience as PI on Clinical Research Projects. Dr. Zimmerman-Bier 
will provide the PI leadership for this study including IRB submission, staff hiring and training, and all 
aspects of project management. Dr Zimmerman-Bier will oversee the Research Coordinator to ensure 
regularly scheduled team meetings and research updates to the clinical team.  
Dr. London (Co-Investigator) is a child psychiatrist specializing in ASD and the head of the Autism 
Treatment Laboratory at the Institute for Basic Research. He has extensive clinical experience in the 
treatment of people with ASD. He is experienced in tDCS dosage, montage design, safety considerations, 
participant screening, and trial reproducibility. He has been using tDCS in clinical settings, from which the 
preliminary data were collected. He will provide technical assistance with IRB submission, hiring and 
training of staff, safety monitoring and data analysis and submission of publications. He will work with the 
team on future studies  
Dr. Yoo is a licensed psychologist and the head of the Applied Behavior Analysis (ABA) Laboratory at the 
Institute for Basic Research. She is experienced in tDCS dosage, montage design, safety considerations, 
participant screening, and trial reproducibility. She is also experienced in behavioral treatments of 
individuals with ASD. She will provide technical assistance with IRB submission, hiring and training of 
staff, desensitizing subjects to tDCS equipment, safety monitoring, data analysis and submission of 
publications. She will work with the team on future studies  She has collaborated with Dr. London on 
earlier tDCS cases. 
Dr. Bosl is leading a series of projects to discover patterns in infant EEG signals that can serve as 
biomarkers for ASD, epilepsy, and other neurodevelopmental pathology in collaboration with Boston 
Childrens Hospital. He runs the laboratory for neuroinformatics at Boston Childrens Hospital 
Computational Health Informatics Program. He was also the founding director and associate professor of 
Health Informatics and Data Science at the University of San Francisco. He is a current collaborator of 
this research group in a project that involves neurodevelopment in premature infants (Rutgers University), 
as well as development of a very early intervention for neural impairments associated with ASD, and 
development of a prototype infant EEG device for primary care use. He will oversee the data 
management and data analysis elements of the project.
2.2 Research Staff Training
Research Staff Training:

In order to ensure that all persons assisting with the research are adequately informed about the 
protocol, the research procedures, and their duties and functions, we will hold one introductory 
group training overview with all staff,. Each research team member will also receive instructions 
from the Research Coordinator and Assistants on RedCap and data entry. Dr. Yoo will train the 
Research Assistants on the tDCS equipment and Dr. Zimmerman-Bier and the Research 
Assistants will receive extensive training on the EEG system by Zeto. 

A mock run-through of all study procedures on a a fictitious participant (e.g.  study staff) through 
all study procedures. Any need for additional training or procedure clarification will be identified..

At weekly team meetings the PI will review the protocol and procedures, review staff knowledge 
and answer questions or new concerns.

Web based videos on the set up, cleaning, and maintenance of the tDCS and EEG devices will 
be on the restricted research drive. 

A detailed study procedure manual, including emergency contact information will be available on 
a shared research drive. 
2.3 Resources Available
Robert Wood Johnson Medical School is one of the professional schools of Rutgers, The State 
University of New Jersey. The Child Health Institute, The Pediatric and Adult Clinical Research Centers, 
The Pediatric Neurology Program are all part of RWJ Medical School/Department of Pediatrics. 
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The Department of Pediatrics at RWJ Medical School conducts many investigator-initiated and 
pharmaceutical industry-sponsored Phase I-V clinical research efforts throughout the campus at UMDNJ-
Robert Wood Johnson Medical School. The faculty and staff are trained and experienced in conducting 
clinical trials in children, adolescents and young adults. RWJ Medical School has a Clinical Research 
Center that is available to facilitate clinical research throughout the entire campus. The Department of 
Pediatrics has many ongoing investigator-initiated and pharmaceutical industry-sponsored Phase I-V 
clinical research. The Department of Pediatrics at RWJMS will be responsible for grant administration and 
reporting to the funding agency 
 
Childrens Specialized Hospital is part of the Barnabas/Rutgers Healthcare system. It is the largest 
provider of medical services to individuals with Autism Spectrum Disorders. Families interested in the 
study but not eligible for enrollment can be referred to outpatient services at the families request. 
Psychological/Behavioral Consultation: At the termination of the research participation (including early 
withdrawal), a licensed clinical psychologist (J. Helen Yoo, co-investigator) will meet with each participant 
and his/her family to make appropriate behavior-analytic recommendations regarding the behavioral 
management of severe challenging behaviors. If necessary, referrals to behavioral providers will be 
made, as well as referrals for support groups. 
Data Systems and Data Support Staff: The RWJ Information Systems, services provided 24-hours a 
day, 7-days a week, 365 days a year. The RWJ has collaborated with The Department of Pediatrics to 
develop a comprehensive HIPPA compliant telemedicine platform. The telemedicine platform utilizes two 
way videoconferencing.  
2.4 Research Sites and Collaborating Instiutitions 
Research Site: Rutgers/RWJMS/The Child Health Institute
The Child Health Institute provides the infrastructure for research studies with Rutgers Robert 
Wood Johnson Medical School's Department of Pediatrics and Pediatric Clinical Research 
Center, The Bristol-Myers Squibb Children's Hospital at Robert Wood Johnson University 
Hospital, and PSE&G Children's Specialized Hospital. The faculty and staff are experienced in 
conducting research studies on children, with ASD. The Rutgers/RWJ Medical School Office of 
Research and Sponsored Programs, Clinical Research Center and Institutional IRB can provide 
logistical and regulatory services needed for clinical research studies. The Children's Health 
Institute (through the Institute for Child Development) will provide the staff office space, 
computers and IT support as well as the research space for this proposal.
All research activities will take place in the subjects home or via video conferencing.  However, 
informed consent / parent training /cognitive assessment may occur in the research offices at 
Childrens Health Institute. 
Collaborative Institutions
Boston Childrens Hospital 
The computational and statistical aspects of the proposed project will be based within the 
Boston Childrens Hospital Computational Health Informatics Program. Informatics 
Infrastructure and Information Services Department of BCH includes state-of-the-art 
email, a wireless and wired network throughout all BCH facilities, and technical support 
for all BCH-located faculty and fellows. Clinical computer systems include computerized 
physician order entry and full availability of data and images on and off campus through a 
secure VPN network. 
Information Services Department (ISD) provides the physical security, hardware 
recovery, contingency planning, and data recovery and backup routines for all informatics 
services. Research data are secured through a combination of network and application-
level user authentication and authorization mechanisms, and data auditing schemes are 
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employed by all clinical data management systems and online workspace 
implementations. Database and applications servers are backed-up daily, and hardware 
recovery and contingency plans are administered by the ISD data center.
Research Computing (RC) is devoted to the specialized computing needs of the research 
community at BCH. RC offers the following services: data storage and backup; desktop 
support and backup services; server support and administration; purchase and 
maintenance of scientific analysis applications (e.g. SAS, STATA); and custom 
application development and developer support for research-specific functions. RC also 
provides services for conducting webinars across multiple sites as well as electronic 
transmission of large data files.  
Institution for Basic Research (IBR):  
Institute for Basic Research (IRB is New York State Psychiatric Institute/NYSPI)  Both 
Drs. London and Yoo will perform research activities for this study as part of their 
research responsibilities at IBR. They will perform all research activities at RWJMS or via 
video conferencing.  
.
3.0 Multi-Center Research
N/A
4.0 Subject Considerations
4.1 Subject Selection and Enrollment Considerations 
1.
Method to Identify Potential Subjects: Participants will be recruited from the local New Jersey 
ABA providers or healthcare providers in New Jersey. New Jersey has one of the highest rates of 
autism in the United States. Based on the gender distribution of ASD in the population, we expect 
that our group will be approximately 75% male) but will include subjects from ethnic groups 
representative of NJ counties. We do not anticipate challenges related to recruitment.
2.
Recruitment Details: 
a.
Identify Potential Subjects- We will begin with a kickoff meeting with local ABA 
providers to discuss the study with the PI Co-Investigators and study coordinator. The 
meeting will be virtual using WebEx. We will also publish an informational study flyer with 
general study details and contact information for the study coordinator.  The flyer will be 
distributed to ABA providers or used to publish on RWJ research website, Autism New 
Jersey, Autism Speaks, ABA provider websites or on other autism websites. 
o
A phone line will be set up for families or ABA providers to discuss the study as well 
as for participants to learn more about the study and set up a telephone screening 
intake if interested.
o
The Research Coordinator /Research Assistants- will complete a telephone 
Screening (determine eligibility by inclusion and exclusion criteria) . Eligible families 
considering participation can ask specific questions and discuss specific study details 
with the research assistant or PI.  Information regarding the study will be emailed to 
participant families to review (consent forms). 
3.
Inclusion Criteria
1.
Males and females between 5 and 12 years with autism
2.
Enrolled in a New Jersey ABA-based program (school or in-home) supervised by a Board-
Certified Behavior Analyst (BCBA)   
3.
Stable medical and behavioral treatments for at least 4 weeks prior to, and during the study
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4.
Able to tolerate wearing tDCS as determined during a week-long daily desensitization 
training.
4.
Exclusion Criteria
1.
Any implanted metal device (heart pacemaker, cochlear implant, surgical clips, etc.)
2.
Severe neurological disorders such as TBI, brain tumor, intracranial infection 
3.
Seizure disorder with a seizure within the last two years 
4.
Skull defect
5.
Peripheral blindness or deafness
6.
Medication that might affect tDCS: There have been a few studies concerning the effect of 
various medications on tDCS. Some may block and others may enhance the effects depending 
on many factors. The assay used to test these medications was its effect on the motor cortex 
after stimulation and this may not apply to our montages, however, in order to minimize the 
chances of having medication affect our results, we will exclude participants taking the following 
medications: 
a. Na or Ca channel blockers which will include all anti-seizure medications
b. Medications that affect the NMDA receptors including dextromethorphan, cycloserine 
c. Serotonin reuptake inhibitors 
d. Dopamine stimulating or blocking medications including pergolide, bromocriptine and all 
antipsychotic medications
e. Norepinephrine stimulating or blocking agents including propranolol and the stimulants
f. Drugs that can lower seizure threshold [imipramine, amitriptyline, doxepine, nortriptyline, 
maprotiline, chlorpromazine, clozapine, foscarnet, ganciclovir, ritonavir, amphetamines, 
phencyclidine, ketamine, gamma-hydroxybutyrate (GHB), alcohol, theophylline]
g. Barbiturates, benzodiazepines, meprobamate, chloral hydrate in the past 4 weeks 
7.
Acute skin disease
8.
History of magnetic or electrical stimulation  
4.2 Secondary Subjects N/A
4.3 Number of Subjects
A. Total Number of Subjects

Total number of subjects screened = 30

Total Number of Subjects eligible: 24 participants eligible and enrolled 

Required Number of Subjects to Complete Research: 20 participants to complete.

B. Total Number of Subjects If Multicenter Study N/A
C. Feasibility
Given the number of participants receiving home-based ABA therapy in NJ, we do not anticipate 
difficulty with recruitment. 
4.4 Consent Procedures
A. Consent Process

Location of Consent Process

Informed consent will take place via a secure video conferencing platform such as Web-
ex or Doxy.me. The consent form will be emailed/ mailed to families to review prior to the 
video conference and shared on screen.  For those families requesting on site 
consenting, we will secure a research room in the Institute for Child Development. 

Parents/guardians will be able to sign the consent All signed copies of consent will be 
emailed and mailed to study participant families
. 

Individual Roles for Researchers Involved in Consent
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
As part of informed consent, the PI or research assistants will explain the aims, methods, 
reasonably anticipated benefits, and potential risks of the study, as well as any discomfort 
that participation in the research may entail. They will be informed that their participation 
is voluntary and that they may withdraw consent to participate at any time. They will be 
informed that choosing not to participate will not affect the care the participant receives. 

The participant and his/her parent, or guardian will receive sufficient time to read the 
informed consent form and ask questions.

After this explanation and before entry into the study, assent and consent will be 
appropriately recorded by means of the participant's assent and the signed and dated 
consent of the participants parent /guardian. Digital signatures will be obtained using a 
secure system with an encrypted identifiable signature. The Research assistant /PI 
obtaining consent will also sign and date the consent. A copy of the informed consent 
form will be given or emailed to the participant and his/her parents or guardian. 

Ongoing Consent

The study length is 20 weeks for each participant.  We will have weekly contact with 
families throughout the study and have an opportunity to follow up regularly with subjects 
regarding their experience, questions or concerns regarding participation. The PI will be 
contacted to follow up with participants for questions/ concerns unable to be addressed 
by the Research Assistants. 

In addition, during the tDCS (4 weeks) or sham treatment (4 weeks) arms we have daily 
contact with participants daily and will ensure there are no changes to medications or 
health conditions that would prevent them from continuing in the study.  

Consent Discussion Duration

The initial informed consent meeting and discussion will take at least 45-minutes. 
Thereafter, the consent (i.e., continuation with study participation) and the upcoming 
study procedures will be discussed prior to each treatment arm.

Coercion or Undue Influence

There is no monetary incentive for participating in this study. During informed 
consent it is emphasized that participation is entirely voluntary and they can withdraw 
consent/assent at any time. In addition, ABA therapists will continue to provide ABA 
therapy regardless of participants enrollment status.  

Subject Understanding

Minors or participants who are unable to comprehend the information provided can only 
be enrolled after obtaining consent of his/her parent or legally acceptable representative. 

Waiver or Alteration of Consent Process Waiver or Alteration Details N/A

Destruction of Identifiers N/A

Use of Deception/Concealment N/A
C.
Documentation of Consent

Documenting Consent

Consent for subjects will be documented with the signature/ digital signature of the consent 
form by the subjects parent/ guardian. Digital signatures will be obtained using a secure 
system with an encrypted identifiable signature. The Research assistant /PI obtaining 
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consent will also sign and date the consent with written or digital signature. Parent/guardians 
will be given copies of the signed consent or emailed /mailed a copy. 

Waiver of Documentation of Consent (i.e., will not obtain subjects signature) N/A
4.5 Special Consent/Populations
A.
Minors-Subjects Who Are Not Yet Adults 

Parental Permission

Our study involves minors between the ages of 5-12 and as such we will obtain consent 
from their parent or legal guardian. This research study is minimal risk to subjects 
and therefore informed consent of one parent/guardian.

Non-Parental Permission N/A

Assent Process

Minors or participants who are unable to comprehend the information provided can only be 
enrolled after obtaining consent of his/her parent or guardian. For subjects capable of 
understanding the nature of the study (typically participants with mental age of approximately 
7 years of age and older), the research assistant or PI will explain the research to the extent 
compatible with the childs understanding. The Research assistant or PI will request the 
assent (affirmative agreement) of the child. If the child indicates that he or she does not want 
to take part in the research study, this process stops, and the subject will not be enrolled in 
the study

Documentation of Assent
For those subjects able to give assent, the study will be discussed through video 
conferencing or on site in the Child Health Institute research room. In the signature block the 
subject will sign and date (written or electronically) or the RA will document if Assent of the 
child was obtained verbally. 

Reaching Age of Majority During Study N/A
B.
Wards of the State N/A
Research Outside of NJ Involving Minors N/A
C.
Non-English-Speaking Subjects N/A
D.
Adults Unable to Consent / Decisional Impaired Adults -N/A
4.6 Economic Burden and/or Compensation for Subjects
A. Expenses 
There will be no cost to the participant and his/her family for participating in this study. Parking 
costs will be reimbursed for study visits that require the participant and/or his/her legally acceptable 
representatives to be present at RWJMS, 
 
B.
Compensation/Incentives- N/A 
C.
Compensation Documentation N/A
4.7 Risks of Harm/Potential for Benefits to Subjects
A.
Description of Risks of Harm to Subjects-Reasonably Foreseeable Risks of Harm
. 
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The safety of tDCS is remarkable, compared to nearly any other biologic treatments which have 
been used. In a review of over 30,000 treatment episodes, there were no serious side effect 
noted (Bikson, Grossman et al., 2016). Safety in children has also been addressed and is 
comparable to adults, The most common side effect is a tingling feeling under the electrode 
(which is short lived) in about 10% of children. Over time children will get used to the tingling.  
About 5% of children report some temporary itching or reddening under the electrode (Krishnan, 
Santos et al., 2015). The redness should dissipate within five minutes. Parents and therapists will 
be instructed to look for any rashes to keep the child from touching or picking at the area. 
B.
Risk of Harm from an Intervention on a Subject with an Existing Condition
tDCS is a considered a safe and tolerable procedure. This research presents the 
prospect of direct benefit to the individual participant, and there is evidence that tDCS improves 
learning and improves the core symptoms of ASD as well as co-morbidities. The risk to 
participants is minimal compared to benefits. In addition, participants will be monitored throughout 
the study for tolerability, any side effects, or changes in health. 
All participant families/guardians will meet with Dr Yoo regarding how to set up the tDCS 
system via video conferencing or at the research room in Child Health Institute. However, even 
with desensitization some children with ASD still experience difficulty tolerating different materials 
or equipment such as tDCS. For example, they may remove the headset, or may be more prone 
to pick at their skin. Children having difficulty tolerating the tDCS with behaviors will have a 
consultation with Dr. Yoo and the desensitization protocol will be reviewed. For subjects with 
behaviors such as crying for more than 5 min, refusal to wear the tDCS or displaying difficulty 
participating in ABA programs with tDCS   or concerns regarding tolerability will be removed from 
the study. In addition, participants will be examined prior to and after each tDCS session for any 
skin irritation. 
C.
Other Foreseeable Risks of Harm
Subjects may experience mild discomfort during EEG cap placement. Subjects having 
difficulty tolerating the EEG device i.e. crying for more than 5 min or continued removal of the 
device will be able to continue with the study without the EEG. This will be recorded as a protocol 
deviation. 
D.
Observation and Sensitive Information
        Sensitive information may be disclosed during study visits, ABA sessions and during video 
conferences. Unless the information relates to direct harm or neglect of those involved, all 
information will be held confidential.
E.
Procedures which Risk Harm to Embryo, Fetus, and/or Pregnant Subjects N/A
F.
Risks of Harm to Non-Subjects N/A
G. Assessment of Social Behavior Considerations N/A
H.
 Minimizing Risks of Harm
Dr Yoo (study psychologist) will ensure participants are comfortable with wearing the tDCS and 
that parents can set up the equipment easily.  Before each session research assistants will ensure 
that participants health was unchanged prior to administering each tDCS session. tDCS will be held 
during illness or other concerns. The study personnel will observe the tDCS placement and removal 
for each session. 
The treatment will be discontinued when the child participant is crying (more than 5 min), is pulling 
at the device or equipment, or asking to stop, . Parents and therapists will be instructed to monitor 
for redness under the electrode site and to keep the child from touching the area ( i.e. cover with 
band aid).  
I.
 Certificate of Confidentiality N/A
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J.
Provisions to Protect the Privacy Interests of Subjects
.
To minimize potential risks associated with privacy, each participant will be assigned and 
identified by a number. The key linking the participants identifying data (e.g., name, DOB) and 
the participant number will be kept separately by the PI in a secure location. Data will be 
recorded, a manner that does not allow participants to be identified, either directly or through 
identifiers linked to them
K.
Potential Benefits to Subjects
Potential benefit of tDCS is an improvement in executive function skills, decrease in the core 
symptoms of ASD, and/or greater learning acquisition during ABA therapy in study participants.  
5.0 Special Considerations
5.1 Health Insurance Portability and Accountability Act (HIPAA) N/A
5.2 Family Educational Rights and Privacy Act (FERPA) N/A

We will review educational records from the parents or legally acceptable representative, when 
available.  We will not be requesting any records from the participants school. These records may 
include individual educational plans or psychological evaluations. We will only record results of recent 
psychological testing in RedCap using the patient identifier. We will not copy / keep any of these 
records. 
5.3 Code of Federal Regulations Title 45 Part 46 (Vulnerable Populations)
A.
Special Populations

This study includes minors with developmental disabilities, however, does not involve greater 
than Minimal Risk to participants. tDCS has been used in research studies with both children 
and adults as well as with individuals with and without cognitive disabilities. This procedure 
presents the prospect of direct benefit for the individual participant compared to the minimal 
risk which will be monitored by the research team throughout the study. For example, it has 
been shown that children in school or ABA programs can plateau at some point and have 
difficulty learning despite intensive one on one teaching using ABA. tDCS has been shown to 
improve learning in children with autism. 

Our team has extensive clinical experience with tDCS and has not encountered any difficulty 
with the tolerability of the treatment. 

Participants will be exposed to the tDCS treatment system before randomization and families 
will be trained on how to enable the participant to feel comfortable with the procedure. 
Participants can withdraw from the study at any time. 

The participants will be between the ages of 5-12 years old. For those participants with a 
mental age > 7, assent will be obtained for the study as well as parent consent. Participants 
will be explained about the research in non-scientific terms compatible with his/her 
understanding.    
5.4 General Data Protection Regulation (GDPR) N/A
5.5 NJ Access to Medical Research Act (Surrogate Consent) N/A
6.0 Data Management Plan
6.1 Data Analysis
Analysis of the data in this study will follow the approach described in Wellek, S., and M. Blettner (2012). 
The following steps are required:
1. Baseline analysis to check the assumption of negligible carryover effects. This test has to be 
performed like an ordinary unpaired t-test
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.2. Test for differences between treatment effects. Formally, this test is carried out according to 
the same scheme as the pre-test. The crucial difference is that the customary formula for the 
unpaired t-test are now applied to the within-subject differences 
3. Significance decisions: The significance of the difference between two treatments (tDCS and 
sham) is determined as well as the significance of carryover effects (step 1). 
These steps are described in more detail below.
Baseline Analysis 
For descriptive purposes, summary statistics of the demographic and outcome variables will be 
calculated. To ensure pre-stimulation (i.e., baseline) equivalence between participants assigned 
to the two treatment orders (i.e., sham-active vs. active-sham), the outcome measures obtained 
during the first baseline period (first baseline assessment session) between these groups will be 
compared using independent �㕡-test comparisons. The primary dependent variable will be the 
BRIEF; fixed factors will be the treatment order (active-sham versus sham-active), and treatment 
condition (active and sham condition) and the secondary dependent variable will be the PDDBI. 
We note that, as described previously, the BRIEF will be used to assess executive functioning 
and the PDDBI is used to differentiate ASD from other conditions as well as to assesses the 
effectiveness of treatments in terms of Response to Interventions (RTI). The goal of this baseline 
assessment is to establish the equivalence of the two groups prior to intervention on the basis of 
the two outcome assessments. 
In addition to summary statistics for the baseline assessments, nonlinear EEG features will be 
computed before testing for all subjects. Machine learning classifiers will be used to demonstrate 
that the two groups are equivalent and cannot be distinguished based on nonlinear EEG analysis 
(see Bosl et al., 2018).
Hypothesis Testing 
As described briefly above, an unpaired t-test is applied to the within-subject differences for the 
outcomes of interest. We note that two summary outcome scores can be used (BRIEF and 
PDDBI), as well as for subscores. Because the subscores and the total scores are not 
independent, a Bonferroni correction is likely too strict and not warranted. Total scores and 
subcategory scores on each assessment will be tested for significant changes over time. The 
dependent or outcomes to be measured for within-subject differences within each group 
assignment (or treatment order: active-sham versus sham-active), treatment condition (active 
versus sham), and time (baseline and 4-week follow-up) will be the dependent variables. 
Independent variables will be group assignment, treatment condition, and time. The differences 
over time in either active or sham condition will be carried out using independent measures 
ANOVA. For all analyses, �㕃 values less than 0.05 will be considered statistically significant. 
Analyses were completed using standard R software. 
EEG as a Biomarker for Treatment Outcome
The signal or time series from each sensor will be decomposed into multiple frequency bands 
using a wavelet transform (Walker, 2008). We note that the Haar wavelet transform yields a 
multiscale decomposition that is mathematically equivalent to the coarse-graining procedure first 
introduced by (Costa, Goldberger, & Peng, 2005) for multiscale entropy analysis of biological 
signals. The use of wavelets for multiscale signal decomposition and relationship of scale to 
traditional EEG frequency bands is discussed in (Bosl et al., 2018). Using the wavelet transform, 
each sensor signal will be decomposed into power-of-two frequency bands that are approximately 
equal to the commonly used definitions of delta, theta, alpha, beta, gamma, and gamma+ bands 
used for EEG analysis. The specific software used for the wavelet transform is publicly available, 
along with instructions and python code, at: https://pywavelets.readthedocs.io. 
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Several nonlinear values will be computed on multiple scales for every sensor, including sample 
entropy, Lyapunov exponents, detrended fluctuation analysis (DFA), and correlation dimension 
(CD). These will be computed on multiple scales using publicly available software Nonlinear 
measures for dynamical systems or nolds, version 0.3.2, which can be downloaded from 
(https://pypi.python.org/pypi/nolds).  
Nonlinear values derived from Recurrence Quantitative Analysis (RQA) will be computed. RQA is 
an empirical approach to analyzing time series data that is in principle capable of characterizing 
all the essential dynamics of a complex system. It has been found to be useful for analyzing real-
world, noisy, high dimensional data (Webber & Zbilut, 2005). Software for computing recurrence 
plot statistics is publicly available python package pyRQA 0.1.0 (Marwan, 2012). At least seven of 
the most commonly used recurrence plot values (RR, DET, LAM, L_max, L_entr, L_mean, and 
TT) will be computed and used in this study. These values have proven to be potential 
biomarkers for autism (Bosl et al., 2018) and absence epilepsy (Bosl et al., 2017) in our previous 
studies. 
EEG analysis will first determine significant group differences between actual and sham tDCS for 
each of the nonlinear signal features computed. We hypothesize that significant changes will be 
observed in the nonlinear signal features. A Bonferroni correction will be required for the set of 
nonlinear measures. In addition to feature comparisons, regression models will be computed 
using the nonlinear EEG features as input variables and the change in assessment scores as 
output. Linear regression and machine learning regression models will be used. 
Taken together, these analyses will provide the information necessary to determine if tDCS 
significantly improves the efficacy of behavioral therapy for improving cognitive function in 
children with ASD. In addition, the usefulness of EEG as a tool for measuring the changes in 
brain function due to tDCS augmented behavioral therapy will be determined.
6.2 Data Security and Quality
6.2a Training and Safeguards
All study personnel will receive training prior to start date of the study. There will be a kick-off meeting 
with the PI and Co PIs as well as research assistants. All study-related staff will receive data safety 
and confidentiality training. Research Staff will ensure the identity of the participants and data 
collected remains confidential. The following safeguards will be implemented to maintain human 
subject confidentiality:

Each participant will be given a unique study identification number. These identifiers will be 
transcribed into a logbook with corresponding subject name. The logbook will be kept in a locked 
cabinet in the PIs office. In addition an excel spread sheet will be kept i(n the research folder of the 
restricted pediatric drive)  with the study ID and subject name. Only the study coordinator and 
research assistants/PI will have access to this drive.

Only the personal study ID will be used on data collection sheets where clinical data will be 
transcribed. Data collection sheets may be stored in the subjects binders until entered into RedCap 
and then destroyed. The subject folders only have the subject ID

School reports such as IEP or psychological testing will be reviewed by the study psychologist and 
research assistants but not copied or stored in research binders. Psychological testing data will be 
extracted onto data sheets with the participants ID but without personal identifiers. 

Information from the data collection sheets (using only subject unique ID) will be entered into the 
RedCap database which will be secured with password protection.  Data collection sheets may be 
stored in the subjects binders until entered into RedCap and then destroyed.  

Subject data will be entered into a password-protected database RedCap Database. 

Subjects parent and legal guardian will complete behavioral data (i.e., questionnaires) online through 
RedCap. Each participant will be emailed a link which opens to a behavioral form with subject ID and 
no identifiers. Once the form is completed by the family member, it is automatically uploaded to the 
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RedCap database.  Subject parent and legal guardian will not be able to view the database or other 
subject files. 

Any publication will not include any identification of the study participants.

The link between the subject unique I. D .and subject names will be destroyed after the completion of 
data collection and data analysis.

The study data will be kept in a RedCap database for a minimum of 6 years after study closure or 
publication of the data. 

Confidential information obtained through written consent will be held exclusively by the studys 
investigators and will in no way influence the access to and quality of medical care provided.

The PIs and the study staff will review all data on an ongoing basis for data completeness and 
accuracy. Data verification will be performed by someone other than the individual originally collecting 
the data.
6.2b Data Security

Study personnel whose responsibilities require access to personal health information will keep 
the identity of the participants and data related to the study confidential. The data will be stored in 
a locked cabinet within a locked office. The information on the data collection sheet will be 
entered into a password-protected database RedCap Database with access limited to the study 
staff. The data will be collected and processed with adequate precautions to ensure 
confidentiality and compliance with applicable data privacy protection laws and regulations.  The 
REDCap application is a secure web application for building and managing online databases. 
REDCap can be installed for compliance with such standards as HIPAA, 21 CFR Part 11, FISMA 
and international standards.  Access to the computerized data will be strictly limited to study 
investigators approved by the Institutional Review Board, except as required by law.

For questionnaires that are collected and transmitted through the internet, the participant parent 
or legally acceptable representative will have the participants assigned code, rather than name, 
when submitting the data. There are no foreseeable risks to participation except for the remote 
possibility that the responders email or IP address would be inadvertently disclosed.   
6.3 Data and Safety Monitoring
Our study meets the NIMH definition of minimal risk. 
6.3aData/Safety Monitoring Plan
. 
Our study meets the NIMH definition of minimal risk (i.e., the probability and magnitude of harm 
or discomfort anticipated in the research risks is no more than minimal risk (SEE ATTACHMENT 
LETTER). Our subjects are Autistic Children who present with unique communication and sensory 
challenges. Therefore, we have included the data and safety monitoring procedures to be followed by 
the research team. The PI will ensure surveillance protections are in place to ensure safety and to 
report any adverse events to the IRB promptly.

Prior to enrollment all parents / caregivers with be trained on how to put on the tDCS device. Dr 
Yoo will work with families having difficulty with placement or to help desensitize subjects to the 
tDCS equipment. Subjects will also be introduced to the EEG system and if needed, Dr Yoo will 
help participants feel comfortable with the headcap.

Each subject will have their own tDCS device to use for the duration of the trial. All tDCS sponges 
are disposable and the system can be easily cleaned and stored between use by the parents. 
The tDCS will be returned to the Research Coordinator at subjects completion of study. The 
tDCS headband can be cleaned with alcohol and placed in a sealed bag that is signed by cleaner 
/ cleaning date. Study visits will be by video conferencing when possible. Equipment will be sent 
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to subjects via Fed- Ex or courier. Rutgers University screening and testing procedures for 
prevention of CoVid19 will be followed.

A study staff will conduct the entire tDCS procedure and train the parents until the parent is fully 
able to apply the headset and use the device. Typically, this parent training is completed in 
approximately 30-mins through a review of a written instruction and modeling from the staff. The 
research assistant will also review the safety precautions with the parent, including instantaneous 
disconnection and proper power off procedures. Based on the 30,000+ sessions reported in the 
literature, tDCS was deemed safe, even in young children.

Then, the parent conducts the tDCS procedure under the supervision of the study staff (via 
telemedicine portal). 

Once trained, the tDCS device will be placed on the subject by the parent. (Note that 
self-administration of tDCS is quite routine practice in other clinical applications of 
tDCS. In fact, the device we are using was developed specifically for home use.)  

A member of the study team will observe the placement and removal of the tDCS 
device for each ABA session via video conferencing. The treatment will be 
discontinued when the child participant is crying (more than 5 min), is pulling at the 
device or equipment, or asking to stop, or if not participating in therapy. Information 
will be recorded on the treatment log. 

  Parents and therapists will be instructed to monitor for redness under the electrode site and to 
keep the child from touching the area (i.e., cover with band aid). Any redness persisting greater 
than 2 hour or if there are any signs of skin abrasion/ lesion will be considered an adverse event 
reportable to the IRB.

tDCS will be suspended during illness such as viral illness with fever, if there are skin irritation 
requiring medical treatment or if the child is being evaluated for new neurological or medical 
conditions i.e., seizures / diabetes. 

Subjects may become be discharged from the study if there are changes in their medical history/ 
/medication treatment (ex. a new medication is prescribed that makes the participant ineligible).   
Following this training, the parent will be able to conduct the entire tDCS procedure 
independently. In certain cases that require additional assistance, a study staff will be available 
through the telemedicine portal to assist the parent during the sessions. We do not anticipate that 
many parents will require more than 1-2 training sessions

6.3bData/Safety Monitoring Board Details N/A
6.4 Reporting Results
A.
Individual Subjects Results N/A
B.
Aggregate Results
Findings from the study such as abstracts or papers/presentations can be shared with all 
participants who express an interest in receiving a summary.  
C.
Professional Reporting
Preliminary research analysis and project related progress will be shared with the New Jersey 
Governors Council for Medical Research and Treatment of Autism in quarterly and annual 
reports and research meetings. We will disseminate our research findings at professional 
meetings and publications in discipline-related journals. 
D.
Clinical Trials Registration, Results Reporting and Consent Posting
                The study will be registered at www.clinicaltrials.gov.
6.5 Secondary Use of the Data   N/A
7.0 Research Repositories  Specimens and/or Data N/A
8.0 Approvals/Authorizations
Letters of Cooperation with Institute for Basic Research as well as Boston Childrens Hospital.
.
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