Brain Plasticity Underlying Acquisition of New Organizational Skills in Children
Phase: NA
Conditions: ADHD, Attention Deficit Hyperactivity Disorder, Neurodevelopmental Disorders
Sponsor: NYU Langone Health

 
 
Official Title: 
Brain Plasticity Underlying Acquisition of New Organizational Skills in 
Children 
NCT Number: 
NCT04108273 
Study Number: 
s17-00263 
Document Type:  
Study Protocol and Statistical Analysis Plan 
Date of the 
Document: 
• 
May 30, 2023 
 
 

 
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Research proposal 
 
 
 
 
 
Brain plasticity underlying acquisition of new organizational skills in children 
 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator: F. Xavier Castellanos, MD 
 
Co-Investigators: Richard Gallagher, PhD and Yuliya Yoncheva, PhD 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The Child Study Center at NYU Langone Health 
 
May 30, 2023 
 
 

 
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Purpose of the Study and Background 
Background 
 
 
Organizational skill impairment occurs in many neurodevelopmental conditions, 
including attention-deficit/hyperactivity disorder (ADHD) 1 and contributes to school 
failure, a pernicious mediator of poor long-term outcomes.2 Impairments in 
organizational skills have not been addressed by standard behavioral interventions, 
nor are standard medications for ADHD sufficiently effective for this specific 
functional domain.3  
 
Organizational skills training (OST) was developed in response to the 
underperformance of stimulant medication to remediate organizational deficits and 
specifically to target the four impaired domains which worsen school performance, 
i.e., Tracking Assignments, Managing Materials, Time Management and Task 
Planning.4 OST comprises in-person sessions with a therapist, during which 
previously learned skills are reviewed, new skills are taught and practiced, and 
instructions are given on when to use the new skill between sessions. Evidence from 
a two-site randomized controlled trial that OST can produce behavioral improvements 
in Children’s Organizational Skills Scales (COSS) as rated by teachers, with large 
effect sizes which were maintained for up to 1 year5 suggests that enduring changes 
in brain connectivity and intrinsic brain properties likely occurred.6  
 
 
Purpose of the Study 
 
We propose to identify functional changes in large-scale neural systems sub-
serving response to intervention in elementary school-age children impaired in 
organizational skills. Specifically, we intend to use resting-state functional magnetic 
resonance imaging (R-fMRI) to capture the physiologic mechanisms underlying 
behavioral improvements following OST, i.e., the intrinsic functional connectivity (iFC) 
between dorsal anterior cingulate cortex (dACC) and anterior ventral striatum (aVS). 
 
Study Design 
This study includes two phases. The first phase (R61) was an open trial, single 
arm study, lasting 2 years, with completion of recruitment and data collection in July 
2019. The second phase is a randomized two-arm (R33 phase) involving 1:1 
randomization to waitlist (WL) control or to OST. In the R61 phase, we screened 
children (elementary school grades 3-5) to identify participants with organizational 
skill difficulties to undergo two magnetic resonance imaging (MRI) sessions: one 
within 2 weeks prior to OST treatment and one within 2 weeks of completion of the 
OST treatment.  
The current randomized two-arm R33 phase will again involve the same 
treatment (OST) and pre- and post-treatment brain MRI scan. However, 50% of 
participants will be randomly assigned to receive OST within 2 weeks of successful 
completion of their first MRI scan (i.e., No-Wait study arm), while the other 50% will 

 
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be randomly assigned to receive OST after 12 weeks of waiting (i.e., Waitlist study 
arm).   
Characteristics of the Research Population 
Number of Subjects 
In the R61 phase, we obtained complete datasets (i.e., high-quality pre- and 
post-OST scans and complete phenotypic data) from at least 22 participants. To 
reach this number, we enrolled over 50 children for in-person clinical/behavioral 
assessments, and scanning at least 30 eligible participants.  
In the R33 phase, we anticipate screening 144 children to yield 86 with 
complete data from two sets of MRI scans, obtained after the same interval.  
Only children are subjects in this study; parents (and if the child’s teacher 
agrees, teachers) are informants who report on child’s behavioral measures and are 
therefore not study subjects. 
 
Gender of Subjects 
We will recruit both males and females. Despite the marked male 
preponderance in neurodevelopmental disorders, we will endeavor to recruit at least 
30% females.  
 
Age of Subjects 
 
This is a study of elementary school children in grades 3 – 5, who have one 
main teacher for at least three of the 4 core academic subjects (English Language & 
Arts; Math; History/Social Science; Science). The OST intervention is specifically 
designed for children in elementary school who have a single teacher. Children in the 
corresponding age ranges (typically 8-12) have been successfully scanned without 
adverse effects at the NYU Langone Medical Center and at numerous other research 
facilities.  
 
Racial and Ethnic Origin 
All races and ethnic origins are eligible. Based on prior studies, we expect 
approximately 25% of participants to self-identify as Hispanic/Latino, and racial 
composition of participants to be approximately 62% Caucasian, 24% African 
American, 4% Asian, 1% American Indian, and 9% Other.  
 
Inclusion Criteria 
 
 Student in grades 3-5 of elementary school having one main teacher 
corresponding to ages between 8 and 12 years-of-age  
 Children may be designated as obtaining special education assistance as 
indicated on an Individualized Education Program (IEP), provided a review of 
the current IEP by the research team under the supervision of the PI indicates 
that the child has a broadly average reading level and language development. 

 
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 Written assent by child and consent by parent or legal guardian 
 IQ: Estimated full scale IQ ≥ 85 and language comprehension standard scores 
≥ 8 is required as in past studies to assure that children are able to comply 
with specific skills training and to minimize neurobiological heterogeneity 
 Organizational skills deficits defined as elevated (≥ 1SD) pre-treatment COSS 
Parent Total T-score and at least one COSS Parent Interference item rated as 
either a 3 or 4 (indicating an above-average level of impairment) 
 Handedness: given the greater prevalence of non-right-handedness in 
neurodevelopmental disorders, we will track handedness but not exclude left-
handed individuals 
 Medication: To minimize variability due to medication effects, we will 
preferentially recruit currently unmedicated individuals (no psychotropic 
medications in the previous month). For allowed medications, we will require 
that dosage be stable for >2 weeks before study entry  
 Must provide adequate MRI data at baseline 
 
 
Exclusion Criteria 
 Enrolled in a self-contained special education classroom or served by a 1:1 
paraprofessional in their classroom 
 Absence of signed consent by parent or legal guardian 
 Children who dissent regardless of parental permission 
 Full scale IQ < 85 
 Children with a recent (past 6 months) or current history of neuroleptic 
treatment or current treatment with psychotropic medications other than 
stimulants, or guanfacine or atomoxetine 
 Per history (and medical records if needed) medical illness requiring chronic 
current treatment  
 History of intrathecal chemotherapy or focal cranial irradiation 
 Premature birth (< 32 weeks estimated gestational age or birth weight < 
1500g) 
 History of leukomalacia or static encephalopathy, intracerebral hemorrhage 
beyond grade 2, other specific or focal neurological or metabolic disorder 
including epilepsy (except for resolved febrile seizures) 
 History of traumatic brain injury 
 Contraindication for MRI scanning (metal implants, pacemakers, metal foreign 
bodies or pregnancy) 
 
Vulnerable Subjects 
This study does not involve greater than minimal risk. It enrolls children in 3rd-
5th grade (typically between ages 8 and 12). In compliance with IRB standards for 
research with vulnerable populations, a description of risks and benefits is included in 
the Risk/Benefit Assessment section. We will not enroll emancipated minors or 
mature minors and will therefore require written consent by a parent or legal guardian 

 
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as well as child assent, in accordance with IRB regulation. We describe the 
procedure for obtaining consent and assent in the relevant section below. 
Methods & Procedures 
 
Methods & Procedures 
 
This study involves the following steps: 
1. Pre-screening. Interested parents/legal guardians will speak with study staff 
over the phone for the purpose of screening 
(“Telephone_screening_form.doc”) to determine basic inclusionary and 
exclusionary information. If the parent/legal guardian endorses any 
exclusionary criteria or fails to endorse inclusionary criteria over the phone, 
then the study staff will inform them that the study would not be appropriate. If 
the parent/legal guardian does not endorse any exclusionary criteria and 
endorses all inclusionary criteria, then the study staff will make the parent 
COSS forms available to the parent (via mail or if preferred, via secure web-
based platforms, e.g., REDCap https://openredcap.nyumc.org/apps/redcap/). If 
inclusionary criteria are met based on these forms (detailed in the Inclusionary 
Criteria section), then the screening visit will be booked during which full 
consent and assent will take place. Only children are subjects; parents (and, if 
the child’s teacher agrees, teachers) are informants on child’s behavior, and 
thus are not study subjects. 
2. In-person evaluation visit. The last set of exclusionary and inclusionary 
information (with the exception of having an MRI scan that provides data 
meeting our quality criteria) will be gathered at the screening visit. The section 
Cognitive Behavioral Measures details all the assessments to take place 
during this visit. During the evaluation visit, children will also practice in the 
MRI simulator (detailed in section MRI session below).  
3. First MRI visit pre-OST treatment (detailed in section MRI session below). 
4. If after the MRI visit the child has met all criteria (i.e., data quality on the MRI 
scan acquired is good), then the child will be assigned to either the No-Wait 
study arm (i.e., to begin receiving the OST intervention, optimally within 2 
weeks of the successful MRI scan) or to the 12-week wait period (Waitlist 
study arm) at the end of which the subject completes their second MRI scan, 
and then proceeds to receive OST.  
5. OST intervention (detailed in section OST intervention below). 
6. Second MRI visit: for the treatment arm, this scan is post-OST treatment, 
optimally within 2 weeks of OST completion (detailed in section MRI session 
below). For the waitlist control condition, this scan is ~12 weeks after their first 
scan and before proceeding to OST. 
 
Cognitive behavioral measures (identical for both the R61 and R33 phases) 
Cognitive capacity for study eligibility will be verified based on full scale IQ ≥ 85 
estimated from the two-subtest Wechsler Abbreviated Scale of Intelligence-2nd ed. 

 
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(WASI-II)7 (or where indiciated, the equivalent Wechsler Intelligence Scale for 
Children-Fifth Edition (WISC-V)18) and scores ≥ 8 on Understanding Spoken 
Paragraphs, Formulated Sentences scales and for children aged 9.0 and above, the 
Multiple Meanings Metalinguistic module of the Clinical Evaluation of Language 
Fundamentals-5th ed (CELF)8. For visits taking place during the COVID-19 pandemic, 
to further support social distancing, the cognitive behavioral measures described 
above will be administered using the digital Pearson’s Q-global platform which has 
been vetted by NYU Langone’s MCIT. As supported by Pearson’s Technical Reports 
“Equivalence of Q-interactive™ and Paper Administrations of Cognitive Tasks: 
WISC®–V” and the “Using the WASI®–II with the WISC®–V”18, estimating IQ using 
either the paper or the digital version of either test is equivalent for children in the 9-
12 years old range. 
 
Parents (COSS-P) (and teachers, if the child’s teacher agrees to be an informant 
(COSS-T)) will serve as informants (only the child is a study subject) who will provide 
baseline and outcome ratings. Furthermore, the Homework Problem Checklist 
(HPCL)9 and Academic Progress Report (APR)5 will be collected to assess 
generalization of OST benefits to progress in school performance.  
 
Additional phenotypic characterization will be obtained to confirm inclusion criteria 
and enable dimensional brain-behavior analyses using the following widely used 
instruments. 
 
Psychiatric disorders will be established by clinicians administering the new 
computerized DSM-5 KSADS-COMP, based on the KSADS-PL,10 to parents; all 
symptoms are measured dimensionally on a 4-point scale and scores and notes 
entered on a computer.  
 
The parent (and, if the teacher agrees to be an informant, the teacher) Strengths and 
Weaknesses of ADHD Symptoms and Normal Behavior (SWAN)11 provide 
dimensional measures of inattention, hyperactivity and oppositionality.  
 
The Wechsler Individual Achievement Test-3rd ed. (WIAT-III) is an abbreviated 
assessment of spelling, mathematics and reading achievement. The Vineland 
Adaptive Behavior Scales, Third Edition (Vineland-3)12 is a parent interview of 
adaptive skills.  
 
Besides interviews, parents will complete questionnaires. The Social Responsiveness 
Scale-2 (SRS-2) is a widely used dimensional index of autism spectrum disorder 
(ASD). To assess psychopathology using empirically validated instruments in 
widespread use, we will include the parent Child Behavior Checklist (CBCL).13  
 
The Family Environment Scale (FES) will be obtained to quantify family conflict.14 
Hollingshead Index of Social Status15 (for comparability with other studies), family 

 
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income,16 birth-date, sex, race, and ethnicity will also be collected as part of the 
demographic questionnaires.  
 
Pre- and post-intervention administrations of the Cogstate Brief Battery17 
https://cogstate.com/featured-batteries/cogstate-brief-battery/ will also be adopted.  
 
In response to encouragement from funding agency program staff, the Clinical Global 
Impressions scale will be included before and after completion of OST.  
 
The Biber Cognitive Estimation Test (questions uploaded on research navigator) will 
more directly capture potential difficulties in estimating time and quantities.   
 
 
OST intervention 
 
We will deliver OST targeting three core organizational skills domains – 
Tracking Assignments, Managing Materials and Time Management – in a program 
consisting of sessions over 12 weeks, each training lasting about 1 hour, and 
corresponding 30-60 minute weekly review sessions with the parent and the child, 2-
3 days following each training session. Sessions will take place remotely by an 
encrypted video call (i.e., via WebEx secure, encrypted online link accessible on 
mobile, desktop and tablet devices https://cisco-
support.webex.com/guest/articles/en_US/Usability_FAQs/WBX70618/). The review 
sessions will allow more timely feedback by the therapist regarding content or 
implementation questions that may have arisen after the training session. If the child 
and parent report no difficulties practicing the new skill, the therapist will reinforce 
continued reporting of child’s progress.  
 
As typical in the field, to ensure the fidelity of OST treatment implementation, 
before commencing the study we will first train therapists to deliver the OST program. 
Training cases will not undergo the MRI scanning, which decreases time-commitment 
burden to the families. Furthermore, children with contraindications for MRI scanning 
(metal in the body, such as braces) would be therefore eligible to receive the OST 
program. Notably, the potential benefit of this study is in the OST intervention; 
therefore training cases still receive the maximum potential benefit as the study 
participants who receive the MRI and the OST.  
 
MRI session 
 
Within a week prior to the MRI session, children will be familiarized with the 
scanner environment by playing a computer game while lying down in a colorfully 
decorated MRI scanner simulator at the Child Study Center. A Social Story will be 
read aloud to prepare the child for the scanning experience. Our team has a long 
track-record of obtaining high-quality imaging data in neurodevelopmental disorders, 
including ADHD and autism, with children as young as 5 years old.  
 
Imaging will be performed using a research-dedicated 3T Siemens Prisma 
MRI scanner with a 32-channel Siemens head/neck coil, both of which have been 
FDA-approved for clinical and research scans as minimal risk devices. No exogenous 

 
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contrast agent will be used in any imaging sequence. At the beginning of the scan 
session, participants will be familiarized with the scanning environment and the 
research team, while the imaging procedures are being carefully explained. The 
Social Story will be read aloud again. The research staff will conduct a metal 
screening interview with the parent(s) to ensure MRI safety, and will use a hand-held 
metal detector to search for any metal on the participant (and the parent if they plan 
on entering the scanner suite while the child is being set-up). Additionally, female 
participants who have begun menstruation (extremely rare occurrence in our targeted 
age range) will be instructed to take a urine pregnancy test to ensure lack of 
pregnancy. If there are no contraindications, participants will be brought into the MRI 
room. The research staff will place earplugs, headphones, pneumatic belt, and finger 
transducer (see below) on the child and have him or her lay down on the scanner 
table. The participant will be positioned on their back on the scanner gantry with head 
straight aligned with the middle of the coil. The radio frequency imaging coil, which 
obtains the imaging data, will be positioned in front of the child’s face. All participants 
will be asked to limit head motion. Foam padding will be used for comfort and to 
comfortably restrict head motion. Once the child is comfortable, we will slide the 
scanner table into the magnet and begin scanning. Between each scan, the child will 
be in contact with the research staff through a microphone mounted in the MRI 
scanner. While scanning is on it gets loud, thus the speaker is turned off and we will 
not be able to hear the child. This is why the child will have a handheld squeeze-ball 
device to let the operator know if s/he wishes to immediately stop scanning and be 
removed from the magnet. The MRI scan can be stopped at any time at her/his 
request; when s/he squeezes the squeeze-ball, it emits a loud sound in the operator 
room to notify the research staff who will immediately stop the scan. We spend time 
during the mock MRI to instruct and coach the child of these procedures so s/he will 
be prepared before the MRI scan. 
 
Data Analysis and Data Monitoring 
Data Analysis 
 
 
Our primary scientific target is iFC between dorsal anterior cingulate cortex 
(dACC) and anterior ventral striatum (aVS). Specifically, we will calculate the effect 
size of the decrease from pre- to post-treatment in dACC-aVS iFC, and will assess 
the amount of variance in improvement in parent COSS total T-scores that is 
explained by the change in iFC between dACC and aVSFP (i.e., within the subset of 
voxels in aVS mask corresponding to the FP subregion: https://osf.io/5m5sx/).  
 
Statistical Plan 
 
 
This study is funded by a phased innovation application (RFA-MH-16-406), 
which entails an initial (R61) open phase of two years for milestone-driven testing of 
our neural target (dACC-aVS iFC) of OST intervention. Accordingly, as mandated by 
NIH, the R61 design is focused on estimating effect size of target engagement (as 
opposed to conventional hypothesis testing).  

 
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R61 phase: The statistical plan, supervised by expert biostatistician Dr. Eva 
Petkova, a staff member on this study, was created in light of the required design for 
the R61 mechanism. Specifically, the corrected effect size Hedges gs (i.e., Cohen’s d 
x 0.98) of change in pre- vs. post-OST-m in dACC-aVS iFC were computed. Second, 
we calculated the correlation between dACC-aVSFP iFC and improvement in COSS-P 
total T-score. Our milestones for proceeding to the R33 phase (1) an effect size of ≥ 
0.4 in the change from pre- to post-OST-m in dACC-aVS iFC and (2) the change in 
dACC-aVSFP iFC from pre- to post-treatment to account for ≥ 10% of variance of the 
improvement in COSS-P total T-score were met resulting in proceeding to the R66 
phase. 
 
 
  
 
R33 phase. Aim 1 H1 (time 1 vs. time 2 dACC-aVS iFC will differ between the group 
receiving OST and the WL group). 
 
R33 phase data will be collected using the identical experimental protocol used in the 
R61, therefore we will aggregate across phases to increase power whenever possible. 
To safeguard against inflating type I errors, we will adopt a “dynamic borrowing” 
Bayesian approach by assigning weight to the R61 data depending on convergence 
across the two phases.2 The Bayesian estimation will be implemented in the R 
package “BEST v0.4.0”7 available at https://CRAN.R-project.org/package=BEST. 
Thus, the effective sample size8 of the OST group will range from ≥43 to ≥65 
individuals, while the WL group will comprise ≥43 individuals.  
 
Analyses testing H1 will utilize the data from all subjects (comprising the samples 
derived from the Bayesian dynamic borrowing) in a linear model for dACC-aVS iFC 
as a function of treatment (OST vs. WL) and controlling for baseline iFC, age and sex. 
A significant regression coefficient for treatment would indicate that the post-
treatment iFC measure differs between those who received OST and those on WL. 
Detectable effects: with estimated sample size of 65 for OST, there is 80% power at 
α=0.05 (2-tailed) to detect a difference between OST and WL of magnitude Cohen’s 
d=0.56. With an estimated sample size of 43 for OST, the detectable effect is d=0.61. 
Such a medium to large effect size is considered clinically significant. 
 
Aim 2 H2, H3a, H3b (dACC-aVSFP iFC changes will mediate changes in clinical and 
academic measures).  
The Sobel mediation test9, 10 in SPSS11 will be employed to evaluate these 
relationships. With 86 children power =80% at =0.05(2-t) to detect r=0.3, between 
change in iFC and change in COSS, ~10% explained variance. Power =80% at 
=0.05 to detect a d=0.61 effect with nOST=43 (or d=0.56, if effective nOST=65).  
 
Data Safety Monitoring 
 
Consistent with the conclusion that MRI studies do not entail greater than 
minimal risk, in 10 years of fMRI studies of children and adults, we have never had 
any reportable events. Nevertheless, as required, we outline our data safety 
monitoring plan:  
 
Types of Data or Events  

 
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Two types of data will be collected: 
 
Interviews and psychological tests. The proposed tests have been used for decades 
with millions of children. There are no physical hazards associated with interviews or 
cognitive testing. Our team is experienced in assessing young children with 
developmental disorders in sessions lasting up to several hours. Sessions are paced 
with breaks, snacks and physical activities as needed by each child. If the child 
becomes tired, we reschedule in collaboration with the family. While we strive for 
collecting complete data from each child, we may defer collecting some measures or 
even forgo collecting some on a case by case basis.  
 
MRI sessions. MRI scans have long been held to be a safe way to noninvasively 
visualize tissue in adults and children. This study will be performed on an FDA 
approved 3-Tesla research dedicated Prisma scanner. The magnetic fields, at the 
strengths used, are considered harmless and our MRI scanning procedures fall within 
the FDA guidelines for radiofrequency and electromagnetic field exposure. There are 
no known significant risks or side effects associated with MRI procedures except the 
risk of metallic projectiles in the magnetic field or metallic objects in the body. 
Therefore, participants and their accompanying parent(s) will be carefully screened 
for previous exposure to metallic fragments or for implanted devices such as 
electrically, magnetically, or mechanically activated implants (e.g., cardiac 
pacemakers), clips on blood vessels in their brain, or other metallic objects in their 
body, e.g., shrapnel, bullets, buckshot, or metal fragments. They will also be asked to 
place all metallic and magnetic objects in their possession (e.g., keys, jewelry) 
outside the magnet room.  
 
The risk associated with collection of these data is minimal, and is also described in 
detail in the Risk section.  
 
Monitoring and reporting  
 
The principal investigator, co-investigator(s), other faculty/staff, and clinical 
research coordinators will ensure all procedures are conducted according to safety 
guidelines. We will monitor all participants during evaluations and scanning and be 
available to participants/parents for any follow-up that may be required. Any 
unexpected, severe adverse events will be reported to the IRB within 10 calendar 
days. 
 
Assessments  
 
Given the above information, risk will be monitored in an ongoing manner, not 
through a formal timed assessment. We do not anticipate any unexpected or harmful 
events. 
 
Data Storage and Confidentiality 
To protect confidentiality, each participant’s name will be removed from all 
data and replaced by an ID number. All identifiable information in paper format (e.g., 
consent and assent forms) will be stored in locked file cabinets. Only research 

 
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personnel directly affiliated with this project will have access to data containing 
protected health information. No portion of data containing protected health 
information will be released without written permission from the participant’s 
parent(s)/guardian(s), to the extent permitted by law. Identifying codes will be 
maintained in the secure web application REDCap 
https://openredcap.nyumc.org/apps/redcap/. All analyses will be linked exclusively to 
the identifying codes.  
This study is being conducted with support from the National Institute of 
Mental Health (NIMH). In accordance with NIH mandates for increased transparency 
and open scientific data sharing, phenotypic and imaging data for each individual will 
be assigned a Global Unique Identifier (GUID) and will be shared NIMH Data Archive 
(NDA). The GUID is a universal subject ID allowing researchers to share data specific 
to a study participant without exposing personally identifiable information while still 
allowing investigators to track participants longitudinally, across multiple research 
sites and studies. The NIH GUID tool will be employed for GUID generation 
https://data-archive.nimh.nih.gov/guid. The GUID Tool is software that accepts the 
personal information of subjects and uses it to create a series of hash codes. These 
codes are sent to the NIH GUID system and checked against the GUID database. If 
these codes have been seen before, that means the information matches an existing 
GUID and this GUID is sent back. If no match is found, a new GUID is created and 
sent back. If someone else enters the same information later, the tool will detect this 
match and send back the same GUID. The GUID itself is a series of alpha-numeric 
characters. The information required for GUID generation is subject’s sex, first name, 
last name, middle name, date of birth, and city/municipality of birth. All of these items 
are entered as they appear on the birth certificate, ensuring that the information will 
not change throughout an individual’s lifespan. 
 
Clinical trial registration 
 
 
This study meets NIH criteria of a clinical trial and accordingly has been 
registered on Clincaltrials.gov. 
Risk/Benefit Assessment 
Risk 
 
Potential Risks to Subjects and Provisions for Treatment of Adverse Events 
 
We expect no adverse events. Nonetheless, as detailed here, we will monitor 
all participants during evaluations, treatment, and scanning and be available to 
parents/guardians for any follow-up that may be required. Any unexpected, serious, 
or severe adverse events will be reported to the IRB within 10 calendar days as per 
NIH policy. 
MRI scans: MRI scans are considered a safe way to noninvasively visualize tissue in 
adults and children. This study will be performed on a FDA approved Siemens 
Prisma scanner. The magnetic fields, at the strengths used, are considered to 

 
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represent less than minimal risk and our MRI scanning procedures fall within FDA 
guidelines for radiofrequency and electromagnetic field exposure. We feel these are 
safe levels. There are no known significant risks or side effects associated with MRI 
procedures except the risk of metallic projectiles in the magnetic field or metallic 
objects in the body. Therefore, participants and their parents/guardians, if they enter 
the scanning suite, will be carefully screened for previous exposure to metallic 
fragments and for devices such as electrically, magnetically or mechanically activated 
implants, e.g., cardiac pacemakers, clips on blood vessels in their brain, or other 
metallic objects in their body, e.g., shrapnel, bullets, buckshot, or metal fragments. 
They will also be asked to place all metallic and magnetic objects in their possession 
(e.g., keys, jewelry, credit cards) in a locker outside the magnet room. 
 
Some participants report mild discomfort when undergoing magnetic 
resonance scans. Some participants have experienced claustrophobia (fear of 
enclosed spaces). If they are prone to claustrophobia, they will be asked to notify the 
researcher in charge of the scan. The MRI scanner makes loud knocking or beeping 
sounds during imaging; earplugs are provided to reduce this noise. Due to the rapid 
rate of change of the magnetic gradients during imaging, peripheral nerve stimulation 
is a possibility. If this happens, participants may feel creeping or tingling sensations, 
typically along their arms or lower back. Dizziness and nausea may occur if 
participants move their head rapidly in the bore of the magnet. Finally, there may be 
some heating from the radio frequency coils, the cables to the coils, and response 
and physiological monitoring devices. We do not use cables that can conduct 
electricity in the proximity of participants, and have had no such untoward events in 
the past.  
 
Participants will also be instructed how to use an emergency handheld device 
to inform the operator if they feel discomfort, and/or wish to immediately stop 
scanning and be removed from the magnet. It is worth noting that the MRI scanning 
environment necessarily predicates the utmost concern for the complete comfort of 
the participant. We emphasize that even slight discomfort tends to result in 
participants moving during the scan, which degrades image quality. Therefore, prior 
to the imaging session, we have participants complete a mock scanner session using 
an MRI-simulator, and also spend extra time when we place them on the gantry to 
make sure they are comfortable, and readjust as needed whenever they let us know 
that they are even slightly uncomfortable. In general, once a participant has gotten 
over the novelty of entering the magnet bore, and has habituated to the knocking 
noises, the main issue is boredom, and staying awake for functional scans. 
Participants are asked to keep their eyes open during resting state scans to facilitate 
monitoring of wake status. Participants are free to sleep or watch a DVD or listen to 
music during several of the scanning sequences (e.g., structural scans). 
 
Given that we are using instruments that are calibrated to deliver energy levels 
judged to be well within safe limits, we expect no adverse events. Nonetheless, we 
will monitor all participants during scanning and be available for any follow-up that 
may be required.  
Pregnancy-related risks: There are no known risks of MRI scanning to a pregnant 
participant or to a fetus, but since these scans are being done strictly for research 

 
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and not to benefit the participant’s medical care, we will not take even minimal 
chances. We considered excluding girls who have entered menarche, which is still 
expected to be infrequent in our age range. However, the median age of menarche 
(onset of menstruation) has been decreasing for many decades, and is lower among 
Black and Latina girls than among White girls. Given the importance of recruiting a 
substantial proportion, albeit a minority, of females, and undesirability of excluding 
individuals from under-represented racial or ethnic groups, we will not exclude girls 
who have begun menstruating. Accordingly, we will continue the approach we have 
followed since 2002, at the insistence of NIMH. Specifically, we will check to be sure 
that participating girls who have begun to menstruate are not pregnant by using a 
urine pregnancy test prior to the scan. If the test shows that a participating minor 
female may be pregnant, we will notify her and her parents and cancel the scan. 
Since minors cannot participate in research studies without their parents’ consent, we 
notify each female minor participant privately in advance that if her pregnancy test is 
positive, both she and her parents will be informed. As confirmation, we ask that 
female minor participants sign that they understand this aspect of participating in the 
study. To avoid putting young people on the spot, we emphasize that prospective 
participants do not have to give any reasons to decline participation. Information that 
the urine pregnancy test is required is provided at the time of telephone screening to 
confirm lack of other MRI contraindications, which we note includes claustrophobia, 
which is an entirely subjective complaint. In over 15 years of pursuing this approach, 
we have never had a positive urine pregnancy test, nor had a situation in which a 
young participant declined to participate because of the pregnancy test. Of course, 
unexpected events may occur, and a participant may not be aware that she may be 
at risk of early pregnancy. In such a case, the PI, a board-certified child and 
adolescent psychiatrist, would be reached prior to informing the participant and her 
parents, so as to supervise this potentially delicate process.  
 
OST treatment: There is no physical hazard associated with the OST treatment but 
possible risks include: increased expectations and non-response. First, for some 
children with a tendency toward anxiety, increased expectations and consequences 
provided by study interventions may increase anxiety. Study therapists will monitor 
children for any such concerns and talk with parents about the best way to address 
this, should it become a concern. Second, some children may not respond to the 
intervention and become discouraged. If this should occur, the treating clinician will 
address this issue with the child and parents to help the child deal with this concern. 
 
Tasks and questionnaires: There is no physical hazard associated with the 
questionnaires or computerized tasks. The participant is not under any obligation to 
answer any questions that feel uncomfortable to answer during the interview. We will 
maintain strict confidentiality about all answers, with the only exceptions being the 
legal requirements to prevent any immediate or future harm to self or others. 
 
Certificate of Confidentiality  
This research is covered by a Certificate of Confidentiality from the National Institutes 
of Health. The researchers with this Certificate may not disclose or use information, 

 
14
documents, or biospecimens that may identify the participant in any federal, state, or 
local civil, criminal, administrative, legislative, or other action, suit, or proceeding, or 
be used as evidence, for example, if there is a court subpoena, unless the 
participant’s parent/guardian has consented for this use. Information, documents, or 
biospecimens protected by this Certificate cannot be disclosed to anyone else who is 
not connected with the research except, if there is a federal, state, or local law that 
requires disclosure (such as to report child abuse or communicable diseases but not 
for federal, state, or local civil, criminal, administrative, legislative, or other 
proceedings, see below); if the participant’s parent has consented to the disclosure, 
including for the participant’s medical treatment; or if it is used for other scientific 
research, as allowed by federal regulations protecting research subjects. The 
Certificate of Confidentiality will not be used to prevent disclosure as required by 
federal, state, or local law.  
 
 
Protection Against Risks 
 
The most likely preventable risk is loss of confidentiality. To protect against 
this risk, each participant’s name will be removed from all data and replaced by an ID 
number. All identifiable data will be stored in locked file cabinets. The sheet indicating 
which participant corresponds to which ID number also will be stored in a locked 
cabinet, but different from the cabinet storing the raw data. Only research personnel 
directly affiliated with this project will have access to data containing protected health 
information. No portion of data containing protected health information will be 
released without written permission from the participant’s parent(s), to the extent 
permitted by law. Identifying codes will be maintained in locked file cabinets and in 
password-protected encrypted computer files. All analyses will be linked exclusively 
to the identifying codes.  
Regarding the OST intervention, significant psychological and physical side 
effects are not expected and none were reported in the efficacy trial. Nevertheless, 
our protection against risks plan includes participants' progress being monitored by 
regular contacts with parents and teachers. Additionally, clinicians will meet with 
participants weekly and if changes in a child's level of adjustment or school 
performance are noted, these will be reviewed immediately with site supervisors, and 
if necessary, the child and his/her parents will be seen by the study OST supervisor. 
In case of an emergency, emergency procedures are available by contacting the child 
and adolescent psychiatric physician on call. If any physical emergencies arise, 
parents can contact the pediatric emergency service at NYU or 911. As required by 
NY State Law, any type of abuse or neglect discovered during the course of the study 
will be reported to the authorities. 
For visits taking place during the COVID-19 pandemic the most up-to-date 
NYU School of Medicine Standard Operating Procedures and CBI Standard 
Operating Procedures for work with research subjects will be observed. The most 
current version of the “CBI Standard Operating Procedures During the COVID-19 

 
15
Pandemic” (v0.3 as of June 23, 2020) involves a combination of individual researcher 
health-check clearance, researcher contact tracing, personal protective equipment 
use, and digitized tracking of proper disinfection of the equipment.  
When contacting the parents of currently enrolled children, the trained 
research associate or trained study team member will use the “Current participants 
phone screen COVID-19 20200817.docx” phone script to discuss current 
understanding of study risks in the context of the COVID-19 pandemic and family’s 
continued participation. When contacting potential new participants, study team will 
use the “Telephone script COVID-19 20200817.docx” which details current 
understanding of study risk in the context of COVID-19. 
 
Potential Benefits to the Subjects 
 
The child may benefit from receiving OST treatment. OST has been shown to 
help some children with ADHD improve in organization, time management, and 
planning. For such children, improved organizational behaviors resulted in better 
parent-child relationships, fewer problems with homework, and improvement in their 
school functioning. While we cannot guarantee that any particular child will improve in 
this manner, prior research has found that this treatment resulted in improvements in 
children’s functioning compared to children in a wait-list condition.  
There is no benefit from the imaging aspects of the study, which are being 
performed for scientific reasons.   
Investigators’ Qualifications & Experience 
 
All research personnel have completed training in the protection of human 
subjects. 
Subject Identification, Recruitment and Consent/Assent 
Method of Subject Identification and Recruitment 
 
We will seek referrals from NYU Child Study Center Clinical Services, local 
school counselors and clinicians. We will disseminate flyers describing our study to 
pediatricians and an established network of behavioral therapists, child psychologists 
and psychiatrists specializing in neurodevelopmental disorders. Study ads have been 
updated to reflect the change to virual and hybrid (in-person/virtual) education (17-
00263 Ad Text2 20200730 tracked; 17-00263 Ad Text3 20200730 tracked; 17-00263 
Ad Text5 20200730 tracked). In the past, these IRB-approved ads posted to the Child 
Study Center newsletter have proven effective in reaching out eligible participants. 
The study has also been posted on the NYU clinical trials website 
https://clinicaltrials.med.nyu.edu/clinicaltrial/1204/brain-plasticity-underlying-
acquisition/?qd=43871. Additional recruitment approaches include social media (e.g., 
Facebook Click ads), ads purchased on traditional media and local parent 

 
16
organizations. As typical for new recruiting studies at NYU, a webpage with our 
study’s description will also be used for recruitment. Since the current study seeks 
children with impairments in a specific domain, our webpage will provide a brief 
definition on the webpage along with an optional informational quiz to help better 
inform any potential participants about the specific deficits we mean by the phrase 
“organizational skills”. Accordingly, our recruitment webpage will include an optional 
organizational skills informational quiz “17-
00263_Optional_Informational_Quiz_20170830.docx”. This quiz is optional and 
completely anonymous (i.e., no PHI or IP address information is recorded) and any 
potential participants who contact us following taking the quiz are under no obligation 
to inform us whether or not they have taken the optional informational quiz. We have 
existing research databases at NYU with permission to contact parents of children 
previously diagnosed with neurodevelopmental disorders (e.g., at NYU, ~180 children 
with a primary diagnosis of ASD and ~145 with a primary diagnosis of ADHD will be 
within the target age-range during the project period) “Telephone script COVID-19 
20200817.docx” details the explanation of the study by research staff and outlines 
also the scenario when interested families call the Child Study Center to enquire 
about our study. Additionally, we will employ an EHR query through NYU Langone 
Health’s DataCore for individuals with an ADHD diagnosis and/or medication to treat 
inattention and use the currently approved (17-00263 direct mail recruitment 
notification.pdf). Finally, we consistently find that ~20% of our referrals come from 
word-of-mouth due to our excellent relationships with families and the professional 
community.  
 
Interested parents/legal guardians will first speak with study staff over the 
phone who will perform a phone screen to determine basic inclusionary and 
exclusionary information. If the parent/legal guardian endorses any exclusionary 
criteria or fails to endorse inclusionary criteria over the phone, then the study staff will 
inform them that the study would not be appropriate and provide referrals. If the 
parent/legal guardian does not endorse any exclusionary criteria and endorses all 
inclusionary criteria, then the study staff will send the parent COSS forms. If 
inclusionary criteria are met based on these forms (detailed in the Inclusionary 
Criteria section), then the screening visit will be booked where full consent and 
assent will take place. The last set of exclusionary and inclusionary information (with 
the exception of the passing MRI scan) will be gathered at the screening visit. If after 
the MRI visit the child has met all criteria, then the child will be randomly assigned to 
receive the OST intervention either within 2 weeks of the successful MRI scan or 
after a 12-week wait period and their second MRI scan.  
 
 
Information obtained for children who do not meet inclusion criteria, or who 
meet exclusion criteria, will be discarded immediately.  
 
Process of Consent 
Only children are research subjects in this study. The parents and teachers 
are informants on child’s behavior and not research participants. Members of the 
research staff will provide parents/legal guardians with information about the study. 
During this time a member of the research team will carefully review the 

 
17
consent/assent document, outline the procedure for the study, explain potential risks 
and answer any questions. The study personnel member who is obtaining consent 
will also sign to indicate that they reviewed the entire consent form with the 
parents/legal guardians. The consenting process is continuous, and parents/legal 
guardians are informed that they may ask questions related to the study at any time. 
If the participant or parent/legal guardian does not provide written authorization, data 
corresponding to that participant will not be retained. We only require that one 
parent/legal guardian sign the consent form, since this is a minimal risk study, it is a 
burden for most families to have two parents attend the visits, and some children live 
in one-parent households. 
 
Children will be asked to provide formal assent to participate in the study. The 
process for determining eligibility to assent is outlined in the section following 
immediately below. A study personnel member will read the assent document out 
loud to the child as the child follows along. After each section, the personnel member 
will ask if the child has any questions, and will also ask the child questions to assess 
their understanding of the study.    
 
Due to COVID-19 and to keep the safety of both our research team and 
research subjects, consent and assent will be conducted remotely via an encrypted 
call (nyumc.WebEx.com, using a secure, encrypted online link accessible on mobile, 
desktop and tablet devices). A trained research assistant or study staff will schedule 
a time with eligible interested families to go over the written consent over the 
encrypted call. Research assistants will email or mail a copy of the consent to 
participants in preparation for remote consent. After going over the written consent, 
research assistants will also email the consent via a REDCap link where the 
participant has the opportunity to read a copy of the written consent and sign 
electronically, confirming that they read and understood the consent. Research 
assistants will also document in REDCap the time and date of the remote consent 
and note that the consent process was done via encrypted call due to COVID-19. The 
completed informed consent and assent forms will be returned via REDCap. 
 
To preserve equitable treatment of study’s subjects, children from public and 
private schools will be considered for enrollment.  
 
Teachers who work for a New York City public school or teachers who decline 
to provide research behavioral ratings of their student will be asked by the child’s 
parent or guardian to communicate with the OST therapist in their capacity as the 
child’s main educator. 
 
Teachers who are willing to provide research data in support of the study will 
be consented over the phone (using Teacher Telephone Consent 20200730 
tracked.pdf) or over encrypted video call if the teacher prefers that option. Study staff 
member will review the Teacher Phone Consent (Teacher Telephone Consent 
20200730 tracked.pdf) and address any questions the teacher has. Consent will be 

 
18
signed electronically using REDCap secure data-capture software in the form 
Teacher Letter of Understanding 20200730 tracked.pdf. 
 
 
 
Subject Capacity and Subject/Representative Comprehension  
 
A requirement to participate in the study is that research subjects have 
sufficient cognitive abilities and language comprehension to understand the study 
procedure including OST treatment. This is determined based on any available prior 
records, history of academic placement and observation at enrollment. The 
appropriate for this age group written assent form will be provided. A detailed verbal 
description of the study is also provided explaining what they will be doing and about 
how long each component will take. Whenever a child indicates they are not willing to 
proceed with any specific portion of the study, we suspend research procedures. We 
repeatedly inform children and their parents that we are unable to obtain any 
research data without the full and continuously provided assent of the child. 
  
Consent Forms 
As in our prior imaging studies conducted at the NYU Langone Medical Center 
and the NYU Center of Brain Imaging, our consent forms follow a standard template 
and changes will be approved by the Center for Brain Imaging, New York University 
and the NYU School of Medicine. 
 
Documentation of Consent 
Consent documentation was described in the Process of Consent section. 
Participants and parents/guardians will receive a copy of the signed consent and 
assent forms. The consent and assent documents are stored in the secure REDCap 
data capture platform (https://openredcap.nyumc.org/apps/redcap/). Only approved 
study personnel members will have access to these records.  
 
Costs to the Subject 
There is no cost to participate in this research study. 
Payment for Participation 
Subject to IRB approval, participants will be compensated $75 for the in-
person evaluation and $75 for each of the two scanning sessions. We will also offer 
reimbursement for transportation via public transit for up to 2 individuals, round trip, 
for each in-person visit, whenever requested on the basis of financial hardship. 
Study management and personnel 
 
 
The proposed study will be executed by the following study personnel: 
 
Responsibility Key:  
A) Participant Recruitment and Screening 
B) Obtains Informed Consent/Assent 
C) Performs Study Assessments 

 
19
D) Quality Assurance of Assessment Data 
E) Performs MRI Scans  
F) 
Quality Assurance of Imaging Data 
G) Assessment of eligibility to proceed to Organizational Skills Training 
H) Performs Organizational Skills Training 
I) 
Performs Assessments of Outcomes at mid-point and end of treatment  
J) 
Quality Assurance of Outcome Data 
K) Data Management  
L) 
Regulatory Reporting and Paperwork Maintenance 
M) Integrative Data Analyses 
 
1) Principal investigator:  
i.Francisco Xavier Castellanos - Oversees/conducts tasks from A to M  
2) Co-Investigator(s):  
i. Richard Gallagher - Oversees/conducts tasks from A to M 
ii. Yuliya Yoncheva – Oversees/conducts tasks from A to M 
3) 
Other Study Staff: 
A) 
Clinical Evaluators and therapists: 
i. Maleeha Haroon - A, B, C, D, E, F, G, H, I, J, K, M 
ii. Samuel Jackson – H 
iii. Emily Kalver – H 
iv. Farah Mahmud – H 
v. Julianna Treene – H 
vi. Allison Parente – H 
 
B) 
Research Coordinator: N/A 
C) 
Other Faculty/Research Scientists/Imaging Specialists: 
i. Hyung Park – M 
ii. Rebecca Shalev - M 
iii. Howard Abikoff – M 
iv. Luis Martinez Agulleiro – A, B, C, D, F, G, I, J, K, M  
D) 
Research Associates: 
i. Lauren Robinson - A, B, C, D, E, F, G, I, J, K, L, M 
 
E) 
Students/interns/volunteers:  
i. Firas Zoha – M 
ii. Hicran Dogru – M 
iii. Angelina Gorbea – J 
iv. Xiaoying Jiang – J 
v. Grace Zhao – J 
vi. Madison Teets – J 
vii. Maria Imas – J 
viii. Rida Saad – J 
 
 
4) Non-NYU affiliated Scientific Collaborator 
Adriana Di Martino, MD, Child Mind Institute, NY, NY - M  
All study personnel have completed all applicable courses in HIPAA and the ethical 
conduct of research. A Delegation of Duties log will be maintained in the study 

 
20
regulatory binder, as per http://www.med.nyu.edu/irb/researchers/faq/your-studys-
regulatory-binder/study-staff-logs-and-cvs. 
 
 

 
21
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