Overlapping Neural Circuits Implicated in Pediatric OCD
Phase: NA
Conditions: Obsessive Compulsive Disorder
Sponsor: New York State Psychiatric Institute

NEW YORK STATE PSYCHIATRIC INSTITUTE 
INSTITUTIONAL REVIEW BOARD 
MEMORANDUM 
 
Signed copy on file at IRB. 
EN/LG/whiteda 
July 24, 2017 
TO:   
RACHEL MARSH, PHD 
 
FROM:  
Dr. Edward Nunes, Co-Chairman, IRB 
 
 
Dr. Laurence Greenhill, Co-Chairman, IRB 
 
SUBJECT:  
EXPEDITED APPROVAL OF PROTOCOL AMENDMENT 
 
 
The amendment to your protocol #7006 entitled: OVERLAPPING NEURAL CIRCUITS 
IMPLICATED IN PEDIATRIC OCD (updated personnel including staff and persons 
designated to obtain consent; updated recruitment materials to change the contact 
person, as per the 7/6/2017 memorandum) has been approved by the Psychiatric 
Institute - Columbia University Department of Psychiatry Institutional Review Board. 
 
Please note that this does not change the IRB's cycle of review.  A progress report 
and an application for continuing review will be required 2 months before the study's 
approval is due to expire: (2/22/2018). 
 
 
 
 
 

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Protocol Title:
Overlapping Neural Circuits Implicated in 
Pediatric OCD
Protocol Number:
7006
First Approval:
03/25/2015
Expiration Date:
02/22/2018
Version Date:
07/24/2017
Clinic:
Child Imaging Studies
Contact Principal Investigator:
Rachel Marsh, PHD
Email: marshr@nyspi.columbia.edu
Telephone: 646-774-5774
Co-Investigator(s):
Moira Rynn, MD
Research Chief:
Moira Rynn, MD
Cover Sheet
Choose ONE option from the following that is applicable to your study
If you are creating a new protocol, select "I am submitting a new protocol." As 5 Year Renewals are no 
longer required, this option remains for historical purposes.
I am proposing an amendment only to an existing protocol
Division & Personnel
Division
What Division/Department does the PI belong to?
Child Psychiatry
Within the division/department, what Center or group are you affiliated with, if any? 
None 
Unaffiliated Personnel
List investigators, if any, who will be participating in this protocol but are not affiliated with New York 
State Psychiatric Institute or Columbia University. Provide: Full Name, Degrees and Affiliation.
All investigators are affiliated with the New York Psychiatric Institute or Columbia University. 

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Amendment
Describe the change(s) being made 
1. We would like to add Kelsey Hill, Kristin Toffey, and Juliet Jenkelowitz. They have all completed CITI 
training and their certificates are on file.
2. We would like to add Kelsey Hill, a research assistant who was recently hired to assist with this study, to 
the list of individuals designated to obtain and discuss consent. 
3. We would like change the contact person on recruitment materials from Dylan Braun to Kelsey Hill.
Provide the rationale for the change(s) 
1. We would like to update our list of personnel to reflect changes in staffing.
 
2. We would like to update our list of individuals designated to obtain and discuss consent to reflect changes 
in staffing.  
 
3. We would like change the contact person on recruitment materials to reflect changes in staffing.  
Comment on the extent to which the proposed change(s) alter or affect risks/benefits to subjects 
The proposed changes will not alter or affect risks/benefits to subjects.
Comment on if the proposed change(s) require a modification to the Consent Form (CF)
The proposed changes will no require a modification to the Consent Form (CF).
Procedures
To create the protocol summary form, first indicate if this research will include any of the following 
procedures
   Psychiatric Assessment
   Neuropsychological Evaluation
   Psychotherapy Trial
   MRI
Population
Indicate which of the following populations will be included in this research
   Children (to age 7)
   Children (ages 8-12)
   Children (ages 13-17)
   Medically and Psychiatrically Healthy Subjects

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Research Support/Funding
Will an existing internal account be used to support the project?
No
Is the project externally funded or is external funding planned?
Yes
Select the number of external sources of funding that will be applicable to this study
2
Funding Source #1
Is the PI of the grant/contract the same as the PI of the IRB protocol? 
Yes
Select one of the following
The grant/contract is currently funded
Source of Funding
Federal
Institute/Agency
NIMH
Grant Name
Overlapping Neural Circuits Implicated in Pediatric OCD
Grant Number
R21MH101441
Select one of the following
Single Site
Business Office
RFMH
Does the grant/contract involve a subcontract? 
Yes
Subcontracted?
To
Name institution(s)
Columbia University
Funding Source #2
Is the PI of the grant/contract the same as the PI of the IRB protocol? 
Yes
Select one of the following
The grant/contract is currently funded
Source of Funding
Federal
Institute/Agency

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Youth Anxiety Center
Grant Name
Youth Anxiety Center
Grant Number
PC002245
Select one of the following
Single Site
Business Office
CU
Does the grant/contract involve a subcontract? 
No
Study Location
Indicate if the research is/will be conducted at any of the following
   NYSPI
This protocol describes research conducted by the PI at other facilities/locations
No
Lay Summary of Proposed Research 
Lay Summary of Proposed Research
This study will use magnetic resonance imaging (MRI) to assess the function and structure of overlapping 
frontostriatal circuits in children and adolescents with Obsessive-Compulsive Disorder (OCD) before and 
after a standard course of evidence based Cognitive Behavioral Therapy (CBT). The functioning of 
frontostriatal control systems will be assessed using the well-validated Simon task. Functioning of the dorsal 
striatum and ventral frontostriatal circuits that support habit learning and reward processing will be assessed 
using a novel fMRI paradigm directly analogous to tasks used to define the neural bases of reward-based 
learning systems in rodents, tailored to a virtual reality environment within the MRI scanner. This study will 
also assess functional and anatomical connectivity within dorsal and ventral frontostriatal circuits in the 
same children and adolescents, and determine whether disturbances in these overlapping circuits are 
associated with OCD symptom severity. Participants will also undergo an MRS scan to measure striatal Glu 
levels. Behavioral measures will be administered to further assess regulatory, learning and memory 
functions. Children and adolescents with OCD will then be offered a evidence based standard course of 
cognitive behavioral therapy before rescanning (along with age-and gender-matched control participants) in 
order to assess how these circuits may change with treatment. In addition, de-identified data may be used in 
the future to conduct secondary data analyses. As we learn more about the diagnoses and neurobiological 
mechanisms of interest in the current study, we may use these data to answer questions beyond those 
described in this protocol. All study procedures will be conducted on-site at the New York State Psychiatric 
Institute. 

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Background, Significance and Rationale
Background, Significance and Rationale
Obsessive-Compulsive Disorder (OCD) is characterized by intrusive thoughts, images, or impulses (i.e., 
obsessions) and repetitive acts performed to prevent or reduce distress (i.e., compulsions). Early-onset (i.e., 
pediatric) OCD is often considered a distinct OCD subtype given its greater familiality, genetic differences, 
comorbidity with tic disorders and ADHD, and male preponderance. Prior work suggests that OCD is 
characterized by dysfunction in the frontostriatal circuits (FS) that subserve inhibitory control. Dysfunction 
in dorsal circuits impairs regulatory control over intrusive thoughts (obsessions) and compulsive behaviors. 
Dysfunction in ventral circuits contributes to reward processing deficits, decreasing the rewarding relief that 
should result from the behaviors and enhancing urges to repeat them. Abnormal maturation of FS circuits 
also contributes to an over-reliance on the dorsal striatum (DS) in OCD, allowing compulsive behaviors to 
evolve into “habits.” This study plans to examine the structure and function of these circuits in a large 
sample of unmedicated OCD children and adolescents. We will combine both well-validated and novel 
fMRI paradigms, along with measures of functional and anatomical connectivity. We will also explore 
measures of cortical thickness and subcortical volumes and changes in circuit-based abnormalities following 
treatment. All study procedures will be conducted on-site at the New York State Psychiatric Institute. 
Specific Aims and Hypotheses
Specific Aims and Hypotheses
The goal of this study is to use multimodal MRI to assess the functioning and structure of overlapping 
frontostriatal circuits in a large sample of unmedicated children and adolescents diagnosed with OCD before 
and after CBT. The brain activity of children and adolescents diagnosed with OCD will be compared to age-
matched healthy controls during performance of the simon task and our virtual reality (VR)-based 
assessment of multiple learning and memory systems. In addition, functional connectivity within 
frontostriatal circuits in children and adolescents with OCD will be compared to age-matched healthy 
control children and adolescents. Anatomical and DTI data will also be collected so that we can begin to 
identify any structural and organizational abnormalities in these neural systems in children and adolescents 
with OCD compared to healthy control participants. Finally, children and adolescents with OCD will be 
offered a standard course of evidence based cognitive behavioral therapy (CBT) before rescanning (along 
with age-and gender-matched control participants) so we can explore changes in these circuits following 
treatment and the improvement of OCD symptoms. We will test the following hypotheses:
1. Compared to healthy controls, children and adolescents with OCD will have increased activation in 
subcortical structures (insula, and putamen) comprising a right hemisphere dorsal frontostriatal circuit while 
performing a self-regulatory control task (Simon task). 
2. Compared to healthy controls, children and adolescents with OCD will have increased activation in the 
dorsal striatum associated with the receipt of rewards during the habit learning task and decreased activation 

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in ventral frontostriatal and mesolimbic areas (amygdala and hippocampus) associated with reward receipt 
during the reward-based spatial learning task. 
3. Compared to healthy controls, children and adolescents with OCD will have increased connectivity 
within task-related dorsal frontostriatal circuits and decreased connectivity within ventral frontostriatal 
circuits during performance of the Simon and reward-based spatial learning tasks, respectively. 
4. Activation within dorsal frontostriatal circuits will correlate positively and activation within ventral 
frontostriatal circuits will correlate inversely with symptom severity in the OCD children and adolescents, 
suggesting that these circuits are functionally more impaired in those with more severe symptoms. 
5. Compared to healthy controls, children and adolescents with OCD will have increased fractional 
anisotropy (FA) within dorsal frontostriatal circuits and decreased FA within ventral frontostriatal circuits.
 
Exploratory Hypotheses:
We will explore change in these circuits in children and adolescents with OCD following CBT compared to 
non-specific changes in the control group. We hypothesize that (1) group differences in the patterns of brain 
activations and connectivity will decrease from baseline. (2) In the children and adolescents with OCD who 
meet the definition of responder status (clinical global impression scale of improvement equaled to 1 or 2), 
we hypothesize that change in the function and connectivity within these circuits will be associated with 
change in OCD symptoms.
Group differences in cortical thickness and subcortical volumes before and after CBT will also be explored. 
Description of Subject Population
Sample #1
Specify subject population
Children/Adolescents diagnosed with OCD
Number of completers required to accomplish study aims
40
Projected number of subjects who will be enrolled to obtain required number of completers
40
Age range of subject population
5-17
Sample #2
Specify subject population
Healthy Controls
Number of completers required to accomplish study aims
40
Projected number of subjects who will be enrolled to obtain required number of completers
40

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Age range of subject population
5-17
Gender, Racial and Ethnic Breakdown
We will recruit all ethnic and racial categories. We plan to recruit a sample that is at least as ethnically and 
racially diverse as the population of the United States. According 2010 U.S. Census, there were 16.3% 
Hispanic and 83.7% %;H racially, there are 72.4% White, 12.6% Black, 4.8% Asian, and 10.2% 
Other. Based on our experience and the demographics served by our institution, we expect the subject racial 
distribution to be approximately 73% White, 18% Black, 9% Asian, and for the ethnic distribution to be 
approximately 22% Hispanic. OCD is believed to occur more frequently in males. Thus, this study 
population will contain a ratio of boys to girls of roughly 3:1.
 
Because of our location in New York City and our history recruiting for studies like these, we do not 
anticipate problems recruiting ethnic or racial minorities. The final ethnic and racial composition of our 
sample will depend not only on who we screen, but also who is eligible and agrees to participate in the 
study.  
 
To encourage minority participation, we will promote awareness of our research project among minority 
individuals in order to ensure the continued diversity of our sample. These efforts will include: 1) placing 
advertisements in media outlets popular with minority $H 2) contacting local minority organizations 
and clergy to provide information about our research $H and 3) involving minority research staff in 
patient recruitment. These efforts are facilitated by the location of our institution in one of the most 
ethnically diverse neighborhoods in New York City (Washington Heights) and by the cultural diversity of 
the staff of the Children’s Day Unit (e.g., bilingual staff of Hispanic background).  
Description of subject population
We plan to recruit approximately 80 individuals ages 5-17 in this study. Participants will have a current 
diagnosis of OCD or no psychiatric diagnosis (healthy control). 
Recruitment Procedures
Describe settings where recruitment will occur
The study will recruit pediatric participants diagnosed with OCD from the CAPES Evaluation Service and 
the Pediatric Anxiety and Mood and Research Clinic (PAMRC), which is part of the Children's Day Unit, 
and is directed by Drs. Rynn and Goldberg. The CAPES/PAMRC provides free expert consultation, 
evaluation, and treatment referrals for children and adolescents suffering from mood and anxiety disorders. 
OCD self-help organizations such as the International OCD Foundation will be contacted to further 
publicize the existence of this study.
Participants and their parent/caregiver will be assessed with an IRB approved phone screen (see attached 

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phone screen). We do not communicate to families that we will destroy their screening
information if they do not come in for a study visit. Regardless of study participation, we enter the 
information from the phone screens into a deindentifed and password protected database.
Morgan Stanley Children's Hospital (CHONY)
Children and adolescents diagnosed with OCD will also be recruited through the patient resources and 
clinics at the Morgan Stanley Children’s Hospital of New York-Presbyterian. After a parent/guardian gives 
permission to the clinic staff to refer a child/adolescent patient to the study, we will follow the screening 
procedures detailed in the study procedures section. We would also like to send a recruitment letter and/or 
pamphlet to all the parents/guardians with children/adolescents who are being treated in these outpatient 
clinics letting them know about our research. We will give this letter and/or pamphlet to the clinicians at 
each clinic and they will distribute the letter to the parents/guardians of their patients. Please see the 
attached recruitment letter and brochure we would like to distribute.
Columbia University Center for Anxiety and Related Disorders (CUCARD) (Director: Anne Marie Albano, 
PhD)
Children and adolescents with OCD will be recruited through the CUCARD. Dr. Albano collaborates with 
Dr. Rynn on other treatment research projects in the area of pediatric anxiety disorders. The CUCARD sees 
300 new children and adolescents per year referred for anxiety disorders, and each child/adolescent and 
family are approached for participation in research projects. Recruitment procedures from this clinic will be 
the same as those above (CHONY). 
Advocacy and Support Groups
OCD participants will also be recruited through scientific presentations to patient advocacy and support 
groups, such as the OCF (Obsessive Compulsive Foundation). We will also set up advertisements in their 
newsletters and on their internet websites and distribute recruitment letters.
Craigslist 
Participants with and without OCD will be recruited through the volunteers section of the Craigslist website. 
We will post advertisements on the website biweekly with a brief description of the study (see attached 
craigslist postings). We will also post this description on other websites and pages relevant to OCD and 
anxiety disorders, consistent with the recruitment methods in IRB #6574. 
Facebook and Twitter 
Participants will be recruited via Facebook (www.facebook.com). We will post a description of this study 
on a page created for Dr. Marsh's Cognitive Development and Neuroimaging Lab and the facebook page for 
the Columbia Pediatric Anxiety and Mood Research Clinic, as well as on other pages relevant to OCD and 
anxiety disorders. The description of our study posted on these Facebook pages will inform treatment 
providers, support group leaders, parents and guardians of the research being conducted under this protocol. 
Facebook will not be utilized to inform children/adolescents of our studies. Facebook will not be used to 
contact children/adolescents. Despite precautionary measures enacted to deter children from responding to 
our postings, if a child/adolescent does respond to a Facebook posting, he/she will be asked to speak with 
her/her parent or guardian regarding he/her interest in participation in the study who then may contact us. 
The same IRB approved description of our study and a list of tweets (see attached list of tweets) will be 
posted on our lab twitter page on twitter.com. 

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Linkedin
We will use Linkedin to communicate with colleagues about our research efforts. A web announcement will 
be sent including our lab website, Facebook, and Twitter page links for their reference and for referring 
potential participants. As with Facebook and Twitter, if a child/adolescents contacts us directly after being 
referred by one of our colleagues, he/she will be asked to speak with a parent or guardian regarding interest 
in participation in the study.
 
RecruitMe: Columbia
Participants with OCD and healthy controls will be recruited through Columbia University's Recruit Me, an 
online tool to connect potential research participants with researchers conducting relevant studies. 
Flyers
Participants diagnosed with OCD and healthy controls will also be recruited through flyers posted in the 
community. We will post flyers on bulletin boards in Columbia University Medical Center buildings as well 
as in local laundromats, grocery stores, public libraries, and community centers. Please see the attached 
flyers. 
Private Practice
Participants diagnosed with OCD will be recruited through colleagues who see patients in private practice. 
Recruiting patients seen in private practice will enable us to gain a more diverse demographic and 
socioeconomic sample than would be found in the Washington Heights area alone. We will provide 
clinicians with a list of target diagnoses and a brief description of the purpose and procedures of our 
protocol, as well as letters for families who express interest in our research. The clinicians will initially 
approach parents or guardians to ascertain their interest in our protocol. Parents/guardians that express 
interest in our MRI study and want to hear more about it will be asked for permission for a member of our 
research team to contact them. With this verbal permission, members of our research team will follow up 
with a telephone call to read through a recruitment script detailing what we want to do and what would be 
expected of their child, and to administer screening procedures (please see recruitment script and screening 
questionnaire).
Healthy Control Recruitment
In addition to advertisements on Craigslist and flyers in the community, normal controls will be
recruited from community-based telemarketing lists of households characterized by zip code, age,
gender, ethnicity, and income level (Info USA based in Omaha, Nebraska. Phone #: 1-888-289-5478).
Healthy Control Recruitment Procedures: Introductory letters will be sent by the research team to randomly 
selected households containing potential participants with a demographic profile matching the clinical 
sample. We will also contact by telephone the parents of the families first contacted by letter. We will 
explain the purpose and design of our study, encouraging parents to ask questions about the project (see 
attached Telephone Recruiting Script). Parents of children who are interested in participating will then be 
screened for eligibility (see attached Telephone Screening Questionnaire). If their child meets inclusion 
criteria for the study, they will be approached for enrollment in the study. 
How and by whom will subjects be approached and/or recruited? 

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Research staff from Dr. Marsh’s Cognitive Development and Neuroimaging Lab and the PAMRC team may 
approach and discuss the research study with potential participants who have given permission to be 
contacted about research. Research staff will be responsible for fully explaining the details of the study, 
answering any questions, and consenting the participants if they are interested in the study.
How will the study be advertised/publicized? 
IRB-approved radio/newspaper/web advertisements and flyers will be used to recruit participants.
The study will be publicized in the following ways:
1. Delivery of letters and pamphlets to patients by clinicians and researchers who practice at one of the 
recruitment sites listed above
2. Advertisements on patient advocacy and support group websites, listservs, and newsletters, as well as 
through scientific presentations to these groups
3. Research study announcements on Craigslist.com and Facebook.com, RecruitMe: Columbia 
4. Mailings to households from community-based telemarketing lists
5. Flyers posted in the community
6. Pamphlets sent to individuals interested in referring individuals from one of the recruitment sites listed 
above
Do you have ads/recruitment material requiring review at this time? 
Yes
Does this study involve a clinical trial?
Yes
Please provide the NCT Registration Number
NCT02421315
Concurrent Research Studies
Will subjects in this study participate in or be recruited from other studies? 
Yes
Describe concurrent research involvement
Participants in this study may be recruited and may be screened using the phone screens from the following 
studies: 
 NYSPI IRB #6019R entitled, “Evaluation at the NYSPI Child Psychiatry Research Clinic.”
 NYSPI IRB #6574 entitled, "Novel Medication Strategies Targeting Brain Mechanisms in Pediatric 
OCD." 
 NYSPI IRB#6345R entitled, "Biobehavioral Assessment of Stress in Adolescent Pregnancy: 
Perinatal Outcomes
 NYSPI IRB# 6450 entitled, "The Effects of Prenatal Stress and Poor Nutrition on Brain and 
Cognition"

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Inclusion/Exclusion Criteria
Name the subject group/sub sample
OCD patient group 
Create or insert table to describe the inclusion criteria and methods to ascertain them
 CRITERION   
 METHODS OF ASCERTAINMENT
1. Participants must be 5-17 
at the time of consent 
 Telephone Screening Questionnaire 
 Inquiry at time of consent by trained 
research staff
2. DSM-IV Diagnosis of 
OCD as the principal 
problem
 IE will administer the Anxiety 
Disorders Interview Schedule (ADIS). 
The ADIS will be used as a diagnosis 
measure
 Study MD will conduct a clinical exam 
to confirm diagnosis 
 CYBOCS scores N 16 
 In addition previous clinicians will be 
contacted to discuss diagnosis 
3. Not on psychotropic 
medication and not 
receiving current 
psychotherapy for OCD
 Telephone Screening Questionnaire
 Clinical interview
 medical records obtained by research 
team 
 In addition previous clinicians will be 
contacted to confirm treatment-naivety 
or psychotropic medication free for at 
least 3 months 
4. Written informed assent 
by the participants (8 and 
older) and consent by the 
parent 
 Consent interview by trained research 
staff (see consent procedures).
5. Participants and a 
parent/guardian must be 
able to read and understand 
English 
 Telephone screening questionnaire 
 Inquiry at time of consent by trained 
research staff 

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Create or insert table to describe the exclusion criteria and methods to ascertain them
 CRITERION
 METHODS OF 
ASCERTAINMENT 
1. DSM-IV current diagnosis of major 
depressive disorder, attention-deficit 
hyperactivity disorder, Tourette's/Tic 
Disorder, or substance/alcohol abuse
 Telephone Screening 
Questionnaire
 Clinical Interview 
2. DSM-IV lifetime diagnosis of 
psychotic disorder, bipolar disorder, 
eating disorder,  pervasive developmental 
disorder, or substance/alcohol abuse 
 Telephone Screening 
Questionnaire
 Clinical Interview 
3. Active suicidal ideation  
 Telephone Screening 
Questionnaire
 Clinical Interview 
4. Females who are pregnant or nursing  
 Telephone Screening 
Questionnaire
 Urine pregnancy test 
5. Major medical or neurological 
problems 
 Telephone Screening 
Questionnaire
 Medical history obtained 
by study psychiatrist 
6. Presence of metallic device or dental 
braces 
 Telephone Screening 
Questionnaire
 New York Psychiatric 
Metal Screening 
Questionnaire 
7. IQ<80 
 All participants will be 
administered 
the Weschsler 
Abbreviated Scale of 
Intelligence II (WASI-II) 
to confirm IQ
8. A current or past diagnosis of pediatric 
autoimmune neuropsychiatric disorders 
associated with streptococcus (PANDAS)
 Telephone Screening 
Questionnaire 
 Clinical Interview 

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9. Individuals who are currently receiving 
CBT, other forms of psychotherapy, or 
psychotropic medications
 Telephone Screening 
Questionnaire
 Inquiry at time of consent 
by trained research staff
 Medical history obtained 
by study doctor 
10. Individuals who have received a full 
course of CBT in the past 
  Telephone Screening 
Questionnaire
 Inquiry at time of consent 
by trained research staff
 Medical history obtained 
by study doctor 
11. A positive pregnancy 
test                               
 Based on pregnancy test 
given to all post-
menarchal females onsite 
prior to the MRI scan 
12. Positive urine screen for illicit drugs 
 Based on urine toxicology 
assessment for 
participants 12 and up 
13. Inability of participant or 
parent/guardian to read or understand 
English 
 Telephone screening 
questionnaire 
 Inquiry at time of consent 
by trained research staff 
member 
Inclusion/Exclusion Criteria #2
Name the subject group/sub sample
Healthy Controls 
Create or insert table to describe the inclusion criteria and methods to ascertain them 
 CRITERION
 METHOD OF 
ASCERTAINMENT
1. Participants must be 5-17 at the time 
of consent
 Telephone Screening 
Questionnaire
 Inquiry at time of consent 

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by trained research staff
2. Written informed assent by the 
participants (8 and older) and consent 
by the parent
 Consent interview by 
trained research staff (see 
consent procedures)
3. Participants and a parent/guardian 
must be able to read and understand 
English
 Telephone Screening 
Questionnaire 
 Inquiry at time of consent 
by trained research staff
Create or insert table to describe the exclusion criteria and methods to ascertain them 
CRITERION 
 METHOD OF ASCERTAINMENT
1. Any current or lifetime psychiatric 
diagnosis 
 Telephone Screening 
Questionnaire 
 Clinical Interview   
2. Active suicidal ideation  
 Telephone Screening 
Questionnaire
 Clinical Interview 
3. Females who are pregnant or 
nursing 
 Telephone Screening 
Questionnaire
 Urine pregnancy test
4.Major medical or neurological 
problems 
 Telephone Screening 
Questionnaire
 Medical history obtained by 
study psychiatrist 
 5. Presence of metallic device or 
dental braces    
 Telephone Screening 
Questionnaire 
 New York Psychiatric Metal 
Screening Questionnaire 
5. IQ <80 
 All participants will be 
administered theWechsler 
Abbreviated Scale of 
Intelligence II (WASI-II) to 

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confirm IQ
6. A current or past diagnosis of 
pediatric autoimmune 
neuropsychiatric disorders associated 
with streptococcus (PANDAS)
 Telephone Screening 
Questionnaire
 Clinical Interview 
7. A positive pregnancy test  
 Based on pregnancy test 
given to post-menarchal 
females onsite prior to MRI 
scan 
8. Positive urine screen for illicit 
drugs
 Based on urine toxicology 
assessment for participants 12 
and older 
9. Inability of participant or 
parent/guardian to read or understand 
English 
 Telephone screening 
questionnaire
 Inquiry at time of consent by 
trained research staff 
Waiver of Consent/Authorization
Indicate if you are requesting any of the following consent waivers
Waiver of consent for use of records that include protected health information (a HIPAA waiver of 
Authorization) 
No
Waiver or alteration of consent
Yes
Waiver of documentation of consent 
No
Waiver of parental consent 
No
Consent Procedures
Is eligibility screening for this study conducted under a different IRB protocol?
No
Describe procedures used to obtain consent during the screening process 

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Prior to initiating screening procedures, research staff will obtain assent from the child and 
adolescent participants and consent from their parent/legal guardian by describing the purpose and nature of 
the research study and answering any questions from the families. The participant's parent/legal guardian 
will receive copies of the signed consent/assent forms. 
  
Describe Study Consent Procedures
Each member of the research team has been extensively trained in consent procedures by Drs. Rynn and 
Marsh and has completed the NYSPI CITI training modules. The person obtaining consent will explain the 
protocol and associated risks to the prospective participant's parent/guardian. They will review the study 
objectives and procedures with the parent/guardian and ask him/her to read the attached consent form. The 
research team will also answer any questions the parent/guardian may have and ensure that the participant's 
parent/guardian understands that information collected as part of this study may be used in the future to 
answer other research questions not specified in this protocol as we learn more about the diagnoses and 
neurobiological mechanisms of interest. Once the research team member obtaining consent feels confident 
the participant is comfortable with the requirements of the study, they will obtain informed consent from the 
parent/guardian by having him/her sign the consent form. The consent process will be conducted after the 
telephone screening but before any other part of the study is conducted. 
Because we will collect medical histories from all participants, each participant's parent/guardian will be 
asked to sign a HIPPA form prior to review of his or her child's medical history and prior to participation in 
the study. Permission to review medical histories is thus documented in writing. This form is designed to 
inform parents/guardians of their child's rights to privacy and of measures that we will take to keep their 
information as secure as possible according to the law. Our HIPAA form is in accordance with all federal 
and state regulations as laid out by the Office for Human Research Protections. 
Indicate which of the following are employed as a part of screening or main study consent procedures
   Consent Form
Justification for Waiver or Alteration of Consent
Waiver of consent is requested for the following
A waiver of consent is needed in order to obtain verbal consent from potential participants during the study 
phone screen. Please refer to 45CFR46.116(d) for justification of this waiver.
Explain why your research can not be practicably carried out without the waiver or alteration
As it is not practical to get written consent prior to conducting the phone screen, we instead get verbal 
consent from participants and/or their parents at the beginning of each phone screen. The staff member 
conducting the phone call documents that verbal consent was obtained.
Describe whether and how subjects will be provided with additional pertinent information after participation
N/A

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Assent Procedures
Describe procedures by which subject assent will be assessed and/or recorded
The trained member of the research team who obtains assent will explain the protocol and associated risks 
in language that is appropriate to the prospective participant's developmental level. Assent will only be 
obtained from children 8 years and older. The trained member of the research team will review the study 
objectives and procedures with the participant and ask him/her to read the attached assent form. The 
research assistant will also answer any questions the participant may have. Once they feel confident the 
participant is comfortable with the requirements of the study, they will obtain parental permission as well as 
assent from the participant by having him/her sign the assent form. The permission and assent process will 
be conducted after the telephone screening but before any other part of the study is conducted. All efforts 
will be made to coordinate procedures (neuropsychological assessment, parent/participant interviews, and 
MRI) into a single day; however, the child/adolescent will be given the option of a second day for the MRI 
if he/she is fatigued or has a preference. If the participant (or parent/guardian) chooses to divide the study 
into two days, the participant will be verbally reminded of the key points of the assent form and procedures 
of the study on the second day. 
Persons designated to discuss and document consent
Select the names of persons designated to obtain consent/assent
Gindea, Sophie
Hill, Kelsey
Stefan, Mihaela
Steinberg, Emily
Wei, Chiaying
Yanes-Lukin, Paula, PHD
Type in the name(s) not found in the above list
Goldberg, Pablo, MD
Marsh, Rachel, PhD 
Study Procedures
Describe the procedures required for this study
Columbia University Pediatric Anxiety and Mood Research Clinic (CU-PAMRC)
The study will be conducted at the Columbia University Pediatric Anxiety and Mood Research Clinic 
(PAMRC). PAMRC is an outpatient clinic and a research day treatment program (CDU) that provides 
services for the psychiatric and educational need of children and adolescents participating in research 

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protocols at NYSPI. Most of the children have either failed or not completely responded to first line 
treatments for mood, OCD, or other anxiety disorders. School services are provided by PS186X, a New 
York City public school located on the unit during the academic year starting from September through June. 
In addition, during the 6 week summer program in July and August, the PAMRC provides educational 
tutoring. This unit provides continued clinical care for children and adolescents after their participation in an 
IRB approved protocol at no cost. Led by Drs. Rynn and Goldberg, the staff consists of a research medical 
director, Dr. Pablo Goldberg, a research nurse, a social worker, psychologists, and trainees. Although this 
protocol is an outpatient protocol, if an adolescent requires additional support or requires a higher level of 
care, the adolescent may be admitted to the PAMRC partial program that runs Monday through Friday from 
8:30AM to 3:30PM where the adolescent can be closely monitored, receive educational credit, and 
additional supportive service. For children under the age of 12, the PAMRC team is available for the child 
and parent to come in for daily check-in visits for support and monitoring, but it does not have educational 
programming for children under 12. 
Screening
Upon consenting, participants will complete all screening procedures. Those participants who turn 18 after 
assenting while still enrolled in the study will be re-consented as adults. Study staff will confirm and 
document that they agree to their parents' continued involvement in the study. Screening visits will be 
coordinated to be completed in 1 day, but may be spread out over the course of 2 days to allow sufficient 
time to obtain thorough medical and psychiatric history to ensure the patient's safety and 
eligibility/ineligibility in the study.  
 Diagnostic Assessments: Anxiety Disorders Interview Schedule- Child/Parent version (The child 
version will be administered to all participants. The parent version will be administered to parents of 
all participants); Yale-Brown Obsessive Compulsive Scale, Child version (CYBOCS), OCD onset 
form; Clinical Global Inventory- Severity Scale; Family History Screen and Isolated Tics/Tic 
Disorder Assessment Questions; Hamilton Depression Scale (HAM-D)
 Feasibility and safety measures: Columbia Suicide-Severity Rating Scale
 Medical: Tanner Scale, vital signs, height and weight measurements to ensure participant safety 
prior to the MRI scan, pregnancy test and urine toxicology 
 MRI: MRI Screening Questionnaire (The screening questionnaire includes questions regarding 
inclusion/exclusion criteria, including the presence of ferromagnetic implants, pubertal status, and 
pregnancy)
Any adverse events that occur during screening and/or any information that warrants clinical attention (i.e. 
suicidal ideation, intent to harm oneself/others) will be reported immediately to Drs. Rynn and Marsh, and 
proper interventions and referrals will be made.
Our teams believe research participation in the study would be enhanced by adding an educational 
opportunity/lesson to the screening or baseline healthy control study visits . During either of these visits, a 
research staff member, under Dr. Marsh's supervision, will educate the participant and their parent/guardian 
about MRI and the application of MRI to the study of brain development and psychiatric illnesses. 
 
Baseline Study Visit 

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After completing the screening procedures, eligible participants will proceed to the baseline study visit. We 
will make every effort to schedule study procedures so that they do not interfere with the school day, 
especially for the control group. Should a family of a child/adolescent with OCD in search of treatment 
decide to participate in an in-person screen during a school day (times), we will leave that decision up to the 
family. The baseline study visit will include optional training in the Mock scanner, pregnancy testing, an 
MRI scan, Neuropsychological testing and completion of self-report forms. These procedures are described 
below:
Mock Scanner or MRI Simulator : The participant will have the option to undergo training for the MRI 
scan in an MRI simulator. Two software programs are used in the MRI simulator: SimFx and Motrack. 
SimFx software simulates the ambient scanner sound and the active scanning noise. Motrack software uses 
trackSTAR to monitor how much a participant moves, through the use of a sensor attached to the 
participant's head. The purpose of the MRI simulator is to provide a realistic scanning experience to help the 
participant gradually acclimate to scanning procedures.
Pregnancy Test: All females who are post-menarchal will be required to take a pregnancy test prior to the 
MRI scan. In addition, all post-menarchal females will be required to take a pregnancy test at the screening 
visit to ensure eligibility. The tests will be conducted on-site after the signing of the consent/assent forms 
and will be paid for by the study. Urine samples will be collected and pregnancy tests done on the day of the 
screen and MRI scan. Children and their parents will be told about the results of pregnancy tests done on 
minors. The participant must have a negative pregnancy test in order to participate in this study. The trained 
clinician (i.e., professionally trained, bachelor's or higher level clinician) will conduct the pregnancy test and 
discuss the results with the parent and child. Whether the parent and the child are told the results of the 
pregnancy test together or separately will be determined on a case-by-case basis by the clinician in 
consultation with Drs. Rynn and Marsh and other senior staff based on all available data on the family. In 
the rare instance of a positive pregnancy test, a trained clinician will provide appropriate information and 
referrals. The participant will be encouraged to consult with heir primary physician or with a family 
planning clinic. 
 
MRI Scan 
 Pulse Sequence
 Approximate Scan Time
 fMRI
 50 minutes
 Anatomical
 25  minutes
 DTI
 10  minutes 
* see attached for full pulse sequence 
For the MRI procedures, the participant will be instructed to lie as still as possible within the magnet for 90 
minutes. All precautions and protections will be given to the participant to ensure that they are as safe and 
comfortable as possible. For the participant’s comfort within the scanner, they will lie on a padded table 
with a pillow on which to rest their heads. A blanket will also be provided to keep participants warm during 
the procedure. If the participant appears nervous or anxious, a trained member of the research staff will 
remain with them inside the scanning suite for the duration of the scan. The participant will be given a 
squeeze ball to terminate the scan at any time. If they squeeze the ball, they will be removed from the 
scanner immediately. All of the MRI procedures will be conducted on the 3-Tesla MRI scanner at the New 
York State Psychiatric Institute. Conducting these procedures will be an accredited Magnetic Resonance 

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Technologist (B.M.R.) and two members of the research staff (Bachelor’s Level or Higher) trained in the 
acquisition of MR images by Dr. Marsh, as well as in procedures for testing human participants.
Functional MRI procedures will include the completion of the Simon Spatial Compatibility Task (Simon) 
and the Virtual Reality Maze Tasks (VR). EyeLink 1000 Plus system will be used during these tasks to 
observe and analyze the participant’s eye movements during each task. By following the participant's gaze 
we will be able to determine whether or not the participant is focused on the stimulus presented on the 
screen. 
The fMRI tasks are as follows:
1. In the Simon Task, participants are instructed to respond with a button press each time an arrow is 
displayed to indicate the direction in which it was pointing. Most of the stimuli will be arrows that were 
displayed on congruent sides of the screen (e.g. left-pointing arrows displayed on the left side of the screen). 
Only a few of the stimuli will be presented on the incongruent side of the screen (e.g. left-pointing arrow 
displayed on the right side of the screen). Participants will be asked to inhibit the response to the location of 
arrow display and indicate their response to the direction of the arrow displayed.
2. The VR task is designed to study declarative and procedural/habit-learning and memory systems. 
Participants will be told that they will find themselves in the center of a virtual maze with 8 arms extending 
outward and that their task is to find hidden rewards ($ signs). The task will use a joystick to navigate 
through the environment. There will be both a spatial (declarative) and an S-R (procedural) learning 
condition. In the declarative version, participants must remember the locations of extra-maze cues (e.g. 
mountains, trees, and a sunset) to find the rewards. In the S-R version, participants must learn to approach lit 
arms to obtain rewards. Here, the extra-maze cues will be randomly interchanged at the end of each trial, 
thus destroying any possibility of using spatial learning to find the rewards.
In total, we will collect data from three modalities of MRI within this study: functional MRI; anatomical 
MRI; and diffusion tensor imaging (DTI). Between the functional and structural (anatomical and DTI) scans 
there will be a break for participants to stretch and use the bathroom. Child participants will be given the 
option to watch a segment of a child-friendly movie during the structural portion of the scan. Although our 
MRI Scans are for research purposes, T-1 weighted FSPGR anatomical images will be sent to a radiologist 
to be examined for evidence of mass effects or hydrocephalus within 1 month, and any significant 
abnormalities will be shared with parent of a child participant. One radiological report will be acquired after 
the baseline scan because the follow-up scan will take place within 16-20 weeks of the first scan. When 
necessary, referrals will be made for clinical scans. We receive written reports once a month from the 
radiologist documenting his findings from all readable scans, and any reports that suggest the need for 
follow up will be addressed by Drs. Rynn and Marsh immediately. In the rare case of obvious, serious 
lesions or tumors that need to be immediately followed up clinically, the radiologist will contact Dr. Marsh 
at the time the reading is completed.
 
MRS Data Acquisition
All MRS data will be acquired on our NYSPI scanner with a standard quadrature single-channel head coil in 
a total examination time of approximately 60 min, including scan setup. First, a standard T1-weighted 
volumetric MRI series will be acquired for use in estimating the proportions of gray matter, white matter 
and CSF content of the head of the caudate through tissue segmentation. Second, glutamate (Glu) levels will 

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be recorded from the head of the caudate using MRS. The recorded 4D raw data set will be processed using 
standard procedures. The striatal voxels will be selected from the spectroscopic imaging grid after 
acquisition and post-processing, and then analyzed for Glu content using versatile software, XsOSNMR, 
developed in Dr. Shungu’s laboratory at Weill Cornell (collaborator on PSF # 6574). The Glu data will be 
quantified as peak area ratios relative to the robust unsuppressed water resonance (W) in a spectroscopic 
imaging data set that will be acquired in just 4 min using the same spatial parameters as in the PRESS SI 
sequence.
Neuropsychological Assessments
All participants will undergo neuropsychological testing that includes measures of intelligence, impulse 
control and sustained attention, memory, and learning. These behavioral measures, conducted either before 
or after (but always within a week of) the scanning session for each participant, will be used in correlation 
analyses with our MRI measures of brain function, connectivity, and morphology.These measures will be 
used in correlation analyses with measures of regional brain activation. (Please see “Instruments” below for 
a complete listing of these measures).The tests assessments will all be administered at the New York State 
Psychiatric Institute by a trained member of the research staff (Bachelor’s level or higher). 
Self-reports 
Participants and their parents will fill out self-report forms during the baseline study visit and during 
screening. Please see the section on assessment instruments for more detail about these self-reports.
 
Cognitive Behavioral (CBT) Treatment
Upon completion of the diagnostic interviews, neuropsychological tests, and baseline MRI scan, pediatric 
participants diagnosed with OCD will be offered standard evidence based CBT treatment in the PAMRC. 
The treatment team will offer a course of CBT (45 minute sessions for 12 to 16 weeks), augmented by 
medication treatment when clinically indicated based on the clinical treatment standards. This treatment will 
be overseen by Drs. Rynn, Goldberg, Yanes-Lukin and Puliafico. Cognitive-behavioral therapy (CBT) is a 
treatment based on learning and cognitive theories. CBT for OCD involves gradually exposing patients to 
anxiety provoking stimuli while having patients refrain from engaging in compulsive rituals and/or 
avoidance behaviors. There are three major components of CBT treatment for OCD, specifically: (1) 
exposure to anxiety provoking stimuli, (2) response prevention, and (3) cognitive techniques intended to 
decrease anxiety during the exposure and response prevention processes. CBT has demonstrated clinically 
significant effects in reducing pediatric OCD symptomatology in several randomized controlled clinical 
trials (Abramowitz, Whiteside, & Deacon, 2005, for review). We will use the following referral sources for 
those for whom treatment in PAMRC might not be suitable (CUCARD, CHONY, NYU Child Study Center, 
private practices etc.) 
The study physician and psychologist will provide ongoing monitoring of treatment cases during the 
PAMRC weekly research meeting and at the midpoint CBT treatment (between 6 to 8 weeks) the study 
physician will be scheduled to clinically evaluate participants with the standard clinical PAMRC protocol. 
At this time, the study physician will administer the CSSRS and the CGI. He will also conduct a clinical 
review of symptoms. Additionally, the study therapist and/or independent evaluator will clinically evaluate 
the participant by administering the CYBOCS. If the study staff believe that the patient meets for clinical 
deterioration, following administration of these assessments, the physician will discuss with the family the 
option of augmenting treatment with medication. In addition to ongoing monitoring and treatment midpoint 

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physician evaluations, the study clinician will complete weekly clinical assessments, including the CGI, as 
indicated in the treatment manual “OCD in Children and Adolescents: A Cognitive-Behavioral Treatment 
Manual” by John March, M.D.
 
To ensure that EX/RP is delivered appropriately, treatment will be provided by clinicians trained in EX/RP 
and supervised by Anthony Puliafico, Ph.D. and Paula Yanes-Lukin, Ph.D., both of whom are experts in 
EX/RP treatment. To ensure fidelity, treatment for all participants will follow the treatment manual “OCD 
in Children and Adolescents: A Cognitive-Behavioral Treatment Manual” by John March, M.D. Clinicians 
will meet weekly with Dr. Puliafico or Dr. Yanes-Lukin for supervision on study treatment cases, and Drs. 
Puliafico and Yanes-Lukin will review treatment procedures to ensure fidelity and appropriate clinical care. 
End of Study Visit
All treatment-seeking OCD participants will be asked to return for an end of study visit following 
completion of their treatment in the PAMRC. We will also ask age-and gender-matched control participants 
to return for an end of study visit, within 16 to 20 weeks of their first scan. Procedures for the end of study 
visit will be similar to those described for the baseline visit. The following assessments will be completed 
during the end of study visit: 
Diagnostic and Safety assessments:
 Diagnostic Assessments: Anxiety Disorders Interview Schedule- Child/Parent version (Subsections 
of ADIS that were endorsed at baseline will be administered to all child/adolescent participants and 
their parents at follow-up.); Yale-Brown Obsessive Compulsive Scale, Child version (CYBOCS), 
Clinical Global Inventory- Severity Scale; Hamilton Anxiety and Depression Scale (HAM-D)
 Feasibility and safety measures: Columbia Suicide-Severity Rating Scale
 Medical: Tanner Scale, vital signs, and height and weight measurements to ensure participant safety 
prior to the MRI scan 
 MRI: MRI Screening Questionnaire (The screening questionnaire includes questions regarding 
inclusion/exclusion criteria, including the presence of ferromagnetic implants, pubertal status, and 
pregnancy)
Self-Report Forms:
 Child Obsessive-Compulsive Impact Scale-Revised (COIS-R), Family Accommodation Scale 
(FAS), Sensitivity to Punishment and Sensitivity to Reward Questionnaire-Children (SPSRQ-C), 
Intolerance of Uncertainty Scale for Children (IUSC), Barratt Impulsivity Scale (BIS) Brief, Media 
Use Questionnaire 
Neuropsychological Testing:
 Stroop Word-Color Interference, Continuous Performance Task, the Reinforcement Learning Go/no-
go task, and the risk/ambiguity tasks 
2nd MRI Scan: 

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 The MRI procedures and pulse sequences used in the second scan will be the same as those 
described for the baseline scan. 
 The MRS data may also be collected from OCD participants who remain symptomatic at end of 
study. MRS procedures and pulse sequences used at end of study will be the same as those described 
for the baseline scan. 
The purpose of the follow-up visit is to have information allowing us to compare brain structure and 
function before and after treatment in children and adolescents with OCD and to be able to examine the 
relationships with treatment response.
Follow-Up Care 
Upon completion of CBT treatment, end of treatment assessments and MRI Scan, participants will be 
offered an additional 3 months of follow up care, consisting of 3 monthly booster sessions, and/or open 
medication management, if applicable. If a participant is withdrawn from the study or drops out of the study, 
he/she will also be offered 3 monthly booster sessions. In the event they prefer to be treated elsewhere, they 
will also be provided referrals to community providers. All participants will be assessed during these 
booster session OCD severity (using the CYBOCS and CGI-S by the IE). Patients and families will have the 
option of completing 1 m and 2m follow up assessments by phone and the 3m assessment will be conducted 
in person. 
 
Clinical Deterioration 
Any patient who is evaluated by the study clinician to have experienced worsening of CGI-S by two levels 
for two consecutive visits will be evaluated by the study physician to determine if medication augmentation 
is indicated and if other types of ancillary treatments are indicated (such as family therapy and education 
support). If the child/adolescent continues to show clinical deterioration during the study and further 
continuation under such circumstances would be detrimental to the child/adolescent, the participant will be 
withdrawn from the study. If the child/adolescent is withdrawn from the protocol, the child/adolescent will 
be eligible for 3 months of no cost treatment in the PAMRC, consisting of 3 monthly booster sessions.If the 
participant or the participant’s parent/guardian would prefer outside referrals, arrangements will be made by 
the research staff. 
 
Future Research
After finishing the study, we may contact healthy control participants about participation in future research 
studies such as ongoing or new research studies. Participants do not have to participate in future research 
and they can decline participation when contacted. Participants may withdraw their permission to be 
contacted at any time by contacting the research team.
You can upload charts or diagrams if any
Criteria for Early Discontinuation  
Criteria for Early Discontinuation
Clinical Deterioration 

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Any patient who is evaluated by the study clinician to have experienced worsening of CGI-S by two 
levels for two consecutive visits will be evaluated by the study physician to determine if medication 
augmentation is indicated and if other types of ancillary treatments are indicated (such as family therapy and 
education support). If the child/adolescent continues to show clinical deterioration during the study and 
further continuation under such circumstances would be detrimental to the child/adolescent, the participant 
will be withdrawn from the study. If the child/adolescent is withdrawn from the protocol, the 
child/adolescent will be eligible for 3 months of no cost treatment in the PAMRC, consisting of 3 monthly 
booster sessions. If the participant or the participant’s parent/guardian would prefer outside referrals, 
arrangements will be made by the research staff.
 
Assessment Instruments
Create a table or give a brief description of the instruments that will be used for assessment
Diagnostic Assessments:
Anxiety Disorders Interview Schedule for Children for DSM-IV (ADIS-C/P Revised): This will be 
administered to the participant and parent/caretaker by the independent evaluator (IE) at screening to 
confirm the diagnosis of OCD and its age of onset. 
Family History Screen (FHS): This screens for the presence of 15 psychiatric disorders among the 
participant’s biological relatives. It is administered to a family informant (for those ages 6-17) or to the 
subject (ages 18-20), who reports on himself/herself and on other biological relatives. It will be 
administered by the MD at screening.
The Tanner Scale: This is a scale of physical development based on external primary and secondary sex 
characteristics. Participants look at pictures of pubertal stages and identify their pubertal stage. 
Yale-Brown Obsessive Compulsive Scale, Child version (CYBOCS): The CYBOCS is a semi-structured 
measure of OCD severity with excellent inter-rater reliability, internal consistency, and test-retest reliability. 
It is validated in those starting at age 7 and used in studies up to age 20. The CYBOCS differs from the 
adult YBOCS only in its use of simpler language. The CYBOCS will be administered by IEs at screening or 
baseline and will be the primary outcome measure. 
Hamilton Depression Scale (HAM-D, 17-item): This semi-structured interview which assesses the severity 
of depressive symptoms is validated for use in ages 7 and above. It will be administered by the IE at 
baseline.  
 
Feasibility and Safety Assessments:
Columbia Suicide-Severity Rating Scale (C-SSRS): This is a semi-structured clinician rating of suicidal 
behavior, suicide attempts, and presence and intensity of suicidal ideation. 
Client Satisfaction Questionnaire (CSQ): Used in prior studies, this scale includes questions about 
satisfaction with treatment (CSQ). It will be completed by the participant (and parent/caretaker for those < 
18 and those 18-20 with permission). For children under the age of 12, the Research Assistant (RA) will be 
present in case of reading comprehension questions. 
Self-Report Forms:

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OCD onset Form- This is a questionnaire completed by parents and children, used previously in IRB # 
6574, to gather information about the onset and severity of OCD symptoms. Following the completion of 
the questionnaire, the Independent Evaluator (IE) completes a composite form taking into account the parent 
and child reports. 
Child Obsessive-Compulsive Impact Scale-Revised (COIS-R): This 27-item self-report questionnaire 
measures OCD-specific functional impairment. The COIS-R-C is a 3-factor structure youth-report form. 
The COIS-R-P is a 4-factor structure parent-report measure (completed by the parent/caretaker for those 
<18 and those 18-20 with permission). Both will be completed at baseline. 
Family Accommodation Scale (FAS) (5 minutes): This scale consists of 12 items to assess the areas and the 
level of family accommodation to the patient’s OCD symptoms. It will be completed by the parent at 
baseline. 
Isolated Tics/Tic Disorder Assessment: The parent(s) of the participant will be asked five questions about 
family history of isolated tics and Tic Disorder. The questions were developed by investigator Blair 
Simpson and are administered as an addendum to the FHS.
Sensitivity to Punishment and Sensitivity to Reward Questionnaire-Children (SPSRQ-C): This questionnaire 
measures Gray's anxiety and impulsivity dimensions. The questionnaire will be used to assess reward 
sensitivity.
Intolerance of Uncertainty Scale for Children (IUSC): The IUSC is a 27-item, 5-point Likert-style 
rating scale of a child’s negative reaction to uncertain or ambiguous situations on emotional, cognitive, or 
behavioral level. The rating scale is completed by parent and child. IUSC Child and Parent forms have been 
validated in samples of youth ages 7-17, and the outcomes of this psychometric study have been published 
in Psychological Assessment (Comer, Roy et al., 2009). Specifically, both the parent and child forms of the 
IUSC have demonstrated strong internal consistency, as well as convergent validity as evidenced by 
significant associations with anxiety, worry, and reassurance-seeking. Children with anxiety disorders score 
higher than matched non-referred community youth on both the parent and child forms. Moreover, receiver 
operating characteristic (ROC) analyses demonstrate acceptable overall utility for the measure in 
distinguishing youth with anxiety disorders from youth without anxiety disorders. In all, findings from this 
psychometric work provide support for the use of the IUSC for continuous measurement of children's ability 
to tolerate uncertainty.
Barratt Impulsivity Scale (BIS) Brief:  The BIS Brief is an 8-item, 4-point Likert-style rating scale, adapted 
from the BIS-11 self report, and  designed to assess the personality/behavioral construct of impulsiveness.
The Short Grit Scale: The Short Grit Scale is an 8-item self-report survey that measures persistence and 
commitment to long-term goals. It takes fewer than 10 minutes to complete and score, and is designed to be 
appropriate for children. The child reads or hears sentences like "I am a hard worker" and then chooses a 
response on a scale of 1 to 5 that best describes himself or herself.  
Media Use Questionnaire: This questionnaire is a 5-item self-report survey that measures media use in 
youth (i.e. time spent on TV, video games, phone; types of video games, etc.) which was adapted from the 
Media Use measure in the PhenX Toolkit (#750700). It will be completed by the parent and child during the 
baseline visit. 
Neuropsychological Testing:
Wechsler Abbreviated Scale of Intelligence (WASI-II): This estimates Full Scale IQ with excellent 
reliability and validity for ages 6-90. It consists of four subtests: Vocabulary, Similarities, Block Design, 
and Matrix Reasoning. The full assessment will be administered by an RA at baseline. 

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Stroop Word-Color Interference: This is a classic task of cognitive interference that is comprised of 3 
subtasks. In task A (color naming), participants are asked to name as quickly as possible the color (red, 
green, or blue) of 126 dots, 5.6 mm in diameter, arrayed randomly in 9 columns and 14 rows on an 8.5 x 11 
inch sheet of white paper, scanned left to right and then top to bottom. In B (word reading), they are asked 
to read as quickly as possible an equal number of similarly arrayed words ("red", "green", or "blue") printed 
in black ink. In C (color-word naming), they are asked to name as quickly as possible the ink color of a 
similar array of words written in incongruent colors. The time to completion of each task is recorded (A, B, 
and C, respectively). Stroop interference is calculated as C-[(AxB)/(A+C)].
The PhenX Toolkit Hand Dominance Measure: This measure assesses one’s handedness, and is based off of 
the Edinburgh Handedness Inventory. The PhenX Toolkit is a collection of measures developed for 
researchers to use to combine or share data. 
Continuous Performance Task: The Continuous Performance Task (CPT)is a standardize measure of 
sustained attention and impulsivity. Subjects are presented with a series of letters on a computer screen and 
are instructed to hit the spacebar on the keyboard whenever a letter is presented. However, subjects are 
instructed to not hit the spacebar when the letter “X” is shown.
Reinforcement Learning Go/no-go task:Participants will be presented with one of 5 images on each trial and 
must learn to press (i.e., ‘Go’) or not to press (i.e., ‘NoGo’) a button for each image. Two of the images are 
more associated with reward (i.e. participants gain points if they press the button upon presentation of those 
images); another two images are more associated with punishment (participants lose points if they press the 
button); and the last image is neutral. Not pressing the button is never associated with feedback and does not 
gain or lose points. By assessing whether subjects learn better to press or not to press the button (for the 
respective images), the task can determine if they learn better from rewards or punishments, respectively. 
The task consists of 150 trials: 3 blocks of 50 trials (each image presented 10 times with images randomly 
intermixed). 
Stop Signal Task: Participants will perform a child-friendly visual stop-signal task, in which they will be 
asked to indicate the direction of an airplane with a button press. Eighty percent of the trials will be simple 
go trials. Unpredictability, on 20% of trials, a stop signal (cross) will appear with a delay after the airplane. 
Behavioral outcome measures will be the subject-specific stop-signal reaction time (speed of the stop 
process), the mean reactions time on the accurate go trials (speed of go process), and the error percentage on 
go trials (overall attention).
 Decision-Making Tasks: These tasks investigate how individuals make decisions under risky or ambiguous 
conditions. Participants will make many choices between different amounts of money that they can receive 
at different times or with different likelihoods. The tasks will begin with a set of instructions and a couple of 
practice trials. Typically, two or more options will be presented simultaneously on the screen. For instance, 
one option might be a money amount to be received soon and the other might be another amount to be 
received later, or one option might be a money amount to be received with some stated or unstated 
likelihood and the other might be another amount to be received for sure. After a brief delay, the options 
will disappear and subjects will be prompted to state their choice by pressing a particular key on the 
computer keyboard. The trial will end with the subject's answer. The program will then move on to the next 
trial after a short delay. Each task will include 100-200 trials and will last approximately 15 minutes. Breaks 
will be provided and available anytime subjects require them. At the end, one of the participant’s choices 
will be selected randomly to count for actual payment that will be given in cash ($0 to $66), immediately 
following their completion of the tasks. This payment mechanism ensures that the experiment is incentive 
compatible: participants don’t know which choice will count for actual payment and will not be able to 

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change their selection during the payment phase, so the best strategy is to select the options they prefer most 
each time. Together these tasks will take approximately 30 minutes to complete. 
The Weather Prediction Task: The Weather Prediction Task is a measure of probabilistic learning. The task 
is administered on a laptop computer (Dell). In the Weather Prediction task, subjects are required to "guess" 
whether card-like stimuli mean that the weather will be sunny or whether the cards mean that it will rain. On 
each of 50 trials, stimuli appear on the left side of the computer screen and subjects are prompted to press a 
key showing a sun or to press a key showing a rain cloud. Following correct responses, a happy face appears 
on the right side of the screen and children hear a high tone. Following incorrect responses, a sad face 
appears on the right side of the screen and subjects hear a low tone.
Please attach copies, unless standard instruments are used
Research Related Delay to Treatment
Will research procedures result in a delay to treatment?
Yes
Maximum duration of delay to any treatment 
It is anticipated that the maximum time from the time of consent to completion of the first MRI scan will be 
no more than 4 weeks. For treatment-seeking OCD participants, this could delay their initiating treatment 
and thus cause them to have ongoing OCD symptoms. Dr. Rynn and her clinical team in the Children's Day 
Unit will be in contact with these participants and their families every week from the time of signing 
consent throughout the MRI scanning to evaluate their ability to continue in the protocol. All attempts will 
be made to schedule the scan within 2 weeks of consent, though we may require 4 weeks to accommodate 
participants’ and their families' schedules. If clinically inappropriate to delay treatment, the case will be 
referred for treatment within our system or elsewhere. If a child suddenly met any exclusion criteria (e.g., 
active suicidal ideation) or no longer met the inclusion criteria of being "able to tolerate a treatment-free 
period," the patient would be removed from the study and referred for treatment. Patients may refuse to 
participate at any point and seek treatment.
Maximum duration of delay to standard care or treatment of known efficacy
same as above 
Treatment to be provided at the end of the study
Following completion of treatment in the PAMRC (including 3 months of follow-up care following 
completion of study treatment) and all other study procedures, children with OCD will be referred to other 
clinical settings (outpatient mental health care clinics or private clinicians specializing in OCD) in the tri-
state area if they need additional care.
Clinical Treatment Alternatives
Clinical treatment alternatives
Currently cognitive-behavioral treatment involving exposure and response prevention (CBT/ERP) and 
serotonin reuptake inhibitor (SRI) medication are considered the first line treatments for OCD. However, 
pharmacotherapies have relatively modest effects in OCD. CBT/ERP treatment is the mainstay of the 
treatment for OCD. Yet, CBT/ERP alone results in response rates of anywhere between 60% and 80%, and 

Protocol Summary Form
7006
Marsh, Rachel
Page 28 of 31
fear of non-adherence to ERP is hypothesized to contribute to the lack of ERP efficacy across age groups.
Risks/Discomforts/Inconveniences 
Risks that could be encountered during the study period
Clinical and Neuropsychological Assessments: No risks are associated with these assessments. If 
the participant no longer wishes to continue the testing, they may stop at any time. All tests will be 
administered at the New York State Psychiatric Institute by a trained member of the research staff 
(Bachelor’s level or higher). Any adverse events that occur during the interview and/or any information that 
warrants clinical attention (i.e. suicidal ideation, intent to harm oneself/others) will be reported immediately 
to Drs. Rynn and Marsh, and proper interventions and referrals will be made.
Diagnostic Interviews: No risks are associated with these diagnostic interviews. If the participant
no longer wishes to continue the interview, they may stop at any time. All interviews will be
conducted at the New York State Psychiatric Institute. The interviews will be performed by a
trained member of the research staff (Bachelor’s level or higher). Any adverse events that occur
during the interview and/or any information that warrants clinical attention (i.e. suicidal ideation,
intent to harm oneself/others) will be immediately reported to Drs. Rynn and Marsh, and proper
interventions and referrals will be made.
Pregnancy Testing: No known risks are associated with pregnancy testing. If the results of the
pregnancy test cause the participant and parent any distress, a trained member of the research staff will
discuss the results with her, and appropriate referrals will be made.
Magnetic Resonance Imaging: Both the FDA and the NYSPI IRB have deemed MRI Scanning on
the GE 3Tesla MRI Scanner at the New York State Psychiatric Institute to be classified as a
non-significant risk. 
 
CBT Treatment: There is a possibility that symptoms may not improve or could worsen during treatment. 
Any patient who is evaluated by the study clinician to be worse (CGI-S score of 5) for two consecutive 
visits will be evaluated by the study physician to determine if medication augmentation or other types of 
ancillary treatments are indicated (such as family therapy and education supporters). At this time, the study 
physician will discuss the possibility of withdrawing from the study or beginning medication treatment in 
conjunction with CBT.  
In the case of combined treatment with medication treatment:
Adverse events will be closely monitored by the study physician and tracked using the CDU adverse event 
form. The study physician will review with the participant and their families the following potential 
serotonin reuptake inhibitor (SSRI) related adverse events: gastrointestinal complaints (nausea, pain, 
diarrhea, and constipation), dizziness, allergic reactions, increased anxiety or irritability, increased 
activation/restlessness, sleep changes (increased or decreased), sexual side effects, appetite changes 
(increase or decreased), unusual thoughts, sweating, fatigue, suicidal ideation/attempts/and or behaviors. In 
addition to these issues, the study physician will discuss with participants and their families the Food and 
Drug Administration advisory that the use of antidepressants like the SSRIs may lead to suicidal 

Protocol Summary Form
7006
Marsh, Rachel
Page 29 of 31
thinking/attempts in depressed and anxious youth and that the FDA has placed product warning label with 
information highlighting the need for close observation for worsening of symptoms and the emergence of 
suicidality in children treated with these medications. This information will be a part of the consent process 
for the study so that families are aware of these issues when considering the addition of medication 
treatment. The study physician will review with the adolescents and their legal guardians, potential adverse 
events and to carefully monitor for any significant changes in mood, thinking, behaviors, and physical 
symptoms especially early in medication treatment. The adolescents and their families will be instructed to 
call the study physician with any concerns, and to call the 24 hour on call service at the Child/Adolescent 
Comprehensive Psychiatric Emergency Program (CPEP) for any emergency.
Describe procedures for minimizing risks
To reduce the potential for participant fatigue, we will offer several breaks to the participants throughout 
study procedures. Prior to the administration of the interviews, participants will be told that if any questions 
make him/her uncomfortable, he/she can ask to move on to the next question. This will be done to minimize 
any potential discomfort from the personal nature of the questions asked. 
In EX/RP treatment, patients confront feared situations that are expected to produce moderate levels of 
distress initially. This initial fear reaction is essential to the treatment, as it allows the patient to habituate to 
situations in which he or she is excessively or irrationally fearful. Exposures to feared situations are carried 
out with the patient’s advance knowledge and full consent. Such exposure procedures have produced 
considerable benefits in studies of children and adolescents with OCD. The only reported side effect has 
been transient increases in anxiety. These reactions will be closely monitored by study clinicians who have 
extensive expertise with pediatric OCD patients.
There is a possibility that symptoms may not improve or could worsen during treatment. Any patient who is 
evaluated by the study clinician to be worse (CGI-S score of 5) for two consecutive visits will be evaluated 
by the study physician to determine if medication augmentation or other types of ancillary treatments are 
indicated (such as family therapy and education supporters). At this time, the study physician will discuss 
the possibility of withdrawing from the study or beginning medication treatment in conjunction with CBT.
Methods to Protect Confidentiality
Describe methods to protect confidentiality
In all records from this study, the names of participants and their family members will be available only to 
the team of researchers working on the study. Neither their names nor any identifying information will be 
used in any scientific reports from this study or from secondary data analyses conducted with de-identified 
data from this study. All the information obtained from the subjects is coded by number and kept in locked, 
confidential files. MRI data from this study will be stored on computers behind firewalls in our laboratory at 
NYSPI. 
Will the study be conducted under a certificate of confidentiality?
No

Protocol Summary Form
7006
Marsh, Rachel
Page 30 of 31
Direct Benefits to Subjects  
Direct Benefits to Subjects
The proposed analyses are unlikely to benefit any participant directly. The findings of this study, however, 
could increase understanding of brain structure and function, potentially, though indirectly, benefiting 
participants. 
There may be benefits from the standard of care treatment received during the study. CBT/ERP is an 
evidenced-based treatment for adults and adolescents with OCD. Adolescents participating in the study will 
receive therapy from psychologists specifically trained in CBT/ERP therapy. The response rate of CBT/ERP 
could be up to 80%. Therefore, there is a good chance patients’ symptoms will improve during the study.
Another direct benefit of study participation is that patients will receive a complete
psychiatric and medical evaluation. During this evaluation, other potential problems may be identified by 
the interviews or questionnaires. In this instance, the study clinician will inform the participant that further 
evaluation and clinical assessment may be indicated, and will provide a brief summary of the information 
obtained to any treatment provider selected by the participant.
Compensation and/or Reimbursement 
Will compensation or reimbursement for expenses be offered to subjects?
Yes
Please describe and indicate total amount and schedule of payment(s). 
Include justification for compensation amounts and indicate if there are bonus payments.
Following completion of the MRI scan and MRI assessments (diagnostic interviews, clinical and 
neuropsychological assessments) healthy control participants, 11 years or younger, will be 
compensated $175 in the form of a gift card ($50 for the MRI scan, $50 for the neuropsychological testing, 
and $75 for the interviews), and OCD participants, 11 years or younger, will be compensated $100 in the 
form of a gift card ($50 for the MRI scan, $25 for the neuropsychological testing, and $25 for the 
interviews). Healthy control participants 12 years and older, will be compensated $175 for their time in the 
form of a check ($50 for the MRI scan, $50 for the neuropsychological testing, and $75 for the interviews). 
OCD participants 12 years and older, will be compensated $100 for their time in the form of a check ($50 
for the MRI scan, $25 for the neuropsychological testing, and $25 for the interviews). Gift cards will be 
given to participants on site following completion of study procedures. For children 12 years and older, 
checks will be mailed to the participant's home address and can be expected to arrive within 2-3 weeks of 
the study visit. 
In addition, participants will have the opportunity to earn $20 in the Virtual Reality (VR) fMRI task. 
Because these are measures of reward-based learning, participants must be rewarded immediately after the 
task has been completed based on their task performance so that we can accurately assess the functioning of 
reward circuits.
 

Protocol Summary Form
7006
Marsh, Rachel
Page 31 of 31
Participants will also be given the opportunity to earn up to $66 while playing computer tasks 
(risk/ambiguity tasks). Each participant can win $0-$66 on these tasks, combined. Participants will be 
rewarded with the amount they won immediately following the completion of these tasks. 
 
Healthy control participants who return for a follow-up scan and assessments will again be compensated 
$175 for their time, and OCD participants who return will again be compensated $100 for their time (in the 
form of a gift card or check depending on their age) and given another opportunity to earn $20 in the VR 
task and up to $66 in the computer task. Compensation methods and procedures will be identical to those for 
the first MRI scan.
 
 Additionally, families may receive up to $30 per visit to reimburse for transportation costs to and from the 
study site, as requested. This reimbursement will be offered in the form of a check mailed to the families' 
home address and can be expected to arrive within 2-3 weeks of the study visit. 
References
References
N/A
Uploads
Upload the entire grant application(s)
Upload copy(ies) of unbolded Consent Form(s)
Upload copy(ies) of bolded Consent Form(s)
Upload copy(ies) of recruitment materials/ads to be reviewed
fMRI OCD Brochure_7 6 17 BOLD.pdf
fMRI OCD Brochure_7 6 17 CLEAN.pdf
Upload copy(ies) of unbolded Assent Form(s)
Upload copy(ies) of bolded Assent Form(s)
Upload copy(ies) of the HIPAA form
HIPAA Child7006_for ACAR.pdf
Upload any additional documents that may be related to this study

Diagnosed with obsessive-
compulsive disorder
5-17 years old
Not currently taking medication
Not diagnosed with psychosis, 
a developmental disorder, tic 
disorder, or substance abuse
Not in psychotherapy
TO PARTICIPATE
Your child may be eligible to participate in this study if he or she is:
We are happy to answer any questions you may have!
Kelsey Hill, B.A.
Pediatric Anxiety and Mood Research Clinic 
Columbia University/New York State Psychiatric Institute
kelsey.hill@nyspi.columbia.edu
646-774-5793
Interested in learning more about our study?
Call us at 646-774-5793
A CBT Treatment and MRI 
Research Study for Children and 
Adolescents with OCD
(Ages 5-17) 
The Cognitive Development and 
Neuroimaging Lab
and
The Columbia University 
Pediatric Anxiety and Mood Research Clinic 
OCD Treatment and Research Program 
1051 Riverside Drive
New York, NY 10032
http://www.columbiapsychiatry.org/pamrc 
NYSPI IRB APPROVED #7006
Columbia PAMRC

What is Obsessive-Compulsive Disorder (OCD)?
We all have habits and routines; however, 
children and adolescents with OCD have 
habits and routines that get in the way 
of their daily lives. If your child’s day-to-
day life is aﬀected by these symptoms, 
OCD may be the cause. 
Symptoms of OCD
Performing repetitive behaviors 
to get rid of the uncomfortable 
fear or thoughts
Repeated and unwanted ideas, 
impulses or thoughts that 
cause nervousness or fear
Obsessions
Compulsions
What is Cognitive Behavioral Therapy (CBT)? 
• Cognitive behavioral therapy is a type of therapy that focuses on 
changing thoughts and behaviors to help your child feel better. 
• Exposure and Response Prevention (ERP) is a specialized type 
of cognitive behavioral 
treatment for OCD, 
where a therapist will 
help your child face their 
“scary” or “unpleasant” 
thoughts and teach 
them skills to be able to 
resist OCD compulsions. 
What are the beneﬁts of participating in this study?
• Free comprehensive diagnostic evaluation 
• Free neuropsychological evaluation
• 12-16 sessions of OCD-speciﬁc CBT treatment by expert clinicians 
at no cost
• Additional medication care by study doctor specializing in OCD 
treatment, if needed 
• 2 brain scans in a Magnetic Resonance Imaging (MRI) machine 
before and after CBT treatment 
• Up to $240 as a “thank you” for participating in this MRI research 
study
What is an MRI?
• An MRI is a large tube shaped machine with a magnet inside that 
allows us to take pictures of your brain. 
• Combining MRI scans from a large number of children allows us 
to learn more about how brain areas are related to OCD. This 
information can help us improve treatments for OCD.

Diagnosed with obsessive-
compulsive disorder
5-17 years old
Not currently taking medication
Not diagnosed with psychosis, 
a developmental disorder, tic 
disorder, or substance abuse
Not in psychotherapy
TO PARTICIPATE
Your child may be eligible to participate in this study if he or she is:
We are happy to answer any questions you may have!
Kelsey Hill, B.A.
Pediatric Anxiety and Mood Research Clinic 
Columbia University/New York State Psychiatric Institute
kelsey.hill@nyspi.columbia.edu
646-774-5793
Interested in learning more about our study?
Call us at 646-774-5793
A CBT Treatment and MRI 
Research Study for Children and 
Adolescents with OCD
(Ages 5-17) 
The Cognitive Development and 
Neuroimaging Lab
and
The Columbia University 
Pediatric Anxiety and Mood Research Clinic 
OCD Treatment and Research Program 
1051 Riverside Drive
New York, NY 10032
http://www.columbiapsychiatry.org/pamrc 
NYSPI IRB APPROVED #7006
Columbia PAMRC

What is Obsessive-Compulsive Disorder (OCD)?
We all have habits and routines; however, 
children and adolescents with OCD have 
habits and routines that get in the way 
of their daily lives. If your child’s day-to-
day life is aﬀected by these symptoms, 
OCD may be the cause. 
Symptoms of OCD
Performing repetitive behaviors 
to get rid of the uncomfortable 
fear or thoughts
Repeated and unwanted ideas, 
impulses or thoughts that 
cause nervousness or fear
Obsessions
Compulsions
What is Cognitive Behavioral Therapy (CBT)? 
• Cognitive behavioral therapy is a type of therapy that focuses on 
changing thoughts and behaviors to help your child feel better. 
• Exposure and Response Prevention (ERP) is a specialized type 
of cognitive behavioral 
treatment for OCD, 
where a therapist will 
help your child face their 
“scary” or “unpleasant” 
thoughts and teach 
them skills to be able to 
resist OCD compulsions. 
What are the beneﬁts of participating in this study?
• Free comprehensive diagnostic evaluation 
• Free neuropsychological evaluation
• 12-16 sessions of OCD-speciﬁc CBT treatment by expert clinicians 
at no cost
• Additional medication care by study doctor specializing in OCD 
treatment, if needed 
• 2 brain scans in a Magnetic Resonance Imaging (MRI) machine 
before and after CBT treatment 
• Up to $240 as a “thank you” for participating in this MRI research 
study
What is an MRI?
• An MRI is a large tube shaped machine with a magnet inside that 
allows us to take pictures of your brain. 
• Combining MRI scans from a large number of children allows us 
to learn more about how brain areas are related to OCD. This 
information can help us improve treatments for OCD.

Form #PP2: HIPAA Authorization for Research 4.1.14 
New York State Psychiatric Institute (NYSPI) 
Authorization to Use or Disclose Health Information during a Research Study 
(Child Version) 
 
 
 
Protocol Number: 
Principal Investigator: 
Name of Study: 
Before researchers can use or share any identifiable health information (“Health Information”) about your child as part of the 
above study (the “Research”), the New York State Psychiatric Institute (NYSPI) is required to obtain your authorization. You agree 
to allow the following individuals and entities to use and disclose Health Information about your child as described below: 
 
x 
New York State Psychiatric Institute (NYSPI), your child’s doctors and other health care providers, if any, and 
x 
The Principal Investigator and his/her staff (together “Researchers”).  Researchers may include staff of NYSPI, the New York  
State Office of Mental Health (OMH), Research Foundation for Mental Hygiene, Inc. (RFMH), and Columbia University (CU), 
provided such staff is a part of the study, and 
x 
Providers of services for the Research at CU, NYSPI and/or RFMH, such as MRI or PET, or Central Reference Laboratories (NKI), 
if indicated in the consent form. 
 
1. 
The Health Information that may be used and disclosed for this Research includes: 
 
 
All information collected during the Research as told to you in the Informed Consent Form. 
Health Information in your child’s clinical research record which includes the results of physical exams, medical and 
psychiatric history, laboratory or diagnostic tests, or Health Information relating to a particular condition that is related to 
the Research. 
Additional information may include: 
 
 
2. 
The Health Information listed above may be used and disclosed to: 
Researchers  and their staff at the following organizations involved with this Research: 
 
 
 
The Sponsor of the Research, 
 
 
and its agents and contractors (together, “Sponsor”); and 
Representatives of regulatory and government agencies, institutional review boards, representatives of the Researchers 
and their institutions to the level needed to carry out their responsibilities related to the conduct of the research. 
Private laboratories and other persons and organizations that analyze your child’s health information in connection with 
this study 
 
 
 
Other (family members or significant others, study buddies, outside agencies etc.) Specify: 
 
 
 
3. 
By giving permission to release your child’s Health Information as described above, you understand that your child’s Health 
Information may be disclosed to individuals or entities which are not required to comply with the federal and state privacy laws 
which govern the use and disclosure of personal Health Information by NYSPI.  This means that once your child’s Health 
 




Overlapping Neural Circuits Implicated in Pediatric OCD
Rachel Marsh Ph.D.
7006

Form #PP2: HIPAA Authorization for Research 4.1.14 
Information has been disclosed to a third party which does not have to follow these laws (e.g., a drug company or the Sponsor 
of the Research), it may no longer be protected under the HIPAA or NYS Mental Hygiene Law requirements but is subject to the 
terms of the consent form and may be subject to other state or federal privacy laws or regulations. 
 
4. 
Please note that: 
• 
You do not have to sign this Authorization form, but if you do not, your child may not be able to participate in the study or 
receive study related care. You may change your mind at any time and for any reason. If you do so, your child may no 
longer be allowed to participate in the study. If you withdraw this Authorization the research staff and the Sponsor, if this 
is sponsored research, may still use or disclose Health Information containing identifying information they already have 
collected about your child as needed to maintain the reliability of the research. Any request to withdraw this Authorization 
must be made in writing to (enter name and contact information below): 
 
 
 
 
• 
While the Research is going on, you may not be allowed to review the Health Information in your child’s clinical research 
record that has been created or collected by NYSPI.  When this research has been completed you may be allowed to see 
this information. If it is needed for your child’s care, your child's Health Information will be given to you or your child’s Doctor. 
 
5. 
This Authorization does not have an end date. 
 
 
6. 
You will be given a copy of this form after you have signed it. 
 
 
I agree to the use and disclosure of Health Information about me as described above: 
 
 
 
 
Signature of Parent/ Legal Representative 
Date 
 
 
 
Printed Name of Parent/Legal Representative 
 
 
 
 
 
Name of child 
 
 
 
 
We also ask you or your legal representative to initial the statements below: 
I have received a copy of the NYSPI/OMH Notice of Privacy Practices. 
 
Rachel Marsh, Ph.D., New York State Psychiatric Institute, 1051 Riverside Drive, Unit 74
New York, NY 10032

STATISTICAL ANALYSIS PLAN 
Functional MRI (fMRI) Data Processing 
The Human Connectome Project (HCP) preprocessing pipelines1 will be used to preprocess all multiband 
functional imaging data. Briefly, this will include gradient unwarping, motion correction, field map-based EPI 
distortion correction, brain-boundary-based registration of EPI to structural T1-weighted scan, non-linear 
(FNIRT) registration into MNI152 space, and grand-mean intensity normalization. The EPI data will be 
smoothed with a 4mm Gaussian kernel. Additional processing will be run in MATLAB (Mathworks, Natick, MA). 
Using commands from Analysis of Functional NeuroImages (AFNI; http://afni.nimh.nih.gov/) and FMRIB 
Software Library (FSL; http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/) software, BOLD signal will be demeaned and 
detrended (AFNI 3dDetrend), despiked (AFNI 3dDespike -localedit), and bandpass filtered (FSL fslmaths 0.01-
0.08 Hz). Nuisance regression of 24 motion parameters (bandpass filtered; 6 motion parameters, derivatives, 
and squares), as well as of average global signal from gray and white matter, and cerebrospinal fluid will be 
performed. Motion censoring2 based on framewise displacement (FD; >0.2mm) and DVARS (z-score>3) will 
also be performed. 
Structural MRI Data Processing 
Two high-resolution T1-weighted BRAVO structural images will be averaged and bias field corrected. Data will 
then be processed in FreeSurfer3,4. This will include subcortical segmentation (left and right thalamus, caudate, 
putamen, pallidum, hippocampus, amygdala, and nucleus accumbens) and cortical parcellation (74 regions per 
hemisphere) based on the Destrieux atlas5. Output images will be visually inspected for quality. 
Diffusion MRI Data Processing 
Diffusion MRI data will be assessed for data quality and head motion. A structural connectivity matrix will be 
estimated for each participant using the standard MRtrix3 preprocessing pipeline6, yielding a 164x164 
symmetrical streamline count matrix for each participant using the FreeSurfer segmentations/parcellations 
noted above (148 cortical, 14 subcortical regions, and the left and right cerebellum). Using this approach, 
streamline count between brain regions is proportional to the cross-sectional area of white matter fibers 
connecting those regions. Thus, streamline count is a biologically plausible metric of "structural connectivity" 
proposed to represent the communicatLRQµEDQGZLGWK¶EHWZHHQUHJLRQVWKRXJKLWPD\LQGLFDWHHLWKHUVSDUVH
but fast (i.e. few large diameter axons) or dense but slow (i.e. many small diameter axons) connections7. 
Furthermore, streamline counts in macaques significantly correlate with connection strength from anatomical 
tract-tracing, supporting its validity as an indicator of fiber connection strength8.  
Hypothesis Testing:  
Primary Outcome Analysis: Brain activation (i.e., BOLD signal) during performance of an fMRI task (Simon) 
that requires self-regulatory control in children and adolescent with OCD compared to age-matched healthy 
control (HC) participants. 
First-level parametric analyses will be performed for each participant using the general linear model (GLM) 
provided by SPM12. For each participant, preprocessed time series data from all three Simon task runs will be 
modeled using a GLM with six conditions: 1) Incongruent correct trails preceded by congruent trials (cI), 2) 
Congruent correct trials preceded by incongruent trials (iC), 3) Incongruent correct trials preceded by 
incongruent trials (iI), 4) Congruent correct trials preceded by congruent trials (cC), 5) fixation trials, and 6) 
incorrect trials (incongruent or congruent), including trials with reaction times below the minimal RT of 200ms 
for stimulus detection and processing. These events will be convolved with the canonical HRF and then least-
squares regression will be used to estimate parameters for each independent variable for each participant. 
Only correct trials will be included, given the limited number of incorrect trials. Runs in which a participant have 
more than 30% error rate on the task will be excluded from analyses. Because activation of task control 
regions is greatest when level of conflict is maximal (i.e., when incongruent stimuli are preceded by congruent 
stimuli)9, analyses will focus on post-congruent trials. Parameter estimates averaged across the three runs will 
be used to produce a post-congruent Incongruent versus post-congruent Congruent (cI-cC) contrast for each 
participant to access brain activation associated with the engagement of self-regulatory control and resolution 
of maximal cognitive conflict. 
Whole-brain second-level analyses of conflict-related BOLD signal will be performed using voxel-wise 
independent t-WHVWVDFURVVJURXSV2&'YV+&DGMXVWLQJIRUSDUWLFLSDQWV¶DJHVH[DQGKHDGPRWLRQLH
mean FD). A cluster-defining threshold (CDT) of p<.001 will be applied to all second-level group comparisons 

maps, with Family Wise Error correction for multiple comparisons of p<.05 at the cluster level (FWEc). For 
each significant group difference detected, the direction of the effect will then be explored using within-group t-
maps (CDT of p<.001, uncorrected). We hypothesize that compared to healthy controls, children and 
adolescents with OCD will have increased activation in subcortical structures (insula, and putamen) comprising 
a right hemisphere dorsal frontostriatal circuit while performing a self-regulatory control task (Simon task). 
Secondary Outcome 1 Analysis: fMRI functional connectivity (FC) in task-control circuits in children and 
adolescent with OCD compared to age-matched HC participants. Whole-Brain Connectome-Level Analyses 
will be performed on the preprocessed fMRI data, computing FC-strength indices using Fisher Z-
Transformation of the pairwise Pearson correlation coefficients between 352 regions (i.e., 333 cortical 
surface10 and 19 subcortical11 parcellated regions). Edge-wise functional connectivity analyses will then be 
conducted whole-brain across the resulting matrix comprised of 352 nodes and 123,904 edges. Analyses 
examining group differences will be adjusted for age at the time of scanning, sex, and head motion (mean FD) 
and conducted using the Network-Based Statistics (NBS) Toolbox12 in MATLAB (Mathworks, Natick, MA). NBS 
controls for family-wise error rate using permutatiRQWHVWLQJWRLGHQWLI\FRPSRQHQWVRU³FOXVWHUV´RIFRQWLJXRXV
region-to-region connections. A statistical threshold of p=.05 with 20,000 permutations will be used. We 
hypothesize that youth with OCD will show altered functional connectivity between task-control circuit regions. 
Secondary Outcome 2 Analysis: Regional subcortical volume and cortical thickness based on structural 
MRI data in children and adolescent with OCD compared to age-matched HC participants. Group differences 
in regional subcortical volume and cortical thickness will be assessed using linear regressions controlling for 
age and sex (ICV covaried subcortical volumes analyses). False discovery rate (FDR) will be used to correct 
for multiple comparisons (14 for subcortical analyses and 148 for cortical analyses).  A follow-up vertex-wise 
analysis (QDEC in FreeSurfer) will probe group differences in cortical thickness (smoothed at 20mm), 
controlling for age and sex. Results will be corrected for multiple comparisons using Monte Carlo simulations 
with a vertex-wise threshold of p<.001 and an analysis-level threshold of p<.05 correcting for tests in each 
hemisphere (mri_glmfit-sim --cache 3 abs --2spaces). Given that prior meta- and mega-analyses of structural 
abnormalities in pediatric OCD by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) 
consortium ENIGMA OCD only showed small effect sizes in unmedicated youth with OCD compared to healthy 
participants13, we do not expect significant group differences in subcortical volumes or cortical thickness.  
Secondary Outcome 3 Analysis: Structural connectivity (streamline count) based on Diffusion Tensor 
Imaging (DTI) data in children and adolescent with OCD compared to age-matched HC participants. 
Structural connectivity matrices will be analyzed using the NBS toolbox12 in MATLAB (Mathworks, Natick, MA). 
To avoid examining very sparse connections, those with median streamline count <100 will be zeroed out for 
exclusion from analysis. Group differences in structural connectivity (streamline count) will be tested using two 
one-tailed contrasts (OCD>healthy and healthy>OCD, controlling for age and sex, and corrected to an 
analysis-level p<.025 (10,000 permutations). We hypothesize that youth with OCD will show altered structural 
connectivity in the corpus callosum and in tracts integrating the fronto-partial and cingulo-opercular networks 
that are functionally altered in OCD. 
Exploratory Analyses: In the children and adolescents with OCD, we will explore whether activation and 
functional connectivity is associated with OCD symptoms pre- to post-treatment with Cognitive Behavioral 
Therapy (CBT). These exploratory analyses will be restricted to regions/circuits in which group differences 
were detected (Primary Outcome and Secondary Outcome 1). Cross-lagged panel models will be constructed 
using IBM SPSS Amos to WHVWIRUGLUHFWLRQDO³FDXVDO´UHODWLRQVKLSVEHWZHHQ2&'V\PSWRPVDQGI05,
measures pre- to post-CBT in the OCD patients. These models provide estimates of the extent to which a 
variable pre-CBT (e.g., connectivity) predicts another variable post-CBT (e.g., symptom severity), over and 
above the variability attributable to scores of that second variable (e.g., symptom severity) pre-CBT14. Thus, by 
controlling for the effects of each variable pre-CBT on the same variable post-CBT, pre-CBT variables then 
predict the residual, or change in that variable from pre- to post-CBT. WKH&KLOGUHQ¶V<DOH-Brown Obsessive 
Compulsive Scale (CY-BOCS)15 total scores at each time point will be used as the OCD symptoms measure. 
The initial model will be adjusted for age, sex, and head motion (mean FD). All variables at each time point will 
be covaried to adjust for shared variance. Non-significant paths (ps>.1) will be removed one at a time within 
each model, and a chi-square difference test will examine whether each removal significantly reduced model 
fit. All stability paths will be retained, even if non-significant, to adjust for baseline levels of each variable.  
 
 

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