Overlapping Neural Circuits in Pediatric OCD

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to examine the brain functioning of children and adolescent with OCD before and after treatment with Exposure and Response Prevention (EXRP) therapy.

Detailed Description
-----------------
The capacity to coordinate thoughts and actions to execute goal-directed behaviors (cognitive control) and the capacity to anticipate, respond to, and learn from reward (reward processing) are key processes for human behavior. Dysfunction in these processes has been hypothesized to contribute to repetitive thoughts and behaviors in many disorders, including obsessive-compulsive disorder (OCD), Tourette Syndrome (TS), and eating disorders. The investigators will use multimodal imaging to investigate neural circuits that support cognitive control and reward processing, using pediatric OCD as a model system. The short-term goal is to clarify how circuit-based abnormalities contribute to repetitive thoughts/behaviors; these data will inform future trans-diagnostic studies. The long-term goal is to identify control and reward circuit-abnormalities as targets for new trans-diagnostic treatments.

Official Title
-----------------
Overlapping Neural Circuits Implicated in Pediatric OCD

Conditions
-----------------
Obsessive Compulsive Disorder

Intervention / Treatment
-----------------
* Behavioral: CBT treatment for OCD based on Exposure & Response Prevention (EX/RP) and when indicated medication treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Patient Inclusion Criteria: Participants must be 5-17 at the time of consent Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Diagnosis of OCD as the principal problem Not on psychotropic medication and not receiving current psychotherapy for OCD Written informed assent by the participants (8 and older) and consent by the parent Participants and a parent/guardian must be able to read and understand English Patient Exclusion Criteria: DSM-IV current diagnosis of major depressive disorder, attention-deficit hyperactivity disorder, Tourette's/Tic Disorder, or substance/alcohol abuse DSM-IV lifetime diagnosis of psychotic disorder, bipolar disorder, eating disorder, pervasive developmental disorder, or substance/alcohol abuse Active suicidal ideation Females who are pregnant or nursing Major medical or neurological problems Presence of metallic device or dental braces IQ<80 A current or past diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) Individuals who are currently receiving CBT, other forms of psychotherapy, or psychotropic medications Individuals who have received a full course of CBT in the past A positive pregnancy test Positive urine screen for illicit drugs Inability of participant or parent/guardian to read or understand English Healthy Control Inclusion Criteria: Participants must be 5-17 at the time of consent Written informed assent by the participants (8 and older) and consent by the parent Participants and a parent/guardian must be able to read and understand English Healthy Control Exclusion Criteria: Any current or lifetime psychiatric diagnosis Active suicidal ideation Females who are pregnant or nursing Major medical or neurological problems Presence of metallic device or dental braces IQ<80 A current or past diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) A positive pregnancy test Positive urine screen for illicit drugs Inability of participant or parent/guardian to read or understand English

Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants With Obsessive-compulsive Disorder (OCD)<br>Children and adolescents who meet DSM-IV diagnostic criteria for OCD and had clinically significant obsessive-compulsive symptoms (CY-BOCS score>15). Comorbid anxiety disorders, but no other lifetime psychiatric diagnoses, were permitted in the OCD group as long as OCD was the primary diagnosis. Participants were unmedicated and had not received a full course of CBT with exposure and response prevention for OCD prior to their participation in the study. Following baseline assessment and scan, patients with OCD underwent a course of manualized treatment of CBT with E/RP adapted for pediatric OCD delivered by a licensed clinical psychologist or advanced supervised graduate student in clinical psychology at the NYSPI. | Behavioral: CBT treatment for OCD based on Exposure & Response Prevention (EX/RP) and when indicated medication treatment<br>* CBT treatment consisted of 12-16 hour-long sessions. For exceptional cases not showing clinical improvement after six CBT treatment sessions, complementary pharmacological treatment (SSRI) was offered as part of our treatment protocol. 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.<br>|
| No Intervention: Healthy Control (HC) Participants<br>Healthy control (HC) participants matched on age and sex with the OCD group. HC participants had no lifetime psychiatric disorders. HC participants were assessed and scanned at baseline and again after 12-16 weeks. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain Activation Associated With the Resolution of Cognitive Conflict | Task-based functional magnetic resonance imaging (fMRI) will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs) during their performance of a Simon Spatial Compatibility Task. In each trial, participants are presented with a leftward or rightward pointing arrow that is either congruent or incongruent with their position (left or right) on the screen. Participants are instructed to respond as quickly and accurately as possible to the direction in which the arrow was pointing by pressing a button on a response box using the index finger for left and the middle finger for right. Brain activation during the resolution of cognitive conflict is computed by contrasting blood-oxygen-level-dependent (BOLD) signal during Incongruent versus Congruent trials. BOLD signal is expressed in arbitrary units (A.U.s). | single time point: baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Connectivity | Functional magnetic resonance imaging (fMRI) will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs) at baseline and after approximately 16-20 weeks (i.e., post-treatment for the participants with OCD). The whole brain is divided in 352 brain regions comprised of 333 cortical surface (Gordon et al. Cereb Cortex 2016;26:288-303) and 19 subcortical (Fischl et al. Neuron 2002;53:341-55) parcellated regions. FC-strength (average of Fisher-r-to-Z transformed Pearson correlation coefficients) between each region was computed. Values >0 indicate regions are positively connected (synchronized), with larger values indicating stronger connection. Values <0 indicate regions are negatively connected (inversely synchronized), with more negative values stronger negative connection. A value of 0 indicates that the regions are not connected. | single time point: Baseline | 
| Brain Gray Matter Thickness | Structural MRI will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs). Regional cortical thickness will be computed in the inferior frontal gyrus | Single time point: Baseline | 
| Structural Connectivity (Streamline Counts) | Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI) will be acquired from children and adolescents diagnosed with OCD and healthy comparison subjects (HCs). A structural connectivity matrix is estimated for each participant using the standard MRtrix3 preprocessing pipeline, yielding 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 communication 'bandwidth' between regions. | Single time point (baseline) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
OCD, Functional Magnetic Resonance Imaging (fMRI), Magnetic Resonance Imaging (MRI)