Dr. Gail Bernstein

Medical School
Twin Cities
Project Title: 
Exploring Brain Connectivity in Youth With Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is a debilitating anxiety disorder that afflicts 1-3% of youth, often causing incapacitation by obsessions and compulsions. Previous research has suggested that dysregulation of the frontal-striatal-thalamic circuitry (FSTC) is associated with OCD. Functional magnetic resonance imaging (fMRI) studies in children and adults with OCD compared to controls have shown decreased activation in FSTC regions during tasks involving cognitive control. Also, emerging research in OCD using resting-state functional magnetic resonance imaging (R-fMRI) and diffusion imaging (DI) has begun to identify alterations in connectivity (i.e., connections within networks) within FSTC and points to alterations in connectivity between the frontal cortex and striatum (caudate and putamen).

In a pilot study of 15 adolescents with OCD (mostly medicated) and 12 controls, these researchers examined 22 specific connections within FSTC (11 per hemisphere) using R-fMRI. Findings demonstrated that in comparison with controls, adolescents with OCD show significantly lower connectivity and high effect sizes in 11 links. Lower functional connectivity in 10 of these segments was associated with significantly higher  severity on the Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Furthermore, the researchers examined how specific dimensions of OCD would map onto this circuitry. They found that bilaterally, for cortical-subcortical connections, the ordering/repeating dimension correlates with orbitofrontal cortex (OFC)-subcortical connections, the hoarding dimension correlates with rostral anterior cingulate cortex (ACC)-subcortical connections, and the forbidden thoughts dimension correlates with caudal  ACC-subcortical  connections.

Selective serotonin reuptake inhibitors (SSRIs) are the pharmacological treatment of choice for pediatric OCD. Twelve weeks of sertraline, an SSRI, was found to be moderately effective in decreasing OCD symptoms in the NIMH-funded Pediatric OCD Treatment Study (POTS). There is some fMRI evidence that SSRIs reduce brain abnormalities in patients with OCD. This project will comprehensively evaluate FSTC using a multi-modal neuroimaging approach (R-fMRI and high angular resolution diffusion imaging [HARDI]) in 25 unmedicated adolescents with OCD and 25 matched healthy controls to confirm our pilot findings at baseline in unmedicated adolescents with OCD. The researchers will examine how treatment with sertraline for 12 weeks impacts FSTC in this OCD sample. Analysis of the neuroimaging data requires a significant amount of storage space, which can be provided by MSI. 

Project Investigators

Dr. Gail Bernstein
Dr. Christine Conelea
Associate Professor Kathryn Cullen
Kathleen Mantell
Dr. Bryon Mueller
Dr Alexander Opitz
Bhaskar Sen
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