# Linking persistent avoidance with abnormalities in the OCD neural network

> **NIH NIH P50** · UNIVERSITY OF ROCHESTER · 2022 · $353,340

## Abstract

ABSTRACT. The goal of Project 3 (P3) is to characterize, in OCD, white matter (WM) bundle and functional
neural abnormalities among regions in a putative OCD neural network that are associated with persistent
avoidance, a characteristic feature of OCD. Our overarching Center renewal hypothesis, building on our present
findings, is that persistent avoidance in OCD is a manifestation of dysfunctional connections among specific
hubs, i.e., subregions that integrate and distribute information from multiple regions, in the ventrolateral prefrontal
cortex (vlPFC) and rostral anterior cingulate cortex (rACC), and other regions in the OCD network, including the
insula, dorsal ACC (dACC), orbitofrontal cortex (OFC) and rostral striatum. These dysfunctional connections
lead to impaired behavioral flexibility in response to changing contextual cues, specifically in situations with
uncertain aversive outcomes. In P3, we will recruit and examine 50 unmedicated/ serotonin reuptake
inhibitor/clomipramine medicated participants with OCD, and 50 healthy participants (18-35 yrs; to minimize
effects of long illness history and medication on neural measures). We will use state-of-the-art diffusion imaging
(dMRI), using tractography, segmentation and tract profiling - tractometry - to examine WM bundles in the
network. We will use functional Magnetic Resonance Imaging (fMRI) to examine activity, functional and effective
connectivity (FC, EC) among network regions during a novel probabilistic approach avoidance task (PAAT) that
we developed to examine the influence of uncertain rewarding and aversive outcomes on choice behavior, and
neural activity, FC and EC during evaluation and anticipation of these outcomes. We will examine relationships
among WM, activity, FC and EC abnormalities in the OCD network in OCD participants and the severity of OCD
symptom dimensions associated with persistent avoidance, e.g., harm avoidance. Gender will be a covariate in
analyses. Aim (A)1 will compare the microstructure of WM bundles that connect vlPFC, rACC, insula, dACC,
OFC and rostral striatum in OCD vs. healthy participants, using a novel combination of tractography,
segmentation and tractometry. A2 will compare activity within and FC and EC among these OCD network regions
in OCD vs. healthy participants during the PAAT, to determine relationships among PAAT performance and fMRI
abnormalities in OCD vs. healthy participants. A3 will examine relationships among OCD symptom dimensions
that are relevant to persistent avoidance: e.g., harm avoidance, contamination/ washing, responsibility for
harm/checking symptoms, and: WM and fMRI abnormalities in A1-2. P3 will benefit from expertise in: NHP
neuroanatomy and physiology in P1, 2 (A2); dMRI data analysis in P1, Core B (A1); clinical assessment and
treatment of OCD in P4, 5 (A3); the study of individual differences in neuroanatomy in Core C (A2-3); and
integration of analyses across projects in Core D. In close collaboration with othe...

## Key facts

- **NIH application ID:** 10411709
- **Project number:** 2P50MH106435-06A1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Mary Louise Phillips
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $353,340
- **Award type:** 2
- **Project period:** 2015-06-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10411709

## Citation

> US National Institutes of Health, RePORTER application 10411709, Linking persistent avoidance with abnormalities in the OCD neural network (2P50MH106435-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10411709. Licensed CC0.

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