Obsessive compulsive disorder (OCD) affects 2-3% of the population and is characterized by obsessional, obtrusive thoughts and compulsive behaviors, that interfere with interpersonal and occupational function, sometimes to a severe extent. Given the critical need for biomarkers of OCD to inform underlying neurobiological processes and provide targets for treatment choices, one way forward to meet this need is to identify in individuals with OCD specific functional and structural abnormalities in neural networks putatively associated with the illness. Our overarching hypothesis is that there is a neural network that is dysfunctional in OCD, and that this may be associated with development of the excessive ritualized behaviors that characterize the illness. This neural network includes dorsal anterior cingulate cortex, orbitofrontal cortex, ventrolateral prefrontal cortex, dorsolateral prefrontal cortex, ventromedial prefrontal cortex, amygdala and dorsal striatum. The overarching goal of Project 2 (P2) in this proposed center is thus to identify key resting state functional connectivity abnormalities, and abnormalities in underlying white matter, in this circuitry in adults with OCD. We will use fMRI to examine resting state connectivity among these regions, and diffusion imaging and probabilistic tractography to examine white matter in tracts connecting these regions in individuals with OCD. We will use state of the art shimming routines to optimize the signal: noise ratio in regions in this neural network. P2 thereby aims to examine in 40 unmedicated/SRI/clomipramine medicated adults with OCD versus 40 healthy adults (aged 18-35 years): 1. Resting state connectivity, to provide a measure of ?tonic? functional connectivity among these regions. 2. White matter connectivity among these regions. 3. We will also determine relationships between these measures of resting state connectivity and white matter in the neural network to better understand the integration between structural and functional connections in this network. P2, together with other projects in the center, will inform understanding of functional and white matter connection abnormalities in the above neural network in OCD, and will provide neurobiological measures to ultimately inform treatment choice and novel treatments for the illness.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH106435-03
Application #
9283620
Study Section
Special Emphasis Panel (ZMH1-ERB-L)
Project Start
Project End
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
3
Fiscal Year
2017
Total Cost
$312,524
Indirect Cost
Name
University of Rochester
Department
Type
Domestic Higher Education
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Brennan, Brian P; Wang, Danhong; Li, Meiling et al. (2018) Use of an Individual-Level Approach to Identify Cortical Connectivity Biomarkers in Obsessive-Compulsive Disorder. Biol Psychiatry Cogn Neurosci Neuroimaging :
Rosas-Vidal, Luis E; Lozada-Miranda, Valeria; Cantres-Rosario, Yisel et al. (2018) Alteration of BDNF in the medial prefrontal cortex and the ventral hippocampus impairs extinction of avoidance. Neuropsychopharmacology 43:2636-2644
Safadi, Ziad; Grisot, Giorgia; Jbabdi, Saad et al. (2018) Functional Segmentation of the Anterior Limb of the Internal Capsule: Linking White Matter Abnormalities to Specific Connections. J Neurosci 38:2106-2117
Diehl, Maria M; Bravo-Rivera, Christian; Rodriguez-Romaguera, Jose et al. (2018) Active avoidance requires inhibitory signaling in the rodent prelimbic prefrontal cortex. Elife 7:
Do-Monte, Fabricio H; Minier-Toribio, Angélica; Quiñones-Laracuente, Kelvin et al. (2017) Thalamic Regulation of Sucrose Seeking during Unexpected Reward Omission. Neuron 94:388-400.e4
Braga, Rodrigo M; Buckner, Randy L (2017) Parallel Interdigitated Distributed Networks within the Individual Estimated by Intrinsic Functional Connectivity. Neuron 95:457-471.e5
Choi, Eun Young; Tanimura, Yoko; Vage, Priti R et al. (2017) Convergence of prefrontal and parietal anatomical projections in a connectional hub in the striatum. Neuroimage 146:821-832
Coizet, Veronique; Heilbronner, Sarah R; Carcenac, Carole et al. (2017) Organization of the Anterior Limb of the Internal Capsule in the Rat. J Neurosci 37:2539-2554
Tang, Wei; Liu, Hesheng; Douw, Linda et al. (2017) Dynamic connectivity modulates local activity in the core regions of the default-mode network. Proc Natl Acad Sci U S A 114:9713-9718
Van't Wout, Mascha; Longo, Sharon M; Reddy, Madhavi K et al. (2017) Transcranial direct current stimulation may modulate extinction memory in posttraumatic stress disorder. Brain Behav 7:e00681

Showing the most recent 10 out of 23 publications