The overall goals of this center are to delineate the neural networks that underlie core behavioral features of OCD in order to broaden our understanding of the disease and the effects of continuous high frequency stimulation (DBS) on those neural networks. A driving hypothesis is that OCD symptoms are, in part, due to impaired extinction of fear that interferes with the normal balance between avoidance and reward-seeking. The neural network that underlies avoidance behaviors, including regions of the prefrontal cortex, ventral striatum and amygdala, is the same general circuit that underlies reward-seeking behaviors. Dysfunction within this circuit, (the anterior cingulate/orbital-basal-ganglia connections), is strongly implicated in OCD. Our goal to improve our understanding of the neural network that underlies OCD-related behaviors will be accomplished through a series of integrated translational experiments that involve high frequency stimulation effects of the ventral internal capsule and ventral striatum on behavior, functional imaging, systems and cellular electrophysiology, and the circuits that are associated with this stimulation. Of particular importance is that dysfunction in the prefrontal-basal ganglia circuit is also implicated across affective, anxiety, impulse-control and addictive disorders. Collectively, this work will provide a blueprint for devising new therapies not only for OCD, but also for other psychiatric disorders. Its interdisciplinary nature will expand our basic knowledge of the neurocircuitry that underlies specific behaviors, (extinction, avoidance and reward seeking behaviors). Results from these studies will also make important new contributions to our understanding of the basic mechanisms of DBS.

Public Health Relevance

Obsessive Compulsive Disorder (OCD) is a chronic psychiatric illness that affects 2-3% of the worldwide population. This is disease is in the top ten dehabilitating diseases. This study will examine the neural network and mechanisms that underlie behaviors associated with OCD. These behaviors not limited to OCD, but are associated with a range of affective and addictive disorders. The collective proposed studies will generate new hypotheses of how dysfunctions within these brain networks are expressed across diseases and provide insight into the mechanisms underlying normal behavioral responses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH086400-05
Application #
8477286
Study Section
Special Emphasis Panel (ZMH1-ERB-F (01))
Program Officer
Zalcman, Steven J
Project Start
2009-09-16
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2013
Total Cost
$1,926,044
Indirect Cost
$235,251
Name
University of Rochester
Department
Pharmacology
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
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Do-Monte, Fabricio H; Quiñones-Laracuente, Kelvin; Quirk, Gregory J (2015) A temporal shift in the circuits mediating retrieval of fear memory. Nature 519:460-3
Crandall, Shane R; Cruikshank, Scott J; Connors, Barry W (2015) A corticothalamic switch: controlling the thalamus with dynamic synapses. Neuron 86:768-82

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