Neurocircuitry Underlying DBS Effects in OCD: A Window Into Mechanisms of Action

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DESCRIPTION (provided by applicant): 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.