The deep brain stimulation target for OCD is centered in the ventral internal capsule, and the ventral striatum. The hypothesis of this proposal is that the behavioral impact of stimulation will vary with electrode location, due to differentially activating subcomponents of the ascending and descending prefrontal circuits. Our laboratory is developing a 3-D atlas of fiber connections and terminals, based on data collected from conventional track tracing methods to delineate and compare of terminal fields and fiber bundle locations from specific cortical regions. This data will be used to develop a model for how cortical fibers travel through the internal capsule leading, to predictions about which structures are most likely be affected for each stimulation site. We will use it to test the validity of diffusion tensor imaging acquisition and analytic algorithms, and explore the ability to extend our findings to humans. There are 3 aims:
Aim 1 will delineate the course of prefrontal cortical and subcortical fiber bundles that pass through different regions of the IC and VS.
Aim 2 will determine which bundles are likely to be the most effective target sites for affecting avoidance-reward conflict behaviors, and the brain regions they connect;
Aim 3 will identify the network activated during DBS within the VCA/S. P2 will inform and be informed by all the proposed projects in the Center. In collaboration with P1, 3, 4, &5, we will gain insight into which pathways (and structures) are involved in avoidance, reward, and extinction behaviors that may be associated with OCD. Results from aims 1 &2 will impact on the choice of stimulation sites used in PI-5.
Aim 3 will inform, and be informed by, rodent models of activation that underlie the mechanisms (P4-6). Overall, combining tracing in monkeys, DTI in monkeys and humans, and computational methods will provide a blueprint for further studies of the anatomical principles that underlie the organization of pathways and terminal fields involved in avoidance and reward.
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.
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| Martínez-Rivera, Freddyson J; Rodriguez-Romaguera, Jose; Lloret-Torres, Mario E et al. (2016) Bidirectional Modulation of Extinction of Drug Seeking by Deep Brain Stimulation of the Ventral Striatum. Biol Psychiatry 80:682-690 |
| Heilbronner, Sarah R; Rodriguez-Romaguera, Jose; Quirk, Gregory J et al. (2016) Circuit-Based Corticostriatal Homologies Between Rat and Primate. Biol Psychiatry 80:509-21 |
| Do-Monte, Fabricio H; Manzano-Nieves, Gabriela; Quiñones-Laracuente, Kelvin et al. (2015) Revisiting the role of infralimbic cortex in fear extinction with optogenetics. J Neurosci 35:3607-15 |
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