This project will focus on studying the circuitry involved in avoidance and reward behavior in awake-behaving primates. Primates are a critical link in this project because they are intelligent and can be trained to perform complex tasks that mimic human behaviors, the homology between areas of interest is fairiy close between primates and humans, and there is a considerable anatomic information regarding areas involved in mediating reward and avoidance, and invoked in obsessive-compulsive disorder (OCD). These areas include the ventro-medial prefrontal cortex (vmPFC), the orbitofrontal cortex (OFC), the anterior dorsal cingulate cortex (dACC) and the ventral striatum (VS). There is considerable data regarding the circuitry of fear extinction in rodents. In particular, the infralimic (IL) and pre-limbic (PL) areas appear to have a reciprocal role in the mediating fear extinction (Quirk). Although the exact homology is not clear, a reasonable hypothesis is that IL corresponds to the vmPFC and that area PL corresponds to the dACC. In contrast, there has been relatively little work studying these areas in primates. The overarching goal of this project is to bridge the gap between rodents and primates, which will then provide an important framework for the rational development of DBS strategies aimed at treating human disorders.
Obsessive Compulsive Disorder (OCD) is a chronic psychiatric illness that affects 2-3% of the woridwide population. This is disease is in the top ten dehabilitating diseases. This study will examine the neural network and mechanisms that underiie 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 underiying normal behavioral responses.
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|Garnaat, Sarah L; Greenberg, Benjamin D; Sibrava, Nicholas J et al. (2014) Who qualifies for deep brain stimulation for OCD? Data from a naturalistic clinical sample. J Neuropsychiatry Clin Neurosci 26:81-6|
|Patel, Shaun R; Ghose, Kaushik; Eskandar, Emad N (2014) An open source 3-d printed modular micro-drive system for acute neurophysiology. PLoS One 9:e94262|
|Sesia, Thibaut; Bizup, Brandon; Grace, Anthony A (2014) Nucleus accumbens high-frequency stimulation selectively impacts nigrostriatal dopaminergic neurons. Int J Neuropsychopharmacol 17:421-7|
|Bravo-Rivera, Christian; Roman-Ortiz, Ciorana; Brignoni-Perez, Edith et al. (2014) Neural structures mediating expression and extinction of platform-mediated avoidance. J Neurosci 34:9736-42|
|Heilbronner, Sarah R; Haber, Suzanne N (2014) Frontal cortical and subcortical projections provide a basis for segmenting the cingulum bundle: implications for neuroimaging and psychiatric disorders. J Neurosci 34:10041-54|
|Mian, Matthew K; Sheth, Sameer A; Patel, Shaun R et al. (2014) Encoding of rules by neurons in the human dorsolateral prefrontal cortex. Cereb Cortex 24:807-16|
|Ewing, Samuel G; Porr, Bernd; Riddell, John et al. (2013) SaBer DBS: a fully programmable, rechargeable, bilateral, charge-balanced preclinical microstimulator for long-term neural stimulation. J Neurosci Methods 213:228-35|
|Ewing, Samuel G; Grace, Anthony A (2013) Deep brain stimulation of the ventral hippocampus restores deficits in processing of auditory evoked potentials in a rodent developmental disruption model of schizophrenia. Schizophr Res 143:377-83|
|Lipski, Witold J; Grace, Anthony A (2013) Activation and inhibition of neurons in the hippocampal ventral subiculum by norepinephrine and locus coeruleus stimulation. Neuropsychopharmacology 38:285-92|
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