This is an application written in response to RFA PA-00-004. It describes a systematic 5-year training plan to launch an independent research career in the cognitive and emotional neuroscience of human cocaine addiction through the use of functional magnetic resonance imaging (fMRI), a powerful technique that allows simultaneous, non-invasive measurement of brain activation and cognitive performance. This plan will allow the candidate, a Clinical Psychologist with background in Neuropsychology, to initiate technologically sophisticated research of relevance to treating cocaine addiction. This goal will be achieved through a rigorous training plan, integrating didactic and research components tailored to the candidate's goals and experience. Brookhaven National Laboratory (BNL) provides an ideal training environment: 1) BNL is home to state-of-the-art functional neuroirnaging technologies; and 2) The mentors of this project are world renowned for the application of these cutting-edge technologies to study mechanisms of drug addiction. Under their supervision the candidate will conduct fMRI (4T) activation projects designed to evaluate whether adaptations to the frontolimbic circuit underlie deficits in salience attribution and response inhibition in cocaine addicted subjects, and whether these neuroadaptations and cognitive-behavioral impairments can be used to predict and monitor relapse. In Project 1, subjects receive different levels of Monetary Incentive for correct performance on a go/no-go task. In Project 2, subjects perform a Drug Stroop task, naming the color of cocaine-related words, neutral words, or non-words. Project 3 is a longitudinal study, where subjects undergo Projects 1 & 2 at baseline (2-4 weeks after detoxification) and 6 months follow-up. In all projects, we measure the blood oxygenation level dependent (BOLD) responses of the frontolimbic circuit including the orbitofrontal cortex (OFC) and anterior cingulate gyrus (ACG). We hypothesize: 1) Task specificity: the Monetary Incentive task will primarily activate the OFC while the Drug Stroop task will primarily activate the ACG; 2) Group specificity: the activation of the frontolimbic circuit by the two cognitive-behavioral tasks will differ as a function of drug addiction; and 3) Relapse prediction and monitoring: increased frontolimbic activation and impaired cognitive-behavioral performance at baseline will characterize the cocaine addicted subjects and predict relapse at 6-months follow up. For the subjects who will relapse, abnormalities in these brain-behavior measures will remain the same or get worse during the follow-up period while for the subjects who will remain abstinent, normalization of these measures will be documented.
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