Dopaminergic activity and release during DBS implantation in humans

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DESCRIPTION (provided by applicant): The convergence of 4 separate innovations has exposed the possibility of gaining unprecedented insights into the function of dopamine systems in humans. The many aspects of cognition, learning, decision-making, and action selection that depend on intact dopaminergic function make this opportunity important, timely, and exciting. The four innovations are (1) the invention, implantation, and successful chronic use of deep brain stimulation electrodes (DBS) in late stage Parkinson's patients, (2) the development of computational models of dopaminergic function that have now been validated at the level of single unit activity in dopamine neurons, dopamine release at target structures, and functional imaging experiments (fMRI) in human subjects, (3) the demonstration that learning signals thought to be encoded by dopamine delivery can be tracked in Parkinson's patients using fMRI and simple conditioning and decision-making tasks, and (4) the development of biocompatible electrodes capable of making sub-second measurements of extracellular dopamine during learning and decision-making tasks. This project will yield unprecedented insight into the function of dopamine systems in the human brain and should prove invaluable to a range of problems involving dopaminergic function including addiction and various forms of mental illness. The primary physical deficit in Parkinson's disease (PD) is the loss of 80-90% of dopamine neurons and so this proposal seeks to use the acute phase of DBS electrode implantation to gain new insights into exactly the pathology that tragically afflicts sufferers of the disease.