Neuroimaging of Neurotransmitter Release in Humans During Cognitive and Behavioral Tasks

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AbstractWith National Science Foundation support, Dr. Zald and colleagues will conduct a three-year project aimed at developing a novel program of research that fuses cognitive neuroimaging techniques with neuroimaging of neurotransmitter release. A wealth of neuropharmacological evidence indicates that dopamine (DA) exerts a profound influence on affective, motor, and cognitive processes. A full understanding of DA.s influence on neurobehavioral systems requires knowledge of how and when DA is released. Recent advances in PET imaging make it possible to safely measure DA release in humans during different cognitive or behavioral tasks. Such data provide novel insights into the functions of DA, and allows assessment of DA during cognitive functions for which animal models are lacking. However, because of the interdisciplinary nature of such studies, few cognitive neuroscientists have exploited these techniques. The project includes: 1) a learning component to facilitate the acquisition of the methodological skills necessary to perform studies of DA release using [11C]raclopride PET; 2) a program of studies aimed at testing specific hypotheses about when endogenous DA is released; and 3) continuing development of teaching skills, including the development of a course on the cognitive neuroscience of emotion. Specific studies focus on 1) the influence of task response demands and reward contingencies on DA release, 2) the impact of novelty on DA release, 3) whether DA is released during tasks involving set shifting (which is disrupted by DA depletions), and 4) the relationship between BOLD fMRI responses and DA release in striatal subregions. The proposal establishes collaborations between two major academic centers that will allow the exchange of ideas and technical developments in this emerging field. Because the field is in its infancy, dissemination of these ideas and techniques at meetings and symposium is likely to have substantial effects in guiding how others approach this area. Moreover, the interdisciplinary nature of the work allows for the integration of ideas across different fields of neuroscience. The grant also provides the opportunity to facilitate training at the graduate level including participation of minority M.D. trainees through the Vanderbilt-Meharry Medical college alliance. At the institutional level, it furthers the department of psychology's goal of becoming a leader in cognitive neuroimaging and will facilitate the expansion of the types of PET studies performed at Vanderbilt.