Functional diversity of the human dopamine system

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Dopamine, a vital neuromodulator in the brain, is involved in many cognitive processes and behaviors, such as how people make decisions and form memories. Recent animal research suggests that dopamine function, namely how dopamine neuron influence brain activity, is more diverse than previously thought. These animal studies show that the diverse function of dopamine does not come just from the existence of different types of dopamine neurons; instead, it comes from variation in the anatomical structure of the dopamine system in the brain. Different dopamine pathways support different cognitive processes and behaviors, such as reward and punishment, which is significant because such pathways are large enough to study with non-invasive techniques such as magnetic resonance imaging (MRI). This project will use MRI in human participants to achieve two goals: (1) to map dopamine pathways in the human brain and (2) to measure activity from brain regions where dopamine neurons are and brain regions that receive dopamine input. This research is important because it employs non-invasive neuroimaging methods in humans to test and expand ideas from animal research. Studying humans has the promise to directly impact and improve understanding of dopamine-mediated behaviors, which are broadly relevant to many areas of psychology and social science. This research project therefore will contribute to an improved understanding of the brain basis of decision-making, enabling insight into how altered brain function, such as occurs with aging and mental health disorders, influences behavior. The dopamine system is involved in many fundamental cognitive and behavioral processes. To date, subclasses of dopamine neurons have been identified that respond to rewards, aversive stimuli, or equally to reward and aversive stimuli. Importantly, recent evidence from both rodent and nonhuman primate studies shows that certain dopaminergic pathways support reward learning and conditioned place preference, while other dopaminergic pathways support learned aversion and conditioned place avoidance. Collectively this body of animal work, which spans multiple labs and species, supports the idea that the dopamine system has anatomically defined heterogeneity. This project proposes to test the hypothesis that dopaminergic function itself is diverse and not consistent with uniform transmission of reward prediction errors. The PIs will use functional magnetic resonance imaging (fMRI) and diffusion-weighted images (DWI) combined with probabilistic tractography methods to study functional and white matter connectivity patterns of mesolimbic dopamine networks, which include the brainstem substantia nigra and ventral tegmental area (SN/VTA), during learning tasks mediated by rewarding and aversive outcomes. This endeavor is noteworthy because it extends neuroimaging of the brainstem to include DWI, which enables white matter connectivity measurements between the mesencephalon, striatum and cortex, and because it has the potential to make a fundamental contribution to how decision neuroscience understands dopamine-mediated behaviors. This research contributes to the central aims of neuroeconomics, an evolving interdisciplinary field that provides an exciting educational opportunity for undergraduate and graduate students interested in neuroscience, decision-making, or the social sciences. Education is a primary aim of the project; students will be directly involved in the conduct of the studies, and data will be made publicly available.