Advances in molecular genetics, endocrinology and neuro-imaging start to unravel the relationships between genes, hormonal status, cognition and functional brain regions and to build new bridges between molecular, cellular and neuroscience systems levels in humans. The goals of this research program are to understand how individual genetic and hormonal variations influence reward processing in humans. Reward processing plays a fundamental role in motivation, learning and cognition. Fundamental electrophysiological results in monkeys indicate that dopaminergic neurons code both a transient reward error prediction signal, that is a discrepancy between the predicted reward and the reward effectively delivered, and a sustained signal covering with reward uncertainty that may be functionally important for risk seeking behaviour. Until recently, it was unknown whether these two modes of activities could also be observed in humans and whether they could be distinguished by post-synaptic dopaminergic projection sites.
Using functional magnetic resonance imaging in a new task that systematically varied monetary reward probability, we have distinguished transient and sustained dynamics of the reward system in healthy humans. We are planning to use this same task in order to pursue the following specific aims: (1) to understand the influence of the polymorphism of the catechol-O-methyltransferase (COMT), an enzyme that metabolises released dopamine, on the pattern of brain activation during reward processing; (2) to investigate how gonadal steroid hormones affect the reward system during the normal menstrual cycle, by studying women during the follicular and luteal phases. This basic research project on the neurobiology of reward is expected to provide new insights to under stand a variety of neuropathologies involving the reward system, including schizophrenia, drug addiction and Parkinson's disease.
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