Brain Mechanisms of Adaptive Memory: Neuromodulation and Behavior in Humans

A fundamental question in the study of memory is: Why do we remember some events but forget others? It has been proposed that people preferentially remember motivationally relevant information, as these memories may be useful in guiding choices in the future, a framework called adaptive memory. This dissertation examined the brain mechanisms that support adaptive memory, specifically focusing on how memory is shaped by rewards and dopamine, using a combination of pharmacological manipulations and behavioral assays. First, we found that rewards retroactively prioritize memory for preceding neutral events, and consistent with models of hippocampal replay, two periods of consolidation are necessary for this effect: a period of rest immediately following encoding and overnight consolidation. Second, motivated by research showing that neurotransmitters, such as dopamine, potentiate motivationally relevant memories to endure over long durations, we administered d-amphetamine (a dopamine agonist) before encoding. We found that when hippocampus dependent memory is tested after a short delay, working memory best accounts for memory performance, but when tested after a long delay, d-amphetamine level directly predicts memory performance. And third, we tested how d-amphetamine modulates different memory systems after a delay, using two different behavioral paradigms in which participants learned about overlapping associations using either stimulus-response learning or deliberate associative encoding. In both experiments, we found that d-amphetamine during encoding enhanced test performance on the trained items a week later; however, we did not detect any evidence that d-amphetamine modulates the integration of the overlapping pairs. Together, the work reported in this dissertation suggests that memory for motivationally relevant information is prioritized, dopamine enhances performance across different memory and learning systems, the effect of both reward and dopamine on memory and learning emerge after consolidation, and dopamine does not bias the hippocampus to encode memories in an integrated manner.