PT - JOURNAL ARTICLE AU - Jessica K. Stanek AU - Kathryn C. Dickerson AU - Kimberly S. Chiew AU - Nathaniel J. Clement AU - R. Alison Adcock TI - Expected reward value and reward uncertainty have temporally dissociable effects on memory formation AID - 10.1101/280164 DP - 2018 Jan 01 TA - bioRxiv PG - 280164 4099 - http://biorxiv.org/content/early/2018/03/11/280164.short 4100 - http://biorxiv.org/content/early/2018/03/11/280164.full AB - Anticipating rewards has been shown to enhance memory formation. While substantial evidence implicates dopamine in this behavioral effect, the precise mechanisms remain ambiguous. Because dopamine nuclei show two distinct physiological signatures of reward prediction, we hypothesized two dissociable effects on memory formation. These two signatures are a phasic dopamine response immediately following a reward cue that encodes its expected value, and a sustained, ramping dopamine response that is greater during high reward uncertainty (Fiorillo, Tobler, & Schultz, 2003). Here, we show in humans that the impact of reward anticipation on memory for an event depends on its timing relative to these physiological signatures. By manipulating reward probability (100%, 50%, or 0%) and the timing of the event to be encoded (just after the reward cue versus just before expected reward outcome), we demonstrated the predicted double dissociation: early during reward anticipation, memory formation was improved by increased expected reward value, whereas late during reward anticipation, memory formation was enhanced by reward uncertainty. Moreover, while the memory benefits of high expected reward in the early interval were consolidation-dependent, the memory benefits of high uncertainty in the later interval were not. These findings support the view that expected reward benefits memory consolidation via phasic dopamine release. The novel finding of a dissociable memory enhancement, temporally consistent with sustained anticipatory dopamine release, points toward new mechanisms of memory modulation by reward now ripe for further investigation.