Hippocampal convergence during anticipatory midbrain activation promotes subsequent memory formation.

The hippocampus has been a focus of memory research since H.M's surgery abolished his ability to form new memories, yet its mechanistic role in memory remains debated. Here, we identify a candidate memory mechanism: an anticipatory hippocampal "convergence state", observed while awaiting valuable information, and which predicts subsequent learning. During fMRI, participants viewed trivia questions eliciting high or low curiosity, followed seconds later by its answer. We reasoned that encoding success requires a confluence of conditions, so that hippocampal states more conducive to memory formation should converge in state space. To operationalize convergence of neural states, we quantified the typicality of multivoxel patterns in the medial temporal lobes during anticipation and encoding of trivia answers. We found that the typicality of anticipatory hippocampal patterns increased during high curiosity. Crucially, anticipatory hippocampal pattern typicality increased with dopaminergic midbrain activation and uniquely accounted for the association between midbrain activation and subsequent recall. We propose that hippocampal convergence states may complete a cascade from motivation and midbrain activation to memory enhancement, and may be a general predictor of memory formation.

Expected Reward Value and Reward Uncertainty Have Temporally Dissociable Effects on Memory Formation.

Anticipating rewards has been shown to enhance memory formation. Although substantial evidence implicates dopamine in this behavioral effect, the precise mechanisms remain ambiguous. Because dopamine nuclei have been associated with 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 response that has been demonstrated during high reward uncertainty [Fiorillo, C. D., Tobler, P. N., & Schultz, W. Discrete coding of reward probability and uncertainty by dopamine neurons. Science, 299, 1898-1902, 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. Notably, although 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 distinct memory enhancement, temporally consistent with sustained anticipatory dopamine release, points toward new mechanisms of memory modulation by reward now ripe for further investigation.

Reward Anticipation Dynamics during Cognitive Control and Episodic Encoding: Implications for Dopamine.

Dopamine (DA) modulatory activity critically supports motivated behavior. This modulation operates at multiple timescales, but the functional roles of these distinct dynamics on cognition are still being characterized. Reward processing has been robustly linked to DA activity; thus, examining behavioral effects of reward anticipation at different timing intervals, corresponding to different putative dopaminergic dynamics, may help in characterizing the functional role of these dynamics. Towards this end, we present two research studies investigating reward motivation effects on cognitive control and episodic memory, converging in their manipulation of rapid vs. multi-second reward anticipation (consistent with timing profiles of phasic vs. ramping DA, respectively) on performance. Under prolonged reward anticipation, both control and memory performances were enhanced, specifically when combined with other experimental factors: task-informative cues (control task) and reward uncertainty (memory task). Given observations of ramping DA under uncertainty (Fiorillo et al., 2003) and arguments that uncertainty may act as a control signal increasing environmental monitoring (Mushtaq et al., 2011), we suggest that task information and reward uncertainty can both serve as "need for control" signals that facilitate learning via enhanced monitoring, and that this activity may be supported by a ramping profile of dopaminergic activity. Observations of rapid (i.e., phasic) reward on control and memory performance can be interpreted in line with prior evidence, but review indicates that contributions of different dopaminergic timescales in these processes are not well-understood. Future experimental work to clarify these dynamics and characterize a cross-domain role for reward motivation and DA in goal-directed behavior is suggested.