Signed Reward Prediction Errors in the Ventral Striatum Drive Episodic Memory

Recent behavioral evidence implicates reward prediction errors (RPEs) as a key factor in the acquisition of episodic memory. Yet, important neural predictions related to the role of RPEs in episodic memory acquisition remain to be tested. Humans (both sexes) performed a novel variable-choice task where we experimentally manipulated RPEs and found support for key neural predictions with fMRI. Our results show that in line with previous behavioral observations, episodic memory accuracy increases with the magnitude of signed (i.e., better/worse-than-expected) RPEs (SRPEs). Neurally, we observe that SRPEs are encoded in the ventral striatum (VS). Crucially, we demonstrate through mediation analysis that activation in the VS mediates the experimental manipulation of SRPEs on episodic memory accuracy. In particular, SRPE-based responses in the VS (during learning) predict the strength of subsequent episodic memory (during recollection). Furthermore, functional connectivity between task-relevant processing areas (i.e., face-selective areas) and hippocampus and ventral striatum increased as a function of RPE value (during learning), suggesting a central role of these areas in episodic memory formation. Our results consolidate reinforcement learning theory and striatal RPEs as key factors subtending the formation of episodic memory.SIGNIFICANCE STATEMENT Recent behavioral research has shown that reward prediction errors (RPEs), a key concept of reinforcement learning theory, are crucial to the formation of episodic memories. In this study, we reveal the neural underpinnings of this process. Using fMRI, we show that signed RPEs (SRPEs) are encoded in the ventral striatum (VS), and crucially, that SRPE VS activity is responsible for the subsequent recollection accuracy of one-shot learned episodic memory associations.