Midbrain–Hippocampus Structural Connectivity Selectively Predicts Motivated Memory Encoding

Motivation is a powerful driver of learning and memory. Functional MRI studies show that interactions among the dopaminergic midbrain substantia nigra/ventral tegmental area (SN/VTA), hippocampus, and nucleus accumbens (NAc) are critical for motivated memory encoding. However, it is not known whether these effects are transient and purely functional, or whether individual differences in the structure of this circuit underlie motivated memory encoding. To quantify individual differences in structure, diffusion-weighted MRI and probabilistic tractography were used to quantify SN/VTA–striatum and SN/VTA–hippocampus pathways associated with motivated memory encoding in humans. Male and female participants completed a motivated source memory paradigm. During encoding, words were randomly assigned to one of three conditions, reward (1. 00), control (0. 00), or punishment (−1. 00). During retrieval, participants were asked to retrieve item and source information of the previously studied words and were rewarded or penalized according to their performance. Source memory for words assigned to both reward and punishment conditions was greater than those for control words, but there were no differences in item memory based on value. Anatomically, probabilistic tractography results revealed a heterogeneous, topological arrangement of the SN/VTA. Tract density measures of SN/VTA–hippocampus pathways were positively correlated with individual differences in reward-and-punishment-modulated memory performance, whereas density of SN/VTA–striatum pathways showed no association. This novel finding suggests that pathways emerging from the human SV/VTA are anatomically separable and functionally heterogeneous. Individual differences in structural connectivity of the dopaminergic hippocampus–VTA loop are selectively associated with motivated memory encoding. SIGNIFICANCE STATEMENT Functional MRI studies show that interactions among the SN/VTA, hippocampus, and NAc are critical for motivated memory encoding. This has led to competing theories that posit either SN/VTA–NAc reward prediction errors or SN/VTA–hippocampus signals underlie motivated memory encoding. Additionally, it is not known whether these effects are transient and purely functional or whether individual differences in the structure of these circuits underlie motivated memory encoding. Using diffusion-weighted MRI and probabilistic tractography, we show that tract density measures of SN/VTA–hippocampus pathways are positively correlated with motivated memory performance, whereas density of SN/VTA–striatum pathways show no association. This finding suggests that anatomic individual differences of the dopaminergic hippocampus–VTA loop are selectively associated with motivated memory encoding.