Cortico-hippocampal representational similarity contributes to learning of multiple motor sequences

Abstract Cortico-hippocampal interaction is integral to memory consolidation during sleep or wakeful rest. However, the extent of its engagement in non-declarative motor memory during skill learning remains largely undefined. Specifically, it remains unclear how neural representations in cortical and hippocampal regions are related to learning multiple motor sequences. Here, we conducted an fMRI experiment in which participants learned four distinct motor sequences in a pseudo-random order with interleaved rest periods. We found pattern separation in the sensorimotor regions was significant, particularly in the anterior motor cortex, related to early learning performance. However, there was no pattern separation in the hippocampus during the rest periods. Intriguingly, the representational similarity between the motor cortex during task periods and the hippocampus during rest periods was highly correlated with overall learning performance. These findings suggest a new role of hippocampal replay in motor sequence learning, that is, learning a more abstract relational structure of sequences instead of representing sequences per se.