Neural substrates related to memory consolidation of learning multiple motor sequences during wakeful rest

Abstract Motor learning has been thought to be independent of the hippocampus since the landmark experiment of the patient H.M. However, recent studies have provided cumulative evidence of the hippocampus's role in motor memory consolidation during both sleep and wakeful rest. Motor memory consolidation due to hippocampal plastic changes could occur faster than previously thought, even during short wakeful rest periods interleaved with practice periods. However, it remains unclear to what extent hippocampal replay or reactivation contributes to motor memory consolidation during wakeful rest. We investigated the fMRI evidence of motor memory consolidation of learning multiple motor sequence during wakeful rest. We found that while sensorimotor regions exhibited sequence-specific activity patterns during practice, these were not reliably discriminable in the sensorimotor regions and hippocampus during brief interleaved rest periods. In contrast, neural activity patterns in the right hippocampus, right putamen, and sensorimotor regions during interleaved rest periods showed greater similarity to post-learning rest patterns than pre-learning rest patterns. These findings suggest that hippocampal reactivation may not be related to a specific sequence as previously claimed, but rather to a more generalized or abstract representation of sequences, potentially to stabilize and integrate newly acquired skills when learning multiple sequences simultaneously.