Motor sequence learning under high levels of contextual interference (CI) disrupts initial performance but supports delayed test and transfer performance when compared to learning under low CI. Integrating findings from early behavioral work and more recent experimental efforts that incorporated neurophysiologic measures led to a novel account of the role of CI during motor sequence learning. This account focuses on important contributions from two neural regions-the dorsal premotor area and the SMA complex-that are recruited earlier and more extensively during the planning of a motor sequence in a high CI context. It is proposed that activation of these regions is critical to early adaptation of sequence structure amenable to long-term storage. Moreover, greater CI enhances access to newly acquired motor sequence knowledge through (1) the emergence of temporary functional connectivity between neural sites previously described as crucial to successful longterm performance of sequential behaviors, and (2) heightened excitability of M1-a key constituent of the temporary coupled neural circuits, and the primary candidate for storage of motor memory.