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Abstract New information is rapidly learned when it is compatible with pre-existing knowledge, i.e. with a previously acquired schematic representation of the learned information. The influence of pre-established schema on learning has been extensively studied in the declarative memory domain, where it was shown that schema-compatible information could be rapidly assimilated into neocortical storage, bypassing the slow hippocampo-neocortical memory transfer process. Schema-mediated learning was recently examined in the motor memory domain; however, its neural substrates remain unknown. The goal of this study was to address this knowledge gap using both univariate and multivariate analyses of functional Magnetic Resonance Imaging (fMRI) data acquired in 60 young healthy participants during the practice of a motor sequence that was either compatible or incompatible with a previously acquired cognitive-motor schema. Consistent with previous literature, our behavioural results suggest that performance of sequential movements was enhanced when practice occurred in a context that was compatible with the previously acquired schema. Brain imaging results show that practice in a schema-compatible context specifically recruited the left primary motor cortex and resulted in a decrease in connectivity between the bilateral motor cortex and a set of task-relevant brain regions including the hippocampus, striatum, and cerebellum. Temporally fine-grained MRI analyses suggest that multivoxel activation patterns in the primary motor and the premotor cortices were modulated by schema-compatibility, with greater pattern similarity detected for sequence elements corresponding to and surrounding novel sequential movements under schema-compatible compared with -incompatible conditions. Altogether, these results suggest that motor cortical regions facilitate schema-mediated integration of novel movements into memory.