Transfer of motor learning is associated with patterns of activity in the default mode network.

An often-desired feature of motor learning is that it generalizes to untrained scenarios. Yet, how this is supported by brain activity remains poorly understood. Here we show, using human functional MRI and a sensorimotor adaptation task involving the transfer of learning from the trained to untrained hand, that the transfer phase of adaptation re-instantiates a highly similar large-scale pattern of brain activity to that observed during initial adaptation. Notably, we find that these neural changes, rather than occurring at the level of sensorimotor regions, predominantly occur across distributed areas of higher-order transmodal cortex, specifically in regions of the default mode network (DMN). Moreover, we show that these learning-related neural changes relate to the structural properties of transmodal cortex (its myelin content and neurotransmitter receptor density), and that intersubject differences in DMN activity relate to both adaptation- and transfer-phase task performance. Together, these findings suggest that the transfer of learning across the hands is supported by the re-expression of the same activity patterns in the DMN as those that support initial learning. Collectively, these results offer a unique characterization of the whole-brain macroscale changes associated with sensorimotor learning and generalization, and establish a key role for higher-order brain areas, such as the DMN, in the transfer of learning to untrained scenarios.