To gain efficiency in performance of a novel complex movement, we must learn to coordinate the action of the pertinent muscle groups. We used functional magnetic resonance imaging (fMRI) to investigate the mechanisms of learning a novel synergic movement in human primary motor cortex (M1). We show for the first time changes in connectivity profiles between muscle representations in relation to learning and short-term plasticity. The abductor pollicis brevis (APB) and the deltoid muscles were trained for fast synchronous co-contraction. This learned synchrony of muscle contractions was related to rapid increase in functional connectivity between the central M1 representations of the participating muscle groups. Directionality and size of use dependent plasticity shifts in APB muscle representation in M1 also showed links to performance of the task and general levels of daily activity. This result suggests that functional connectivity between M1 representations of participating muscle groups are a basic central mechanism for establishing movement synergies. The timing of the increased connectivity and directional nature of the plasticity provide insight into the cortical integration of M1 muscle representations as a function of lifestyle and learning processes. Greater levels of daily activity may increase the integration of muscle representations across the motor cortex, enabling faster learning of novel movements.