Studies on neural plasticity associated with brain-machine interface (BMI) exposure have primarily documented changes in single neuron activity, and largely in intact subjects. Here, we demonstrate significant changes in ensemble-level functional connectivity among primary motor cortical (MI) neurons of chronically amputated monkeys exposed to control a multiple-degree-of-freedom robot arm. A multi-electrode array was implanted in M1 contralateral or ipsilateral to the amputation in three animals. Two clusters of stably recorded neurons were arbitrarily assigned to control reach and grasp movements, respectively. With exposure, network density increased in a nearly monotonic fashion in the contralateral monkeys, whereas the ipsilateral monkey pruned the existing network before re-forming a denser connectivity. Excitatory connections among neurons within a cluster were denser, whereas inhibitory connections were denser among neurons across the two clusters. These results indicate that cortical network connectivity can be modified with BMI learning, even among neurons that have been chronically de-efferented and de-afferented due to amputation.