A method and neurostimulation system of providing therapy to a patient is provided. A plurality of electrodes are placed in contact with tissue of a patient, a conditioning pulse is conveyed from the plurality of electrodes in one of a monopolar manner and a multipolar manner, and a stimulation pulse is conveyed from the plurality of electrodes in a different one of the monopolar manner and the multipolar manner. As one example, the sub-threshold conditioning pulse may be a depolarizing pulse conveyed from the plurality of electrodes to render a first region of the tissue less excitable to stimulation, and the stimulation pulse may be conveyed from the plurality of electrodes to stimulate a second different region of the tissue.