Systems and methods for reducing neurostimulation electrode configuration and parameter search space and controlling electrostimulation are discussed. An exemplary system includes an implantable stimulator to provide electrostimulation via a lead comprising a plurality of electrodes, and a programming device. The programing device receives electrode position information relative to an anatomical region of interest or physiological signals respectively sensed by the plurality of electrodes, and identifies a search space of electrode configurations and parameter values for the lead with respect to the neural target. The programing device can determine a target stimulation setting based on a clinical response to electrostimulation delivered using electrodes and stimulation parameter values from the identified search space, and generate a control signal to the control the implantable stimulator to deliver electrostimulation in accordance with the target stimulation setting.