An electrical neurostimulation therapy system comprising: a plurality of electrodes disposed along a lead inserted across an anatomical midline of a spinal cord of a patient and angled relative to the anatomical midline of the spinal cord, the lead connected to an electrical neurostimulation therapy device; a therapy delivery circuit of the electrical neurostimulation therapy device configured to deliver electrical neurostimulation therapy to the patient via a plurality of combinations of the plurality of electrodes; and one or more processors configured to: control delivery of the electrical neurostimulation therapy to the patient for each of the plurality of combinations of the plurality of electrodes; determine a response of a tissue of the patient to the electrical neurostimulation therapy, wherein the response is an evoked compound action potential (eCAP) response of a nerve fiber of the patient arising from the therapy delivery circuit; determine, based on the delivery of the electrical neurostimulation therapy for each of the plurality of combinations of the plurality of electrodes and the response of the tissue, a location of a physiological midline of the spinal cord of the patient; based on the location of the physiological midline of the spinal cord of the patient, select at least one electrode of the plurality of electrodes for subsequent delivery of electrical neurostimulation therapy to the patient; and control delivery of electrical neurostimulation therapy to the patient by the electrical neurostimulation therapy device via the selected at least one electrode of the plurality of electrodes. a plurality of electrodes disposed along a lead inserted across an anatomical midline of a spinal cord of a patient and angled relative to the anatomical midline of the spinal cord, the lead connected to an electrical neurostimulation therapy device; a therapy delivery circuit of the electrical neurostimulation therapy device configured to deliver electrical neurostimulation therapy to the patient via a plurality of combinations of the plurality of electrodes; and one or more processors configured to: control delivery of the electrical neurostimulation therapy to the patient for each of the plurality of combinations of the plurality of electrodes; determine a response of a tissue of the patient to the electrical neurostimulation therapy, wherein the response is an evoked compound action potential (eCAP) response of a nerve fiber of the patient arising from the therapy delivery circuit; determine, based on the delivery of the electrical neurostimulation therapy for each of the plurality of combinations of the plurality of electrodes and the response of the tissue, a location of a physiological midline of the spinal cord of the patient; based on the location of the physiological midline of the spinal cord of the patient, select at least one electrode of the plurality of electrodes for control delivery of the electrical neurostimulation therapy to the patient for each of the plurality of combinations of the plurality of electrodes; determine a response of a tissue of the patient to the electrical neurostimulation therapy, wherein the response is an evoked compound action potential (eCAP) response of a nerve fiber of the patient arising from the therapy delivery circuit; determine, based on the delivery of the electrical neurostimulation therapy for each of the plurality of combinations of the plurality of electrodes and the response of the tissue, a location of a physiological midline of the spinal cord of the patient; based on the location of the physiological midline of the spinal cord of the patient, select at least one electrode of the plurality of electrodes for subsequent delivery of electrical neurostimulation therapy to the patient; and control delivery of electrical neurostimulation therapy to the patient by the electrical neurostimulation therapy device via the selected at least one electrode of the plurality of electrodes.